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Sample records for link mechanisms leading

  1. Current Leads, Links and Buses

    CERN Document Server

    Ballarino, A

    2014-01-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  2. Current Leads, Links and Buses

    Energy Technology Data Exchange (ETDEWEB)

    Ballarino, A [European Organization for Nuclear Research, Geneva (Switzerland)

    2014-07-01

    Electrical transfer from a room temperature power source to a superconducting system is done via conventional or superconducting current leads and superconducting buses or links. The principles of optimization of these devices are presented, with emphasis on the cryogenic, electrical, and superconductor related aspects that drive choices for a system.

  3. Identifying links between origami and compliant mechanisms

    Directory of Open Access Journals (Sweden)

    H. C. Greenberg

    2011-12-01

    Full Text Available Origami is the art of folding paper. In the context of engineering, orimimetics is the application of folding to solve problems. Kinetic origami behavior can be modeled with the pseudo-rigid-body model since the origami are compliant mechanisms. These compliant mechanisms, when having a flat initial state and motion emerging out of the fabrication plane, are classified as lamina emergent mechanisms (LEMs. To demonstrate the feasibility of identifying links between origami and compliant mechanism analysis and design methods, four flat folding paper mechanisms are presented with their corresponding kinematic and graph models. Principles from graph theory are used to abstract the mechanisms to show them as coupled, or inter-connected, mechanisms. It is anticipated that this work lays a foundation for exploring methods for LEM synthesis based on the analogy between flat-folding origami models and linkage assembly.

  4. Lead free solder mechanics and reliability

    CERN Document Server

    Pang, John Hock Lye

    2012-01-01

    Lead-free solders are used extensively as interconnection materials in electronic assemblies and play a critical role in the global semiconductor packaging and electronics manufacturing industry. Electronic products such as smart phones, notebooks and high performance computers rely on lead-free solder joints to connect IC chip components to printed circuit boards. Lead Free Solder: Mechanics and Reliability provides in-depth design knowledge on lead-free solder elastic-plastic-creep and strain-rate dependent deformation behavior and its application in failure assessment of solder joint reliability. It includes coverage of advanced mechanics of materials theory and experiments, mechanical properties of solder and solder joint specimens, constitutive models for solder deformation behavior; numerical modeling and simulation of solder joint failure subject to thermal cycling, mechanical bending fatigue, vibration fatigue and board-level drop impact tests. This book also: Discusses the mechanical prope...

  5. Mechanism of lead removal by waste materials

    International Nuclear Information System (INIS)

    Qaiser, S.; Saleemi, A.R.; Ahmed, M.M.

    2007-01-01

    Heavy metal ions are priority pollutants, due to their toxicity and mobility in natural water ecosystems. The discharge of heavy metals into aquatic ecosystems has become a matter of concern in Pakistan over the last few decades. These contaminants are introduced into the aquatic systems significantly as a result of various industrial operations. The metals of concern include lead, chromium, zinc, copper, nickel and uranium. Lead is one of the most hazardous and toxic metals. It is used as industrial raw material in the manufacture of storage batteries, pigments, leaded glass, fuels, photographic materials, matches and explosives. Conventional methods for treatment of dissolved lead include precipitation, adsorption, coagulation/notation, sedimentation, reverse osmosis and ion exchange. Each process has its merits and limitations in applications. Adsorption by activated carbon and ion exchange using commercial ion exchange resins are very expensive processes, especially for a developing country like Pakistan. The present research was conducted to identify some waste materials, which can be utilized to remove lead from industrial wastewater. Natural wastes in the form of leaves and ash have considerable amounts of CaO, MgO, Na/sub 2/O, SiO/sub 2/ and Al/sub 2/O/sub 3/ which can be utilized for precipitation and adsorption. Utilization of waste materials to remove lead from industrial wastewater is the basic theme of this research. The waste materials used in this research were maple leaves, pongamia pinata leaves, coal ash and maple ago leave ash. Parameters studied were reaction time, precipitant dose, pH and temperature. It was found that maple leaves ash has maximum lead removal capacity 19.24 mg g/sup -1/ followed by coal ash 13.2 mg g/sup -1/. The optimal pH was 5 for maple leaves and pongamia Pinata leaves; and 4 for coal ash and maple leaves ash. Removal capacity decreased with increase in temperature. The major removal mechanisms were adsorption and

  6. Biosorption of lead phosphates by lead-tolerant bacteria as a mechanism for lead immobilization.

    Science.gov (United States)

    Rodríguez-Sánchez, Viridiana; Guzmán-Moreno, Jesús; Rodríguez-González, Vicente; Flores-de la Torre, Juan Armando; Ramírez-Santoyo, Rosa María; Vidales-Rodríguez, Luz Elena

    2017-08-01

    The study of metal-tolerant bacteria is important for bioremediation of contaminated environments and development of green technologies for material synthesis due to their potential to transform toxic metal ions into less toxic compounds by mechanisms such as reduction, oxidation and/or sequestration. In this study, we report the isolation of seven lead-tolerant bacteria from a metal-contaminated site at Zacatecas, México. The bacteria were identified as members of the Staphylococcus and Bacillus genera by microscopic, biochemical and 16S rDNA analyses. Minimal inhibitory concentration of these isolates was established between 4.5 and 7.0 mM of Pb(NO 3 ) 2 in solid and 1.0-4.0 mM of Pb(NO 3 ) 2 in liquid media. A quantitative analysis of the lead associated to bacterial biomass in growing cultures, revealed that the percentage of lead associated to biomass was between 1 and 37% in the PbT isolates. A mechanism of complexation/biosorption of lead ions as inorganic phosphates (lead hydroxyapatite and pyromorphite) in bacterial biomass, was determined by Fourier transform infrared spectroscopy and X-ray diffraction analyses. Thus, the ability of the lead-tolerant isolates to transform lead ions into stable and highly insoluble lead minerals make them potentially useful for immobilization of lead in mining waste.

  7. Fracture mechanisms in lead zirconate titanate ceramics

    International Nuclear Information System (INIS)

    Freiman, S.W.; Chuck, L.; Mecholsky, J.J.; Shelleman, D.L.

    1986-01-01

    Lead Zirconate Titanate (PZT) ceramics can be formed over a wide range of PbTiO 3 /PbZrO 3 ratios and exist in a number of crystal structures. This study involved the use of various fracture mechanics techniques to determine critical fracture toughness, K /SUB IC/ , as a function of composition, microstructure, temperature, and electrical and thermal history. The results of these experiments indicate that variations in K /SUB IC/ are related to phase transformations in the material as well as to other toughening mechanisms such as twinning and microcracking. In addition, the strength and fracture toughness of selected PZT ceramics were determined using specimens in which a crack was introduced by a Vicker's hardness indentor. The variation of K /SUB IC/ with composition and microstructure was related to the extent of twin-crack interaction. Comparison of the plot of strength as a function of indentation load with that predicted from indentation fracture models indicates the presence of internal stresses which contribute to failure. The magnitude of these internal stresses has been correlated with electrical properties of the ceramic. Fractographic analysis was used to determine the magnitude of internal stresses in specimens failing from ''natural flaws.''

  8. Mechanisms linking excess adiposity and carcinogenesis promotion

    Directory of Open Access Journals (Sweden)

    Ana I. Pérez-Hernández

    2014-05-01

    Full Text Available Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well-established for several tumor types, such as breast cancer in postmenopausal women, colorectal and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: i inflammatory changes leading to macrophage polarization and altered adipokine profile; ii insulin resistance development; and iii adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.

  9. Linking plants, fungi and soil mechanics

    Science.gov (United States)

    Yildiz, Anil; Graf, Frank

    2017-04-01

    Plants provide important functions in respect soil strength and are increasingly considered for slope stabilisation within eco-engineering methods, particularly to prevent superficial soil failure. The protective functions include hydrological regulation through interception and evapo-transpiration as well as mechanical stabilisation through root reinforcement and, to a certain extent, chemical stabilisation through sticky metabolites. The ever-growing application of plants in slope stabilisation demanded more precise information of the vegetation effects and, concomitant, led the models for quantifying the reinforcement shoot up like mushrooms. However, so far, the framework and interrelationships for both the role of plants and the quantification concepts have not been thoroughly analysed and comprehensively considered, respectively, often resulting in unsatisfactory results. Although it seems obvious and is implicitly presupposed that the plant specific functions related to slope stability require growth and development, this is anything but given, particularly under the often hostile conditions dominating on bare and steep slopes. There, the superficial soil layer is often characterised by a lack of fines and missing medium-sized and fine pores due to an unstable soil matrix, predominantly formed by coarse grains. Low water retention capacity and substantial leaching of nutrients are the adverse consequences. Given this general set-up, sustainable plant growth and, particularly, root development is virtually unachievable. At exactly this point mycorrhizal fungi, the symbiotic partners of almost all plants used in eco-engineering, come into play. Though, they are probably well-known within the eco-engineering community, mycorrhizal fungi lead a humble existence. This is in spite of the fact that they supply their hosts with water and nutrients, improving the plant's ability to master otherwise unbridgeable environmental conditions. However, in order to support

  10. Microchannel boiling mechanisms leading to burnout

    International Nuclear Information System (INIS)

    Landram, C.S.; Riddle, R.A.

    1994-01-01

    The authors are analyzing the thermal performance of microchannel heat sinks to extend their applied heat loads beyond coolant single-phase limits. This is the first investigation of boiling in the narrow (50-μm) microchannels having typically high-aspect-ratio (of order 10/1) flow cross-sections. The prescription of local, wall-coolant, interfacial, two-phase correlations first required development of a validated, approximate, thermal-model accounting for conjugate heat transfer. The strongest mechanism for heat transfer in two-phase microchannel flow was found to be saturated boiling in a channel region near the heated base. When this region dried out, burnout occurred, both in the computations and in the experiment

  11. Modular overconstrained weak-link mechanism for ultraprecision motion control

    International Nuclear Information System (INIS)

    Shu Deming; Toellner, Thomas S.; Alp, Esen E.

    2001-01-01

    We have designed and constructed a novel miniature overconstrained weak-link mechanism that will allow positioning of two crystals with better than 50 nrad angular resolution and nanometer linear driving sensitivity. The precision and stability of this structure allow the user to align or adjust an assembly of crystals to achieve the same performance as does a single channel-cut crystal, so we call it an ''artificial channel-cut crystal.'' Unlike the traditional kinematic linear spring mechanisms, the overconstrained weak-link mechanism provides much higher structure stiffness and stability. Using a laminar structure configured and manufactured by chemical etching and lithography techniques, we are able to design and build a planar-shape, high stiffness, high precision weak-link mechanism. In this paper, we present recent developments for the overconstrained weak-link mechanism. Applications of this new technique to synchrotron radiation instrumentation are also discussed

  12. Mechanism linking diabetes mellitus and obesity

    Directory of Open Access Journals (Sweden)

    Al-Goblan AS

    2014-12-01

    Full Text Available Abdullah S Al-Goblan,1 Mohammed A Al-Alfi,1 Muhammad Z Khan2 1Diabetes Center, King Fahad Specialist Hospital, Buraidah, Qassim, Kingdom of Saudi Arabia; 2Sulaiman AlRajhi Colleges, Al Bukairiyah, Kingdom of Saudi Arabia Abstract: Body mass index has a strong relationship to diabetes and insulin resistance. In obese individuals, the amount of nonesterified fatty acids, glycerol, hormones, cytokines, proinflammatory markers, and other substances that are involved in the development of insulin resistance, is increased. The pathogenesis in the development of diabetes is based on the fact that the β-islet cells of the pancreas are impaired, causing a lack of control of blood glucose. The development of diabetes becomes more inevitable if the failure of β-islet cells of the pancreas is accompanied by insulin resistance. Weight gain and body mass are central to the formation and rising incidence of type 1 and type 2 diabetes. This literature review will demonstrate the facts that link obesity with insulin resistance and pancreatic β-cell dysfunction. In conclusion, new approaches in managing and preventing diabetes in obese individuals must be studied and investigated based on the facts. Keywords: diabetes mellitus, obesity, insulin resistance

  13. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

    Science.gov (United States)

    Alexandre, Leo; Long, Elizabeth; Beales, Ian LP

    2014-01-01

    In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits. PMID:25400997

  14. Pathogenic mechanisms linking periodontal diseases with adverse pregnancy outcomes.

    Science.gov (United States)

    Cetin, I; Pileri, P; Villa, A; Calabrese, S; Ottolenghi, L; Abati, S

    2012-06-01

    In the last 2 decades, a large proportion of studies have focused on the relationship between maternal periodontal disease and poor obstetric outcomes. The aim of the present review is to summarize the current knowledge about human studies on the pathogenetic mechanisms linking periodontal diseases with adverse pregnancy outcomes. A search of the medical literature was conducted using NIH (National Institute of Health) Pubmed through April 2011. Articles were identified with the Medical Subject Heading (MeSH) and free text terms "small for gestational age (SGA)," "preeclampsia," "preterm labor," and "periodontal disease." Experimental human studies have shown that periodontal pathogens may disseminate toward placental and fetal tissues accompanied by an increase in inflammatory mediators in the placenta. As such, new inflammatory reactions within the placental tissues of the pregnant woman may occur, the physiological levels of prostaglandin E(2) (PGE(2)) and tumor necrosis factor-α (TNF-α) in the amniotic fluid may increase and eventually lead to premature delivery. Although many data from clinical trials suggest that periodontal disease may increase the adverse pregnancy outcome, the exact pathogenetic mechanism involved remains controversial. The findings explain the potential link between periodontal infections and adverse pregnancy outcomes. First, periodontal bacteria can directly cause infections both of the uteroplacenta and the fetus; second, systemic inflammatory changes induced by periodontal diseases can activate responses at the maternal-fetal interface. Of note, associative studies have produced different results in different population groups and no conclusive evidence has still been produced for the potential role of preventive periodontal care to reduce the risk factors of preterm birth.

  15. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    Science.gov (United States)

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  16. Directed networks' different link formation mechanisms causing degree distribution distinction

    Science.gov (United States)

    Behfar, Stefan Kambiz; Turkina, Ekaterina; Cohendet, Patrick; Burger-Helmchen, Thierry

    2016-11-01

    Within undirected networks, scientists have shown much interest in presenting power-law features. For instance, Barabási and Albert (1999) claimed that a common property of many large networks is that vertex connectivity follows scale-free power-law distribution, and in another study Barabási et al. (2002) showed power law evolution in the social network of scientific collaboration. At the same time, Jiang et al. (2011) discussed deviation from power-law distribution; others indicated that size effect (Bagrow et al., 2008), information filtering mechanism (Mossa et al., 2002), and birth and death process (Shi et al., 2005) could account for this deviation. Within directed networks, many authors have considered that outlinks follow a similar mechanism of creation as inlinks' (Faloutsos et al., 1999; Krapivsky et al., 2001; Tanimoto, 2009) with link creation rate being the linear function of node degree, resulting in a power-law shape for both indegree and outdegree distribution. Some other authors have made an assumption that directed networks, such as scientific collaboration or citation, behave as undirected, resulting in a power-law degree distribution accordingly (Barabási et al., 2002). At the same time, we claim (1) Outlinks feature different degree distributions than inlinks; where different link formation mechanisms cause the distribution distinctions, (2) in/outdegree distribution distinction holds for different levels of system decomposition; therefore this distribution distinction is a property of directed networks. First, we emphasize in/outlink formation mechanisms as causal factors for distinction between indegree and outdegree distributions (where this distinction has already been noticed in Barker et al. (2010) and Baxter et al. (2006)) within a sample network of OSS projects as well as Java software corpus as a network. Second, we analyze whether this distribution distinction holds for different levels of system decomposition: open

  17. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Antonio F. Hernández

    2016-03-01

    Full Text Available Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation. Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  18. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators

    International Nuclear Information System (INIS)

    Schmitz, Andreas

    2013-01-01

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb 1-x Ca x Te were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while its thermoelectric properties

  19. Mechanical performances of lead-free solder joint connections with applications in the aerospace domain

    Directory of Open Access Journals (Sweden)

    Georgiana PADURARU

    2016-03-01

    Full Text Available The paper presents some theoretical and experimental aspects regarding the tribological performances of lead-free solder joint connections, with application in the aerospace domain. In order to highlight the mechanical and tribological properties of solder joint in correlation with different pad finishes, there were made some mechanical determinations using a dedicated Share Test System. The theoretical model highlights the link between the experimental results and the influence of gravitational acceleration on the mechanical and functional integrity of the electronic assemblies that works in vibration environment. The paper novelty is provided by the interdisciplinary experiment that offers results that can be used in the mechanical, tribological, electronical and aerospace domains.

  20. Linking Mechanisms of Work-Family Conflict and Segmentation

    Science.gov (United States)

    Michel, Jesse S.; Hargis, Michael B.

    2008-01-01

    Despite the abundance of work and family research, few studies have compared the linking mechanisms specified in theoretical models of work-family conflict and segmentation. Accordingly, the current study provides a greater degree of empirical clarity concerning the interplay of work and family by directly examining the indirect effects of…

  1. Effects of lead on the killing mechanisms of polymorphonuclear leukocytes

    International Nuclear Information System (INIS)

    Silberstein, C.F.

    1984-01-01

    The effects of lead on the killing mechanisms of rat polymorphonuclear leukocytes (PMN) were investigated, using male Long-Evans rats exposed to 1% lead acetate in the drinking water for varying periods of time to achieve blood lead levels ranging from 20-200 μg/dl. Studies of PMN bacterial and fungal killing activity, chemotaxis and phagocytosis demonstrated that: 1) bactericidal activity of PMN from rats exposed to lead was not altered; 2) chemotactic activity remained within normal limits; 3) the phagocytic ability of the PMN also remained unaltered. In addition to these normal findings, one major abnormality was demonstrated: a significant decrease in the ability of PMN from rats exposed to lead to kill Candida albicans. This defect was not related to age or to length of exposure. It could not be produced by addition of lead to the test system in vitro. Further investigation revealed significant decreases in PMN glucose-6-phosphate dehydrogenase, catalase, and myeloperoxidase activities. These data support two possible mechanisms for the abnormal fungicidal activity of PMN from lead-exposed rats: decrease in ability to reduce oxygen to active metabolites, or reduction in myeloperoxidase activity due to diminshed synthesis of the heme moiety required for its function

  2. Linking cases of illegal shootings of the endangered California condor using stable lead isotope analysis

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, Myra E., E-mail: myraf@ucsc.edu [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States); Kuspa, Zeka E. [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States); Welch, Alacia [National Park Service, Pinnacles National Park, 5000 Highway 146, Paicines, CA 95043 (United States); Eng, Curtis; Clark, Michael [Los Angeles Zoo and Botanical Gardens, 5333 Zoo Drive, Los Angeles, CA 90027 (United States); Burnett, Joseph [Ventana Wildlife Society, 19045 Portola Dr. Ste. F-1, Salinas, CA 93908 (United States); Smith, Donald R. [Microbiology and Environmental Toxicology Department, University of California, Santa Cruz, CA 95064 (United States)

    2014-10-15

    Lead poisoning is preventing the recovery of the critically endangered California condor (Gymnogyps californianus) and lead isotope analyses have demonstrated that ingestion of spent lead ammunition is the principal source of lead poisoning in condors. Over an 8 month period in 2009, three lead-poisoned condors were independently presented with birdshot embedded in their tissues, evidencing they had been shot. No information connecting these illegal shooting events existed and the timing of the shooting(s) was unknown. Using lead concentration and stable lead isotope analyses of feathers, blood, and recovered birdshot, we observed that: i) lead isotope ratios of embedded shot from all three birds were measurably indistinguishable from each other, suggesting a common source; ii) lead exposure histories re-constructed from feather analysis suggested that the shooting(s) occurred within the same timeframe; and iii) two of the three condors were lead poisoned from a lead source isotopically indistinguishable from the embedded birdshot, implicating ingestion of this type of birdshot as the source of poisoning. One of the condors was subsequently lead poisoned the following year from ingestion of a lead buckshot (blood lead 556 µg/dL), illustrating that ingested shot possess a substantially greater lead poisoning risk compared to embedded shot retained in tissue (blood lead ∼20 µg/dL). To our knowledge, this is the first study to use lead isotopes as a tool to retrospectively link wildlife shooting events. - Highlights: • We conducted a case-based analysis of illegal shootings of California condors. • Blood and feather Pb isotopes were used to reconstruct the illegal shooting events. • Embedded birdshot from the three condors had the same Pb isotope ratios. • Feather and blood Pb isotopes indicated that the condors were shot in a common event. • Ingested shot causes substantially greater lead exposure compared to embedded shot.

  3. Analysis of Links Positions in Landing Gear Mechanism

    Science.gov (United States)

    Brewczyński, D.; Tora, G.

    2014-08-01

    This article contains a kinematic analysis of an aircraft chassis mechanism in a range of positions. The mechanism of the chassis is made up of several smaller subsystems with different functions. The first mechanism is used to eject the chassis before landing (touchdown) and fold it to hatchway after the lift off. The second mechanism is designed to perform rotation of the crossover with the wheel, in order to adjust the position of the wheel to fit it in the limited space in the hold. The third mechanism allows movement of the chassis resulting from the change in length of the damper. To determine the position of the following links of the mechanism calculus of vectors was applied in which unit vectors were used to represent the angular position of the links. The aim of the analysis is to determine the angle of convergence and the angle of heel wheels as a function of the variable length of hydraulic cylinder, length of the shock absorber, length of the regulations rods

  4. Leading Change in Tissue Viability Best Practice: An Action Learning Programme for Link Nurse Practitioners

    Science.gov (United States)

    Kellie, Jean; Henderson, Eileen; Milsom, Brian; Crawley, Hayley

    2010-01-01

    This account of practice reports on an action learning initiative designed and implemented in partnership between a regional NHS Acute Trust and a UK Business School. The central initiative was the implementation of an action learning programme entitled "Leading change in tissue viability best practice: a development programme for Link Nurse…

  5. Links between fluid mechanics and quantum mechanics: a model for information in economics?

    Science.gov (United States)

    Haven, Emmanuel

    2016-05-28

    This paper tallies the links between fluid mechanics and quantum mechanics, and attempts to show whether those links can aid in beginning to build a formal template which is usable in economics models where time is (a)symmetric and memory is absent or present. An objective of this paper is to contemplate whether those formalisms can allow us to model information in economics in a novel way. © 2016 The Author(s).

  6. Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms.

    Science.gov (United States)

    Wu, Xin-Ping; Gagliardi, Laura; Truhlar, Donald G

    2018-05-30

    Combined quantum mechanical and molecular mechanical (QM/MM) methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM-MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM-MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM-MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

  7. Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms

    Directory of Open Access Journals (Sweden)

    Xin-Ping Wu

    2018-05-01

    Full Text Available Combined quantum mechanical and molecular mechanical (QM/MM methods are the most powerful available methods for high-level treatments of subsystems of very large systems. The treatment of the QM−MM boundary strongly affects the accuracy of QM/MM calculations. For QM/MM calculations having covalent bonds cut by the QM−MM boundary, it has been proposed previously to use a scheme with system-specific tuned fluorine link atoms. Here, we propose a broadly parametrized scheme where the parameters of the tuned F link atoms depend only on the type of bond being cut. In the proposed new scheme, the F link atom is tuned for systems with a certain type of cut bond at the QM−MM boundary instead of for a specific target system, and the resulting link atoms are call bond-tuned link atoms. In principle, the bond-tuned link atoms can be as convenient as the popular H link atoms, and they are especially well adapted for high-throughput and accurate QM/MM calculations. Here, we present the parameters for several kinds of cut bonds along with a set of validation calculations that confirm that the proposed bond-tuned link-atom scheme can be as accurate as the system-specific tuned F link-atom scheme.

  8. Fundamental link between system theory and statistical mechanics

    International Nuclear Information System (INIS)

    Atmanspacher, H.; Scheingraber, H.

    1987-01-01

    A fundamental link between system theory and statistical mechanics has been found to be established by the Kolmogorov entropy. By this quantity the temporal evolution of dynamical systems can be classified into regular, chaotic, and stochastic processes. Since K represents a measure for the internal information creation rate of dynamical systems, it provides an approach to irreversibility. The formal relationship to statistical mechanics is derived by means of an operator formalism originally introduced by Prigogine. For a Liouville operator L and an information operator M tilde acting on a distribution in phase space, it is shown that i[L, M tilde] = KI (I = identity operator). As a first consequence of this equivalence, a relation is obtained between the chaotic correlation time of a system and Prigogine's concept of a finite duration of presence. Finally, the existence of chaos in quantum systems is discussed with respect to the existence of a quantum mechanical time operator

  9. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    Science.gov (United States)

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  10. Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention.

    Science.gov (United States)

    Zeng, Huawei; Lazarova, Darina L; Bordonaro, Michael

    2014-02-15

    Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which modifies the host's metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gut microbiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.

  11. Linking geology and health sciences to assess childhood lead poisoning from artisanal gold mining in Nigeria

    Science.gov (United States)

    Plumlee, Geoffrey S.; Durant, James T.; Morman, Suzette A.; Neri, Antonio; Wolf, Ruth E.; Dooyema, Carrie A.; Hageman, Philip L.; Lowers, Heather; Fernette, Gregory L.; Meeker, Gregory P.; Benzel, William M.; Driscoll, Rhonda L.; Berry, Cyrus J.; Crock, James G.; Goldstein, Harland L.; Adams, Monique; Bartrem, Casey L.; Tirima, Simba; Behrooz, Behbod; von Lindern, Ian; Brown, Mary Jean

    2013-01-01

    Background: In 2010, Médecins Sans Frontières discovered a lead poisoning outbreak linked to artisanal gold processing in northwestern Nigeria. The outbreak has killed approximately 400 young children and affected thousands more. Objectives: Our aim was to undertake an interdisciplinary geological- and health-science assessment to clarify lead sources and exposure pathways, identify additional toxicants of concern and populations at risk, and examine potential for similar lead poisoning globally. Methods: We applied diverse analytical methods to ore samples, soil and sweep samples from villages and family compounds, and plant foodstuff samples. Results: Natural weathering of lead-rich gold ores before mining formed abundant, highly gastric-bioaccessible lead carbonates. The same fingerprint of lead minerals found in all sample types confirms that ore processing caused extreme contamination, with up to 185,000 ppm lead in soils/sweep samples and up to 145 ppm lead in plant foodstuffs. Incidental ingestion of soils via hand-to-mouth transmission and of dusts cleared from the respiratory tract is the dominant exposure pathway. Consumption of water and foodstuffs contaminated by the processing is likely lesser, but these are still significant exposure pathways. Although young children suffered the most immediate and severe consequences, results indicate that older children, adult workers, pregnant women, and breastfed infants are also at risk for lead poisoning. Mercury, arsenic, manganese, antimony, and crystalline silica exposures pose additional health threats. Conclusions: Results inform ongoing efforts in Nigeria to assess lead contamination and poisoning, treat victims, mitigate exposures, and remediate contamination. Ore deposit geology, pre-mining weathering, and burgeoning artisanal mining may combine to cause similar lead poisoning disasters elsewhere globally.

  12. Linking geological and health sciences to assess childhood lead poisoning from artisanal gold mining in Nigeria.

    Science.gov (United States)

    Plumlee, Geoffrey S; Durant, James T; Morman, Suzette A; Neri, Antonio; Wolf, Ruth E; Dooyema, Carrie A; Hageman, Philip L; Lowers, Heather A; Fernette, Gregory L; Meeker, Gregory P; Benzel, William M; Driscoll, Rhonda L; Berry, Cyrus J; Crock, James G; Goldstein, Harland L; Adams, Monique; Bartrem, Casey L; Tirima, Simba; Behbod, Behrooz; von Lindern, Ian; Brown, Mary Jean

    2013-06-01

    In 2010, Médecins Sans Frontières discovered a lead poisoning outbreak linked to artisanal gold processing in northwestern Nigeria. The outbreak has killed approximately 400 young children and affected thousands more. Our aim was to undertake an interdisciplinary geological- and health-science assessment to clarify lead sources and exposure pathways, identify additional toxicants of concern and populations at risk, and examine potential for similar lead poisoning globally. We applied diverse analytical methods to ore samples, soil and sweep samples from villages and family compounds, and plant foodstuff samples. Natural weathering of lead-rich gold ores before mining formed abundant, highly gastric-bioaccessible lead carbonates. The same fingerprint of lead minerals found in all sample types confirms that ore processing caused extreme contamination, with up to 185,000 ppm lead in soils/sweep samples and up to 145 ppm lead in plant foodstuffs. Incidental ingestion of soils via hand-to-mouth transmission and of dusts cleared from the respiratory tract is the dominant exposure pathway. Consumption of water and foodstuffs contaminated by the processing is likely lesser, but these are still significant exposure pathways. Although young children suffered the most immediate and severe consequences, results indicate that older children, adult workers, pregnant women, and breastfed infants are also at risk for lead poisoning. Mercury, arsenic, manganese, antimony, and crystalline silica exposures pose additional health threats. Results inform ongoing efforts in Nigeria to assess lead contamination and poisoning, treat victims, mitigate exposures, and remediate contamination. Ore deposit geology, pre-mining weathering, and burgeoning artisanal mining may combine to cause similar lead poisoning disasters elsewhere globally.

  13. Linking Geological and Health Sciences to Assess Childhood Lead Poisoning from Artisanal Gold Mining in Nigeria

    Science.gov (United States)

    Durant, James T.; Morman, Suzette A.; Neri, Antonio; Wolf, Ruth E.; Dooyema, Carrie A.; Hageman, Philip L.; Lowers, Heather A.; Fernette, Gregory L.; Meeker, Gregory P.; Benzel, William M.; Driscoll, Rhonda L.; Berry, Cyrus J.; Crock, James G.; Goldstein, Harland L.; Adams, Monique; Bartrem, Casey L.; Tirima, Simba; Behbod, Behrooz; von Lindern, Ian; Brown, Mary Jean

    2013-01-01

    Background: In 2010, Médecins Sans Frontières discovered a lead poisoning outbreak linked to artisanal gold processing in northwestern Nigeria. The outbreak has killed approximately 400 young children and affected thousands more. Objectives: Our aim was to undertake an interdisciplinary geological- and health-science assessment to clarify lead sources and exposure pathways, identify additional toxicants of concern and populations at risk, and examine potential for similar lead poisoning globally. Methods: We applied diverse analytical methods to ore samples, soil and sweep samples from villages and family compounds, and plant foodstuff samples. Results: Natural weathering of lead-rich gold ores before mining formed abundant, highly gastric-bioaccessible lead carbonates. The same fingerprint of lead minerals found in all sample types confirms that ore processing caused extreme contamination, with up to 185,000 ppm lead in soils/sweep samples and up to 145 ppm lead in plant foodstuffs. Incidental ingestion of soils via hand-to-mouth transmission and of dusts cleared from the respiratory tract is the dominant exposure pathway. Consumption of water and foodstuffs contaminated by the processing is likely lesser, but these are still significant exposure pathways. Although young children suffered the most immediate and severe consequences, results indicate that older children, adult workers, pregnant women, and breastfed infants are also at risk for lead poisoning. Mercury, arsenic, manganese, antimony, and crystalline silica exposures pose additional health threats. Conclusions: Results inform ongoing efforts in Nigeria to assess lead contamination and poisoning, treat victims, mitigate exposures, and remediate contamination. Ore deposit geology, pre-mining weathering, and burgeoning artisanal mining may combine to cause similar lead poisoning disasters elsewhere globally. PMID:23524139

  14. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

    2017-02-01

    The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Linking HRM and Knowledge Transfer via Individual-level Mechanisms

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Mäkelä, Kristiina; Rabbiosi, Larissa

    2012-01-01

    In response to recent calls for more research on micro-foundations, we seek to link human resource management (HRM) and knowledge transfer through individual-level mechanisms, arguing that individual-level conditions of action influence the extent to which employees engage in knowledge exchange. We...... examine four such conditions empirically using data from 811 employees in three Danish multinational corporations (MNCs). Our findings suggest that individual-level perceptions of organizational commitment to knowledge sharing, and extrinsic motivation, directly influence the extent to which employees...... engage in firm-internal knowledge exchange. We also find that intrinsic motivation and engagement in social interaction significantly mediate the relationship between perceived organizational commitment and knowledge exchange. Given that HRM can influence such conditions through an overall signaling...

  16. GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

    Science.gov (United States)

    de Jonge, Jeroen C.; Vinkers, Christiaan H.; Hulshoff Pol, Hilleke E.; Marsman, Anouk

    2017-01-01

    Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course. PMID:28848455

  17. GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Jeroen C. de Jonge

    2017-08-01

    Full Text Available Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course.

  18. Mechanisms of gender-linked ischemic brain injury

    Science.gov (United States)

    Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

    2010-01-01

    Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

  19. Mechanisms of leading edge protrusion in interstitial migration

    Science.gov (United States)

    Wilson, Kerry; Lewalle, Alexandre; Fritzsche, Marco; Thorogate, Richard; Duke, Tom; Charras, Guillaume

    2013-01-01

    While the molecular and biophysical mechanisms underlying cell protrusion on two-dimensional substrates are well understood, our knowledge of the actin structures driving protrusion in three-dimensional environments is poor, despite relevance to inflammation, development and cancer. Here we report that, during chemotactic migration through microchannels with 5 μm × 5 μm cross-sections, HL60 neutrophil-like cells assemble an actin-rich slab filling the whole channel cross-section at their front. This leading edge comprises two distinct F-actin networks: an adherent network that polymerizes perpendicular to cell-wall interfaces and a ‘free’ network that grows from the free membrane at the cell front. Each network is polymerized by a distinct nucleator and, due to their geometrical arrangement, the networks interact mechanically. On the basis of our experimental data, we propose that, during interstitial migration, medial growth of the adherent network compresses the free network preventing its retrograde movement and enabling new polymerization to be converted into forward protrusion. PMID:24305616

  20. Linked Environments for Atmospheric Discovery (LEAD): A Cyberinfrastructure for Mesoscale Meteorology Research and Education

    Science.gov (United States)

    Droegemeier, K.

    2004-12-01

    A new National Science Foundation Large Information Technology Research (ITR) grant - known as Linked Environments for Atmospheric Discovery (LEAD) - has been funded to facilitate the identification, access, preparation, assimilation, prediction, management, analysis, mining, and visualization of a broad array of meteorological data and model output, independent of format and physical location. A transforming element of LEAD is dynamic workflow orchestration and data management, which will allow use of analysis tools, forecast models, and data repositories as dynamically adaptive, on-demand systems that can a) change configuration rapidly and automatically in response to weather; b) continually be steered by new data; c) respond to decision-driven inputs from users; d) initiate other processes automatically; and e) steer remote observing technologies to optimize data collection for the problem at hand. Having been in operation for slightly more than a year, LEAD has created a technology roadmap and architecture for developing its capabilities and placing them within the academic and research environment. Further, much of the LEAD infrastructure being developed for the WRF model, particularly workflow orchestration, will play a significant role in the nascent WRF Developmental Test Bed Center located at NCAR. This paper updates the status of LEAD (e.g., the topics noted above), its ties with other community activities (e.g., CONDUIT, THREDDS, MADIS, NOMADS), and the manner in which LEAD technologies will be made available for general use. Each component LEAD application is being created as a standards-based Web service that can be run in stand-alone configuration or chained together to build an end-to-end environment for on-demand, real time NWP. We describe in this paper the concepts, implementation plans, and expected impacts of LEAD, the underpinning of which will be a series of interconnected, heterogeneous virtual IT "Grid environments" designed to provide a

  1. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Science.gov (United States)

    Matioli, Maria Niures P.S.; Nitrini, Ricardo

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

  2. Mechanisms linking brain insulin resistance to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Maria Niures P.S. Matioli

    Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

  3. Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

    Science.gov (United States)

    Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

    2015-01-01

    Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health. © 2015 S. Karger AG, Basel.

  4. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

    Science.gov (United States)

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

    2016-07-01

    A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

  5. Neurocomputational mechanisms of prosocial learning and links to empathy.

    Science.gov (United States)

    Lockwood, Patricia L; Apps, Matthew A J; Valton, Vincent; Viding, Essi; Roiser, Jonathan P

    2016-08-30

    Reinforcement learning theory powerfully characterizes how we learn to benefit ourselves. In this theory, prediction errors-the difference between a predicted and actual outcome of a choice-drive learning. However, we do not operate in a social vacuum. To behave prosocially we must learn the consequences of our actions for other people. Empathy, the ability to vicariously experience and understand the affect of others, is hypothesized to be a critical facilitator of prosocial behaviors, but the link between empathy and prosocial behavior is still unclear. During functional magnetic resonance imaging (fMRI) participants chose between different stimuli that were probabilistically associated with rewards for themselves (self), another person (prosocial), or no one (control). Using computational modeling, we show that people can learn to obtain rewards for others but do so more slowly than when learning to obtain rewards for themselves. fMRI revealed that activity in a posterior portion of the subgenual anterior cingulate cortex/basal forebrain (sgACC) drives learning only when we are acting in a prosocial context and signals a prosocial prediction error conforming to classical principles of reinforcement learning theory. However, there is also substantial variability in the neural and behavioral efficiency of prosocial learning, which is predicted by trait empathy. More empathic people learn more quickly when benefitting others, and their sgACC response is the most selective for prosocial learning. We thus reveal a computational mechanism driving prosocial learning in humans. This framework could provide insights into atypical prosocial behavior in those with disorders of social cognition.

  6. The void nucleation mechanism within lead phase during spallation of leaded brass

    Science.gov (United States)

    Yang, Yang; Wang, Can; Chen, Xingzhi; Chen, Kaiguo; Hu, Haibo; Fu, Yanan

    2018-07-01

    The incipient spall behaviours of Cu-34%Zn-3%Pb leaded brass samples with annealed and cryogenic-treated conditions were loaded using one-stage light gas gun experiments. The effect of Pb-phase on dynamic damage nucleation in leaded brass specimens was investigated by means of optical microscopy, scanning electron microscopy and x-ray computer tomography. It was found that the voids of incipient spall were mainly nucleated in the interior of the lead (no tensile stress would be produced within lead according to the impact theory) instead of nucleated at the phase interface as expected by quasi-static damage fracture theory. A nucleation model is proposed in the present work that is the asymmetry high compression zones in the centre of the lead-phase were formed by the rarefaction wave convergence effects of matrix/quasi-spherical lead interface, which caused adiabatic temperature rise that exceeded melting point of lead due to severe plastic deformation, finally led to local melting and void nucleation. In addition, the spall strength and damage rate increased with the increase in the Pb-phase number.

  7. Double strand break repair: two mechanisms in competition but tightly linked to cell cycle

    International Nuclear Information System (INIS)

    Delacote, F.

    2002-11-01

    DNA double strand breaks (DSB) are highly toxic damage although they can be induced to create genetic diversity. Two distinct pathways can repair DSB: Homologous Recombination (HR) and Non Homologous End Joining (NHEJ). If un- or mis-repaired, this damage can lead to cancer. Thus, it is essential to investigate how these two pathways are regulated for DSB repair. NHEJ inhibition leads to HR DSB repair stimulation. However, this channeling to HR is tightly linked to cell cycle since NHEJ and HR are active in G1/early S and late S/G2, respectively. Our results suggest that G1-unrepaired DSB go through S phase to be repaired by HR in G2. Those results allow a better understanding of DSB repair mechanisms regulation. (author)

  8. Pannus-Related Mechanical Valve Dysfunction Leading to Hemodynamic Shock

    Directory of Open Access Journals (Sweden)

    Manabu Shiraishi

    2012-02-01

    Full Text Available Mechanical prosthetic valve dysfunction caused by pannus formation is rare. Pannus restricts movement of prosthetic valve leaflets, resulting in severe aortic regurgitation. We describe the case of a 77-year-old woman who presented to the emergency room with increasing dyspnea, ischemia, and shock secondary to mechanical aortic valve dysfunction. Transesophageal echocardiography showed a blockade of the leaflets of the mechanical aortic valve, with severe aortic regurgitation. She underwent emergent cardiac surgery for aortic valve replacement. Pannus formation should be considered as a potential cause of acute severe aortic regurgitation in a patient with a small-sized mechanical aortic prosthesis in the supra-annular position. On a pathological exam, extensive pannus was found on the ventricular side of the prosthetic valve, extending from the ring into the central orifice. [Arch Clin Exp Surg 2012; 1(1.000: 50-53

  9. Basic Mechanisms Leading to Fatigue Failure of Structural Materials

    Czech Academy of Sciences Publication Activity Database

    Polák, Jaroslav; Petráš, Roman; Mazánová, Veronika

    2016-01-01

    Roč. 69, č. 2 (2016), s. 289-294 ISSN 0972-2815. [International Conference on CREEP , FATIGUE and CREEP -FATIGUE INTERACTION /7./. Kalpakkam, 19.01.2016-22.01.2016] R&D Projects: GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : Damage mechanism * Fatigue crack initiation * Austenitic steel * Oxide cracking Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.533, year: 2016

  10. Molecular and cellular mechanisms that lead to Candida biofilm formation

    NARCIS (Netherlands)

    ten Cate, J.M.; Klis, F.M.; Pereira-Cenci, T.; Crielaard, W.; de Groot, P.W.J.

    2009-01-01

    Fungal infections in the oral cavity are mainly caused by C. albicans, but other Candida species are also frequently identified. They are increasing in prevalence, especially in denture-wearers and aging people, and may lead to invasive infections, which have a high mortality rate. Attachment to

  11. Applications of Laminar Weak-Link Mechanisms for Ultraprecision Synchrotron Radiation Instruments

    International Nuclear Information System (INIS)

    Shu, D.; Toellner, T. S.; Alp, E. E.; Maser, J.; Ilavsky, J.; Shastri, S. D.; Lee, P. L.; Narayanan, S.; Long, G. G.

    2007-01-01

    Unlike traditional kinematic flexure mechanisms, laminar overconstrained weak-link mechanisms provide much higher structure stiffness and stability. Using a laminar structure configured and manufactured by chemical etching and lithography techniques, we are able to design and build linear and rotary weak-link mechanisms with ultrahigh positioning sensitivity and stability for synchrotron radiation applications. Applications of laminar rotary weak-link mechanism include: high-energy-resolution monochromators for inelastic x-ray scattering and x-ray analyzers for ultra-small-angle scattering and powder-diffraction experiments. Applications of laminar linear weak-link mechanism include high-stiffness piezo-driven stages with subnanometer resolution for an x-ray microscope. In this paper, we summarize the recent designs and applications of the laminar weak-link mechanisms at the Advanced Photon Source

  12. 49 CFR 238.207 - Link between coupling mechanism and car body.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Link between coupling mechanism and car body. 238.207 Section 238.207 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL... Requirements for Tier I Passenger Equipment § 238.207 Link between coupling mechanism and car body. All...

  13. A PKC-MARCKS-PI3K regulatory module links Ca2+ and PIP3 signals at the leading edge of polarized macrophages.

    Science.gov (United States)

    Ziemba, Brian P; Falke, Joseph J

    2018-01-01

    trigger the opposite effects. Comparison of the findings for the ameboid chemotaxis of leukocytes with recently published findings for the mesenchymal chemotaxis of fibroblasts suggests that some features of the emerging leukocyte leading edge core pathway (PLC-DAG-Ca2+-PKC-MARCKS-PIP2-PI3K-PIP3) may well be shared by all chemotaxing eukaryotic cells, while other elements of the leukocyte pathway may be specialized features of these highly optimized, professional gradient-seeking cells. More broadly, the findings suggest a molecular mechanism for the strong links between phospho-MARCKS and many human cancers.

  14. A PKC-MARCKS-PI3K regulatory module links Ca2+ and PIP3 signals at the leading edge of polarized macrophages.

    Directory of Open Access Journals (Sweden)

    Brian P Ziemba

    inhibitors trigger the opposite effects. Comparison of the findings for the ameboid chemotaxis of leukocytes with recently published findings for the mesenchymal chemotaxis of fibroblasts suggests that some features of the emerging leukocyte leading edge core pathway (PLC-DAG-Ca2+-PKC-MARCKS-PIP2-PI3K-PIP3 may well be shared by all chemotaxing eukaryotic cells, while other elements of the leukocyte pathway may be specialized features of these highly optimized, professional gradient-seeking cells. More broadly, the findings suggest a molecular mechanism for the strong links between phospho-MARCKS and many human cancers.

  15. Opioid receptor desensitization: mechanisms and its link to tolerance

    Directory of Open Access Journals (Sweden)

    Stéphane eAllouche

    2014-12-01

    Full Text Available Opioid receptors are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization and post-endocytic fate of the receptor.

  16. Mechanism of electric fatigue crack growth in lead zirconate titanate

    International Nuclear Information System (INIS)

    Westram, Ilona; Oates, William S.; Lupascu, Doru C.; Roedel, Juergen; Lynch, Christopher S.

    2007-01-01

    A series of experiments was performed with through-thickness cracks in ferroelectric double cantilever beam (DCB) specimens. Cyclic electric fields of different amplitudes were applied which resulted in cyclic crack propagation perpendicular to the electric field direction. Crack propagation was observed optically and three regimes were identified: a pop-in from a notch, steady-state crack growth and a decrease of the crack growth rate with increasing cycle number. Crack growth only occurred if the applied field exceeded the coercive field strength of the material. Furthermore, the crack extended during each field reversal and the crack growth rate increased with increasing field. Based on the experimental observations, a mechanistic understanding was developed and contrasted with a nonlinear finite element analysis which quantified the stress intensity in the DCB specimens. The driving forces for crack formation at the notch and subsequent fatigue crack growth were computed based on the distribution of residual stresses due to ferroelectric switching. The finite element results are in good agreement with the experimental observations and support the proposed mechanism

  17. Europe hones an edge in technology Continent leads U.S. in linking PC "grids"

    CERN Multimedia

    Markoff, John

    2003-01-01

    The Swiss-based pharmaceutical company, Novartis, is using a grid to help create drugs. Although the US leads technical developments it is European organisations who have the lead on practical grid projects (2 pages)

  18. A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks.

    Science.gov (United States)

    Jin, Zhigang; Wang, Ning; Su, Yishan; Yang, Qiuling

    2018-02-07

    Underwater acoustic sensor networks (UASNs) have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider's sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider's trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15-33% compared with cooperative opportunistic routing (OVAR), the hop-by-hop vector-based forwarding (HH-VBF) and the vector based forward (VBF) methods, and reduce communication energy consumption by 20-58% for a typical network's setting.

  19. A Glider-Assisted Link Disruption Restoration Mechanism in Underwater Acoustic Sensor Networks

    Directory of Open Access Journals (Sweden)

    Zhigang Jin

    2018-02-01

    Full Text Available Underwater acoustic sensor networks (UASNs have become a hot research topic. In UASNs, nodes can be affected by ocean currents and external forces, which could result in sudden link disruption. Therefore, designing a flexible and efficient link disruption restoration mechanism to ensure the network connectivity is a challenge. In the paper, we propose a glider-assisted restoration mechanism which includes link disruption recognition and related link restoring mechanism. In the link disruption recognition mechanism, the cluster heads collect the link disruption information and then schedule gliders acting as relay nodes to restore the disrupted link. Considering the glider’s sawtooth motion, we design a relay location optimization algorithm with a consideration of both the glider’s trajectory and acoustic channel attenuation model. The utility function is established by minimizing the channel attenuation and the optimal location of glider is solved by a multiplier method. The glider-assisted restoration mechanism can greatly improve the packet delivery rate and reduce the communication energy consumption and it is more general for the restoration of different link disruption scenarios. The simulation results show that glider-assisted restoration mechanism can improve the delivery rate of data packets by 15–33% compared with cooperative opportunistic routing (OVAR, the hop-by-hop vector-based forwarding (HH-VBF and the vector based forward (VBF methods, and reduce communication energy consumption by 20–58% for a typical network’s setting.

  20. Composite Control of the n–link Chained Mechanical Systems

    Czech Academy of Sciences Publication Activity Database

    Zikmund, Jiří

    2008-01-01

    Roč. 44, č. 5 (2008), s. 664-684 ISSN 0023-5954 R&D Projects: GA ČR(CZ) GA102/08/0186 Institutional research plan: CEZ:AV0Z10750506 Keywords : nonlinear systems * exact linearization * underactuated mechanical systems Subject RIV: BC - Control Systems Theory Impact factor: 0.281, year: 2008

  1. Dissolution mechanism of austenitic stainless steels in lead-bismuth eutectic at 500 deg. C

    International Nuclear Information System (INIS)

    Roy, M.

    2012-01-01

    In the framework of the future nuclear power plants studies, lead-bismuth eutectic (LBE) is foreseen as a coolant in the primary or the secondary circuit in three nuclear systems. The use of this liquid alloy induces corrosion issues for structural steels. In liquid lead alloys, steels can undergo two corrosion phenomena: dissolution or oxidation depending on the temperature and the dissolved oxygen content in LBE. The goal of this study is to identify the dissolution mechanisms of austenitic steels in LBE at 500 deg. C. Four Fe-Cr-Ni model austenitic steels, the 316L steel and five other industrial steels were corroded in LBE up to, respectively, 3000, 6000 and 200 h. The dissolution mechanism is identical for all steels: it starts by a preferential dissolution of chromium and nickel. This dissolution leads to the formation of a ferritic corrosion layer penetrated by LBE and containing between 5 and 10 at% of chromium and almost no nickel. This study demonstrates that dissolutions of nickel and chromium are linked. Otherwise, the corrosion kinetics is linear whatever the tested austenitic steel. The controlling steps of the austenitic steels' corrosion rates have been identified. Natural convection in the LBE bath leads to the formation of a diffusion boundary layer at the steel surface. Chromium diffusion in this diffusion boundary layer seems to control the corrosion rates of the model and industrial austenitic steels except the 316L steel. Indeed, the corrosion rate of the 316L steel is controlled by an interfacial reaction which is either the simultaneous dissolution of nickel and chromium in Ni, Cr compounds or the nickel and chromium dissolution catalyzed by the dissolved oxygen in LBE. This study has permitted to highlight the major role of chromium on the corrosion mechanisms and the corrosion rates of austenitic steels: the corrosion rate increases when chromium activity increases. Finally, the impact of the dissolved oxygen and the minor alloying

  2. Ecological mechanisms linking protected areas to surrounding lands.

    Science.gov (United States)

    Hansen, Andrew J; DeFries, Ruth

    2007-06-01

    Land use is expanding and intensifying in the unprotected lands surrounding many of the world's protected areas. The influence of this land use change on ecological processes is poorly understood. The goal of this paper is to draw on ecological theory to provide a synthetic framework for understanding how land use change around protected areas may alter ecological processes and biodiversity within protected areas and to provide a basis for identifying scientifically based management alternatives. We first present a conceptual model of protected areas embedded within larger ecosystems that often include surrounding human land use. Drawing on case studies in this Invited Feature, we then explore a comprehensive set of ecological mechanisms by which land use on surrounding lands may influence ecological processes and biodiversity within reserves. These mechanisms involve changes in ecosystem size, with implications for minimum dynamic area, species-area effect, and trophic structure; altered flows of materials and disturbances into and out of reserves; effects on crucial habitats for seasonal and migration movements and population source/sink dynamics; and exposure to humans through hunting, poaching, exotics species, and disease. These ecological mechanisms provide a basis for assessing the vulnerability of protected areas to land use. They also suggest criteria for designing regional management to sustain protected areas in the context of surrounding human land use. These design criteria include maximizing the area of functional habitats, identifying and maintaining ecological process zones, maintaining key migration and source habitats, and managing human proximity and edge effects.

  3. Developmental phonagnosia: Linking neural mechanisms with the behavioural phenotype.

    Science.gov (United States)

    Roswandowitz, Claudia; Schelinski, Stefanie; von Kriegstein, Katharina

    2017-07-15

    Human voice recognition is critical for many aspects of social communication. Recently, a rare disorder, developmental phonagnosia, which describes the inability to recognise a speaker's voice, has been discovered. The underlying neural mechanisms are unknown. Here, we used two functional magnetic resonance imaging experiments to investigate brain function in two behaviourally well characterised phonagnosia cases, both 32 years old: AS has apperceptive and SP associative phonagnosia. We found distinct malfunctioned brain mechanisms in AS and SP matching their behavioural profiles. In apperceptive phonagnosia, right-hemispheric auditory voice-sensitive regions (i.e., Heschl's gyrus, planum temporale, superior temporal gyrus) showed lower responses than in matched controls (n AS =16) for vocal versus non-vocal sounds and for speaker versus speech recognition. In associative phonagnosia, the connectivity between voice-sensitive (i.e. right posterior middle/inferior temporal gyrus) and supramodal (i.e. amygdala) regions was reduced in comparison to matched controls (n SP =16) during speaker versus speech recognition. Additionally, both cases recruited distinct potential compensatory mechanisms. Our results support a central assumption of current two-system models of voice-identity processing: They provide the first evidence that dysfunction of voice-sensitive regions and impaired connectivity between voice-sensitive and supramodal person recognition regions can selectively contribute to deficits in person recognition by voice. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

    Science.gov (United States)

    Tronnier, V M; Domingo, A; Moll, C K; Rasche, D; Mohr, C; Rosales, R; Capetian, P; Jamora, R D; Lee, L V; Münchau, A; Diesta, C C; Tadic, V; Klein, C; Brüggemann, N; Moser, A

    2015-08-01

    Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  6. Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment

    DEFF Research Database (Denmark)

    Hojman, Pernille; Gehl, Julie; Christensen, Jesper F.

    2018-01-01

    The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose...... that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications......, as this understanding may lead to changes in cancer treatment strategies. Hojman et al. discuss the role of exercise in controlling cancer progression through direct effects on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of cancer...

  7. Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms.

    Science.gov (United States)

    Penninx, Brenda W J H

    2017-03-01

    Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations). A summary of the literature findings as well as relevant results from the large-scale Netherlands Study of Depression and Anxiety (N=2981) are presented. Persons with MDD have significantly worse lifestyles as well as more pathophysiological disturbances as compared to healthy controls. Some of these differences seem to be specific for (typical versus 'atypical', or antidepressant treated versus drug-naive) subgroups of MDD patients. Alternative explanations are also present, namely undetected confounding, iatrogenic effects or 'third factors' such as genetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Mechanically Strong, Polymer Cross-linked Aerogels (X-Aerogels)

    Science.gov (United States)

    Leventis, Nicholas

    2006-01-01

    Aerogels comprise a class of low-density, high porous solid objects consisting of dimensionally quasi-stable self-supported three-dimensional assemblies of nanoparticles. Aerogels are pursued because of properties above and beyond those of the individual nanoparticles, including low thermal conductivity, low dielectric constant and high acoustic impedance. Possible applications include thermal and vibration insulation, dielectrics for fast electronics, and hosting of functional guests for a wide variety of optical, chemical and electronic applications. Aerogels, however, are extremely fragile materials, hence they have found only limited application in some very specialized environments, for example as Cerenkov radiation detectors in certain types of nuclear reactors, aboard spacecraft as collectors of hypervelocity particles (refer to NASA's Stardust program) and as thermal insulators on planetary vehicles on Mars (refer to Sojourner Rover in 1997 and Spirit and Opportunity in 2004). Along these lines, the X-Aerogel is a new NASA-developed strong lightweight material that has resolved the fragility problem of traditional (native) aerogels. X-Aerogels are made by applying a conformal polymer coating on the surfaces of the skeletal nanoparticles of native aerogels (see Scanning Electron Micrographs). Since the relative amounts of the polymeric crosslinker and the backbone are comparable, X-Aerogels can be viewed either as aerogels modified by the templated accumulation of polymer on the skeletal nanoparticles, or as nanoporous polymers made by remplated casting of polymer on a nanostructured framework. The most striking feature of X-Aerogels is that for a nominal 3-fold increase in density (still a ultralighweight material), the mechanical strength can be up to 300 times higher than the strength of the underlying native aerogel. Thus, X-Aerogels combine a multiple of the specific compressive strength of steel, with the the thermal conductivity of styrofoam. X

  9. The Leading Edge of Early Childhood Education: Linking Science to Policy for a New Generation

    Science.gov (United States)

    Lesaux, Nonie K., Ed.; Jones, Stephanie M., Ed.

    2016-01-01

    "The Leading Edge of Early Childhood Education" aims to support the effort to simultaneously scale up and improve the quality of early childhood education by bringing together relevant insights from emerging research to provide guidance for this critical, fledgling field. It reflects the growing recognition that early childhood…

  10. Glacier surge mechanism based on linked cavity configuration of the basal water conduit system

    Science.gov (United States)

    Kamb, Barclay

    1987-08-01

    to 5 bars below ice overburden pressure for water fluxes in the range from about 2 to 20 m3/s, which matches reasonably the observed conditions in Variegated Glacier in surge; in contrast, the calculated water pressure for a single-tunnel model is about 14 to 17 bars below overburden over the same flux range. The contrast in water pressures for the two types of basal conduit system furnishes the basis for a surge mechanism involving transition from a tunnel system at low pressure to a linked cavity system at high pressure. The parameter Ξ is about 0.2 for the linked cavity models evaluated, meaning that they are stable but that a modest change in system parameters could produce instability. Unstable orifice growth results in the generation of tunnel segments, which may connect up in a cooperative fashion, leading to conversion of the linked cavity system to a tunnel system, with large decrease in water pressure and sliding velocity. This is what probably happens in surge termination. Glaciers for which Ξ ≲ 1 can go into surge, while those for which Ξ ≳ 1 cannot. Because Ξ varies as α3/2 (where α is surface slope), low values of Ξ are more probable for glaciers of low slope, and because slope correlates inversely with glacier length in general, the model predicts a direct correlation between glacier length and probability of surging; such a correlation is observed (Clarke et al., 1986). Because Ξ varies inversely with the basal shear stress τ, the increase of τ that takes place in the reservoir area in the buildup between surges causes a decrease in Ξ there, which, by reducing Ξ below the critical value ˜1, can allow surge initiation and the start of a new surge cycle. Transition to a linked cavity system without tunnels should occur spontaneously at low enough water flux, in agreement with observed surge initiation in winter.

  11. Physical and mechanical properties of gamma radiation cross-linked polyethylene

    International Nuclear Information System (INIS)

    Gonzalez, Maria E.; Romero, G.; Smolko, Eduardo E.

    1999-01-01

    Granulated LDPE 2003 polyethylene was extruded and irradiated under nitrogen with 150, 200 and 300 kGy gamma rays doses to produce cross-linking. The study of the physical and mechanical properties shows that the product has a high degree of molecular cross-linking, can be heated up to 200 C for 2 hours without deformation and that the mechanical properties improve. Preliminary aging tests indicate that after heating at 60 C for 4 weeks no physical or mechanical deterioration can be observed. (author)

  12. Molecular dynamics of palmitic acid and lead palmitate in cross-linked linseed oil films: Implications from deuterium magnetic resonance for lead soap formation in traditional oil paintings.

    Science.gov (United States)

    Catalano, Jaclyn; Murphy, Anna; Yao, Yao; Zumbulyadis, Nicholas; Centeno, Silvia A; Dybowski, Cecil

    2018-02-01

    Many oil paintings, dating from the 15th century to the present, are affected by the formation of heavy-metal carboxylates (soaps) that alter the structural integrity and appearance of the works. Through transport phenomena not yet understood, free fatty acids formed from oils used as binders migrate through the paint film and react with heavy-metal ions that are constituents of pigments and/or driers, forming metal carboxylates. The local molecular dynamics of fatty acids and metal carboxylates are factors influencing material transport in these systems. We report temperature-dependent 2 H NMR spectra of palmitic acid and lead palmitate as pure materials, in cross-linked linseed oil films, and in a lead white linseed oil paint film as part of our broader research into metal soap formation. Local dynamics at the α carbon, at the terminal methyl group, and at the middle of the fatty acid chain were observed in specifically deuterated materials. Changes in the dynamic behavior with temperature were observed by the appearance of two species, a solid-like material and a liquid-like material. The relative amounts of the two phases and their deuterium NMR parameters indicate that the amount of liquid-like material and the local dynamics at that site increase with temperature. At the three locations along the chain and at all temperatures, there is a larger percentage of acyl chains of both palmitic acid and lead palmitate that are "mobile" or liquid-like in linseed oil films than there are in the pure materials. However, the percentage of liquid-like species is decreased in a lead white paint film, as compared to a linseed oil matrix. In addition, these experiments indicate that there is a larger percentage of liquid-like acyl chains of palmitic acid than of lead palmitate under identical conditions in these model paint systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Encapsulation of lead from hazardous CRT glass wastes using biopolymer cross-linked concrete systems

    International Nuclear Information System (INIS)

    Kim, Daeik; Quinlan, Michael; Yen, Teh Fu

    2009-01-01

    Discarded computer monitors and television sets are identified as hazardous materials due to the high content of lead in their cathode ray tubes (CRTs). Over 98% of lead is found in CRT glass. More than 75% of obsolete electronics including TV and CRT monitors are in storage because appropriate e-waste management and remediation technologies are insufficient. Already an e-waste tsunami is starting to roll across the US and the whole world. Thus, a new technology was developed as an alternative to current disposal methods; this method uses a concrete composite crosslinked with minute amounts of biopolymers and a crosslinking agent. Commercially available microbial biopolymers of xanthan gum and guar gum were used to encapsulate CRT wastes, reducing Pb leachability as measured by standard USEPA methods. In this investigation, the synergistic effect of the crosslinking reaction was observed through blending two different biopolymers or adding a crosslinking agent in biopolymer solution. This CRT-biopolymer-concrete (CBC) composite showed higher compressive strength than the standard concrete and a considerable decrease in lead leachability

  14. Study on predicting residual life of elevator links by fracture mechanics approach

    Energy Technology Data Exchange (ETDEWEB)

    Li Helin; Zhang Yi; Deng Zengjie [China National Petroleum Corp., Xi`an, Shaanxi (China). Tubular Goods Research Center; Jin Dazeng [Xi`an Jiaotong Univ., Xi`an, Shaanxi (China)

    1995-12-31

    On the basis of investigation, failure and fracture analysis of elevator links, residual life prediction of links using fracture mechanics approach is studied, and mechanical properties, fracture toughness value K{sub IC} and fatigue crack propagation rage da/dN of the steel for elevator links are determined. Using the relation between stress intensity factor K{sub I} and the strain-energy release rate, the two-dimensional conversion thickness finite element method has been used to calculate the stress intensity factors K{sub I} for dangerous sections in the ring part of links. Furthermore, the reliability of calculations of the finite element stress intensity factors K{sub I} for dangerous sections of elevator links and the residual life computation for links are verified by fatigue tests of actual links. Finally, the experimental verification of computed results by 150T link fractured at site indicates that the computed critical crack lengths and residual life tally well with those measured and meet the needs of oil drilling.

  15. Wind Climate in Kongsfjorden, Svalbard, and Attribution of Leading Wind Driving Mechanisms through Turbulence-Resolving Simulations

    Directory of Open Access Journals (Sweden)

    Igor Esau

    2012-01-01

    Full Text Available This paper presents analysis of wind climate of the Kongsfjorden-Kongsvegen valley, Svalbard. The Kongsfjorden-Kongsvegen valley is relatively densely covered with meteorological observations, which facilitate joint statistical analysis of the turbulent surface layer structure and the structure of the higher atmospheric layers. Wind direction diagrams reveal strong wind channeled in the surface layer up to 300 m to 500 m. The probability analysis links strong wind channeling and cold temperature anomalies in the surface layer. To explain these links, previous studies suggested the katabatic wind flow mechanism as the leading driver responsible for the observed wind climatology. In this paper, idealized turbulence-resolving simulations are used to distinct between different wind driving mechanisms. The simulations were performed with the real surface topography at resolution of about 60 m. These simulations resolve the obstacle-induced turbulence and the turbulence in the non-stratified boundary layer core. The simulations suggest the leading roles of the thermal land-sea breeze circulation and the mechanical wind channeling in the modulation of the valley winds. The characteristic signatures of the developed down-slope gravity-accelerated flow, that is, the katabatic wind, were found to be of lesser significance under typical meteorological conditions in the valley.

  16. Linking project-based mechanisms with domestic greenhouse gas emissions trading schemes

    International Nuclear Information System (INIS)

    Bygrave, S.; Bosi, M.

    2004-01-01

    Although there are a number of possible links between emission trading and project-based mechanisms, the focus of this paper is on linking domestic GHG emission trading schemes with: (1) domestic; and, (2) international (JI and CDM) GHG reduction project activities. The objective is to examine some of the challenges in linking DETs and project-based mechanisms, as well as some possible solutions to address these challenges. The link between JI / CDM and intergovernmental international emissions trading (i.e. Article 17 of the Kyoto Protocol) is defined by the Kyoto Protocol, and therefore is not covered in this paper. The paper is written in the context of: (a) countries adhering to the Kyoto Protocol and elaborating their strategies to meet their GHG emission commitments, including through the use of the emissions trading and project-based mechanisms. For example, the European Union (EU) will be commencing a GHG Emissions Trading Scheme in January 2005, and recently, the Council of ministers and the European Parliament agreed on a text for an EU Linking Directive allowing the use of JI and CDM emission units in the EU Emission Trading Scheme (EU-ETS); and (b) all countries (and/or regions within countries) with GHG emission obligations that may choose to use domestic emissions trading and project-based mechanisms to meet their GHG commitments. The paper includes the following elements: (1) an overview of the different flexibility mechanisms (i.e. GHG emissions trading and PBMs), including a brief description and comparisons between the mechanisms (Section 3); (2) an exploration of the issues that emerge when project-based mechanisms link with domestic emissions trading schemes, as well as possible solutions to address some of the challenges raised (Section 4); (3) a case study examining the EU-ETS and the EU Linking Directive on project-based mechanisms, in particular on how the EU is addressing in a practical context relevant linking issues (Section 5); (4) a

  17. Mechanical and thermo-mechanical response of a lead-core bearing device subjected to different loading conditions

    Directory of Open Access Journals (Sweden)

    Zhelyazov Todor

    2018-01-01

    Full Text Available The contribution is focused on the numerical modelling, simulation and analysis of a lead-core bearing device for passive seismic isolation. An accurate finite element model of a lead-core bearing device is presented. The model is designed to analyse both mechanical and thermo-mechanical responses of the seismic isolator to different loading conditions. Specifically, the mechanical behaviour in a typical identification test is simulated. The response of the lead-core bearing device to circular sinusoidal paths is analysed. The obtained shear displacement – shear force relationship is compared to experimental data found in literature sources. The hypothesis that heating of the lead-core during cyclic loading affects the degrading phenomena in the bearing device is taken into account. Constitutive laws are defined for each material: lead, rubber and steel. Both predefined constitutive laws (in the used general–purpose finite element code and semi-analytical procedures aimed at a more accurate modelling of the constitutive relations are tested. The results obtained by finite element analysis are to be further used to calibrate a macroscopic model of the lead-core bearing device seen as a single-degree-of-freedom mechanical system.

  18. Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors.

    Science.gov (United States)

    Kohlmann, Anna; Zech, Stephan G; Li, Feng; Zhou, Tianjun; Squillace, Rachel M; Commodore, Lois; Greenfield, Matthew T; Lu, Xiaohui; Miller, David P; Huang, Wei-Sheng; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Zhang, Sen; Dodd, Rory; Liu, Shuangying; Xu, Rongsong; Xu, Yongjin; Miret, Juan J; Rivera, Victor; Clackson, Tim; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C

    2013-02-14

    Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (K(d)) and enzyme inhibition (IC(50)) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, respectively. The binding modes of selected fragments were investigated by X-ray crystallography. Fragment growing and linking, followed by chemical optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected molecules inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.

  19. The origins of cognitive vulnerability in early childhood: mechanisms linking early attachment to later depression.

    Science.gov (United States)

    Morley, Tara E; Moran, Greg

    2011-11-01

    This paper examines the theory and research linking attachment relationships to cognitive vulnerability to depression and assesses evidence that early attachment experiences contribute to the development of these cognitive processes. Most research in this area has involved adult participants using self-report measures of both attachment and depressive vulnerabilities and thus cannot convincingly speak to the existence of such a developmental pathway. Several studies, however, have followed individuals from infancy and examined the emergence of self-esteem and responses to failure throughout childhood and adolescence. These studies suggest that early experiences in non-secure attachment relationships place an individual at-risk for developing a cognitive framework that increases their vulnerability to depression following stressful life events. The paper concludes with a discussion of how future research might best explore specific mechanisms through which distinct attachment relationships may lead to divergent developmental pathways sharing the common outcome of cognitive processes that place individuals at risk for depression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A Postulated Mechanism That Leads to Materialization and Dematerialization of Matter and to Antigravity.

    Science.gov (United States)

    Bearden, Thomas E.

    This document presents a discussion of the postulated mechanism that leads to the materialization and dematerialization of matter and to antigravity. The mechanism also explains why an orbital electron does not radiate energy, in contradiction to classical electromagnetic theory. One of the paradoxes of special relativity is explained. A new model…

  1. In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

    Science.gov (United States)

    Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

    1992-04-01

    A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

  2. Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins.

    Science.gov (United States)

    Hanas, J S; Rodgers, J S; Bantle, J A; Cheng, Y G

    1999-11-01

    The association of lead with chromatin in cells suggests that deleterious metal effects may in part be mediated through alterations in gene function. To elucidate if and how lead may alter DNA binding of cysteine-rich zinc finger proteins, lead ions were analyzed for their ability to alter the DNA binding mechanism of the Cys(2)His(2) zinc finger protein transcription factor IIIA (TFIIIA). As assayed by DNase I protection, the interaction of TFIIIA with the 50-bp internal control region of the 5S ribosomal gene was partially inhibited by 5 microM lead ions and completely inhibited by 10 to 20 microM lead ions. Preincubation of free TFIIIA with lead resulted in DNA-binding inhibition, whereas preincubation of a TFIIIA/5S RNA complex with lead did not result in DNA-binding inhibition. Because 5S RNA binds TFIIIA zinc fingers, this result is consistent with an inhibition mechanism via lead binding to zinc fingers. The complete loss of DNase I protection on the 5S gene indicates the mechanism of inhibition minimally involves the N-terminal fingers of TFIIIA. Inhibition was not readily reversible and occurred in the presence of an excess of beta-mercaptoethanol. Inhibition kinetics were fast, progressing to completion in approximately 5 min. Millimolar concentrations of sulfhydryl-specific arsenic ions were not inhibitory for TFIIIA binding. Micromolar concentrations of lead inhibited DNA binding by Sp1, another Cys(2)His(2) finger protein, but not by the nonfinger protein AP2. Inhibition of Cys(2)His(2) zinc finger transcription factors by lead ions at concentrations near those known to have deleterious physiological effects points to new molecular mechanisms for lead toxicity in promoting disease.

  3. A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

    Science.gov (United States)

    Schernthaner-Reiter, Marie Helene; Adams, David; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fabio R; Nilsson, Ola; Nella, Aikaterini A; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William; Stratakis, Constantine A

    2016-05-01

    X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis. • X-linked nephrogenic diabetes insipidus is caused by AVPR2 mutations, and disease severity can vary depending on the functional effect of the mutation. What is New: • We demonstrate here that a splice site mutation in AVPR2 leads to partial X-linked NDI in two brothers. • Treatment with high-dose DDAVP led to improvement of polyuria and polydipsia, weight gain, and growth.

  4. Analytical expression for an optimised link bar mechanism for a beta-type Stirling engine

    DEFF Research Database (Denmark)

    Carlsen, Henrik; Bovin, Jonas Kabell

    2007-01-01

    The design of a mechanism for kinematic beta-type Stirling engines, where the displacer piston and the working piston share the same cylinder, is complicated. A well-known solution is the rhombic drive, but this solution depends on oil lubrication because of the gear wheels connecting the two...... counter rotating crank shafts. In a hermetically sealed Stirling engine it is an advantage to avoid oil in the crank case, making the application of the rhombic drive difficult. In this paper, another crank mechanism is presented, which has been developed for a 9 kW single cylinder engine. The new crank...... mechanism is a further development of the mechanism in a previous 9 kW engine. The crank mechanism for the beta-type Stirling engine is based on two four-link straight line mechanisms pointing up and down, respectively. The mechanism pointing upwards is connected to the working piston, while the mechanism...

  5. Imprinted Genes and the Environment: Links to the Toxic Metals Arsenic, Cadmium and Lead

    Directory of Open Access Journals (Sweden)

    Lisa Smeester

    2014-06-01

    Full Text Available Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR, some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, lead and mercury. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology.

  6. Imprinted Genes and the Environment: Links to the Toxic Metals Arsenic, Cadmium and Lead

    Science.gov (United States)

    Smeester, Lisa; Yosim, Andrew E.; Nye, Monica D.; Hoyo, Cathrine; Murphy, Susan K.; Fry, Rebecca C.

    2014-01-01

    Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR), some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, and lead. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology. PMID:24921406

  7. Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury.

    Science.gov (United States)

    Smeester, Lisa; Yosim, Andrew E; Nye, Monica D; Hoyo, Cathrine; Murphy, Susan K; Fry, Rebecca C

    2014-06-11

    Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR), some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, lead and mercury. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology.

  8. Blood lead concentrations in Alaskan tundra swans: linking breeding and wintering areas with satellite telemetry.

    Science.gov (United States)

    Ely, Craig R; Franson, J Christian

    2014-04-01

    Tundra swans (Cygnus columbianus) like many waterfowl species are susceptible to lead (Pb) poisoning, and Pb-induced mortality has been reported from many areas of their wintering range. Little is known however about Pb levels throughout the annual cycle of tundra swans, especially during summer when birds are on remote northern breeding areas where they are less likely to be exposed to anthropogenic sources of Pb. Our objective was to document summer Pb levels in tundra swans throughout their breeding range in Alaska to determine if there were population-specific differences in blood Pb concentrations that might pose a threat to swans and to humans that may consume them. We measured blood Pb concentrations in tundra swans at five locations in Alaska, representing birds that winter in both the Pacific Flyway and Atlantic Flyway. We also marked swans at each location with satellite transmitters and coded neck bands, to identify staging and wintering sites and determine if winter site use correlated with summer Pb concentrations. Blood Pb levels were generally low (<0.2 μg/ml) in swans across all breeding areas. Pb levels were lower in cygnets than adults, suggesting that swans were likely exposed to Pb on wintering areas or on return migration to Alaska, rather than on the summer breeding grounds. Blood Pb levels varied significantly across the five breeding areas, with highest concentrations in birds on the North Slope of Alaska (wintering in the Atlantic Flyway), and lowest in birds from the lower Alaska Peninsula that rarely migrate south for winter.

  9. In-situcross-linked PVDF membranes with enhanced mechanical durability for vacuum membrane distillation

    KAUST Repository

    Zuo, Jian; Chung, Neal Tai-Shung

    2016-01-01

    A novel and effective one-step method has been demonstrated to fabricate cross-linked polyvinylidene fluoride (PVDF) membranes with better mechanical properties and flux for seawater desalination via vacuum membrane distillation (VMD). This method involves the addition of two functional nonsolvent additives; namely, water and ethylenediamine (EDA), into the polymer casting solution. The former acts as a pore forming agent, while the latter performs as a cross-linking inducer. The incorporation of water tends to increase membrane flux via increasing porosity and pore size but sacrifices membrane mechanical properties. Conversely, the presence of EDA enhances membrane mechanical properties through in-situ cross-linking reaction. Therefore, by synergistically combining the effects of both functional additives, the resultant PVDF membranes have shown good MD performance and mechanical properties simultaneously. The parameters that affect the cross-link reaction and membrane mechanical properties such as reaction duration and EDA concentration have been systematically studied. The membranes cast from an optimal reaction condition comprising 0.8 wt % EDA and 3-hour reaction not only shows a 40% enhancement in membrane Young's Modulus compared to the one without EDA but also achieves a good VMD flux of 43.6 L/m2-h at 60°C. This study may open up a totally new approach to design next-generation high performance MD membranes. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4013–4022, 2016

  10. In-situcross-linked PVDF membranes with enhanced mechanical durability for vacuum membrane distillation

    KAUST Repository

    Zuo, Jian

    2016-05-12

    A novel and effective one-step method has been demonstrated to fabricate cross-linked polyvinylidene fluoride (PVDF) membranes with better mechanical properties and flux for seawater desalination via vacuum membrane distillation (VMD). This method involves the addition of two functional nonsolvent additives; namely, water and ethylenediamine (EDA), into the polymer casting solution. The former acts as a pore forming agent, while the latter performs as a cross-linking inducer. The incorporation of water tends to increase membrane flux via increasing porosity and pore size but sacrifices membrane mechanical properties. Conversely, the presence of EDA enhances membrane mechanical properties through in-situ cross-linking reaction. Therefore, by synergistically combining the effects of both functional additives, the resultant PVDF membranes have shown good MD performance and mechanical properties simultaneously. The parameters that affect the cross-link reaction and membrane mechanical properties such as reaction duration and EDA concentration have been systematically studied. The membranes cast from an optimal reaction condition comprising 0.8 wt % EDA and 3-hour reaction not only shows a 40% enhancement in membrane Young\\'s Modulus compared to the one without EDA but also achieves a good VMD flux of 43.6 L/m2-h at 60°C. This study may open up a totally new approach to design next-generation high performance MD membranes. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4013–4022, 2016

  11. Elevated lead levels from e-waste exposure are linked to decreased olfactory memory in children.

    Science.gov (United States)

    Zhang, Bo; Huo, Xia; Xu, Long; Cheng, Zhiheng; Cong, Xiaowei; Lu, Xueling; Xu, Xijin

    2017-12-01

    Lead (Pb) is a developmental neurotoxicant and can cause abnormal development of the nervous system in children. Hence, the aim of this study was to investigate the effect of Pb exposure on child olfactory memory by correlating the blood Pb levels of children in Guiyu with olfactory memory tests. We recruited 61 preschool children, 4- to 7-years of age, from Guiyu and 57 children from Haojiang. The mean blood Pb level of Guiyu children was 9.40 μg/dL, significantly higher than the 5.04 μg/dL mean blood Pb level of Haojiang children. In addition, approximately 23% of Guiyu children had blood Pb levels exceeding 10.00 μg/dL. The correlation analysis showed that blood Pb levels in children highly correlated with e-waste contact (r s  = 0.393). Moreover, the mean concentration of serum BDNF in Guiyu children (35.91 ng/ml) was higher than for Haojiang (28.10 ng/ml) and was positively correlated with blood Pb levels. Both item and source olfactory memory tests at 15 min, 5 h and 24 h after odor exposure showed that scores were lower in Guiyu children indicative of reduced olfactory memory in Guiyu children. Olfactory memory tests scores negatively correlated with blood Pb and serum BDNF levels, but were positively associated with parental education levels. At the same time, scores of both tests on children in the high blood Pb level group (blood Pb levels > 5.00 μg/dL) were lower than those in the low blood Pb level group (blood Pb levels ≤ 5.00 μg/dL), implying that Pb exposure decreases olfactory memory in children. Our findings suggest that Pb exposure in e-waste recycling and dismantling areas could result in an increase in serum BDNF level and a decrease in child olfactory memory, in addition, BDNF might be involved in olfactory memory impairment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A novel strategy for preparing mechanically robust ionically cross-linked alginate hydrogels

    International Nuclear Information System (INIS)

    Jejurikar, Aparna; Lawrie, Gwen; Groendahl, Lisbeth; Martin, Darren

    2011-01-01

    The properties of alginate films modified using two cross-linker ions (Ca 2+ and Ba 2+ ), comparing two separate cross-linking techniques (the traditional immersion (IM) method and a new strategy in a pressure-assisted diffusion (PD) method), are evaluated. This was achieved through measuring metal ion content, water uptake and film stability in an ionic solution ([Ca 2+ ] = 2 mM). Characterization of the internal structure and mechanical properties of hydrated films were established by cryogenic scanning electron microscopy and tensile testing, respectively. It was found that gels formed by the PD technique possessed greater stability and did not exhibit any delamination after 21 day immersion as compared to gels formed by the IM technique. The Ba 2+ cross-linked gels possessed significantly higher cross-linking density as reflected in lower water content, a more dense internal structure and higher Young's modulus compared to Ca 2+ cross-linked gels. For the Ca 2+ cross-linked gels, a large improvement in the mechanical properties was observed in gels produced by the PD technique and this was attributed to thicker pore walls observed within the hydrogel structure. In contrast, for the Ba 2+ cross-linked gels, the PD technique resulted in gels that had lower tensile strength and strain energy density and this was attributed to phase separation and larger macropores in this gel.

  13. Mechanical and fatigue properties of martensitic Fe-13Cr steel in contact with lead and lead-bismuth melts

    Energy Technology Data Exchange (ETDEWEB)

    Yaskiv, O.I., E-mail: oleh.yaskiv@ipm.lviv.ua; Fedirko, V.M.

    2014-01-15

    Highlights: •We investigated the influence of Pb and Pb-Bi melts on mechanical properties of Fe-13Cr steel at high temperatures. •We revealed the temperature interval of liquid metal embrittlement of Fe-13Cr steel. •Pb-Bi has more negative impact as compared with Pb for both plasticity and fatigue. -- Abstract: The influence of stagnant liquid-metal environments (Pb and Pb-Bi) on mechanical (strength and plasticity) and fatigue properties (low cycle fatigue) of martensitic Fe-13Cr steel in temperature interval of 250–600 °S have been investigated. Heavy liquid metals facilitate decreasing in ultimate strength by 10–20% against that in vacuum. The increase of temperature enhances this effect. Fe-13Cr steel is susceptible to liquid-metal embrittlement in the temperature interval of 350–450 °S, which manifests itself more substantially in lead-bismuth eutectic. The decrease of plasticity in Pb is 11% at 450 °S and in Pb-Bi is 30% in temperature interval 350–400 °S. Liquid metal environments significantly reduce fatigue life of Fe-13Cr steel. Pb-Bi has a more negative impact. In particular, with increasing total strain amplitude (up to 1.0%), the decrease in the cycle number to fracture by more than two orders of magnitude occurs.

  14. How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (∼95% of SMA cases or mutation (∼5% of SMA cases of the survival motor neuron 1 gene SMN1. As the product of SMN1, SMN is a component of the SMN complex, and is also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs, which play critical roles in pre-mRNA splicing in the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are described in this article. Of extraordinary interest, the structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136 with SMA-linked missense mutations, which cause disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface.

  15. Photo-degradation of poly(neopentyl isophthalate). Part II: Mechanism of cross-linking.

    NARCIS (Netherlands)

    Malanowski, P.; Benthem, van R.A.T.M.; Ven, van der L.G.J.; Laven, J.; Kisin, S.; With, de G.

    2011-01-01

    The mechanism of cross-linking of poly(neopentyl isophthalate) (PNI) by photo-degradation in nitrogen atmosphere was investigated. The exposure of PNI to UV light resulted in gel (insoluble material) formation. The gel material was collected and the morphology of the gel material was characterized

  16. Psychosocial mechanisms linking the social environment to mental health in African Americans

    Science.gov (United States)

    Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African Amer...

  17. Air rudder mechanism dynamics considering two elements:Joint clearance and link flexibility

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuntao; Quan, Qiquan; Li, He; Tang, Dewei; Li, Zhonghong; Fan, Wenyang; Deng, Zongquan [Harbin Institute of Technology, Harbin (China)

    2017-07-15

    Both the impact phenomenon in the clearance revolute joint and the link deformation will influence the dynamics of the air rudder transmission mechanism, which could reduce the flight quality of an aircraft. Given the effect of the two elements, a feasible simulation method with two improvements of previous methods is proposed to analyze the dynamic characteristics of the mechanism. In previous studies, the parameters of the contact force model in multi-body dynamics software were generally determined by experience, which may cause uncertainty in the calculation precision of the contact force. Furthermore, it is difficult to solve for the elastic link deformation in the practical mechanism using the available analytical methods due to the complicated section of the link. In this paper, a Continuous contact force (CCF) model was proposed and embedded in the ADAMS by developing a routine of the CCF model. Then, the flexible model was obtained by ANSYS to obtain the elastic link deformation. The experimental results indicate that the proposed simulation method can be effectively applied to predict the dynamic behavior of the mechanism.

  18. Evaluation of potential reaction mechanisms leading to the formation of coniferyl alcohol α-linkages in lignin: a density functional theory study.

    Science.gov (United States)

    Watts, Heath D; Mohamed, Mohamed Naseer Ali; Kubicki, James D

    2011-12-21

    Five potential reaction mechanisms, each leading to the formation of an α-O-4-linked coniferyl alcohol dimer, and one scheme leading to the formation of a recently proposed free-radical coniferyl alcohol trimer were assessed using density functional theory (DFT) calculations. These potential reaction mechanisms were evaluated using both the calculated Gibbs free energies, to predict the spontaneity of the constituent reactions, and the electron-density mapped Fukui function, to determine the most reactive sites of each intermediate species. The results indicate that each reaction in one of the six mechanisms is thermodynamically favorable to those in the other mechanisms; what is more, the Fukui function for each free radical intermediate corroborates with the thermochemical results for this mechanism. This mechanism proceeds via the formation of two distinct free-radical intermediates, which then react to produce the four α-O-4 stereoisomers.

  19. Microstructure And Mechanical Properties Of Lead Oxide- Thermoplastic Elas Tomer Composite

    International Nuclear Information System (INIS)

    Sudirman; Handayani, Ari; Darwinto, Tri; Teguh, Yulius S.P.P.; Sunarni, Anik; Marlijanti, Isni

    2000-01-01

    Research on microstructure and mechanical properties of lead oxide-thermoplastic elastomer composite with Pb 3 O 4 as lead oxide. Thermoplastic elastomer synthesized from natural rubber as the elastomer and methyl metacrilate as the thermoplastic and irradiated simultaneously with optimum gamma ray. Thermoplastic elastomer (NR-PMMA) grind in a laboplastomill and Pb 3 O 4 was added in varied amount of 10%. 30%. 40% and 50%wt.The results showed that mechanical properties (tensile strength and elongation break) decreased as the Pb 3 O 4 composition increased. Microstructure from SEM observation showed that Pb 3 O 4 distributed evenly and having function as filler in composite

  20. Mechanical Strength Improvements of Carbon Nanotube Threads through Epoxy Cross-Linking

    Directory of Open Access Journals (Sweden)

    Qingyue Yu

    2016-01-01

    Full Text Available Individual Carbon Nanotubes (CNTs have a great mechanical strength that needs to be transferred into macroscopic fiber assemblies. One approach to improve the mechanical strength of the CNT assemblies is by creating covalent bonding among their individual CNT building blocks. Chemical cross-linking of multiwall CNTs (MWCNTs within the fiber has significantly improved the strength of MWCNT thread. Results reported in this work show that the cross-linked thread had a tensile strength six times greater than the strength of its control counterpart, a pristine MWCNT thread (1192 MPa and 194 MPa, respectively. Additionally, electrical conductivity changes were observed, revealing 2123.40 S·cm−1 for cross-linked thread, and 3984.26 S·cm−1 for pristine CNT thread. Characterization suggests that the obtained high tensile strength is due to the cross-linking reaction of amine groups from ethylenediamine plasma-functionalized CNT with the epoxy groups of the cross-linking agent, 4,4-methylenebis(N,N-diglycidylaniline.

  1. Fracture Mechanics Analyses of the Slip-Side Joggle Regions of Wing-Leading-Edge Panels

    Science.gov (United States)

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

    2011-01-01

    The Space Shuttle wing-leading edge consists of panels that are made of reinforced carbon-carbon. Coating spallation was observed near the slip-side region of the panels that experience extreme heating. To understand this phenomenon, a root-cause investigation was conducted. As part of that investigation, fracture mechanics analyses of the slip-side joggle regions of the hot panels were conducted. This paper presents an overview of the fracture mechanics analyses.

  2. The mechanism of collagen cross-linking in diabetes: a puzzle nearing resolution.

    Science.gov (United States)

    Monnier, V M; Glomb, M; Elgawish, A; Sell, D R

    1996-07-01

    Considerable interest has been focused in recent years on the mechanism of collagen cross-linking by high glucose in vitro and in vivo. Experiments in both diabetic humans and in animals have shown that over time collagen becomes less soluble, less digestible by collagenase, more stable to heat-induced denaturation, and more glycated. In addition, collagen becomes more modified by advanced products of the Maillard reaction, i.e., immunoreactive advanced glycation end products and the glycoxidation markers carboxymethyllysine and pentosidine. Mechanistic studies have shown that collagen cross-linking in vitro can be uncoupled from glycation by the use of antioxidants and chelating agents. Experiments in the authors' laboratory revealed that approximately 50% of carboxymethyllysine formed in vitro originates from pathways other than oxidation of Amadori products, i.e., most likely the oxidation of Schiff base-linked glucose. In addition, the increase in thermal stability of rat tail tendons exposed to high glucose in vitro or in vivo was found to strongly depend on H2O2 formation. The final missing piece of the puzzle is that of the structure of the major cross-link. We speculate that it is a nonfluorescent nonultraviolet active cross-link between two lysine residues, which includes a fragmentation product of glucose linked in a nonreducible bond labile to both strong acids and bases.

  3. Thermo-mechanical tests on W7-X current lead flanges

    International Nuclear Information System (INIS)

    Dhard, Chandra Prakash; Rummel, Thomas; Zacharias, Daniel; Bykov, Victor; Moennich, Thomas; Buscher, Klaus-Peter

    2013-01-01

    Highlights: • There are significant mechanical loads on the cryostat and radial flanges for W7-X current leads. • These are due to evacuation of W7-X cryostat, cool-down of cold mass, electro-magnetic forces and self weight of leads. • The actual mechanical loads were reduced to simplify the experimental set-up. • The tests were carried out on mock-up flanges test assembly at ambient temperature and at 77 K. • The thermo-mechanical tests on W7-X current lead flanges validate the design and joints of these flanges to the leads. -- Abstract: Fourteen pieces of high temperature superconducting current leads (CL) arranged in seven pairs, will be installed on the outer vessel of Wendelstein 7-X (W7-X) stellarator. In order to support the CL, it is provided with two glass fiber reinforce plastic (GFRP) flanges, namely, the lower cryostat flange (CF) remaining at room temperature and upper radial flange (RF) at about 5 K. Both the flanges i.e. CF and RF experience high mechanical loads with respect to the CL, due to the evacuation of W7-X cryostat, cool-down of cold mass including the CL, electro-magnetic forces due to current and plasma operations and self weight of CL. In order to check the integrity of these flanges for such mechanical loads, thermo-mechanical tests were carried out on these flanges at room temperatures and at liquid nitrogen (LN2) temperatures. The details of test set-up, results and modeling are described in the paper

  4. A Mobility-Aware Link Enhancement Mechanism for Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Kai-Wen Hu

    2008-04-01

    Full Text Available With the growth up of internet in mobile commerce, researchers have reproduced various mobile applications that vary from entertainment and commercial services to diagnostic and safety tools. Mobility management has widely been recognized as one of the most challenging problems for seamless access to wireless networks. In this paper, a novel link enhancement mechanism is proposed to deal with mobility management problem in vehicular ad hoc networks. Two machine learning techniques, namely, particle swarm optimization and fuzzy logic systems, are incorporated into the proposed schemes to enhance the accuracy of prediction of link break and congestion occurrence. The experimental results verify the effectiveness and feasibility of the proposed schemes.

  5. A Mobility-Aware Link Enhancement Mechanism for Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Huang Chenn-Jung

    2008-01-01

    Full Text Available Abstract With the growth up of internet in mobile commerce, researchers have reproduced various mobile applications that vary from entertainment and commercial services to diagnostic and safety tools. Mobility management has widely been recognized as one of the most challenging problems for seamless access to wireless networks. In this paper, a novel link enhancement mechanism is proposed to deal with mobility management problem in vehicular ad hoc networks. Two machine learning techniques, namely, particle swarm optimization and fuzzy logic systems, are incorporated into the proposed schemes to enhance the accuracy of prediction of link break and congestion occurrence. The experimental results verify the effectiveness and feasibility of the proposed schemes.

  6. Mechanical design of ultraprecision weak-link stages for nanometer-scale x-ray imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shu, D [APS Engineering Support Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Maser, J, E-mail: shu@aps.anl.go [Center for Nanoscale Materials, Argonne National Laboratory, Argonne, IL 60439 (United States)

    2009-09-01

    A nanopositioning diagnostic setup has been built to support the Argonne Center for Nanoscale Materials (CNM) nanoprobe instrument commissioning process at the APS. Its laser Doppler interferometer system provides subnanometer positioning diagnostic resolution with large dynamic range. A set of original APS designed ultraprecision PZT-driven weak-link stages with high-stiffness motor-driven stages has been tested with this diagnostic setup. In this paper we present a preliminary test result of the ultraprecision weak-link stage system developed for the CNM hard x-ray nanoprobe instrument at APS sector 26. A test result for a novel laminar weak-link mechanism with sub-centimeter travel range and sub-nanometer positioning resolution is also introduced in this paper as a future work.

  7. Design of a deterministic link initialization mechanism for serial LVDS interconnects

    International Nuclear Information System (INIS)

    Schatral, S; Lemke, F; Bruening, U

    2014-01-01

    The Compressed Baryonic Matter experiment at FAIR in Darmstadt has special requirements for the Data Acquisition Network. One of them is deterministic latency for all the links from the back-end to the front-end, which enables synchronization in the whole read-out tree. Since the front-end electronics (FEE) contain mixed-signal circuits for processing the raw detector data, special ASICs were developed. DDR LVDS links are used to interconnect the FEEs and readout controllers. An adapted link initialization mechanism ensures determinism for them by balancing cable lengths, adjusting for phase differences, and handling environmental behavior. After re-initialization, timing must be accurate to the bit-clock level

  8. Behavioural evidence for separate mechanisms of audiovisual temporal binding as a function of leading sensory modality.

    Science.gov (United States)

    Cecere, Roberto; Gross, Joachim; Thut, Gregor

    2016-06-01

    The ability to integrate auditory and visual information is critical for effective perception and interaction with the environment, and is thought to be abnormal in some clinical populations. Several studies have investigated the time window over which audiovisual events are integrated, also called the temporal binding window, and revealed asymmetries depending on the order of audiovisual input (i.e. the leading sense). When judging audiovisual simultaneity, the binding window appears narrower and non-malleable for auditory-leading stimulus pairs and wider and trainable for visual-leading pairs. Here we specifically examined the level of independence of binding mechanisms when auditory-before-visual vs. visual-before-auditory input is bound. Three groups of healthy participants practiced audiovisual simultaneity detection with feedback, selectively training on auditory-leading stimulus pairs (group 1), visual-leading stimulus pairs (group 2) or both (group 3). Subsequently, we tested for learning transfer (crossover) from trained stimulus pairs to non-trained pairs with opposite audiovisual input. Our data confirmed the known asymmetry in size and trainability for auditory-visual vs. visual-auditory binding windows. More importantly, practicing one type of audiovisual integration (e.g. auditory-visual) did not affect the other type (e.g. visual-auditory), even if trainable by within-condition practice. Together, these results provide crucial evidence that audiovisual temporal binding for auditory-leading vs. visual-leading stimulus pairs are independent, possibly tapping into different circuits for audiovisual integration due to engagement of different multisensory sampling mechanisms depending on leading sense. Our results have implications for informing the study of multisensory interactions in healthy participants and clinical populations with dysfunctional multisensory integration. © 2016 The Authors. European Journal of Neuroscience published by Federation

  9. Mechanical properties and collagen cross-linking of the patellar tendon in old and young men

    DEFF Research Database (Denmark)

    Couppé, C; Hansen, P; Kongsgaard, M

    2009-01-01

    were higher in OM than in YM (73 +/- 13 vs. 11 +/- 2 mmol/mol; P appreciably influence the dimensions or mechanical properties of the human patellar tendon in vivo. Collagen concentration was reduced, whereas both enzymatic......Age-related loss in muscle mass and strength impairs daily life function in the elderly. However, it remains unknown whether tendon properties also deteriorate with age. Cross-linking of collagen molecules provides structural integrity to the tendon fibrils and has been shown to change with age...... in animals but has never been examined in humans in vivo. In this study, we examined the mechanical properties and pyridinoline and pentosidine cross-link and collagen concentrations of the patellar tendon in vivo in old (OM) and young men (YM). Seven OM (67 +/- 3 years, 86 +/- 10 kg) and 10 YM (27 +/- 2...

  10. Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

    Science.gov (United States)

    Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

    2014-09-01

    An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Impulsivity as a mechanism linking child abuse and neglect with substance use in adolescence and adulthood.

    Science.gov (United States)

    Oshri, Assaf; Kogan, Steve M; Kwon, Josephine A; Wickrama, K A S; Vanderbroek, Lauren; Palmer, Abraham A; MacKillop, James

    2018-05-01

    Emerging developmental perspectives suggest that adverse rearing environments promote neurocognitive adaptations that heighten impulsivity and increase vulnerability to risky behavior. Although studies document links between harsh rearing environments and impulsive behavior on substance use, the developmental hypothesis that impulsivity acts as mechanism linking adverse rearing environments to downstream substance use remains to be investigated. The present study investigated the role of impulsivity in linking child abuse and neglect with adult substance use using data from (a) a longitudinal sample of youth (Study 1, N = 9,421) and (b) a cross-sectional sample of adults (Study 2, N = 1,011). In Study 1, the links between child abuse and neglect and young adult smoking and marijuana use were mediated by increases in adolescent impulsivity. In Study 2, indirect links between child abuse and neglect and substance use were evidenced via delayed reward discounting and impulsivity traits. Among impulsivity subcomponents, robust indirect effects connecting childhood experiences to cigarette use emerged for negative urgency. Negative urgency, positive urgency, and sensation seeking mediated the effect of child abuse and neglect on cannabis and alcohol use. Results suggest that child abuse and neglect increases risk for substance use in part, due to effects on impulsivity. Individuals with adverse childhood experiences may benefit from substance use preventive intervention programs that target impulsive behaviors.

  12. Urban gardens: Lead exposure, recontamination mechanisms, and implications for remediation design

    International Nuclear Information System (INIS)

    Clark, Heather F.; Hausladen, Debra M.; Brabander, Daniel J.

    2008-01-01

    Environmental lead contamination is prevalent in urban areas where soil represents a significant sink and pathway of exposure. This study characterizes the speciation of lead that is relevant to local recontamination and to human exposure in the backyard gardens of Roxbury and Dorchester, MA, USA. One hundred forty-one backyard gardens were tested by X-ray fluorescence, and 81% of gardens have lead levels above the US EPA action limit of 400 μg/g. Raised gardening beds are the in situ exposure reduction method used in the communities to promote urban gardening. Raised beds were tested for lead and the results showed that the lead concentration increased from an initial range of 150±40 μg/g to an average of 336 μg/g over 4 years. The percent distribution of lead in the fine grain soil (<100 μm) and the trace metal signature of the raised beds support the conclusion that the mechanism of recontamination is wind-transported particles. Scanning electron microscopy and sequential extraction were used to characterize the speciation of lead, and the trace metal signature of the fine grain soil in both gardens and raised gardening beds is characteristic of lead-based paint. This study demonstrates that raised beds are a limited exposure reduction method and require maintenance to achieve exposure reduction goals. An exposure model was developed based on a suite of parameters that combine relevant values from the literature with site-specific quantification of exposure pathways. This model suggests that consumption of homegrown produce accounts for only 3% of children's daily exposure of lead while ingestion of fine grained soil (<100 μm) accounts for 82% of the daily exposure. This study indicates that urban lead remediation on a yard-by-yard scale requires constant maintenance and that remediation may need to occur on a neighborhood-wide scale

  13. Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits.

    Science.gov (United States)

    Beurel, E; Jope, R S

    2014-12-16

    Suicide is one of the leading causes of death in the United States, yet it remains difficult to understand the mechanistic provocations and to intervene therapeutically. Stress is recognized as a frequent precursor to suicide. Psychological stress is well established to cause activation of the inflammatory response, including causing neuroinflammation, an increase of inflammatory molecules in the central nervous system (CNS). Neuroinflammation is increasingly recognized as affecting many aspects of CNS functions and behaviors. In particular, much evidence demonstrates that inflammatory markers are elevated in traits that have been linked to suicidal behavior, including aggression, impulsivity and depression. Lithium is recognized as significantly reducing suicidal behavior, is anti-inflammatory and diminishes aggression, impulsivity and depression traits, each of which is associated with elevated inflammation. The anti-inflammatory effects of lithium result from its inhibition of glycogen synthase kinase-3 (GSK3). GSK3 has been demonstrated to strongly promote inflammation, aggressive behavior in rodents and depression-like behaviors in rodents, whereas regulation of impulsivity by GSK3 has not yet been investigated. Altogether, evidence is building supporting the hypothesis that stress activates GSK3, which in turn promotes inflammation, and that inflammation is linked to behaviors associated with suicide, including particularly aggression, impulsivity and depression. Further investigation of these links may provide a clearer understanding of the causes of suicidal behavior and provide leads for the development of effective preventative interventions, which may include inhibitors of GSK3.

  14. Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available A new memory is initially labile and becomes stabilized through a process of consolidation, which depends on gene expression. Stable memories, however, can again become labile if reactivated by recall and require another phase of protein synthesis in order to be maintained. This process is known as reconsolidation. The functional significance of the labile phase of reconsolidation is unknown; one hypothesis proposes that it is required to link new information with reactivated memories. Reconsolidation is distinct from the initial consolidation, and one distinction is that the requirement for specific proteins or general protein synthesis during the two processes occurs in different brain areas. Here, we identified an anatomically distinctive molecular requirement that doubly dissociates consolidation from reconsolidation of an inhibitory avoidance memory. We then used this requirement to investigate whether reconsolidation and consolidation are involved in linking new information with reactivated memories. In contrast to what the hypothesis predicted, we found that reconsolidation does not contribute to the formation of an association between new and reactivated information. Instead, it recruits mechanisms similar to those underlying consolidation of a new memory. Thus, linking new information to a reactivated memory is mediated by consolidation and not reconsolidation mechanisms.

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

    Science.gov (United States)

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

    2017-10-01

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

  16. Cardiac implantable electronic device lead extraction using the lead-locking device system: keeping it simple, safe, and inexpensive with mechanical tools and local anesthesia.

    Science.gov (United States)

    Manolis, Antonis S; Georgiopoulos, Georgios; Metaxa, Sofia; Koulouris, Spyridon; Tsiachris, Dimitris

    2017-10-01

    We have previously reported our successful approach for percutaneous cardiac implantable electronic device (CIED) lead extraction using inexpensive tools, which we have continued over the years. Herein we report the results of the systematic use of a unique stylet, the lead-locking device (LLD), which securely locks the entire lead lumen, aided with non-powered telescoping sheaths in 54 patients to extract 98 CIED leads. This prospective observational clinical study included 38 men and 16 women aged 68.9±13.1 years undergoing lead extraction for device infection (n=46), lead malfunction (n=5), or prior to defibrillator implant (n=3). Leads were in place for 6.7±4.3 years. Infections were more commonly due to Staphylococcus species (n=40). There were 78 pacing (31 ventricular, 37 atrial, 4 VDD, and 6 coronary sinus leads) and 20 defibrillating leads. Using simple traction (6 leads) and the LLD stylets (92 leads) aided with telescoping sheaths (15 patients), 96 (98%) leads in 52 (96.3%) patients were successfully removed, with all but one leads removed using a subclavian approach; in 1 patient, the right femoral approach was also required. In 2 patients, distal fragments from one ventricular pacing and one defibrillating lead could not be removed. Finally, lead removal was completely (52/54) (96.3%) or partially (2/54) (3.7%) successful in 54 patients for 96 of 98 leads (98%) without major complications. Percutaneous lead extraction can be successful with mechanical tools using the LLD locking stylet aided with non-powered telescoping sheaths through a simplified, safe, and inexpensive procedure using local anesthesia.

  17. Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion.

    Science.gov (United States)

    Weltens, N; Zhao, D; Van Oudenhove, L

    2014-03-01

    Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology ('comfort foods') and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression. This review paper aims to give an overview of current knowledge on the neurophysiological mechanisms underlying the link between (fatty) foods, their reward value, and emotional responses to (anticipation of) their intake in humans. Firstly, the influence of exteroceptive sensory signals, including visual, olfactory ('anticipatory food reward'), and gustatory ('consummatory food reward'), on the encoding of reward value in the (ventral) striatum and of subjective pleasantness in the cingulate and orbitofrontal cortex will be discussed. Differences in these pathways and mechanisms between lean and obese subjects will be highlighted. Secondly, recent studies elucidating the mechanisms of purely interoceptive fatty acid-induced signaling from the gastrointestinal tract to the brain, including the role of gut peptides, will be presented. These studies have demonstrated that such subliminal interoceptive stimuli may impact on hedonic circuits in the brain, and thereby influence the subjective and neural responses to negative emotion induction. This suggests that the effect of foods on mood may even occur independently from their exteroceptive sensory properties. © 2014 John Wiley & Sons Ltd.

  18. Reconstitution of a eukaryotic replisome reveals suppression mechanisms that define leading/lagging strand operation

    Science.gov (United States)

    Georgescu, Roxana E; Schauer, Grant D; Yao, Nina Y; Langston, Lance D; Yurieva, Olga; Zhang, Dan; Finkelstein, Jeff; O'Donnell, Mike E

    2015-01-01

    We have reconstituted a eukaryotic leading/lagging strand replisome comprising 31 distinct polypeptides. This study identifies a process unprecedented in bacterial replisomes. While bacteria and phage simply recruit polymerases to the fork, we find that suppression mechanisms are used to position the distinct eukaryotic polymerases on their respective strands. Hence, Pol ε is active with CMG on the leading strand, but it is unable to function on the lagging strand, even when Pol δ is not present. Conversely, Pol δ-PCNA is the only enzyme capable of extending Okazaki fragments in the presence of Pols ε and α. We have shown earlier that Pol δ-PCNA is suppressed on the leading strand with CMG (Georgescu et al., 2014). We propose that CMG, the 11-subunit helicase, is responsible for one or both of these suppression mechanisms that spatially control polymerase occupancy at the fork. DOI: http://dx.doi.org/10.7554/eLife.04988.001 PMID:25871847

  19. Lead levels in some biological samples of auto-mechanics in Abeokuta, Nigeria.

    Science.gov (United States)

    Babalola, O O; Ojo, L O; Aderemi, M O

    2005-12-01

    Lead levels were determined in the blood, scalp hair and fingernails of 38, all male auto-mechanics (aged 18-45 years) from Abeokuta, South-western Nigeria. The subjects were classified into four sub-groups based on the period of exposure namely: 1-5, 6-10, 11-15, and >16 years. Thirty-two occupationally unexposed subjects (mainly office workers) served as the control. The weight, height and body mass indexes of all subjects were noted, in addition to other information obtained through structured questionnaire. The mean values of blood lead (BPb), hair lead (HPb) and fingernail lead (NPb) of the occupationally exposed subjects (n=38) were 48.50 +/- 9.08 microg/dL, 17.75 +/- 5.16 microg/g, and 5.92 +/- 3.30 microg/g respectively, while the corresponding mean values for these parameters in the control subjects (n = 32) were 33.(,5 +/- 10.09 microg/dL, 14.30 +/- 5.90 microg/g and 5.31 +/- 2.77 microg/g respectively. The differences in BPb and HPb levels of the two groups were statistically significant (P <0.05 and P <0.01 respectively), while that of NPb was not significant. The levels of lead in the biological samples appeared to have no relationship with the number of years on the job. From these results, it was obvious that the higher levels of lead in the biological samples of test subjects, compared with those of the controls were from environmental sources.

  20. Mechanism of formation and spatial distribution of lead atoms in quartz tube atomizers

    Science.gov (United States)

    Johansson, M.; Baxter, D. C.; Ohlsson, K. E. A.; Frech, W.

    1997-05-01

    The cross-sectional and longitudinal spatial distributions of lead atoms in a quartz tube (QT) atomizers coupled to a gas chromatograph have been investigated. A uniform analyte atom distribution over the cross-section was found in a QT having an inner diameter (i.d.) of 7 mm, whereas a 10 mm i.d. QT showed an inhomogeneous distribution. These results accentuate the importance of using QTs with i.d.s below 10 mm to fulfil the prerequirement of the Beer—Lambert law to avoid bent calibration curves. The influence of the make up gas on the formation of lead atoms from alkyllead compounds has been studied, and carbon monoxide was found equally efficient in promoting free atom formation as hydrogen. This suggests that hydrogen radicals are not essential for mediating the atomization of alkyllead in QT atomizers at ˜ 1200 K. Furthermore, thermodynamic equilibrium calculations describing the investigated system were performed supporting the experimental results. Based on the presented data, a mechanism for free lead atom formation in continuously heated QT atomizers is proposed; thermal atomization occurs under thermodynamic equilibrium conditions in a reducing gas. The longitudinal atom distribution has been further investigated applying other make up gases, N 2 and He. These results show the effect of the influx of atmospheric oxygen on the free lead atom formation. Calculations of the partial pressure of oxygen in the atomizer gas phase assuming thermodynamic equilibrium have been undertaken using a convective-diffusional model.

  1. Microwave emission from lead zirconate titanate induced by impulsive mechanical load

    Energy Technology Data Exchange (ETDEWEB)

    Aman, A., E-mail: alexander.aman@ovgu.de [Department of Engineering, Brandenburg University of Applied Science, 14470 Brandenburg an derHavel (Germany); Packaging Group, Institute of Micro- and Sensorsytems, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg (Germany); Majcherek, S. [Packaging Group, Institute of Micro- and Sensorsytems, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg (Germany); Hirsch, S. [Department of Engineering, Brandenburg University of Applied Science, 14470 Brandenburg an derHavel (Germany); Schmidt, B. [Chair of Micorsystem Technology, Institute of Micro- and Sensorsytems, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg (Germany)

    2015-10-28

    This paper focuses on microwave emission from Lead zirconate titanate Pb [Zr{sub x}Ti{sub 1−x}] O{sub 3} (PZT) induced by mechanical stressing. The mechanical stress was initiated by impact of a sharp tungsten indenter on the upper surface of PZT ceramic. The sequences of microwave and current impulses, which flew from indenter to electric ground, were detected simultaneously. The voltage between the upper and lower surface of ceramic was measured to obtain the behavior of mechanical force acting on ceramic during the impact. It was found that the amplitude, form, and frequency of measured microwave impulses were different by compression and restitution phase of impact. Two different mechanisms of electron emission, responsible for microwave impulse generation, were proposed based on the dissimilar impulse behavior. The field emission from tungsten indenter is dominant during compression, whereas ferroemission dominates during restitution phase. Indeed, it was observed that the direction of the current flow, i.e., sign of current impulses is changed by transitions from compression to restitution phase of impact. The observed dissimilar behavior of microwave impulses, caused by increasing and decreasing applied force, can be used to calculate the contact time and behavior of mechanical force during mechanical impact on ceramic surface. It is shown that the generation of microwave impulses exhibits high reproducibility, impulse intensity, a low damping factor, and high mechanical failure resistance. Based on these microwave emission properties of PZT, the development of new type of stress sensor with spatial resolution of few microns becomes possible.

  2. Mechanisms of collective cell movement lacking a leading or free front edge in vivo.

    Science.gov (United States)

    Uechi, Hiroyuki; Kuranaga, Erina

    2017-08-01

    Collective cell movement is one of the strategies for achieving the complex shapes of tissues and organs. In this process, multiple cells within a group held together by cell-cell adhesion acquire mobility and move together in the same direction. In some well-studied models of collective cell movement, the mobility depends strongly on traction generated at the leading edge by cells located at the front. However, recent advances in live-imaging techniques have led to the discovery of other types of collective cell movement lacking a leading edge or even a free edge at the front, in a diverse array of morphological events, including tubule elongation, epithelial sheet extension, and tissue rotation. We herein review some of the developmental events that are organized by collective cell movement and attempt to elucidate the underlying cellular and molecular mechanisms, which include membrane protrusions, guidance cues, cell intercalation, and planer cell polarity, or chirality pathways.

  3. Lead toxicity in rice: effects, mechanisms, and mitigation strategies--a mini review.

    Science.gov (United States)

    Ashraf, Umair; Kanu, Adam Sheka; Mo, Zhaowen; Hussain, Saddam; Anjum, Shakeel Ahmad; Khan, Imran; Abbas, Rana Nadeem; Tang, Xiangru

    2015-12-01

    Lead (Pb) is a major environmental pollutant that affects plant morpho-physiological and biochemical attributes. Its higher levels in the environment are not only toxic to human beings but also harmful for plants and soil microbes. We have reviewed the uptake, translocation, and accumulation mechanisms of Pb and its toxic effects on germination, growth, yield, nutrient relation, photosynthesis, respiration, oxidative damage, and antioxidant defense system of rice. Lead toxicity hampers rice germination, root/shoot length, growth, and final yield. It reduces nutrient uptake through roots, disrupts chloroplastic ultrastructure and cell membrane permeability, induces alterations in leaves respiratory activities, produces reactive oxygen species (ROS), and triggers some enzyme and non-enzymatic antioxidants (as defense to oxidative damage). In the end, biochar amendments and phytoremediation technologies have been proposed as soil remediation approaches for Pb tainted soils.

  4. Cardiovascular reactivity as a mechanism linking child trauma to adolescent psychopathology

    Science.gov (United States)

    Heleniak, Charlotte; McLaughlin, Katie A.; Ormel, Johan; Riese, Harriette

    2016-01-01

    Alterations in physiological reactivity to stress are argued to be central mechanisms linking adverse childhood environmental experiences to internalizing and externalizing psychopathology. Childhood trauma exposure may influence physiological reactivity to stress in distinct ways from other forms of childhood adversity. This study applied a novel theoretical model to investigate the impact of childhood trauma on cardiovascular stress reactivity – the biopsychosocial model of challenge and threat. This model suggests that inefficient cardiovascular responses to stress – a threat as opposed to challenge profile – are characterized by blunted cardiac output (CO) reactivity and increased vascular resistance. We examined whether childhood trauma exposure predicted an indicator of the threat profile of cardiovascular reactivity and whether such a pattern was associated with adolescent psychopathology in a population-representative sample of 488 adolescents (M = 16.17 years old, 49.2% boys) in the TRacking Adolescents’ Individual Lives Survey (TRAILS). Exposure to trauma was associated with both internalizing and externalizing symptoms and a pattern of cardiovascular reactivity consistent with the threat profile, including blunted CO reactivity during a social stress task. Blunted CO reactivity, in turn, was positively associated with externalizing, but not internalizing symptoms and mediated the link between trauma and externalizing psychopathology. None of these associations varied by gender. The biopsychosocial model of challenge and threat provides a novel theoretical framework for understanding disruptions in physiological reactivity to stress following childhood trauma exposure, revealing a potential pathway linking such exposure with externalizing problems in adolescents. PMID:27568327

  5. Neural mechanisms linking social status and inflammatory responses to social stress.

    Science.gov (United States)

    Muscatell, Keely A; Dedovic, Katarina; Slavich, George M; Jarcho, Michael R; Breen, Elizabeth C; Bower, Julienne E; Irwin, Michael R; Eisenberger, Naomi I

    2016-06-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. When and how does labour lead to love? The ontogeny and mechanisms of the IKEA effect.

    Science.gov (United States)

    Marsh, Lauren E; Kanngiesser, Patricia; Hood, Bruce

    2018-01-01

    We elevate our constructions to a special status in our minds. This 'IKEA' effect leads us to believe that our creations are more valuable than items that are identical, but constructed by another. This series of studies utilises a developmental perspective to explore why this bias exists. Study 1 elucidates the ontogeny of the IKEA effect, demonstrating an emerging bias at age 5, corresponding with key developmental milestones in self-concept formation. Study 2 assesses the role of effort, revealing that the IKEA effect is not moderated by the amount of effort invested in the task in 5-to-6-year olds. Finally, Study 3 examines whether feelings of ownership moderate the IKEA effect, finding that ownership alone cannot explain why children value their creations more. Altogether, results from this study series are incompatible with existing theories of the IKEA bias. Instead, we propose a new framework to examine biases in decision making. Perhaps the IKEA effect reflects a link between our creations and our self-concept, emerging at age 5, leading us to value them more positively than others' creations. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2010-10-01

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

  8. INFRASTRUCTURAL MECHANISMS LEADING TOWARD PRO-ACCOUNTABLE CARE ORGANISATION ORIENTATION: A SURVEY OF HOSPITAL MANAGERS

    Science.gov (United States)

    Wan, Thomas T.H.; Masri, Maysoun Dimachkie; Ortiz, Judith

    2013-01-01

    Organisations across the country are transforming the way they deliver care, in ways similar to the accountable care organisation (ACO) model supported by Medicare. ACOs modalities are varying in size, type, and financing structure. Little is known about how specific infrastructural mechanisms influence hospital managers’ pro-ACO orientation. Using an electronic-survey of hospital managers, this study explores how pro-ACO orientation, as a latent construct, is captured from the perceptions of hospital managers; and identify infrastructural mechanisms leading to the formation of pro-ACO orientation. Of the total hospital respondents, 58% are moving toward the establishment of ACOs; 56% are planning to join in the next two years; 48% are considering joining ACOs; while 25% had already participated in ACOs during 2012. Urban hospitals are more likely than rural hospitals to be engaged in ACO development. The health provider network size is one of the strongest indicators in predicting pro-ACO orientation. PMID:25374609

  9. Time with friends and physical activity as mechanisms linking obesity and television viewing among youth.

    Science.gov (United States)

    Vandewater, Elizabeth A; Park, Seoung Eun; Hébert, Emily T; Cummings, Hope M

    2015-07-27

    Though bivariate relationships between childhood obesity, physical activity, friendships and television viewing are well documented, empirical assessment of the extent to which links between obesity and television may be mediated by these factors is scarce. This study examines the possibility that time with friends and physical activity are potential mechanisms linking overweight/obesity to television viewing in youth. Data were drawn from children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002 wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics (PSID) (n = 1,545). Data were collected both directly and via self-report from children and their parents. Path analysis was employed to examine a model whereby the relationships between youth overweight/obesity and television viewing were mediated by time spent with friends and moderate-to-vigorous physical activity (MVPA). Overweight/obesity was directly related to less time spent with friends, but not to MVPA. Time spent with friends was directly and positively related to MVPA, and directly and negatively related to time spent watching television without friends. In turn, MVPA was directly and negatively related to watching television without friends. There were significant indirect effects of both overweight/obesity and time with friends on television viewing through MVPA, and of overweight/obesity on MVPA through time with friends. Net of any indirect effects, the direct effect of overweight/obesity on television viewing remained. The final model fit the data extremely well (χ2 = 5.77, df = 5, ptelevision viewing in youth. These findings highlight the importance of moving from examinations of bivariate relationships between weight status and television viewing to more nuanced explanatory models which attempt to identify and unpack the possible mechanisms linking them.

  10. Fracture Mechanics Analyses of Reinforced Carbon-Carbon Wing-Leading-Edge Panels

    Science.gov (United States)

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

    2010-01-01

    Fracture mechanics analyses of subsurface defects within the joggle regions of the Space Shuttle wing-leading-edge RCC panels are performed. A 2D plane strain idealized joggle finite element model is developed to study the fracture behavior of the panels for three distinct loading conditions - lift-off and ascent, on-orbit, and entry. For lift-off and ascent, an estimated bounding aerodynamic pressure load is used for the analyses, while for on-orbit and entry, thermo-mechanical analyses are performed using the extreme cold and hot temperatures experienced by the panels. In addition, a best estimate for the material stress-free temperature is used in the thermo-mechanical analyses. In the finite element models, the substrate and coating are modeled separately as two distinct materials. Subsurface defects are introduced at the coating-substrate interface and within the substrate. The objective of the fracture mechanics analyses is to evaluate the defect driving forces, which are characterized by the strain energy release rates, and determine if defects can become unstable for each of the loading conditions.

  11. Biochemical mechanism of phytoremediation process of lead and cadmium pollution with Mucor circinelloides and Trichoderma asperellum.

    Science.gov (United States)

    Zhang, Xu; Li, Xinxin; Yang, Huanhuan; Cui, Zhaojie

    2018-08-15

    This study focused on the bioremediation mechanisms of lead (0, 100, 500, 1000 mg kg -1 ) and cadmium (0,10,50,100 mg kg -1 ) contaminated soil using two indigenous fungi selected from mine tailings as the phytostimulation of Arabidopsis thaliana. The two fungal strains were characterized as Mucor circinelloides (MC) and Trichoderma asperellum (TA) by internal transcribed spacer sequencing at the genetic levels. Our research revealed that Cadmium was more toxic to plant growth than lead and meanwhile, MC and TA can strengthen A. thaliana tolerance to cadmium and lead with 40.19-117.50% higher root length and 58.31-154.14% shoot fresh weight of plant compared to non-inoculation. In this study, TA exhibited a higher potential to the inactivation of cadmium; however, MC was more effective in lead passivation. There was a direct correlation between the type of fungi, heavy metal content, heavy metal type and oxidative damage in plant. Both lead and cadmium induced oxidative damage as indicated by increased superoxide dismutase and catalase activities, while the antioxidant levels were significantly higher in fungal inoculated plants compared with those non-inoculated. The analysis of soil enzyme activity and taxonomic richness uncovered that the dominant structures of soil microbial community were altered by exogenous microbial agents. MC enhanced higher microbial diversity and soil enzyme activity than TA. The two indigenous fungi lessened several limiting factors with respect to phytoremediation technology, such as soil chemistry, contamination level and transformation, and metal solubility. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Leading High School Transformation for College and Career Success: A Guide for Developing a System of Linked Learning Pathways

    Science.gov (United States)

    Stearns, Roman

    2014-01-01

    This ConnectEd Guide for Developing a System of Linked Learning Pathways will introduce school district leaders and their community partners to Linked Learning and a system of quality pathways that can transform high schools, instructional practice, and the student experience. Not intended to be prescriptive, this document can and should be…

  13. Cross-linking of cell surface amyloid precursor protein leads to increased β-amyloid peptide production in hippocampal neurons: implications for Alzheimer's disease.

    Science.gov (United States)

    Lefort, Roger; Pozueta, Julio; Shelanski, Michael

    2012-08-01

    The accumulation of the β-amyloid peptide (Aβ) in Alzheimer's disease (AD) is thought to play a causative role in triggering synaptic dysfunction in neurons, leading to their eventual demise through apoptosis. Aβ is produced and secreted upon sequential cleavage of the amyloid precursor protein (APP) by β-secretases and γ-secretases. However, while Aβ levels have been shown to be increased in the brains of AD patients, little is known about how the cleavage of APP and the subsequent generation of Aβ is influenced, or whether the cleavage process changes over time. It has been proposed that Aβ can bind APP and promote amyloidogenic processing of APP, further enhancing Aβ production. Proof of this idea has remained elusive because a clear mechanism has not been identified, and the promiscuous nature of Aβ binding complicates the task of demonstrating the idea. To work around these problems, we used an antibody-mediated approach to bind and cross-link cell-surface APP in cultured rat primary hippocampal neurons. Here we show that cross-linking of APP is sufficient to raise the levels of Aβ in viable neurons with a concomitant increase in the levels of the β-secretase BACE1. This appears to occur as a result of a sorting defect that stems from the caspase-3-mediated inactivation of a key sorting adaptor protein, namely GGA3, which prevents the lysosomal degradation of BACE1. Together, our data suggest the occurrence of a positive pathogenic feedback loop involving Aβ and APP in affected neurons possibly allowing Aβ to spread to nearby healthy neurons.

  14. The Kynurenine Pathway: a Proposed Mechanism Linking Diabetes and Periodontal Disease in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Rishabh Kapila

    2011-07-01

    Full Text Available Introduction: Diabetes mellitus is a metabolic disease characte-rized by dysregulation of carbohydrate, protein and lipid metabolism. Diabetes could result, in part, in activation of tryptophan metabolism. Diabetic patients are more susceptible to gingivitis and periodontitis than healthy subjects. The salivary kynurenine derivatives are also implicated in the onset and development of periodontal dis-ease in humans.The hypothesis: We propose that the tryptophan metabolites via kynurenine pathway may lead to diabetes and an increased severity of periodontal disease in diabetic patients, thus linking both diabetes and periodontal disease.Evaluation of the hypothesis: Tryptophan has been found in significant amount in saliva in diabetic individuals in some studies, particularly tryptophan metabolites like kynurenine and anthranilic acid. Moreover, altered tryptophan metabolism has also been reported in the onset of periodontal disease. Thus, this correlation between diabetes mellitus, periodontal disease and salivary tryptophan metabolite levels could be related to the impaired kynurenine pathway metabolism of tryptophan.

  15. Endocrine and metabolic mechanisms linking postpartum glucose with early embryonic and foetal development in dairy cows.

    Science.gov (United States)

    Lucy, M C; Butler, S T; Garverick, H A

    2014-05-01

    Milk and milk solids production per cow is increasing annually in dairy systems. Peak milk production is in early lactation when the uterus and ovary are recovering from the previous pregnancy. The competing processes of milk production and restoration of reproductive function can be at odds, particularly if unique homeorhetic mechanisms that typify early lactation become imbalanced and cows experience metabolic disease. Homeorhesis leads to an increase in the synthesis of glucose that is irreversibly lost to milk lactose. Irreversible loss of glucose during lactation can invoke an endocrine and metabolic state that impinges upon postpartum uterine health, oestrous cyclicity and subsequent establishment of pregnancy. The first 30 days postpartum may be most critical in terms of the impact that metabolites and metabolic hormones have on reproduction. Depressed immune function caused in part by the postpartum metabolic profile leads to a failure in uterine involution and uterine disease. Oestrous cyclicity (interval to first ovulation and subsequent periodicity) is affected by the same hormones and metabolites that control postpartum immune function. Slower growth of the embryo or foetus perhaps explained by the unique metabolic profile during lactation may predispose cows to pregnancy loss. Understanding homeorhetic mechanisms that involve glucose and collectively affect postpartum uterine health, oestrous cyclicity and the establishment of pregnancy should lead to methods to improve postpartum fertility in dairy cows.

  16. Forever Young: Mechanisms of Natural Anoxia Tolerance and Potential Links to Longevity

    Directory of Open Access Journals (Sweden)

    Anastasia Krivoruchko

    2010-01-01

    Full Text Available While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity.

  17. Forever young: Mechanisms of natural anoxia tolerance and potential links to longevity

    Science.gov (United States)

    Krivoruchko, Anastasia

    2010-01-01

    While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity. PMID:20716943

  18. Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

    Science.gov (United States)

    Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

    2017-06-01

    Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Theoretical study on mechanical and electron-transport properties of conjugated molecular junctions with carboxylic or methyl sulfide links

    Energy Technology Data Exchange (ETDEWEB)

    Bao, De-Liang; Liu, Ran [College of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Leng, Jian-Cai [College of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); School of Science, Qilu University of Technology, Jinan 250353 (China); Zuo, Xi; Jiao, Yang [College of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Li, Zong-Liang, E-mail: lizongliang@sdnu.edu.cn [College of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Wang, Chuan-Kui [College of Physics and Electronics, Shandong Normal University, Jinan 250014 (China)

    2014-03-01

    The mechanical and electronic transport properties of 4-(methylthio)benzoic acid (M1), 1,4-bis(methylthio) benzene (M2) and methyl 4-(methylthio)benzoate (M3) molecular junctions are studied employing density functional theory and elastic scattering Green's function method. The numerical results show that the rupture force of M1 and M2 junctions are both about 0.6±0.1 nN as experiment probed, which is much smaller than the force to break COO{sup −}–Au bond. The COO{sup −} group strongly influenced on M1 molecular junction and further strengthened SMe–Au bond at the other end of the junction. The M3 junction is less stable because the CH{sub 3} group linked to COO group destroyed the mechanical stability of COO–Au connection. The conductance of M2 junction is about an order larger than that of M1 junction as the experiment probed. The less stable feature of M3 junction leads the absence of conductive peak.

  20. Dually cross-linked single network poly(acrylic acid) hydrogels with superior mechanical properties and water absorbency.

    Science.gov (United States)

    Zhong, Ming; Liu, Yi-Tao; Liu, Xiao-Ying; Shi, Fu-Kuan; Zhang, Li-Qin; Zhu, Mei-Fang; Xie, Xu-Ming

    2016-06-28

    Poly(acrylic acid) (PAA) hydrogels with superior mechanical properties, based on a single network structure with dual cross-linking, are prepared by one-pot free radical polymerization. The network structure of the PAA hydrogels is composed of dual cross-linking: a dynamic and reversible ionic cross-linking among the PAA chains enabled by Fe(3+) ions, and a sparse covalent cross-linking enabled by a covalent cross-linker (Bis). Under deformation, the covalently cross-linked PAA chains remain intact to maintain their original configuration, while the Fe(3+)-enabled ionic cross-linking among the PAA chains is broken to dissipate energy and then recombined. It is found that the mechanical properties of the PAA hydrogels are significantly influenced by the contents of covalent cross-linkers, Fe(3+) ions and water, which can be adjusted within a substantial range and thus broaden the applications of the hydrogels. Meanwhile, the PAA hydrogels have excellent recoverability based on the dynamic and reversible ionic cross-linking enabled by Fe(3+) ions. Moreover, the swelling capacity of the PAA hydrogels is as high as 1800 times in deionized water due to the synergistic effects of ionic and covalent cross-linkings. The combination of balanced mechanical properties, efficient recoverability, high swelling capacity and facile preparation provides a new method to obtain high-performance hydrogels.

  1. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices

    Directory of Open Access Journals (Sweden)

    Fernanda M. Carbinatto

    2014-02-01

    Full Text Available Cross-linked pectin/high amylose mixtures were evaluated as a new excipient for matrix tablets formulations, since the mixing of polymers and cross-linking reaction represent rational tools to reach materials with modulated and specific properties that meet specific therapeutic needs. Objective: In this work the influence of polymer ratio and cross-linking process on the swelling and the mechanism driving the drug release from swellable matrix tablets prepared with this excipient was investigated. Methods: Cross-linked samples were characterized by their micromeritic properties (size and shape, density, angle of repose and flow rate and liquid uptake ability. Matrix tablets were evaluated according their physical properties and the drug release rates and mechanisms were also investigated. Results: Cross-linked samples demonstrated size homogeneity and irregular shape, with liquid uptake ability insensible to pH. Cross-linking process of samples allowed the control of drug release rates and the drug release mechanism was influenced by both polymer ratio and cross-linking process. The drug release of samples with minor proportion of pectin was driven by an anomalous transport and the increase of the pectin proportion contributed to the erosion of the matrix. Conclusion: The cross-linked mixtures of high amylose and pectin showed a suitable excipient for slowing the drug release rates.

  2. Signaling in a polluted world: oxidative stress as an overlooked mechanism linking contaminants to animal communication

    Directory of Open Access Journals (Sweden)

    Valeria Marasco

    2016-08-01

    Full Text Available The capacity to communicate effectively with other individuals plays a critical role in the daily life of an individual and can have important fitness consequences. Animals rely on a number of visual and non-visual signals, whose production brings costs to the individual. The theory of honest signaling states that these costs are higher for low than for high-quality individuals, which prevents cheating and makes signals, such as skin and plumage colouration, indicators of individual’s quality or condition. The condition-dependent nature of signals makes them ideally suited as indicators of environmental quality, implying that signal production might be affected by contaminants. In this mini-review article, we have made the point that oxidative stress (OS is one overlooked mechanism linking exposure to contaminants to signaling because (i many contaminants can influence the individual’s oxidative balance, and (ii generation of both visual and non-visual signals is sensitive to oxidative stress. To this end, we have provided the first comprehensive review on the way both non-organic (heavy metals, especially mercury and organic (persistent organic pollutants contaminants may influence either OS or sexual signaling. We have also paid special attention to emerging classes of pollutants like brominated flame-retardants and perfluoroalkoxy alkanes in order to stimulate research in this area. We have finally provided suggestions and warnings for future work on the links among OS, sexual signaling and contaminant exposure.

  3. Mechanisms leading to increased risk of preterm birth in growth-restricted guinea pig pregnancies.

    Science.gov (United States)

    Palliser, Hannah K; Kelleher, Meredith A; Welsh, Toni N; Zakar, Tamas; Hirst, Jonathan J

    2014-02-01

    Intrauterine growth restriction (IUGR) is a risk factor for preterm labor; however, the mechanisms of the relationship remain unknown. Prostaglandin (PG), key stimulants of labor, availability is regulated by the synthetic enzymes, prostaglandin endoperoxidases 1 and 2 (PTGS1 and 2), and the metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (HPGD). We hypothesized that IUGR increases susceptibility to preterm labor due to the changing balance of synthetic and metabolizing enzymes and hence greater PG availability. We have tested this hypothesis using a surgically induced IUGR model in guinea pigs, which results in significantly shorter gestation. Myometrium, amnion, chorion, and placentas were collected from sham operated or IUGR pregnancies, and PTGS1 and HPGD protein expression were quantified throughout late gestation (>62 days) and labor. The PTGS1 expression was significantly upregulated in the myometrium of IUGR animals, and chorionic HPGD expression was markedly decreased (P production over metabolism in IUGR pregnancies leads to a greater susceptibility to preterm birth.

  4. An introduction to the mechanisms leading to density-wave instabilities in BWRs

    International Nuclear Information System (INIS)

    March-Leuba, Jose

    2004-01-01

    This paper presents a review of the physical mechanisms that lead to density-wave instabilities in boiling water reactors (BWRs). The goal of this paper is not to present new information; but ideas that are generally known and accepted in the field of BWR stability. The number of people working in the field of BWR stability has grown over the past years to a significant number; nevertheless, the field is still small enough so that personal communication is an effective way of conveying information. The unfortunate consequence is that this field has a large component of ''art'' as opposed to science.'' This paper attempts to summarize these basic ideas for the reader. (author)

  5. Comparison of the key mechanisms leading to rollovers in Liquefied Natural Gas using Computational Fluid Dynamics

    Science.gov (United States)

    Hubert, Antoine; Dadonau, Maksim; Dembele, Siaka; Denissenko, Petr; Wen, Jennifer

    2017-11-01

    Growing demand for the LNG fosters growth of the number of production sites with varying composition and density. Combining different sources of LNG may result in a stably stratified system, in which heat and mass transfer between the layers is limited. Heating of the LNG due to wall thermal conductivity leads to formation of convection cells confined within the layers. While the upper layer can release the extra energy via preferential methane boil-off, the bottom layer cannot and hence becomes superheated. Gradual density equilibration reduces stratification and may eventually lead to a sudden mixing event called ``rollover'', accompanied by violent evaporation of the superheated LNG. Three phenomena are potentially responsible for density equilibration. The first is the growing difference in thermal expansion of the layers due to the reduced ability of the bottom layer to reject heat. The second is the penetration of the heated near-wall boundary layer into the upper layer. The third is the ``entrainment mixing'' occurring at the contact surface between the two layers. The present study uses CFD to compare these mechanisms. Boussinesq approximation and an extended version of the k- ɛ model is used. The code is validated by comparison with a large-scale LNG rollover experiment.

  6. Space Shuttle Orbiter Wing-Leading-Edge Panel Thermo-Mechanical Analysis for Entry Conditions

    Science.gov (United States)

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

    2010-01-01

    Linear elastic, thermo-mechanical stress analyses of the Space Shuttle Orbiter wing-leading-edge panels is presented for entry heating conditions. The wing-leading-edge panels are made from reinforced carbon-carbon and serve as a part of the overall thermal protection system. Three-dimensional finite element models are described for three configurations: integrated configuration, an independent single-panel configuration, and a local lower-apex joggle segment. Entry temperature conditions are imposed and the through-the-thickness response is examined. From the integrated model, it was concluded that individual panels can be analyzed independently since minimal interaction between adjacent components occurred. From the independent single-panel model, it was concluded that increased through-the-thickness stress levels developed all along the chord of a panel s slip-side joggle region, and hence isolated local joggle sections will exhibit the same trend. From the local joggle models, it was concluded that two-dimensional plane-strain models can be used to study the influence of subsurface defects along the slip-side joggle region of these panels.

  7. Fracture Mechanics Analyses of the Slip-Side Joggle Regions of Wing-Leading Edge Panels

    Science.gov (United States)

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

    2010-01-01

    The Space Shuttle Orbiter wing comprises of 22 leading edge panels on each side of the wing. These panels are part of the thermal protection system that protects the Orbiter wings from extreme heating that take place on the reentry in to the earth atmosphere. On some panels that experience extreme heating, liberation of silicon carbon (SiC) coating was observed on the slip side regions of the panels. Global structural and local fracture mechanics analyses were performed on these panels as a part of the root cause investigation of this coating liberation anomaly. The wing-leading-edge reinforced carbon-carbon (RCC) panels, Panel 9, T-seal 10, and Panel 10, are shown in Figure 1 and the progression of the stress analysis models is presented in Figure 2. The global structural analyses showed minimal interaction between adjacent panels and the T-seal that bridges the gap between the panels. A bounding uniform temperature is applied to a representative panel and the resulting stress distribution is examined. For this loading condition, the interlaminar normal stresses showed negligible variation in the chord direction and increased values in the vicinity of the slip-side joggle shoulder. As such, a representative span wise slice on the panel can be taken and the cross section can be analyzed using plane strain analysis.

  8. Fluorometric detection of nitroaromatics by fluorescent lead complexes: A spectroscopic assessment of detection mechanism

    Science.gov (United States)

    Chattopadhyay, Tanmay; Chatterjee, Sourav; Majumder, Ishani; Ghosh, Soumen; Yoon, Sangee; Sim, Eunji

    2018-04-01

    Three Schiff base ligands such as 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL1), 2-[(2-Hydroxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL2), 2-[(3,5-Dichloro-2-hydroxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL3) have been synthesized by condensation of aldehydes (such as 3,5-Dichloro-2-hydroxy benzaldehyde, 2-Hydroxy-benzaldehyde, and 2-Hydroxy-3-methoxy-benzaldehyde) with Tris-(hydroxymethyl)amino methane and characterized by IR, UV-vis and 1H NMR spectroscopy. Then all these three ligands have been used to prepare Pb(II) complexes by reaction with lead(II) acetate tri-hydrate in methanol. In view of analytical and spectral (IR, UV-vis and Mass) studies, it has been concluded that, except HL2, other two ligands form 1:1 metal complexes (1 and 3) with lead. Between two complexes, complex 3 is highly fluorescent and this property has been used to identify the pollutant nitroaromatics. Finally, the quenching mechanism has been established by means of spectroscopic investigation.

  9. Dual strain mechanisms in a lead-free morphotropic phase boundary ferroelectric

    DEFF Research Database (Denmark)

    Walker, Julian; Simons, Hugh; Alikin, Denis O

    2016-01-01

    Electromechanical properties such as d33 and strain are significantly enhanced at morphotropic phase boundaries (MPBs) between two or more different crystal structures. Many actuators, sensors and MEMS devices are therefore systems with MPBs, usually between polar phases in lead (Pb)-based ferroe......Electromechanical properties such as d33 and strain are significantly enhanced at morphotropic phase boundaries (MPBs) between two or more different crystal structures. Many actuators, sensors and MEMS devices are therefore systems with MPBs, usually between polar phases in lead (Pb......)-based ferroelectric ceramics. In the search for Pb-free alternatives, systems with MPBs between polar and non-polar phases have recently been theorized as having great promise. While such an MPB was identified in rare-earth (RE) modified bismuth ferrite (BFO) thin films, synthesis challenges have prevented its...... realization in ceramics. Overcoming these, we demonstrate a comparable electromechanical response to Pb-based materials at the polar-to-non-polar MPB in Sm modified BFO. This arises from 'dual' strain mechanisms: ferroelectric/ferroelastic switching and a previously unreported electric-field induced...

  10. Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations.

    Science.gov (United States)

    Moysés-Oliveira, Mariana; Guilherme, Roberta Dos Santos; Dantas, Anelisa Gollo; Ueta, Renata; Perez, Ana Beatriz; Haidar, Mauro; Canonaco, Rosane; Meloni, Vera Ayres; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-05-01

    To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. Retrospective and case-control study. University-based research laboratory. Three women with balanced X-autosome translocation and primary amenorrhea. Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. Karyotype, copy number variation, breakpoint mapping, and gene expression levels. All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. A first principles study of the mechanical, electronic, and vibrational properties of lead oxide

    Science.gov (United States)

    Zhuravlev, Yu. N.; Korabel'nikov, D. V.

    2017-11-01

    The first principles study of the crystal structure, chemical bonds, elastic and mechanical properties, electron energy band structure and density, and normal long-wave vibrations of nine phases of lead monoxide, dioxide, and tetraoxide has been performed under normal and external pressure within the framework of density functional theory (DFT) with the Perdew-Becke-Ernzerhof (PBE) gradient exchange-correlation functional and its hybrid version with a 25-% Hartree-Fock (HF) exchange contribution in the basis of localized atom orbitals. The behavior of physical parameters has been studied using the cold four- and threeparameter equations of state. The parameters of the crystal structures are in satisfactory agreement with experimental data, and elastic constants indicate their mechanical stability and anisotropy in the elastic properties. The elasticity, shear, and Young moduli, hardness, acoustic velocities, and Debye temperature of dioxide on the one hand and monoxide and tetraoxide on the other hand appreciably differ from each other. The difference between electron properties may be explained by the character of hybridization in the upper filled and lower empty energy bands as evident from the density of states. In monoxide, the indirect band gap width decreases with increasing pressure at a rate of 0.16 eV/GPa, and the direct band gap width increases at a rate of 0.13 eV/GPa. To identify crystalline phases, the frequencies and intensities of long-wave modes active in IR and Raman spectra have been calculated.

  12. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Science.gov (United States)

    Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

  13. Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

    Science.gov (United States)

    Lättig, Jens; Böhl, Markus; Fischer, Petra; Tischer, Sandra; Tietböhl, Claudia; Menschikowski, Mario; Gutzeit, Herwig O.; Metz, Peter; Pisabarro, M. Teresa

    2007-08-01

    The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

  14. Translating Mechanism-Based Strategies to Break the Obesity-Cancer Link: A Narrative Review.

    Science.gov (United States)

    Smith, Laura A; O'Flanagan, Ciara H; Bowers, Laura W; Allott, Emma H; Hursting, Stephen D

    2018-04-01

    Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity-cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  15. Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

    Science.gov (United States)

    Mama, Scherezade K; Li, Yisheng; Basen-Engquist, Karen; Lee, Rebecca E; Thompson, Deborah; Wetter, David W; Nguyen, Nga T; Reitzel, Lorraine R; McNeill, Lorna H

    2016-01-01

    Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

  16. Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

    Directory of Open Access Journals (Sweden)

    Scherezade K Mama

    Full Text Available Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467 completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination, and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001 and U.S. (p < .001 and low social support (p < .001 were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

  17. A Mechanism of Unidirectional Transformation, Leading to Antibiotic Resistance, Occurs within Nasopharyngeal Pneumococcal Biofilm Consortia.

    Science.gov (United States)

    Lattar, Santiago M; Wu, Xueqing; Brophy, Jennifer; Sakai, Fuminori; Klugman, Keith P; Vidal, Jorge E

    2018-05-15

    Streptococcus pneumoniae acquires genes for resistance to antibiotics such as streptomycin (Str) or trimethoprim (Tmp) by recombination via transformation of DNA released by other pneumococci and closely related species. Using naturally transformable pneumococci, including strain D39 serotype 2 (S2) and TIGR4 (S4), we studied whether pneumococcal nasopharyngeal transformation was symmetrical, asymmetrical, or unidirectional. Incubation of S2 Tet and S4 Str in a bioreactor simulating the human nasopharynx led to the generation of Spn Tet/Str recombinants. Double-resistant pneumococci emerged soon after 4 h postinoculation at a recombination frequency (rF) of 2.5 × 10 -4 while peaking after 8 h at a rF of 1.1 × 10 -3 Acquisition of antibiotic resistance genes by transformation was confirmed by treatment with DNase I. A high-throughput serotyping method demonstrated that all double-resistant pneumococci belonged to one serotype lineage (S2 Tet/Str ) and therefore that unidirectional transformation had occurred. Neither heterolysis nor availability of DNA for transformation was a factor for unidirectional transformation given that the density of each strain and extracellular DNA (eDNA) released from both strains were similar. Unidirectional transformation occurred regardless of the antibiotic-resistant gene carried by donors or acquired by recipients and regardless of whether competence-stimulating peptide-receptor cross talk was allowed. Moreover, unidirectional transformation occurred when two donor strains (e.g., S4 Str and S19F Tmp ) were incubated together, leading to S19F Str/Tmp but at a rF 3 orders of magnitude lower (4.9 × 10 -6 ). We finally demonstrated that the mechanism leading to unidirectional transformation was due to inhibition of transformation of the donor by the recipient. IMPORTANCE Pneumococcal transformation in the human nasopharynx may lead to the acquisition of antibiotic resistance genes or genes encoding new capsular variants

  18. Supramolecular Cross-Links in Poly(alkyl methacrylate) Copolymers and Their Impact on the Mechanical and Reversible Adhesive Properties.

    Science.gov (United States)

    Heinzmann, Christian; Salz, Ulrich; Moszner, Norbert; Fiore, Gina L; Weder, Christoph

    2015-06-24

    Hydrogen-bonded, side-chain-functionalized supramolecular poly(alkyl methacrylate)s were investigated as light- and temperature-responsive reversible adhesives that are useful for bonding and debonding on demand applications. Here, 2-hydroxyethyl methacrylate (HEMA) was functionalized with 2-ureido-4[1H]pyrimidinone (UPy) via a hexamethylenediisocyanate (HMDI) linker, to create a monomer (UPy-HMDI-HEMA) that serves to form supramolecular cross-links by way of forming quadruple hydrogen bonded dimers. UPy-HMDI-HEMA was copolymerized with either hexyl methacrylate or butyl methacrylate to create copolymers comprising 2.5, 5, or 10 mol % of the cross-linker. The mechanical properties of all (co)polymers were investigated with stress-strain experiments and dynamic mechanical analysis. Furthermore, the adhesive properties were studied at temperatures between 20 and 60 °C by testing single lap joints formed with stainless steel substrates. It was found that increasing the concentration of the UPy-HMDI-HEMA cross-linker leads to improved mechanical and adhesive properties at elevated temperatures. Concurrently, the reversibility of the bond formation remained unaffected, where rebonded samples displayed the same adhesive strength as regularly bonded samples. Debonding on demand abilities were also tested exemplarily for one copolymer, which for light-induced debonding experiments was blended with a UV-absorber that served as light-heat converter. Single lap joints were subjected to a constant force and heated or irradiated with UV light until debonding occurred. The necessary debonding temperature was comparable for direct heating and UV irradiation and varied between 28 and 82 °C, depending on the applied force. The latter also influenced the debonding time, which under the chosen conditions ranged from 30 s to 12 min.

  19. A Neurobehavioral Mechanism Linking Behaviorally Inhibited Temperament and Later Adolescent Social Anxiety.

    Science.gov (United States)

    Buzzell, George A; Troller-Renfree, Sonya V; Barker, Tyson V; Bowman, Lindsay C; Chronis-Tuscano, Andrea; Henderson, Heather A; Kagan, Jerome; Pine, Daniel S; Fox, Nathan A

    2017-12-01

    Behavioral inhibition (BI) is a temperament identified in early childhood that is a risk factor for later social anxiety. However, mechanisms underlying the development of social anxiety remain unclear. To better understand the emergence of social anxiety, longitudinal studies investigating changes at behavioral neural levels are needed. BI was assessed in the laboratory at 2 and 3 years of age (N = 268). Children returned at 12 years, and an electroencephalogram was recorded while children performed a flanker task under 2 conditions: once while believing they were being observed by peers and once while not being observed. This methodology isolated changes in error monitoring (error-related negativity) and behavior (post-error reaction time slowing) as a function of social context. At 12 years, current social anxiety symptoms and lifetime diagnoses of social anxiety were obtained. Childhood BI prospectively predicted social-specific error-related negativity increases and social anxiety symptoms in adolescence; these symptoms directly related to clinical diagnoses. Serial mediation analysis showed that social error-related negativity changes explained relations between BI and social anxiety symptoms (n = 107) and diagnosis (n = 92), but only insofar as social context also led to increased post-error reaction time slowing (a measure of error preoccupation); this model was not significantly related to generalized anxiety. Results extend prior work on socially induced changes in error monitoring and error preoccupation. These measures could index a neurobehavioral mechanism linking BI to adolescent social anxiety symptoms and diagnosis. This mechanism could relate more strongly to social than to generalized anxiety in the peri-adolescent period. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

  20. Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

    Science.gov (United States)

    Stanhope, K L; Goran, M I; Bosy-Westphal, A; King, J C; Schmidt, L A; Schwarz, J-M; Stice, E; Sylvetsky, A C; Turnbaugh, P J; Bray, G A; Gardner, C D; Havel, P J; Malik, V; Mason, A E; Ravussin, E; Rosenbaum, M; Welsh, J A; Allister-Price, C; Sigala, D M; Greenwood, M R C; Astrup, A; Krauss, R M

    2018-05-14

    Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis. © 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

  1. The link between bond forfeiture and pretrial release mechanism: The case of Dallas County, Texas.

    Science.gov (United States)

    Clipper, Stephen J; Morris, Robert G; Russell-Kaplan, Amanda

    2017-01-01

    The goal of this study was to evaluate the efficacy of four pretrial jail release mechanisms (i.e., bond types) commonly used during the pretrial phase of the criminal justice process in terms of their ability to discriminate between defendants failing to appear in court (i.e., bond forfeiture). These include attorney bonds, cash bonds, commercial bail bonds, and release via a pretrial services agency. A multi-treatment propensity score matching protocol was employed to assess between-release-mechanism differences in the conditional probability of failure to appear/bond forfeiture. Data were culled from archival state justice records comprising all defendants booked into the Dallas County, Texas jail during 2008 (n = 29,416). The results suggest that defendants released via commercial bail bonds were less likely to experience failure to appear leading to the bond forfeiture process compared to equivalent defendants released via cash, attorney, and pretrial services bonds. This finding held across different offense categories. The study frames these differences within a discussion encompassing procedural variation within and between each release mechanism, thereby setting the stage for further research and dialog regarding potential justice reform.

  2. The link between bond forfeiture and pretrial release mechanism: The case of Dallas County, Texas.

    Directory of Open Access Journals (Sweden)

    Stephen J Clipper

    Full Text Available The goal of this study was to evaluate the efficacy of four pretrial jail release mechanisms (i.e., bond types commonly used during the pretrial phase of the criminal justice process in terms of their ability to discriminate between defendants failing to appear in court (i.e., bond forfeiture. These include attorney bonds, cash bonds, commercial bail bonds, and release via a pretrial services agency.A multi-treatment propensity score matching protocol was employed to assess between-release-mechanism differences in the conditional probability of failure to appear/bond forfeiture. Data were culled from archival state justice records comprising all defendants booked into the Dallas County, Texas jail during 2008 (n = 29,416.The results suggest that defendants released via commercial bail bonds were less likely to experience failure to appear leading to the bond forfeiture process compared to equivalent defendants released via cash, attorney, and pretrial services bonds. This finding held across different offense categories. The study frames these differences within a discussion encompassing procedural variation within and between each release mechanism, thereby setting the stage for further research and dialog regarding potential justice reform.

  3. Mechanistic Target of Rapamycin Is a Novel Molecular Mechanism Linking Folate Availability and Cell Function.

    Science.gov (United States)

    Silva, Elena; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2017-07-01

    Folate deficiency has been linked to a wide range of disorders, including cancer, neural tube defects, and fetal growth restriction. Folate regulates cellular function mediated by its involvement in the synthesis of nucleotides, which are needed for DNA synthesis, and its function as a methyl donor, which is critical for DNA methylation. Here we review current data showing that folate sensing by mechanistic target of rapamycin (mTOR) constitutes a novel and distinct pathway by which folate modulates cell functions such as nutrient transport, protein synthesis, and mitochondrial respiration. The mTOR signaling pathway responds to growth factors and changes in nutrient availability to control cell growth, proliferation, and metabolism. mTOR exists in 2 complexes, mTOR complex (mTORC) 1 and mTORC2, which have distinct upstream regulators and downstream targets. Folate deficiency in pregnant mice caused a marked inhibition of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues, downregulation of placental amino acid transporters, and fetal growth restriction. In addition, folate deficiency in primary human trophoblast (PHT) cells resulted in inhibition of mTORC1 and mTORC2 signaling and decreased the activity of key amino acid transporters. Folate sensing by mTOR in PHT cells is independent of the accumulation of homocysteine and requires the proton-coupled folate transporter (PCFT; solute carrier 46A1). Furthermore, mTORC1 and mTORC2 regulate trophoblast folate uptake by modulating the cell surface expression of folate receptor α and the reduced folate carrier. These findings, which provide a novel link between folate availability and cell function, growth, and proliferation, may have broad biological significance given the critical role of folate in normal cell function and the multiple diseases that have been associated with decreased or excessive folate availability. Low maternal folate concentrations are linked to restricted fetal growth, and we

  4. Glutaraldehyde Cross-Linking of TendonMechanical Effects at the Level of the Tendon Fascicle and Fibril

    DEFF Research Database (Denmark)

    Hansen, P.; Svensson, R.B.; Aagaard, P.

    2009-01-01

    were examined by atomic force microscopy. Peak forces increased from 1379 to 2622 pN while an extended Hertz fit of force-indentation data showed a 24 fold increase in Young's modulus on indentation. The effect of glutaraldehyde cross-linking on the tensile properties of a single collagen fibril......Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy...... allowed for a detailed characterization of the effect of cross-linking in rat-tail tendon. The cross-link inducing agent glutaraldehyde augmented the tensile strength of tendon fascicles. Stress at failure increased from 8 MPa to 39 MPa. The mechanical effects of glutaraldehyde at the tendon fibril level...

  5. Status on DEMO Helium Cooled Lithium Lead breeding blanket thermo-mechanical analyses

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, J., E-mail: julien.aubert@cea.fr [CEA-Saclay, DEN, DM2S, F-91191 Gif-sur-Yvette (France); Aiello, G.; Jaboulay, J.-C. [CEA-Saclay, DEN, DM2S, F-91191 Gif-sur-Yvette (France); Kiss, B. [Institute of Nuclear Techniques, Budapest University of Technology and Economics, Budapest (Hungary); Morin, A. [CEA-Saclay, DEN, DM2S, F-91191 Gif-sur-Yvette (France)

    2016-11-01

    Highlights: • CEA with the support of Wigner-RCP and IPP-CR, is in charge of the design of the HCLL blanket for DEMO. The DEMO HCLL breeding blanket design capitalizes on the experience acquired on the HCLL Test Blanket Module designed for ITER. Design improvements are being implemented to adapt the design to DEMO specifications and performance objectives. • Thermal and mechanical analyses have been carried out in order to justify the design of the HCLL breeding blanket showing promising results for tie rods modules’ attachments system and relatively good behavior of the box in case of LOCA when comparing to RCC-MRx criteria. • CFD thermal analyses on generic breeding unit have enabled the consolidation of the results obtained with previous FEM design analyses. - Abstract: The EUROfusion Consortium develops a design of a fusion power demonstrator (DEMO) in the framework of the European “Horizon 2020” innovation and research program. One of the key components in the fusion reactor is the breeding blanket surrounding the plasma, ensuring tritium self-sufficiency, heat removal for conversion into electricity, and neutron shielding. The Helium Cooled Lithium Lead (HCLL) blanket is one of the concepts which is investigated for DEMO. It is made of a Eurofer structure and uses the eutectic liquid lithium–lead as tritium breeder and neutron multiplier, and helium gas as coolant. Within the EUROfusion organization, CEA with the support of Wigner-RCP and IPP-CR, is in charge of the design of the HCLL blanket for DEMO. This paper presents the status of the thermal and mechanical analyses carried out on the HCLL breeding blanket in order to justify the design. CFD thermal analyses on generic breeding unit including stiffening plates and cooling plates have been performed with ANSYS in order to consolidate results obtained with previous FEM design analyses. Moreover in order to expand the justification of the HCLL Breeding blanket design, the most loaded area of

  6. Electrical Transport Mechanisms and Photoconduction in Undoped Crystalline Flash-Evaporated Lead Iodide Thin Films

    Science.gov (United States)

    Al-Daraghmeh, Tariq M.; Saleh, Mahmoud H.; Ahmad, Mais Jamil A.; Bulos, Basim N.; Shehadeh, Khawla M.; Jafar, Mousa M. Abdul-Gader

    2018-03-01

    The flash-evaporation technique was utilized to fabricate undoped 1.35-μm and 1.2-μm thick lead iodide films at substrate temperatures T_{{s}} = 150 °C and 200°C, respectively. The films were deposited onto a coplanar comb-like copper (Cu-) electrode pattern, previously coated on glass substrates to form lateral metal-semiconductor-metal (MSM-) structures. The as-measured constant- temperature direct-current (dc)-voltage ( I( {V;T} ) - V ) curves of the obtained lateral coplanar Cu-PbI2-Cu samples (film plus electrode) displayed remarkable ohmic behavior at all temperatures ( T = 18 - 90°C). Their dc electrical resistance R_{{dc}} (T ) revealed a single thermally-activated conduction mechanism over the temperature range with activation energy E_{{act}} ≈ 0.90 - 0.98 {eV} , slightly less than half of room-temperature bandgap energy E_{{g}} ( ≈ 2.3 {eV} ) of undoped 2H-polytype PbI2 single crystals. The undoped flash-evaporated {PbI}_{{x}} thin films were homogeneous and almost stoichiometric ( x ≈ 1.87 ), in contrast to findings on lead iodide films prepared by other methods, and were highly crystalline hexagonal 2H-polytypic structure with c-axis perpendicular to the surface of substrates maintained at T_{s} ≳ 150°C. Photoconductivity measurements made on these lateral Cu-PbI2-Cu-structures under on-off visible-light illumination reveal a feeble photoresponse for long wavelengths ( λ > 570 {nm} ), but a strong response to blue light of photon energy E_{{ph}} ≈ 2.73 {eV} ( > E_{{g}} ), due to photogenerated electron-hole (e-h) pairs via direct band-to-band electronic transitions. The constant-temperature/dc voltage current-time I( {T,V} ) - t curves of the studied lateral PbI2 MSM-structures at low ambient temperatures ( T < 50°C), after cutting off the blue-light illumination, exhibit two trapping mechanisms with different relaxation times. These strongly depend on V and T , with thermally generated charge carriers in the PbI2 mask photogenerated

  7. Ionoregulatory disruption as the acute toxic mechanism for lead in the rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Rogers, J.T.; Richards, J.G.; Wood, C.M.

    2003-01-01

    The mechanism for acute toxicity of lead (Pb) in rainbow trout (Oncorhynchus mykiss) was investigated at Pb concentrations close to the 96 h LC50 of 1.0 mg dissolved Pb l -1 (0.8-1.4, 95% C.I.) determined in dechlorinated Hamilton city tap water (from Lake Ontario, hardness=140 mg l -1 CaCO 3 ). Tissue Pb accumulation associated with death was highest in the gill, followed by kidney and liver. Significant ionoregulatory impacts were observed in adult rainbow trout (200-300 g) fitted with indwelling dorsal aortic catheters and exposed to 1.1±0.04 mg dissolved Pb l -1 . Decreased plasma [Ca 2+ ], [Na + ] and [Cl - ] occurred after 48 h of exposure through to 120 h, with increases in plasma [Mg 2+ ], ammonia, and cortisol. No marked changes in PaO 2 , PaCO 2 , pH, glucose, or hematological parameters were evident. Branchial Na + /K + ATPase activity in juvenile trout exposed to concentrations close to the 96 h LC50 was inhibited by approximately 40% after 48 h of Pb exposure. Calcium ion flux measurements using 45 Ca as a radiotracer showed 65% inhibition of Ca 2+ influx after 0, 12, 24 or 48 h exposure to the 96 h LC50 concentration of Pb. There was also significant inhibition (40-50%) of both Na + and Cl - uptake, measured with 22 Na and 36 Cl simultaneously. We conclude that the mechanism of acute toxicity for Pb in rainbow trout occurs by ionoregulatory disruption rather than respiratory or acid/base distress at Pb concentrations close to the 96 h LC50 in moderately hard water

  8. Ionoregulatory disruption as the acute toxic mechanism for lead in the rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, J.T.; Richards, J.G.; Wood, C.M

    2003-07-16

    The mechanism for acute toxicity of lead (Pb) in rainbow trout (Oncorhynchus mykiss) was investigated at Pb concentrations close to the 96 h LC50 of 1.0 mg dissolved Pb l{sup -1} (0.8-1.4, 95% C.I.) determined in dechlorinated Hamilton city tap water (from Lake Ontario, hardness=140 mg l{sup -1} CaCO{sub 3}). Tissue Pb accumulation associated with death was highest in the gill, followed by kidney and liver. Significant ionoregulatory impacts were observed in adult rainbow trout (200-300 g) fitted with indwelling dorsal aortic catheters and exposed to 1.1{+-}0.04 mg dissolved Pb l{sup -1}. Decreased plasma [Ca{sup 2+}], [Na{sup +}] and [Cl{sup -}] occurred after 48 h of exposure through to 120 h, with increases in plasma [Mg{sup 2+}], ammonia, and cortisol. No marked changes in PaO{sub 2}, PaCO{sub 2}, pH, glucose, or hematological parameters were evident. Branchial Na{sup +}/K{sup +} ATPase activity in juvenile trout exposed to concentrations close to the 96 h LC50 was inhibited by approximately 40% after 48 h of Pb exposure. Calcium ion flux measurements using {sup 45}Ca as a radiotracer showed 65% inhibition of Ca{sup 2+} influx after 0, 12, 24 or 48 h exposure to the 96 h LC50 concentration of Pb. There was also significant inhibition (40-50%) of both Na{sup +} and Cl{sup -} uptake, measured with {sup 22}Na and {sup 36}Cl simultaneously. We conclude that the mechanism of acute toxicity for Pb in rainbow trout occurs by ionoregulatory disruption rather than respiratory or acid/base distress at Pb concentrations close to the 96 h LC50 in moderately hard water.

  9. Framing Mechanisms Linking HIV-Related Stigma, Adherence to Treatment, and Health Outcomes

    Science.gov (United States)

    Hatcher, Abigail M.; Weiser, Sheri D.; Johnson, Mallory O.; Rice, Whitney S.; Turan, Janet M.

    2017-01-01

    We present a conceptual framework that highlights how unique dimensions of individual-level HIV-related stigma (perceived community stigma, experienced stigma, internalized stigma, and anticipated stigma) might differently affect the health of those living with HIV. HIV-related stigma is recognized as a barrier to both HIV prevention and engagement in HIV care, but little is known about the mechanisms through which stigma leads to worse health behaviors or outcomes. Our conceptual framework posits that, in the context of intersectional and structural stigmas, individual-level dimensions of HIV-related stigma operate through interpersonal factors, mental health, psychological resources, and biological stress pathways. A conceptual framework that encompasses recent advances in stigma science can inform future research and interventions aiming to address stigma as a driver of HIV-related health. PMID:28426316

  10. Affect the Cross Linking Degree and Polymer Composition on the Mechanical Properties of Poly (vinyl alcohol/ Pullu-lan Films

    Directory of Open Access Journals (Sweden)

    Shemaa Abdul Satar Soud

    2018-04-01

    Full Text Available In this study Cross-linked PVA/Pullulan film was prepared. Cross-linking reaction done by addi-tion of gluteraldehyde at different reaction time (10,30and 60 min. Chemical interaction, me-chanical, thermal properties, water solubility and film morphology was studied for cross-linked PVA/Pullulan, PVA and Pullulan only. Thus FTIR investigated formation of hydrogen bonding between pullulan and PVA with (GA. Tensile strength, tensile modulus and elongation (% at break for PVA/Pullulan film was improved with addition of (GA as the reaction time proceed equivalent with increasing PVA content

  11. Performance and mechanism for cadmium and lead adsorption from water and soil by corn straw biochar

    Institute of Scientific and Technical Information of China (English)

    Tong Chi; Jiane Zuo; Fenglin Liu

    2017-01-01

    Cadmium (Cd) and lead (Pb) in water and soil could be adsorbed by biochar produced fiom corn straw.Biochar pyrolyzed under 400℃ for 2 h could reach the ideal removal efficiencies (99.24% and 98.62% for Cd and Pb,respectively) from water with the biochar dosage of 20 g· L-1 and imtial concentration of 20 mg·L-1.The pH value of 4-7 was the optimal range for adsorption reaction.The adsorption mechanism was discussed on the basis of a range of characterizations,including X-ray diffraction (XRD),X-my photoelectron spectroscopy (XPS),Fourier transform infrared spectroscopy (FTIR) and Raman analysis;it was concluded as surface complexation with active sorption sites (-OH-COO-) coordination with π electrons (C =C,C =O) and precipitation with morganic anions (OH-,CO32-,SO42-) for both Cd and Pb.The sorption isotherms fit Langmuir model better than Freundlich model,and the saturated sorption capacities for Cd and Pb were 38.91 mg.g-1 and 28.99 mg· g-1,respectively.When mixed with soil,biochar could effectively increase alkalinity and reduce bioavailability of heavy metals.Thus,biochar derived from corn straw would be a green material for both removal of heavy metals and amelioration of soil.

  12. Planning and leading of the technological processes by mechanical working with microsoft project

    Science.gov (United States)

    Nae, I.; Grigore, N.

    2016-08-01

    Nowadays, fabrication systems and methods are being modified; new processing technologies come up, flow sheets develop a minimum number of phases, the flexibility of the technologies grows up, new methods and instruments of monitoring and leading the processing operations also come up. The technological course (route, entry, scheme, guiding) referring to the series of the operation, putting and execution phases of a mark in order to obtain the final product from the blank is represented by a sequence of activities realized by a logic manner, on a well determined schedule, with a determined budget and resources. Also, a project can be defined as a series of specific activities, methodical structured which they aim to finish a specific objective, within a fixed schedule and budget. Within the homogeneity between the project and the technological course, this research is presenting the defining of the technological course of mechanical chip removing process using Microsoft Project. Under these circumstances, this research highlights the advantages of this method: the celerity using of other technological alternatives in order to pick the optimal process, the job scheduling being constrained by any kinds, the standardization of some processing technological operations.

  13. Conceptual design of the blanket mechanical attachment for the helium-cooled lithium-lead reactor

    International Nuclear Information System (INIS)

    Barrera, G.; Branas, B.; Lucas, J.; Doncel, J.; Medrano, M.; Garcia, A.; Giancarli, L.; Ibarra, A.; Li Puma, A.; Maisonnier, D.; Sardain, P.

    2008-01-01

    The conceptual design of a new type of fusion reactor based on the helium-cooled lithium-lead (HCLL) blanket has been performed within the European Power Plant Conceptual Studies. As part of this activity, a new attachment system suitable for the HCLL blanket modules had to be developed. This attachment is composed of two parts. The first one is the connection between module and the first part of a shield, called high temperature shield, which operates at a temperature around 500 deg. C, close to that of the blanket module. This connection must be made at the lateral walls, in order to avoid openings through the first wall and breeding zone thus avoiding complex design and fabrication issues of the module. The second connection is the one between the high temperature shield and a second shield called low temperature shield, which has a temperature during reactor operation around 150 deg. C. The design of this connection is complex because it must allow the large differential thermal expansion (up to 30 mm) between the two components. Design proposals for both connections are presented, together with the results of finite element mechanical analyses which demonstrate the feasibility to support the blanket and shield modules during normal and accidental operation conditions

  14. 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)

  15. Highly Efficient Lead Distribution by Magnetic Sewage Sludge Biochar: Sorption Mechanisms and Bench Applications.

    Science.gov (United States)

    Ifthikar, Jerosha; Wang, Jia; Wang, Qiliang; Wang, Ting; Wang, Huabin; Khan, Aimal; Jawad, Ali; Sun, Tingting; Jiao, Xiang; Chen, Zhuqi

    2017-08-01

    Highly efficient magnetic sewage sludge biochar (MSSBC) discloses feasible fabrication process with lower production cost, superior adsorption capacity, usage of waste sewage sludge as resource, selected by external magnetic field and exceptional regeneration property. 2gL -1 MSSBC exhibited a high adsorption capacity of 249.00mgg -1 in 200ppmPb(II) and the lead-MSSBC equilibrium was achieved within one hour, owing to the existence of the copious active sites. The adsorption kinetics was well described by the pseudo-second-order model while the adsorption isotherm could be fitted by Langmuir model. Mechanism study demonstrated the adsorption involved electrostatic attraction, ion exchange, inner-sphere complexation and formation of co-precipitates at the surface of MSSBC. Additionally, adsorption performance maintained remarkable in a broad pH window. These outcomes demonstrated the promising waste resource utilization by a feasible approach that turns the solid waste of sewage sludge into biochar adsorbent with auspicious applications in elimination of Pb(II) from wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Mechanism of Water Droplet Breakup Near the Leading Edge of an Airfoil

    Science.gov (United States)

    Vargas, Mario; Sor, Suthyvann; Magarino, Adelaida, Garcia

    2012-01-01

    This work presents results of an experimental study on droplet deformation and breakup near the leading edge of an airfoil. The experiment was conducted in the rotating rig test cell at the Instituto Nacional de Tecnica Aeroespacial (INTA) in Madrid, Spain. The airfoil model was placed at the end of the rotating arm and a monosize droplet generator produced droplets that fell from above, perpendicular to the path of the airfoil. The interaction between the droplets and the airfoil was captured with high speed imaging and allowed observation of droplet deformation and breakup as the droplet approached the airfoil near the stagnation line. Image processing software was used to measure the position of the droplet centroid, equivalent diameter, perimeter, area, and the major and minor axes of an ellipse superimposed over the deforming droplet. The horizontal and vertical displacement of each droplet against time was also measured, and the velocity, acceleration, Weber number, Bond number, Reynolds number, and the drag coefficients were calculated along the path of the droplet to the beginning of breakup. Droplet deformation is defined and studied against main parameters. The high speed imaging allowed observation of the actual mechanism of breakup and identification of the sequence of configurations from the initiation of the breakup to the disintegration of the droplet. Results and comparisons are presented for droplets of diameters in the range of 500 to 1800 microns, and airfoil velocities of 70 and 90 m/sec.

  17. Vegetation and erosion: comments on the linking mechanisms from the perspective of the Australian drylands.

    Science.gov (United States)

    Dunkerley, D.

    2009-04-01

    John Thorne's wide-ranging research included an emphasis on the diverse roles of vegetation in modifying erosion processes under Mediterranean conditions, with primary field studies in Spain. Different global drylands reflect some differences in the nature or strength of the mechanisms linking vegetation and erosion. In Australia, low topographic gradients and plants adapted to water scarcity have facilitated the widespread development of contour-aligned vegetation groves. In these landscapes, the role of individual plants in modifying raindrop impact energy or overland flow erosivity is secondary to the community-level effects of the grove structures. Erosion in common rain events is limited to quite local redistribution of soil materials on metre scales. This highlights one of the unresolved issues that warrants more attention in drylands globally: under what range of rain events does the protective role of individual plants (or of groves) operate, and what is the threshold event size beyond which their effect is swamped by integrated overland flow arriving from upslope? In contrast with, for example, the well-understood role of bankfull flows in river architecture, general principles underlying dryland hillslope and channel responses to events of various magnitudes remain obscure. Clearly, however, there is no single role for plant cover; rather, that role varies with event magnitude and related properties such as the time since the last rain event. An important conclusion is therefore that context is important when evaluating the links between vegetation and erosion. The developing view of overland flow generally, but particularly relevant in drylands where plant cover is sparse, is that the connectedness of runoff flowpaths is a key parameter. It partly determines the extent to which the downslope movement of resources (soil, water, organic matter) is free or constrained, and this conception has the potential to support the formulation of some general models

  18. Characterization and performance evaluation of a vertical seismic isolator using link and crank mechanism

    International Nuclear Information System (INIS)

    Tsujiuchi, N; Ito, A; Sekiya, Y; Nan, C; Yasuda, M

    2016-01-01

    In recent years, various seismic isolators have been developed to prevent earthquake damage to valuable art and other rare objects. Many seismic isolators only defend against horizontal motions, which are the usual cause of falling objects. However, the development of a seismic isolator designed for vertical vibration is necessary since such great vertical vibration earthquakes as the 2004 Niigata Prefecture Chuetsu Earthquake have occurred, and their increased height characteristics are undesirable. In this study, we developed a vertical seismic isolator that can be installed at a lower height and can support loads using a horizontal spring without requiring a vertical spring. It has a mechanism that combines links and cranks. The dynamic model was proposed and the frequency characteristics were simulated when the sine waves were the input. Shaking tests were also performed. The experimental value of the natural frequency was 0.57 Hz, and the theoretical values of the frequency characteristics were close to the experimental values. In addition, we verified this vertical seismic isolator's performance through shaking tests and simulation for typical seismic waves in Japan. We verified the seismic isolation's performance from the experimental result because the average reduction rate of the acceleration was 0.21. (paper)

  19. ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha; Ren, Ting; Lewis, Peter W.; Cochrane, Jesse C.; Allis, C. David; Picketts, David J.; Patel, Dinshaw J.; Li, Haitao; Shi, Yang (Harvard-Med); (Ottawa Hosp.); (MSKCC); (Rockefeller); (CH-Boston); (Tsinghua); (Mass. Gen. Hosp.)

    2011-07-19

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

  20. ATRX ADD Domain Links an Atypical Histone Methylation Recognition Mechanism to Human Mental-Retardation Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    S Iwase; B Xiang; S Ghosh; T Ren; P Lewis; J Cochrane; C Allis; D Picketts; D Patel; et al.

    2011-12-31

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

  1. Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report.

    Science.gov (United States)

    Hine, R Jean; Srivastava, Sudhir; Milner, John A; Ross, Sharon A

    2003-11-01

    Adenocarcinoma of the pancreas is one of most catastrophic and least understood of cancers. Evidence from clinical studies indicates that the development of pancreas cancer progresses over many years before symptoms appear. Most people with pancreatic cancer die within six months of diagnosis. The lack of early disease markers, the paucity of direct subject/patient interview data and limited availability of high quality biological samples have slowed progress toward identifying environmental and genetic disease risk factors. Much remains to be learned about the development of pancreatic cancer and about potential interventions for disease prevention. Epidemiological and mechanistic studies examining risk factors for pancreatic cancer supply little consistent or strong evidence to provide a cohesive prevention strategy for this cancer, but offer clues for future research concerning the prevention and early detection of this devastating disease. This Executive Summary provides background discussion on pancreatic cancer and summaries of each of the topics discussed at the workshop, including 1) Molecular aspects, 2) Dietary and other risk factors for pancreatic cancer, 3) The metabolic hypothesis for pancreatic cancer, 4) Preclinical studies on pancreatic cancer, 5) Methylation, 6) Oxidative stress and 7) Biomarker Profiling. This document also contains a compilation of recommendations for future research, concluding remarks, a list of speakers and participants attending the workshop, and a selection of key references to aid future research into nutritional links to mechanisms underlying pancreas cancer. The recommendations section suggests gaps in current knowledge and articulates future directions for this area of investigation.

  2. Linking lipid architecture to bilayer structure and mechanics using self-consistent field modelling

    International Nuclear Information System (INIS)

    Pera, H.; Kleijn, J. M.; Leermakers, F. A. M.

    2014-01-01

    To understand how lipid architecture determines the lipid bilayer structure and its mechanics, we implement a molecularly detailed model that uses the self-consistent field theory. This numerical model accurately predicts parameters such as Helfrichs mean and Gaussian bending modulus k c and k ¯ and the preferred monolayer curvature J 0 m , and also delivers structural membrane properties like the core thickness, and head group position and orientation. We studied how these mechanical parameters vary with system variations, such as lipid tail length, membrane composition, and those parameters that control the lipid tail and head group solvent quality. For the membrane composition, negatively charged phosphatidylglycerol (PG) or zwitterionic, phosphatidylcholine (PC), and -ethanolamine (PE) lipids were used. In line with experimental findings, we find that the values of k c and the area compression modulus k A are always positive. They respond similarly to parameters that affect the core thickness, but differently to parameters that affect the head group properties. We found that the trends for k ¯ and J 0 m can be rationalised by the concept of Israelachivili's surfactant packing parameter, and that both k ¯ and J 0 m change sign with relevant parameter changes. Although typically k ¯ 0 m ≫0, especially at low ionic strengths. We anticipate that these changes lead to unstable membranes as these become vulnerable to pore formation or disintegration into lipid disks

  3. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    International Nuclear Information System (INIS)

    McMahon, Laura W.; Zhang Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced αIISp and XPF nuclear foci. Thus depletion of αIISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair.

  4. Linking lipid architecture to bilayer structure and mechanics using self-consistent field modelling

    Energy Technology Data Exchange (ETDEWEB)

    Pera, H.; Kleijn, J. M.; Leermakers, F. A. M., E-mail: Frans.leermakers@wur.nl [Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6307 HB Wageningen (Netherlands)

    2014-02-14

    To understand how lipid architecture determines the lipid bilayer structure and its mechanics, we implement a molecularly detailed model that uses the self-consistent field theory. This numerical model accurately predicts parameters such as Helfrichs mean and Gaussian bending modulus k{sub c} and k{sup ¯} and the preferred monolayer curvature J{sub 0}{sup m}, and also delivers structural membrane properties like the core thickness, and head group position and orientation. We studied how these mechanical parameters vary with system variations, such as lipid tail length, membrane composition, and those parameters that control the lipid tail and head group solvent quality. For the membrane composition, negatively charged phosphatidylglycerol (PG) or zwitterionic, phosphatidylcholine (PC), and -ethanolamine (PE) lipids were used. In line with experimental findings, we find that the values of k{sub c} and the area compression modulus k{sub A} are always positive. They respond similarly to parameters that affect the core thickness, but differently to parameters that affect the head group properties. We found that the trends for k{sup ¯} and J{sub 0}{sup m} can be rationalised by the concept of Israelachivili's surfactant packing parameter, and that both k{sup ¯} and J{sub 0}{sup m} change sign with relevant parameter changes. Although typically k{sup ¯}<0, membranes can form stable cubic phases when the Gaussian bending modulus becomes positive, which occurs with membranes composed of PC lipids with long tails. Similarly, negative monolayer curvatures appear when a small head group such as PE is combined with long lipid tails, which hints towards the stability of inverse hexagonal phases at the cost of the bilayer topology. To prevent the destabilisation of bilayers, PG lipids can be mixed into these PC or PE lipid membranes. Progressive loading of bilayers with PG lipids lead to highly charged membranes, resulting in J{sub 0}{sup m}≫0, especially at low ionic

  5. Hormones and phenotypic plasticity in an ecological context: linking physiological mechanisms to evolutionary processes.

    Science.gov (United States)

    Lema, Sean C

    2014-11-01

    Hormones are chemical signaling molecules that regulate patterns of cellular physiology and gene expression underlying phenotypic traits. Hormone-signaling pathways respond to an organism's external environment to mediate developmental stage-specific malleability in phenotypes, so that environmental variation experienced at different stages of development has distinct effects on an organism's phenotype. Studies of hormone-signaling are therefore playing a central role in efforts to understand how plastic phenotypic responses to environmental variation are generated during development. But, how do adaptive, hormonally mediated phenotypes evolve if the individual signaling components (hormones, conversion enzymes, membrane transporters, and receptors) that comprise any hormone-signaling pathway show expressional flexibility in response to environmental variation? What relevance do these components hold as molecular targets for selection to couple or decouple correlated hormonally mediated traits? This article explores how studying the endocrine underpinnings of phenotypic plasticity in an ecologically relevant context can provide insights into these, and other, crucial questions into the role of phenotypic plasticity in evolution, including how plasticity itself evolves. These issues are discussed in the light of investigations into how thyroid hormones mediate morphological plasticity in Death Valley's clade of pupfishes (Cyprinodon spp.). Findings from this work with pupfish illustrate that the study of hormone-signaling from an ecological perspective can reveal how phenotypic plasticity contributes to the generation of phenotypic novelty, as well as how physiological mechanisms developmentally link an organism's phenotype to its environmental experiences. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  6. Mechanisms That Link Parenting Practices to Adolescents' Risky Sexual Behavior: A Test of Six Competing Theories.

    Science.gov (United States)

    Simons, Leslie Gordon; Sutton, Tara E; Simons, Ronald L; Gibbons, Frederick X; Murry, Velma McBride

    2016-02-01

    Risky sexual behavior, particularly among adolescents, continues to be a major source of concern. In order to develop effective education and prevention programs, there is a need for research that identifies the antecedents of such behavior. This study investigated the mediators that link parenting experiences during early adolescence to subsequent risky sexual behaviors among a diverse sample of African American youth (N = 629, 55 % female). While there is ample evidence that parenting practices (e.g., supportive parenting, harsh parenting, parental management) are antecedent to risky sexual behavior, few studies have examined whether one approach to parenting is more strongly related to risky sex than others. Using a developmental approach, the current study focused on factors associated with six theories of risky sexual behavior. While past research has provided support for all of the theories, few studies have assessed the relative contribution of each while controlling for the processes proposed by the others. The current study addresses these gaps in the literature and reports results separately by gender. Longitudinal analyses using structural equation modeling revealed that the mediating mechanisms associated with social learning and attachment theories were significantly related to the risky sexual behavior of males and females. Additionally, there was support for social control and self-control theories only for females and for life history theory only for males. We did not find support for problem behavior theory, a perspective that dominates the risky sex literature, after controlling for the factors associated with the other theories. Finally, supportive parenting emerged as the parenting behavior most influential with regard to adolescents' risky sexual behavior. These results provide insight regarding efficacious approaches to education and preventative programs designed to reduce risky sexual behaviors among adolescents.

  7. Lead titanate nanotubes synthesized via ion-exchange method: Characteristics and formation mechanism

    International Nuclear Information System (INIS)

    Song Liang; Cao Lixin; Li Jingyu; Liu Wei; Zhang Fen; Zhu Lin; Su Ge

    2011-01-01

    Highlights: → Lead titanate nanotubes PbTi 3 O 7 were firstly synthesized by ion-exchange method. → Sodium titanate nanotubes have ion exchangeability. → Lead titanate nanotubes show a distinct red shift on absorption edge. - Abstract: A two-step method is presented for the synthesis of one dimensional lead titanate (PbTi 3 O 7 ) nanotubes. Firstly, titanate nanotubes were prepared by an alkaline hydrothermal process with TiO 2 nanopowder as precursor, and then lead titanate nanotubes were formed through an ion-exchange reaction. We found that sodium titanate nanotubes have ion exchangeability with lead ions, while protonated titanate nanotubes have not. For the first time, we distinguished the difference between sodium titanate nanotubes and protonated titanate nanotubes in the ion-exchange process, which reveals a layer space effect of nanotubes in the ion-exchange reaction. In comparison with sodium titanate, the synthesized lead titanate nanotubes show a narrowed bandgap.

  8. Glutaraldehyde cross-linking of tendon mechanical effects at the level of the tendon fascicle and fibril

    DEFF Research Database (Denmark)

    Hansen, Philip; Hassenkam, Tue; Svensson, Rene Bruggebusch

    2009-01-01

    at the tendon fibril level were examined by atomic force microscopy. Peak forces increased from approximately 1379 to approximately 2622 pN while an extended Hertz fit of force-indentation data showed a approximately 24 fold increase in Young's modulus on indentation. The effect of glutaraldehyde cross......Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy...... allowed for a detailed characterization of the effect of cross-linking in rat-tail tendon. The cross-link inducing agent glutaraldehyde augmented the tensile strength of tendon fascicles. Stress at failure increased from approximately 8 MPa to approximately 39 MPa. The mechanical effects of glutaraldehyde...

  9. From Theory-Inspired to Theory-Based Interventions: A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action.

    Science.gov (United States)

    Michie, Susan; Carey, Rachel N; Johnston, Marie; Rothman, Alexander J; de Bruin, Marijn; Kelly, Michael P; Connell, Lauren E

    2018-05-18

    Understanding links between behaviour change techniques (BCTs) and mechanisms of action (the processes through which they affect behaviour) helps inform the systematic development of behaviour change interventions. This research aims to develop and test a methodology for linking BCTs to their mechanisms of action. Study 1 (published explicit links): Hypothesised links between 93 BCTs (from the 93-item BCT taxonomy, BCTTv1) and mechanisms of action will be identified from published interventions and their frequency, explicitness and precision documented. Study 2 (expert-agreed explicit links): Behaviour change experts will identify links between 61 BCTs and 26 mechanisms of action in a formal consensus study. Study 3 (integrated matrix of explicit links): Agreement between studies 1 and 2 will be evaluated and a new group of experts will discuss discrepancies. An integrated matrix of BCT-mechanism of action links, annotated to indicate strength of evidence, will be generated. Study 4 (published implicit links): To determine whether groups of co-occurring BCTs can be linked to theories, we will identify groups of BCTs that are used together from the study 1 literature. A consensus exercise will be used to rate strength of links between groups of BCT and theories. A formal methodology for linking BCTs to their hypothesised mechanisms of action can contribute to the development and evaluation of behaviour change interventions. This research is a step towards developing a behaviour change 'ontology', specifying relations between BCTs, mechanisms of action, modes of delivery, populations, settings and types of behaviour.

  10. Examples of processing problematic waste and material. A-3. Processing of lead by mechanical decontamination at UKAEA Harwell

    International Nuclear Information System (INIS)

    2006-01-01

    The UKAEA and its contractor (NNC) have decontaminated lead blocks arising from the decommissioning of a metallurgical site that comprised three concrete shielded remote handling cells and 36 lead shielded enclosures. The primary decommissioning and dismantling work entailed the dismantling of the 36 lead enclosures, which were expected to yield over 1000 t of lead shielding bricks as waste. During the initial dismantling of the lead shielded enclosures, all the lead bricks were monitored for radioactive contamination; clean items were segregated and set aside for detailed clearance and assurance checks. The contaminated blocks were sent for assessment and decontamination treatment, as necessary. The decontamination process utilized a purpose built partitioned containment tent, ventilated with a HEPA filtration system, so that the receipt, decontamination and radiological monitoring of individual items could be segregated in order to minimize any cross-contamination. The dismantled lead blocks comprised a range of standard thicknesses (2, 4, 9 and 10 in, or 3, 8, 13 and 15 cm) and incorporated a variety of chevron, concave and convex shapes, which are utilized to avoid weaknesses within the assembled shielding. The primary technical issues for the mechanical processing of the contaminated lead blocks were consideration of the individual lead brick shapes (i.e. the bricks were contoured) and the individual weight of the bricks, which had a range of 10-75 kg. The preferred option was a manual dry cutting technique using a handheld rotary industrial planer (the selected planer is normally associated with the joinery trade). The dry cutting option considered the malleability of the lead, which under certain circumstances during dry cutting could give rise to localized heating effects, leading to melted lead over the cutting surface, resulting in limited effectiveness in the removal of the contaminated layer. To mitigate this effect the planer was set to take cuts

  11. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators; Bleitellurid mit erhoehter mechanischer Stabilitaet fuer zylindrische thermoelektrische Generatoren

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Andreas

    2013-04-30

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb{sub 1-x}Ca{sub x}Te were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while its thermoelectric

  12. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators; Bleitellurid mit erhoehter mechanischer Stabilitaet fuer zylindrische thermoelektrische Generatoren

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Andreas

    2013-04-30

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb{sub 1-x}Ca{sub x}Te were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while

  13. Mechanical and fatigue properties of martensitic 20X13 and austenitic 12X18H10T at interaction with lead nad lead-bismuth melts

    International Nuclear Information System (INIS)

    Yas'kiv, O.I.; Fedirko, V.M.

    2013-01-01

    The effect of Pb and Pb-Bi melts on mechanical properties and fatigue of Fe-13Cr and Fe-18Cr-10Ni-Ti steels in temperature interval 250...750 deg C has been investigated. It was shown that metal melts lead to increasing of strength of Fe-13Cr steel on 10...20 % as compared with vacuum and this effect increases with temperature rising. Fe-13Cr steel is prone to liquid metal embrittlement in temperature interval 350...450 deg C, particularly in Pb-Bi melt. Mechanical properties of Fe-18Cr-10Ni-Ti are not affected by metal melts. Both Pb and Pb-Bi assist in reducing of fatigue life of steels and this effect is more significant in Pb-Bi

  14. ONE PROBABLE MECHANISM OF THE LEARNING-MEMORY DAMAGE BY LEAD: THE CHANGES OF NOS IN HIPPOCAMPUS

    Institute of Scientific and Technical Information of China (English)

    王静; 赵义; 杨章民; 张进; 李积胜; 司履生; 王一理

    2003-01-01

    Objective To study the effects of lead on the activity and expression of nitric oxide synthase (NOS) and relationship between the effects of lead on learning-memory and changes of NOS in subfields of hippocampus. Methods Y-maze test was used to study the effects of lead on ability of learning-memory; NADPH-d histochemistry and immunohistochemistry methods were used to investigate the changes of NOS in subfields of hippocampus. Results Compared with the control group, the ability of learning- memory in lead-exposed rats was significantly decreased (P<0.05); the number of NOS positive neurons in CA1 region and dentate gyrus of lead-exposed rats was significantly decreased(P<0.05), but no marked changes in CA3 region; the number of nNOS positive neurons in CA1 of lead-exposed rats was also significantly decreased(P<0.05), but no obvious changes in CA3. Conclusion Lead could damage the ability of learning-memory in rats. Lead could decrease the activity and expression of NOS in hippocampus and had different effects on NOS in different subfields of hippocampus. The changes of NOS in hippocampus induced by lead may be the mechanism of the learning-memory damage by lead.

  15. Expression of ALS/FTD-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype.

    Science.gov (United States)

    Hogan, Alison L; Don, Emily K; Rayner, Stephanie L; Lee, Albert; Laird, Angela S; Watchon, Maxinne; Winnick, Claire; Tarr, Ingrid S; Morsch, Marco; Fifita, Jennifer A; Gwee, Serene S L; Formella, Isabel; Hortle, Elinor; Yuan, Kristy C; Molloy, Mark P; Williams, Kelly L; Nicholson, Garth A; Chung, Roger S; Blair, Ian P; Cole, Nicholas J

    2017-07-15

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease characterised by the death of upper and lower motor neurons. Approximately 10% of cases have a known family history of ALS and disease-linked mutations in multiple genes have been identified. ALS-linked mutations in CCNF were recently reported, however the pathogenic mechanisms associated with these mutations are yet to be established. To investigate possible disease mechanisms, we developed in vitro and in vivo models based on an ALS-linked missense mutation in CCNF. Proteomic analysis of the in vitro models identified the disruption of several cellular pathways in the mutant model, including caspase-3 mediated cell death. Transient overexpression of human CCNF in zebrafish embryos supported this finding, with fish expressing the mutant protein found to have increased levels of cleaved (activated) caspase-3 and increased cell death in the spinal cord. The mutant CCNF fish also developed a motor neuron axonopathy consisting of shortened primary motor axons and increased frequency of aberrant axonal branching. Importantly, we demonstrated a significant correlation between the severity of the CCNF-induced axonopathy and a reduced motor response to a light stimulus (photomotor response). This is the first report of an ALS-linked CCNF mutation in vivo and taken together with the in vitro model identifies the disruption of cell death pathways as a significant consequence of this mutation. Additionally, this study presents a valuable new tool for use in ongoing studies investigating the pathobiology of ALS-linked CCNF mutations. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Different mechanisms for lead acetate, aluminum and cadmium sulfate in rat corpus cavernosum

    International Nuclear Information System (INIS)

    Senbel, Amira M.; Saad, Evan I.; Taha, Safaa S.; Mohamed, Hosny F.

    2016-01-01

    Introduction: Some heavy metals show adverse vascular and neurological effects, however, their effect on erection is underestimated. This study aims to investigate the effect of Pb, Cd and Al on erectile function and their potential mechanism of action in rats. Methods: Measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP) changes elicited by electrical stimulation of cavernous nerve in anesthetized rats treated with Pb-acetate, Al-sulfate, or Cd-sulfate acutely, and subacutely for 7 days. Serum creatinine, testosterone, TBARs, GSH levels and metal accumulation in corpus cavernosum were measured. Results: Pb, Al and Cd significantly reduced ICP/MAP in rats after acute (2,10–2,10 and 1,3 mg/kg respectively) and sub-acute (3, 3, and 1 mg/kg/day respectively) treatments. They selectively accumulated in the corpus cavernosum reaching 25.107 ± 2.081 μg/g wet weight for Pb, 1.029 ± 0.193 for Cd, 31.343 ± 1.991 for Al, compared to 7.084 ± 1.517, 0.296 ± 0.067, and 8.86 ± 1.115 as controls respectively. Serum creatinine levels were not altered. Cd and Al significantly reduced testosterone level to 0.483 ± 0.059 and 0.419 ± 0.037 ng/ml respectively compared to 0.927 ± 0.105 ng/ml as control. Aluminum elevated TBARs significantly by 27.843%. The acute anti-erectile action of Pb was blocked by non-selective NOS and GC inhibitors and potassium channel blocker. Lead also masked the potentiatory effect of L-arginine and diazoxide on ICP/MAP. No interaction with muscarinic or nicotinic modulators was observed. Conclusions: Pb, Cd and Al show anti-erectile effect independent on renal injury. They don not modulate cholinergic nor ganglionic transmission in corpus cavernosum. Pb may inhibit NO/cGMP/K + channel pathway. The effect of Cd and Al but not Pb seems to be hormonal dependent.

  17. Urban gardens: lead exposure, recontamination mechanisms, and implications for remediation design.

    Science.gov (United States)

    Clark, Heather F; Hausladen, Debra M; Brabander, Daniel J

    2008-07-01

    Environmental lead contamination is prevalent in urban areas where soil represents a significant sink and pathway of exposure. This study characterizes the speciation of lead that is relevant to local recontamination and to human exposure in the backyard gardens of Roxbury and Dorchester, MA, USA. One hundred forty-one backyard gardens were tested by X-ray fluorescence, and 81% of gardens have lead levels above the US EPA action limit of 400 microg/g. Raised gardening beds are the in situ exposure reduction method used in the communities to promote urban gardening. Raised beds were tested for lead and the results showed that the lead concentration increased from an initial range of 150+/-40 microg/g to an average of 336 microg/g over 4 years. The percent distribution of lead in the fine grain soil (lead, and the trace metal signature of the fine grain soil in both gardens and raised gardening beds is characteristic of lead-based paint. This study demonstrates that raised beds are a limited exposure reduction method and require maintenance to achieve exposure reduction goals. An exposure model was developed based on a suite of parameters that combine relevant values from the literature with site-specific quantification of exposure pathways. This model suggests that consumption of homegrown produce accounts for only 3% of children's daily exposure of lead while ingestion of fine grained soil (lead remediation on a yard-by-yard scale requires constant maintenance and that remediation may need to occur on a neighborhood-wide scale.

  18. Mechanisms Leading to Co-Existence of Gas Hydrate in Ocean Sediments [Part 1 of 2

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Steven; Juanes, Ruben

    2011-12-31

    In this project we have sought to explain the co-existence of gas and hydrate phases in sediments within the gas hydrate stability zone. We have focused on the gas/brine interface at the scale of individual grains in the sediment. The capillary forces associated with a gas/brine interface play a dominant role in many processes that occur in the pores of sediments and sedimentary rocks. The mechanical forces associated with the same interface can lead to fracture initiation and propagation in hydrate-bearing sediments. Thus the unifying theme of the research reported here is that pore scale phenomena are key to understanding large scale phenomena in hydrate-bearing sediments whenever a free gas phase is present. Our analysis of pore-scale phenomena in this project has delineated three regimes that govern processes in which the gas phase pressure is increasing: fracturing, capillary fingering and viscous fingering. These regimes are characterized by different morphology of the region invaded by the gas. On the other hand when the gas phase pressure is decreasing, the corresponding regimes are capillary fingering and compaction. In this project, we studied all these regimes except compaction. Many processes of interest in hydrate-bearing sediments can be better understood when placed in the context of the appropriate regime. For example, hydrate formation in sub-permafrost sediments falls in the capillary fingering regime, whereas gas invasion into ocean sediments is likely to fall into the fracturing regime. Our research provides insight into the mechanisms by which gas reservoirs are converted to hydrate as the base of the gas hydrate stability zone descends through the reservoir. If the reservoir was no longer being charged, then variation in grain size distribution within the reservoir explain hydrate saturation profiles such as that at Mt. Elbert, where sand-rich intervals containing little hydrate are interspersed between intervals containing large hydrate

  19. Mechanisms Leading to Co-Existence of Gas Hydrate in Ocean Sediments [Part 2 of 2

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Steven; Juanes, Ruben

    2011-12-31

    In this project we have sought to explain the co-existence of gas and hydrate phases in sediments within the gas hydrate stability zone. We have focused on the gas/brine interface at the scale of individual grains in the sediment. The capillary forces associated with a gas/brine interface play a dominant role in many processes that occur in the pores of sediments and sedimentary rocks. The mechanical forces associated with the same interface can lead to fracture initiation and propagation in hydrate-bearing sediments. Thus the unifying theme of the research reported here is that pore scale phenomena are key to understanding large scale phenomena in hydrate-bearing sediments whenever a free gas phase is present. Our analysis of pore-scale phenomena in this project has delineated three regimes that govern processes in which the gas phase pressure is increasing: fracturing, capillary fingering and viscous fingering. These regimes are characterized by different morphology of the region invaded by the gas. On the other hand when the gas phase pressure is decreasing, the corresponding regimes are capillary fingering and compaction. In this project, we studied all these regimes except compaction. Many processes of interest in hydrate-bearing sediments can be better understood when placed in the context of the appropriate regime. For example, hydrate formation in sub-permafrost sediments falls in the capillary fingering regime, whereas gas invasion into ocean sediments is likely to fall into the fracturing regime. Our research provides insight into the mechanisms by which gas reservoirs are converted to hydrate as the base of the gas hydrate stability zone descends through the reservoir. If the reservoir was no longer being charged, then variation in grain size distribution within the reservoir explain hydrate saturation profiles such as that at Mt. Elbert, where sand-rich intervals containing little hydrate are interspersed between intervals containing large hydrate

  20. On the Quantum Mechanical Wave Function as a Link Between Cognition and the Physical World A Role for Psychology

    CERN Document Server

    Snyder, D

    2002-01-01

    A straightforward explanation of fundamental tenets of quantum mechanics concerning the wave function results in the thesis that the quantum mechanical wave function is a link between human cognition and the physical world. The reticence on the part of physicists to adopt this thesis is discussed. A comparison is made to the behaviorists' consideration of mind, and the historical roots of how the problem concerning the quantum mechanical wave function arose are discussed. The basis for an empirical demonstration that the wave function is a link between human cognition and the physical world is provided through developing an experiment using methodology from psychology and physics. Based on research in psychology and physics that relied on this methodology, it is likely that Einstein, Podolsky, and Rosen's theoretical result that mutually exclusive wave functions can simultaneously apply to the same concrete physical circumstances can be implemented on an empirical level.

  1. Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate

    Science.gov (United States)

    Geng, Guoqing; Myers, Rupert J.; Li, Jiaqi; Maboudian, Roya; Carraro, Carlo; Shapiro, David A.; Monteiro, Paulo J. M.

    2017-03-01

    The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.

  2. Electro-mechanical response of a 3D nerve bundle model to mechanical loads leading to axonal injury.

    Science.gov (United States)

    Cinelli, I; Destrade, M; Duffy, M; McHugh, P

    2018-03-01

    Traumatic brain injuries and damage are major causes of death and disability. We propose a 3D fully coupled electro-mechanical model of a nerve bundle to investigate the electrophysiological impairments due to trauma at the cellular level. The coupling is based on a thermal analogy of the neural electrical activity by using the finite element software Abaqus CAE 6.13-3. The model includes a real-time coupling, modulated threshold for spiking activation, and independent alteration of the electrical properties for each 3-layer fibre within a nerve bundle as a function of strain. Results of the coupled electro-mechanical model are validated with previously published experimental results of damaged axons. Here, the cases of compression and tension are simulated to induce (mild, moderate, and severe) damage at the nerve membrane of a nerve bundle, made of 4 fibres. Changes in strain, stress distribution, and neural activity are investigated for myelinated and unmyelinated nerve fibres, by considering the cases of an intact and of a traumatised nerve membrane. A fully coupled electro-mechanical modelling approach is established to provide insights into crucial aspects of neural activity at the cellular level due to traumatic brain injury. One of the key findings is the 3D distribution of residual stresses and strains at the membrane of each fibre due to mechanically induced electrophysiological impairments, and its impact on signal transmission. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.

    Science.gov (United States)

    Iacovazzo, Donato; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Yuan, Bo; Hernández-Ramírez, Laura C; Kapur, Sonal; Caimari, Francisca; Evanson, Jane; Ferraù, Francesco; Dang, Mary N; Gabrovska, Plamena; Larkin, Sarah J; Ansorge, Olaf; Rodd, Celia; Vance, Mary L; Ramírez-Renteria, Claudia; Mercado, Moisés; Goldstone, Anthony P; Buchfelder, Michael; Burren, Christine P; Gurlek, Alper; Dutta, Pinaki; Choong, Catherine S; Cheetham, Timothy; Trivellin, Giampaolo; Stratakis, Constantine A; Lopes, Maria-Beatriz; Grossman, Ashley B; Trouillas, Jacqueline; Lupski, James R; Ellard, Sian; Sampson, Julian R; Roncaroli, Federico; Korbonits, Márta

    2016-06-01

    Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101

  4. The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with the metal and the mixture ratio.

    Science.gov (United States)

    Wildemann, Tanja M; Siciliano, Steven D; Weber, Lynn P

    2016-01-02

    stress and kidney damage for lead, while increased RAS activation links methylmercury to hypertension, but these mechanisms along with hypertension disappear when metals are present in some mixtures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecinetype pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed.

  6. Lead generation strategy as a multichannel mechanism of growth of a modern enterprise

    Directory of Open Access Journals (Sweden)

    Łukowski Wojciech

    2016-09-01

    Full Text Available Lead generation strategy describes the marketing process of involvement and capture of interest in a product or service which is aimed at developing sales plans and, as a consequence, soliciting new clients. Lead generation is becoming an increasingly popular demand-generating strategy, which – through its multichannelled dissemination of the generated message – gives it a much greater reach. Lead generation assists organisations in achieving a greater brand awareness, building relationships and attracting more potential clients to fill their sales pipeline. The primary purpose of this publication is identifying the possibilities that the implementation of lead generation strategies provides to modern enterprises. It discusses the key aspects of this issue, demonstrating how the significance of organisations change, how their value effectively increases as a result of the implementation of tools furnished by processes that form an integral part of lead generation. The article defines the factors and processes that affect the effective course of actions undertaken within lead generation campaigns.

  7. Decreased blood hepatitis B surface antibody levels linked to e-waste lead exposure in preschool children

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xijin [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong (China); Chen, Xiaojuan; Zhang, Jian [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Guo, Pi [Department of Public Health, Shantou University Medical College, Shantou 515041, Guangdong (China); Fu, Tingzao; Dai, Yifeng [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Lin, Stanley L. [Department of Pathophysiology and Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, Guangdong (China); Huo, Xia, E-mail: xhuo@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China)

    2015-11-15

    Highlights: • Secondary exploratory analyses displayed a correlation of blood Pb to HBsAb levels. • Generalized linear mixed models were used to analyze two-phase data. • Children from an e-waste area had higher blood Pb levels and lower HBsAb titers. • Nearly 50% of Pb-exposed children fail to develop sufficient HBV immunity. • Different vaccination strategies are required for in e-waste areas. - Abstract: Lead (Pb) is a widespread environmental contaminant that can profoundly affect the immune system in vaccinated children. To explore the association between blood Pb and HBsAb levels in children chronically exposed to Pb, we measured hepatitis B surface antibody (HBsAb) titers, to reflect the immune response in the children of Guiyu, an electronic and electrical waste (e-waste) recycling area well known for environmental Pb contamination. We performed secondary exploratory analyses of blood Pb levels and plasma HBsAb titers in samples, taken in two phases between 2011 and 2012, from 590 children from Guiyu (exposed group) and Haojiang (reference group). Children living in the exposed area had higher blood Pb levels and lower HBsAb titers compared with children from the reference area. At each phase, generalized linear mixed models (GLMMs) showed that HBsAb titers were significantly negatively associated with child blood Pb levels. This work shows that a decreased immune response to hepatitis B vaccine and immune system might have potential harm to children with chronic Pb exposure. Importantly, nearly 50% of chronically exposed children failed to develop sufficient immunity to hepatitis in response to vaccination. Thus different vaccination strategies are needed for children living under conditions of chronic Pb exposure.

  8. Decreased blood hepatitis B surface antibody levels linked to e-waste lead exposure in preschool children

    International Nuclear Information System (INIS)

    Xu, Xijin; Chen, Xiaojuan; Zhang, Jian; Guo, Pi; Fu, Tingzao; Dai, Yifeng; Lin, Stanley L.; Huo, Xia

    2015-01-01

    Highlights: • Secondary exploratory analyses displayed a correlation of blood Pb to HBsAb levels. • Generalized linear mixed models were used to analyze two-phase data. • Children from an e-waste area had higher blood Pb levels and lower HBsAb titers. • Nearly 50% of Pb-exposed children fail to develop sufficient HBV immunity. • Different vaccination strategies are required for in e-waste areas. - Abstract: Lead (Pb) is a widespread environmental contaminant that can profoundly affect the immune system in vaccinated children. To explore the association between blood Pb and HBsAb levels in children chronically exposed to Pb, we measured hepatitis B surface antibody (HBsAb) titers, to reflect the immune response in the children of Guiyu, an electronic and electrical waste (e-waste) recycling area well known for environmental Pb contamination. We performed secondary exploratory analyses of blood Pb levels and plasma HBsAb titers in samples, taken in two phases between 2011 and 2012, from 590 children from Guiyu (exposed group) and Haojiang (reference group). Children living in the exposed area had higher blood Pb levels and lower HBsAb titers compared with children from the reference area. At each phase, generalized linear mixed models (GLMMs) showed that HBsAb titers were significantly negatively associated with child blood Pb levels. This work shows that a decreased immune response to hepatitis B vaccine and immune system might have potential harm to children with chronic Pb exposure. Importantly, nearly 50% of chronically exposed children failed to develop sufficient immunity to hepatitis in response to vaccination. Thus different vaccination strategies are needed for children living under conditions of chronic Pb exposure

  9. Li-ion Battery Separators, Mechanical Integrity and Failure Mechanisms Leading to Soft and Hard Internal Shorts.

    Science.gov (United States)

    Zhang, Xiaowei; Sahraei, Elham; Wang, Kai

    2016-09-01

    Separator integrity is an important factor in preventing internal short circuit in lithium-ion batteries. Local penetration tests (nail or conical punch) often produce presumably sporadic results, where in exactly similar cell and test set-ups one cell goes to thermal runaway while the other shows minimal reactions. We conducted an experimental study of the separators under mechanical loading, and discovered two distinct deformation and failure mechanisms, which could explain the difference in short circuit characteristics of otherwise similar tests. Additionally, by investigation of failure modes, we provided a hypothesis about the process of formation of local "soft short circuits" in cells with undetectable failure. Finally, we proposed a criterion for predicting onset of soft short from experimental data.

  10. Investigations into the Mechanisms of Cell Death: The Common Link between Anticancer Nanotherapeutics and Nanotoxicology

    Science.gov (United States)

    Minocha, Shalini

    breast cancer cells for inducing apoptosis. Cytochrome c is an endogenous mitochondrial protein and upon its release to cytosol, leads to apoptotic cell death. Although the mechanism by which Cyt c induces apoptosis theoretically makes it an attractive anti-cancer therapeutic agent, the lack of physicochemical characteristics required for successful cell permeation requires the use of delivery systems such as nanocarriers to facilitate its intracellular delivery. Cytochrome c, being a protein, is susceptible to changes in structural integrity and aggregation which might occur upon exposure to organic solvents and high shear/stress conditions, often used during nanoparticle preparation. Furthermore, successful delivery to cell cytosol requires endosomal release. Therefore, to deliver Cyt c intracellularly, while maintaining conditions for its stability, entrapment was performed using a film hydration method with 1,2-dioleoyl-3-trimethylammonium-propane and cholesterol (DOTAP-Chol) liposomes. It was shown that modulation of hydration buffer pH from 7 to 8.5 increased entrapment of Cyt c in DOTAP-Chol liposomes from 2% to 30%. The optimized formulation showed apoptotic activity in MDA-MB-231 cells. It was also shown that no aggregation, secondary and heme crevice structure change and deamidation was observed for Cyt c released from optimized formulation and that released Cyt c retained apoptotic activity after storage of formulation for twenty eight days at 4 °C.

  11. Lead extraction from Cathode Ray Tube (CRT) funnel glass: Reaction mechanisms in thermal reduction with addition of carbon (C).

    Science.gov (United States)

    Lu, Xingwen; Ning, Xun-An; Chen, Da; Chuang, Kui-Hao; Shih, Kaimin; Wang, Fei

    2018-06-01

    This study quantitatively determined the extraction of lead from CRT funnel glass and examined the mechanisms of thermally reducing lead in the products of sintering Pb-glass with carbon in the pre-heated furnace. The experimentally derived results indicate that a 90.3 wt% lead extraction efficiency can be achieved with 20 wt% of C addition at 950 °C for 3 min under air. The formation of viscous semi-liquid glass blocked the oxygen supply between the interaction of C and Pb-glass, and was highly effective for the extraction of metallic Pb. A maximum of 87.3% lead recover was obtained with a C to Na 2 CO 3 ratio of 1/3 at 1200 °C. The decrease of C/Na 2 CO 3 ratio enhanced the metallic lead recovery by increasing the glass viscosity for effective sedimentation of metallic lead in the bottom. However, with the further increase of temperature and treatment time, re-vitrification of lead back to silicate-glass matrix was detected in both Pb-glass/C and Pb-glass/C/Na 2 CO 3 systems. The findings indicated that with proper controls, using C as an inexpensive reagent can effectively reduce treatment time and energy, which is crucial to a waste-to-resource technology for economically recovering lead from the waste CRT glass. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Research and development regarding the retaining mechanism of lead ions in industrial wastewaters using natural matter with remarkable properties

    Science.gov (United States)

    Pop, A.; Iepure, G.

    2017-05-01

    The paper shows the studying of the retaining mechanism of lead ions in industrial wastewaters through static and dynamic ion exchange mechanisms. In the experimental determinations of the lead metallic ion retention, metallurgical industry wastewaters have been used on samples of volcanic zeolite tuff (from Barsana, Maramures), samples that show a high concentration of lead ions and an acidic pH. The results showed that both the static and the dynamic ion exchanges ended with good results and they were consistent with other studies conducted on clinoptilolite zeolite tuff. Knowing that the industrial sector is an important source of environment pollution and degradation and being aware of what a serious threat the heavy metal pollution is, due to their high toxicity and stability, the experiment may find applicability in different aspects, both in the Maramures mining basing as well as in the worldwide controlling and directing of the polluting processes.

  13. A mechanism of leading-edge protrusion in the absence of Arp2/3 complex.

    Science.gov (United States)

    Suraneni, Praveen; Fogelson, Ben; Rubinstein, Boris; Noguera, Philippe; Volkmann, Niels; Hanein, Dorit; Mogilner, Alex; Li, Rong

    2015-03-01

    Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading-edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an ability to move, albeit with altered responses to different environmental signals. We show that formin-family actin nucleators are required for the extension of FLPs but are insufficient to produce a continuous leading edge in fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions of the leading edge in between FLPs, and its activity is required for coordinated advancement of these regions with formin-generated FLPs. We propose that actomyosin contraction acting against membrane tension advances the web of arcs between FLPs. Predictions of this model are verified experimentally. The dependence of myosin II in leading-edge advancement helps explain the previously reported defect in directional movement in the Arpc3-null fibroblasts. We provide further evidence that this defect is cell autonomous during chemotaxis. © 2015 Suraneni et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication 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).

  14. Does the Fit Between Competitive Strategy and Administrative Mechanisms Lead to Superior Performance?

    OpenAIRE

    Barth, Henrik

    2000-01-01

    At least two different administrative mechanisms are available for the small business manager to develop and pursue a competitive strategy. One refers to managerial skills needed to implement and follow the competitive strategy chosen by the firm. The other refers to the design of organisation structure i.e. how job tasks are divided, grouped and coordinated. This paper argues that the fit between the competitive strategy followed by a firm and the utilisation of the administrative mechanisms...

  15. Optimal Ordering Policy and Coordination Mechanism of a Supply Chain with Controllable Lead-Time-Dependent Demand Forecast

    Directory of Open Access Journals (Sweden)

    Hua-Ming Song

    2011-01-01

    Full Text Available This paper investigates the ordering decisions and coordination mechanism for a distributed short-life-cycle supply chain. The objective is to maximize the whole supply chain's expected profit and meanwhile make the supply chain participants achieve a Pareto improvement. We treat lead time as a controllable variable, thus the demand forecast is dependent on lead time: the shorter lead time, the better forecast. Moreover, optimal decision-making models for lead time and order quantity are formulated and compared in the decentralized and centralized cases. Besides, a three-parameter contract is proposed to coordinate the supply chain and alleviate the double margin in the decentralized scenario. In addition, based on the analysis of the models, we develop an algorithmic procedure to find the optimal ordering decisions. Finally, a numerical example is also presented to illustrate the results.

  16. Compassionate love as a mechanism linking sacred qualities of marriage to older couples' marital satisfaction.

    Science.gov (United States)

    Sabey, Allen K; Rauer, Amy J; Jensen, Jakob F

    2014-10-01

    Previous work has underscored the robust links between sanctification of marriage and marital outcomes, and recent developments in the literature suggest that compassionate love, which is important for intimate relationships, may act as a mediator of that relationship. Accordingly, the current study used actor-partner interdependence models to examine the relationship between a spiritual cognition (i.e., perceived sacred qualities of marriage) and marital satisfaction, and to determine whether that relationship is mediated by compassionate love, in a sample of older married couples (N = 64). Results revealed that wives' greater sacred qualities of marriage were significantly and positively linked to marital satisfaction on the part of both spouses, and that these links were partially mediated by couples' reports of compassionate love. These findings highlight the importance of moving beyond simply establishing the existence of the link between global markers of involvement of religion and marriage to understanding how specific spiritual cognitions may foster better relationship quality, especially among older couples. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  17. Children's Attentional Biases and "5-HTTLPR" Genotype: Potential Mechanisms Linking Mother and Child Depression

    Science.gov (United States)

    Gibb, Brandon E.; Benas, Jessica S.; Grassia, Marie; McGeary, John

    2009-01-01

    In this study, we examined the roles of specific cognitive (attentional bias) and genetic ("5-HTTLPR") risk factors in the intergenerational transmission of depression. Focusing first on the link between maternal history of major depressive disorder (MDD) and children's attentional biases, we found that children of mothers with a history…

  18. The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms

    NARCIS (Netherlands)

    Sahami, S.; Kooij, I. A.; Meijer, S. L.; van den Brink, G. R.; Buskens, C. J.; te Velde, A. A.

    2016-01-01

    The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the

  19. Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases (also published in Journal of Periodontology 2013 Apr 84 (4 Suppl): S51-69)

    NARCIS (Netherlands)

    Schenkein, H.A.; Loos, B.G.

    2013-01-01

    Aims In this article, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases are reviewed. Methods This article is a literature review. Results Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory

  20. Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes.

    Science.gov (United States)

    Pena, A E; Kuntaegowdanahalli, S S; Abbas, J J; Patrick, J; Horch, K W; Jung, R

    2017-12-01

    A neural interface system has been developed that consists of an implantable stimulator/recorder can with a 15-electrode lead that trifurcates into three bundles of five individual wire longitudinal intrafascicular electrodes. This work evaluated the mechanical fatigue resistance of the branched lead and distributed electrode system under conditions designed to mimic anticipated strain profiles that would be observed after implantation in the human upper arm. Custom test setups and procedures were developed to apply linear or angular strain at four critical stress riser points on the lead and electrode system. Each test was performed to evaluate fatigue under a high repetition/low amplitude paradigm designed to test the effects of arm movement on the leads during activities such as walking, or under a low repetition/high amplitude paradigm designed to test the effects of more strenuous upper arm activities. The tests were performed on representative samples of the implantable lead system for human use. The specimens were fabricated using procedures equivalent to those that will be used during production of human-use implants. Electrical and visual inspections of all test specimens were performed before and after the testing procedures to assess lead integrity. Measurements obtained before and after applying repetitive strain indicated that all test specimens retained electrical continuity and that electrical impedance remained well below pre-specified thresholds for detection of breakage. Visual inspection under a microscope at 10×  magnification did not reveal any signs of damage to the wires or silicone sheathing at the stress riser points. These results demonstrate that the branched lead of this implantable neural interface system has sufficient mechanical fatigue resistance to withstand strain profiles anticipated when the system is implanted in an arm. The novel test setups and paradigms may be useful in testing other lead systems.

  1. Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes

    Science.gov (United States)

    Pena, A. E.; Kuntaegowdanahalli, S. S.; Abbas, J. J.; Patrick, J.; Horch, K. W.; Jung, R.

    2017-12-01

    Objective. A neural interface system has been developed that consists of an implantable stimulator/recorder can with a 15-electrode lead that trifurcates into three bundles of five individual wire longitudinal intrafascicular electrodes. This work evaluated the mechanical fatigue resistance of the branched lead and distributed electrode system under conditions designed to mimic anticipated strain profiles that would be observed after implantation in the human upper arm. Approach. Custom test setups and procedures were developed to apply linear or angular strain at four critical stress riser points on the lead and electrode system. Each test was performed to evaluate fatigue under a high repetition/low amplitude paradigm designed to test the effects of arm movement on the leads during activities such as walking, or under a low repetition/high amplitude paradigm designed to test the effects of more strenuous upper arm activities. The tests were performed on representative samples of the implantable lead system for human use. The specimens were fabricated using procedures equivalent to those that will be used during production of human-use implants. Electrical and visual inspections of all test specimens were performed before and after the testing procedures to assess lead integrity. Main results. Measurements obtained before and after applying repetitive strain indicated that all test specimens retained electrical continuity and that electrical impedance remained well below pre-specified thresholds for detection of breakage. Visual inspection under a microscope at 10×  magnification did not reveal any signs of damage to the wires or silicone sheathing at the stress riser points. Significance. These results demonstrate that the branched lead of this implantable neural interface system has sufficient mechanical fatigue resistance to withstand strain profiles anticipated when the system is implanted in an arm. The novel test setups and paradigms may be useful in

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

    OpenAIRE

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

    2017-01-01

    ABSTRACT CONTEXT AND OBJECTIVE: Some studies have suggested a wide range of possible mechanisms through which probiotics may play a role in diabetes prevention and treatment. However, the underlying mechanisms are not fully understood. We conducted this study to review the potential mechanisms suggested for the effect of probiotics in diabetes. DESIGN AND SETTING: Narrative review conducted at the Food Security Research Center of Isfahan. METHODS: A search in the electronic databases ME...

  3. Mechanical Properties of a High Lead Glass Used in the Mars Organic Molecule Analyzer

    Science.gov (United States)

    Salem, Jonathan A.; Smith, Nathan A.; Ersahin, Akif

    2015-01-01

    The elastic constants, strength, fracture toughness, slow crack growth parameters, and mirror constant of a high lead glass supplied as tubes and funnels were measured using ASTM International (formerly ASTM, American Society for Testing and Materials) methods and modifications thereof. The material exhibits lower Young's modulus and slow crack growth exponent as compared to soda-lime silica glass. Highly modified glasses exhibit lower fracture toughness and slow crack growth exponent than high purity glasses such as fused silica.

  4. When and how does labour lead to love? The ontogeny and mechanisms of the IKEA effect

    OpenAIRE

    Marsh, Lauren E.; Kanngiesser, Patricia; Hood, Bruce

    2018-01-01

    We elevate our constructions to a special status in our minds. This ‘IKEA’ effect leads us to believe that our creations are more valuable than items that are identical, but constructed by another. This series of studies utilises a developmental perspective to explore why this bias exists. Study 1 elucidates the ontogeny of the IKEA effect, demonstrating an emerging bias at age 5, corresponding with key developmental milestones in self-concept formation. Study 2 assesses the role of effort, r...

  5. Optical coherence tomography (OCT) leading to more insight into cochlear mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Egbert de [Academic Medical Centre, University of Amsterdam, Amsterdam (Netherlands); Oregon Health & Science University, Portland, Oregon (United States); Chen, Fangyi; Zha, Dingjun; Nuttall, Alfred L. [Oregon Health & Science University, Portland, Oregon (United States)

    2015-12-31

    Optical Coherence Tomography (OCT) was used to measure vibrations of the basilar membrane (BM) and the Reticular Lamina (RL) in the cochlea of the guinea pig, at frequencies up to 25 kHz. Because of the difficulty of the experiments the data have limited sets of parameters and are subject to high noise levels. In a viable guinea-pig cochlea, the RL moves in the region of maximum response with a larger amplitude than the BM. We cannot rule out that some of that difference is due to a geometrical factor. We also found a consistent increase of this amplitude difference with frequency, which points to a low-pass filtering process. That process might be linked to the mass of the fluid contained in the Organ of Corti channel (OoC channel)

  6. Removing lead from metallic mixture of waste printed circuit boards by vacuum distillation: factorial design and removal mechanism.

    Science.gov (United States)

    Li, Xingang; Gao, Yujie; Ding, Hui

    2013-10-01

    The lead removal from the metallic mixture of waste printed circuit boards by vacuum distillation was optimized using experimental design, and a mathematical model was established to elucidate the removal mechanism. The variables studied in lead evaporation consisted of the chamber pressure, heating temperature, heating time, particle size and initial mass. The low-level chamber pressure was fixed at 0.1 Pa as the operation pressure. The application of two-level factorial design generated a first-order polynomial that agreed well with the data for evaporation efficiency of lead. The heating temperature and heating time exhibited significant effects on the efficiency, which was validated by means of the copper-lead mixture experiments. The optimized operating conditions within the region studied were the chamber pressure of 0.1 Pa, heating temperature of 1023 K and heating time of 120 min. After the conditions were employed to remove lead from the metallic mixture of waste printed circuit boards, the efficiency was 99.97%. The mechanism of the effects was elucidated by mathematical modeling that deals with evaporation, mass transfer and condensation, and can be applied to a wider range of metal removal by vacuum distillation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

    NARCIS (Netherlands)

    D. Hasan (Djo); P. Blankman (Paul); G.F. Nieman (Gary F.)

    2017-01-01

    textabstractSevere pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high

  8. Effects of voids on thermal-mechanical reliability of lead-free solder joints

    Directory of Open Access Journals (Sweden)

    Benabou Lahouari

    2014-06-01

    Full Text Available Reliability of electronic packages has become a major issue, particularly in systems used in electrical or hybrid cars where severe operating conditions must be met. Many studies have shown that solder interconnects are critical elements since many failure mechanisms originate from their typical response under thermal cycles. In this study, effects of voids in solder interconnects on the electronic assembly lifetime are estimated based on finite element simulations.

  9. Glutamate transporter type 3 knockout leads to decreased heart rate possibly via parasympathetic mechanism

    OpenAIRE

    Deng, Jiao; Li, Jiejie; Li, Liaoliao; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

    2013-01-01

    Parasympathetic tone is a dominant neural regulator for basal heart rate. Glutamate transporters (EAAT) via their glutamate uptake functions regulate glutamate neurotransmission in the central nervous system. We showed that EAAT type 3 (EAAT3) knockout mice had a slower heart rate than wild-type mice when they were anesthetized. We design this study to determine whether non-anesthetized EAAT3 knockout mice have a slower heart rate and, if so, what may be the mechanism for this effect. Young a...

  10. AFM and SEM-FEG study on fundamental mechanisms leading to fatigue crack initiation

    Czech Academy of Sciences Publication Activity Database

    Man, Jiří; Valtr, M.; Petrenec, Martin; Dluhoš, J.; Kuběna, Ivo; Obrtlík, Karel; Polák, Jaroslav

    2015-01-01

    Roč. 76, JUL (2015), s. 11-18 ISSN 0142-1123 R&D Projects: GA ČR(CZ) GAP108/10/2371; GA MŠk(CZ) ED1.1.00/02.0068; GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : fatigue crack initiation * 316L austenitic steel * atomic force microscopy * extrusion * intrusion Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.162, year: 2015

  11. Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.

    Science.gov (United States)

    Crespo, Alejandro; Rodriguez-Granillo, Agustina; Lim, Victoria T

    2017-01-01

    The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Replisome-mediated Translesion Synthesis and Leading Strand Template Lesion Skipping Are Competing Bypass Mechanisms*

    Science.gov (United States)

    Gabbai, Carolina B.; Yeeles, Joseph T. P.; Marians, Kenneth J.

    2014-01-01

    A number of different enzymatic pathways have evolved to ensure that DNA replication can proceed past template base damage. These pathways include lesion skipping by the replisome, replication fork regression followed by either correction of the damage and origin-independent replication restart or homologous recombination-mediated restart of replication downstream of the lesion, and bypass of the damage by a translesion synthesis DNA polymerase. We report here that of two translesion synthesis polymerases tested, only DNA polymerase IV, not DNA polymerase II, could engage productively with the Escherichia coli replisome to bypass leading strand template damage, despite the fact that both enzymes are shown to be interacting with the replicase. Inactivation of the 3′ → 5′ proofreading exonuclease of DNA polymerase II did not enable bypass. Bypass by DNA polymerase IV required its ability to interact with the β clamp and act as a translesion polymerase but did not require its “little finger” domain, a secondary region of interaction with the β clamp. Bypass by DNA polymerase IV came at the expense of the inherent leading strand lesion skipping activity of the replisome, indicating that they are competing reactions. PMID:25301949

  13. Mechanical properties of a 316L/T91 weld joint tested in lead-bismuth liquid

    International Nuclear Information System (INIS)

    Serre, Ingrid; Vogt, Jean-Bernard

    2009-01-01

    The mechanical strength of T91/316L weld joint assembled by electron beam process is investigated in air and in a liquid lead bismuth bath at 300 and 380 o C using the small punch test. It is shown that the mechanical response in air of the weld joint is similar to that of the T91 base material. The plastic deformation is mainly concentrated in the T91 part of the weld joint which promotes cracking in this material. Testing in liquid lead bismuth bath results in a reduction in ductility and the formation of brittle cracks. The T91/weld interface is found to be rather resistant as it cracks late in the test and after a large crack propagated in the T91 steel.

  14. Kinetic and mechanism studies of the adsorption of lead onto waste cow bone powder (WCBP) surfaces.

    Science.gov (United States)

    Cha, Jihoon; Cui, Mingcan; Jang, Min; Cho, Sang-Hyun; Moon, Deok Hyun; Khim, Jeehyeong

    2011-01-01

    This study examines the adsorption isotherms, kinetics and mechanisms of Pb²(+) sorption onto waste cow bone powder (WCBP) surfaces. The concentrations of Pb²(+) in the study range from 10 to 90 mg/L. Although the sorption data follow the Langmuir and Freundlich isotherm, a detailed examination reveals that surface sorption or complexation and co-precipitation are the most important mechanisms, along with possibly ion exchange and solid diffusion also contributing to the overall sorption process. The co-precipitation of Pb²(+) with the calcium hydroxyapatite (Ca-HAP) is implied by significant changes in Ca²(+) and PO₄³⁻ concentrations during the metal sorption processes. The Pb²(+) sorption onto the WCBP surface by metal complexation with surface functional groups such as ≡ POH. The major metal surface species are likely to be ≡ POPb(+). The sorption isotherm results indicated that Pb²(+) sorption onto the Langmuir and Freundlich constant q(max) and K( F ) is 9.52 and 8.18 mg g⁻¹, respectively. Sorption kinetics results indicated that Pb²(+) sorption onto WCBP was pseudo-second-order rate constants K₂ was 1.12 g mg⁻¹ h⁻¹. The main mechanism is adsorption or surface complexation (≡POPb(+): 61.6%), co-precipitation or ion exchange [Ca₃(.)₉₃ Pb₁(.)₀₇ (PO₄)₃ (OH): 21.4%] and other precipitation [Pb 50 mg L⁻¹ and natural pH: 17%). Sorption isotherms showed that WCBP has a much higher Pb²(+) removal rate in an aqueous solution; the greater capability of WCBP to remove aqueous Pb²(+) indicates its potential as another promising way to remediate Pb²(+)-contaminated media.

  15. MOLECULAR MECHANISMS THAT LEAD TO CHOLANGIOCARCINOMA, DURING CHRONIC INFECTION OF LIVER FLUKES

    Directory of Open Access Journals (Sweden)

    A. O. Bogdanov

    2015-01-01

    Full Text Available Cholangiocarcinoma is a malignant tumor, characterized by poor prognosis and a low five-year survival rate. There is a clear correlation between the incidence of opisthorchiasis and high incidence of cholangiocarcinoma in South-East Asia. Liver flukes Clonorchis sinensis and Opisthorchis viverrini are I class carcinogens. There are some endemic regions of opisthorchiasis In the Russian Federation. The most important factor that leads to carcinogenesis during liver fluke infection is chronic inflammation. This review article focuses on the communication of chronic inflammation caused by invasion of liver flukes and cholangiocarcinoma. This paper summarizes the current knowledge about the risk factors for cholangiocarcinoma, as well as knowledge about the molecular aspects of the induction of carcinogenesis by liver flukes.

  16. Transport Mechanisms Governing initial Leading-Edge Vortex Development on a Pitching Wing

    Science.gov (United States)

    Wabick, Kevin; Berdon, Randall; Buchholz, James; Johnson, Kyle; Thurow, Brian

    2017-11-01

    The formation and evolution of Leading Edge Vortices (LEVs) are ubiquitous in natural fliers and maneuvering wings, and have a profound impact on aerodynamic loads. The formation of an LEV is experimentally investigated on a pitching flat-plate wing of aspect-ratio 2, and dimensionless pitch rates of k = Ωc / 2 U of 0.1, 0.2, and 0.5, at a Reynolds number of 104. The sources and sinks of vorticity that contribute to the growth and evolution of the LEV are investigated at spanwise regions of interest, and their relative balance is compared to other wing kinematics, and the case of a two-dimensional pitching wing. This work is supported by the Air Force Office of Scientific Research (Grant Number FA9550-16-1-0107, Dr. Douglas Smith, program manager).

  17. INFLUENCE OF MECHANICAL ALLOYING AND LEAD CONTENT ON MICROSTRUCTURE, HARDNESS AND TRIBOLOGICAL BEHAVIOR OF 6061 ALUMINIUM ALLOYS

    Directory of Open Access Journals (Sweden)

    M. Paidpilli

    2017-03-01

    Full Text Available In the present work, one batch of prealloyed 6061Al powder was processed by mixing and another one was ball milled with varying amount of lead content (0-15 vol. %. These powders were compacted at 300MPa and sintered at 590˚C under N2. The instrumented hardness and the young’s modulus of as-sintered 6061Al-Pb alloys were examined as a function of lead content and processing route. The wear test under dry sliding condition has been performed at varying loads (10-40 N using pin-on-disc tribometer. The microstructure and worn surfaces have been investigated using SEM to evaluate the change in topographical features due to mechanical alloying and lead content. The mechanically alloyed materials showed improved wear characteristics as compared to as-mixed counterpart alloys. Delamination of 6061Al-Pb alloys decreases up to an optimum lead composition in both as-mixed and ball-milled 6061Al-Pb alloys. The results indicated minimum wear rate for as-mixed and ball-milled 6061Al alloy at 5 and 10 vol. % Pb, respectively.

  18. Physical mechanisms leading to high currents of highly charged ions in laser-driven ion sources

    International Nuclear Information System (INIS)

    Haseroth, Helmut; Hora, Heinrich; Regensburg Inst. of Tech.

    1996-01-01

    Heavy ion sources for the big accelerators, for example, the LHC, require considerably more ions per pulse during a short time than the best developed classical ion source, the electron cyclotron resonance (ECR) provides; thus an alternative ion source is needed. This can be expected from laser-produced plasmas, where dramatically new types of ion generation have been observed. Experiments with rather modest lasers have confirmed operation with one million pulses of 1 Hz, and 10 11 C 4+ ions per pulse reached 2 GeV/u in the Dubna synchrotron. We review here the complexities of laser-plasma interactions to underline the unique and extraordinary possibilities that the laser ion source offers. The complexities are elaborated with respect to keV and MeV ion generation, nonlinear (ponderomotive) forces, self-focusing, resonances and ''hot'' electrons, parametric instabilities, double-layer effects, and the few ps stochastic pulsation (stuttering). Recent experiments with the laser ion source have been analyzed to distinguish between the ps and ns interaction, and it was discovered that one mechanism of highly charged ion generation is the electron impact ionization (EII) mechanism, similar to the ECR, but with so much higher plasma densities that the required very large number of ions per pulse are produced. (author)

  19. Physical mechanisms leading to high currents of highly charged ions in laser-driven ion sources

    Energy Technology Data Exchange (ETDEWEB)

    Haseroth, Helmut [European Organization for Nuclear Research, Geneva (Switzerland); Hora, Heinrich [New South Wales Univ., Kensington, NSW (Australia)]|[Regensburg Inst. of Tech. (Germany). Anwenderzentrum

    1996-12-31

    Heavy ion sources for the big accelerators, for example, the LHC, require considerably more ions per pulse during a short time than the best developed classical ion source, the electron cyclotron resonance (ECR) provides; thus an alternative ion source is needed. This can be expected from laser-produced plasmas, where dramatically new types of ion generation have been observed. Experiments with rather modest lasers have confirmed operation with one million pulses of 1 Hz, and 10{sup 11} C{sup 4+} ions per pulse reached 2 GeV/u in the Dubna synchrotron. We review here the complexities of laser-plasma interactions to underline the unique and extraordinary possibilities that the laser ion source offers. The complexities are elaborated with respect to keV and MeV ion generation, nonlinear (ponderomotive) forces, self-focusing, resonances and ``hot`` electrons, parametric instabilities, double-layer effects, and the few ps stochastic pulsation (stuttering). Recent experiments with the laser ion source have been analyzed to distinguish between the ps and ns interaction, and it was discovered that one mechanism of highly charged ion generation is the electron impact ionization (EII) mechanism, similar to the ECR, but with so much higher plasma densities that the required very large number of ions per pulse are produced. (author).

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

    Directory of Open Access Journals (Sweden)

    Maryam Miraghajani

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

  1. Hypoxic ischemia encephalopathy leading to external hydrocephalus and the cerebral atrophy: mechanism and differential diagnosis

    International Nuclear Information System (INIS)

    Huang Zhenglin; Mo Xiaorong

    2002-01-01

    Objective: It is a study of the mechanism and differential diagnosis of the infant external hydrocephalus and cerebral atrophy. Methods: In total 84 cases of neonatal hypoxic ischemia encephalopathy followed by infant external hydrocephalus were investigated, among which 26 patients gradually were found having developed cerebral atrophy in follow up. Results: Characteristic dilation of the frontal-parietal subarachnoid space and the adjacent cistern was noted on the CT images of the external hydrocephalus. CT revealed the enlarged ventricle besides the dilated subarachnoid space in the cases of cerebral atrophy, while these two entities were indistinguishable on CT in the early stage. Conclusion: Clinical manifestations make a major differential diagnosis of the external hydrocephalus and cerebral atrophy: tic and mild delayed development of locomotion over major presentation of external hydrocephalus, while cerebral atrophy is featured by remarkable dysnoesia and severe delayed development of locomotion. In addition, hemiplegia and increased muscular tension are presented in a few cases of cerebral atrophy

  2. Nontraumatic Fracture of the Femoral Condylar Prosthesis in a Total Knee Arthroplasty Leading to Mechanical Failure

    Directory of Open Access Journals (Sweden)

    Girish N. Swamy

    2014-01-01

    Full Text Available This paper reports a case of fatigue fracture of the femoral component in a cruciate-retaining cemented total knee arthroplasty (TKA. A 64-year-old man had undergone a primary TKA for osteoarthritis 10 years previously at another institution using the PFC-Sigma prosthesis. The patient recovered fully and was back to his regular activities. He presented with a history of sudden onset pain and locking of the left knee since the preceding three months. There was no history of trauma, and the patient was mobilizing with difficulty using crutches. Radiographs revealed fracture of the posterior condyle of the femoral prosthesis. Revision surgery was performed as an elective procedure revealing the broken prosthesis. The TC3RP-PFC revision prosthesis was used with a medial parapatellar approach. The patient recovered fully without any squeal. Mechanical failure of the knee arthroplasty prosthesis is rare, and nontraumatic fracture of the femoral metallic component has not been reported before.

  3. Nontraumatic fracture of the femoral condylar prosthesis in a total knee arthroplasty leading to mechanical failure.

    Science.gov (United States)

    Swamy, Girish N; Quah, Conal; Bagouri, Elmunzar; Badhe, Nitin P

    2014-01-01

    This paper reports a case of fatigue fracture of the femoral component in a cruciate-retaining cemented total knee arthroplasty (TKA). A 64-year-old man had undergone a primary TKA for osteoarthritis 10 years previously at another institution using the PFC-Sigma prosthesis. The patient recovered fully and was back to his regular activities. He presented with a history of sudden onset pain and locking of the left knee since the preceding three months. There was no history of trauma, and the patient was mobilizing with difficulty using crutches. Radiographs revealed fracture of the posterior condyle of the femoral prosthesis. Revision surgery was performed as an elective procedure revealing the broken prosthesis. The TC3RP-PFC revision prosthesis was used with a medial parapatellar approach. The patient recovered fully without any squeal. Mechanical failure of the knee arthroplasty prosthesis is rare, and nontraumatic fracture of the femoral metallic component has not been reported before.

  4. In case of obesity, longevity-related mechanisms lead to anti-inflammation.

    Science.gov (United States)

    Kaya, Mehmet Salih; Bayıroglu, Fahri; Mis, Leyla; Kilinc, Dide; Comba, Bahat

    2014-04-01

    The exact mechanisms which contribute to longevity have not been figured out yet. Our aim was to find out a common way for prompting longevity by bringing together the well-known applications such as food restriction, exercise, and probiotic supplementing in an experimental obesity model. Experimental obesity was promoted in a total of 32 young (2 months old) and 32 aged (16 months old) male Wistar albino rats through 8-week cafeteria diet (salami, chocolate, chips, and biscuits). Old and young animals were divided into groups each consisting of eight animals and also divided into four subgroups as obese control, obese food restriction, obese probiotic-fed and obese exercise groups. Probiotic group diet contained 0.05 %w/total diet inactive and lyophilized Lactobacillus casei str. Shirota. The exercise group was subjected to treadmill running 1 h/day, at 21 m/min and at an uphill incline of 15 % for 5 days a week. Food restriction group was formed by giving 40 % less food than the others. The control group was fed regular pellet feed ad libitum. This program was continued for 16 weeks. Blood samples from all the groups were analyzed for fasting glucose, insulin, IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3), interleukin (IL)-6, IL-12, malondialdehyde (MDA), fT3, TT3, fT4, TT4, and liver tissue MDA levels were measured. All applications showed anti-inflammatory effects through the observed changes in the levels of IGFBP-3, IL-6, and IL-12 in the young and old obese rats. While the interventions normally contribute to longevity by recruiting different action mechanisms, anti-inflammatory effect is the only mode of action for all the applications in the obesity model.

  5. Epigenetics as a mechanism linking developmental exposures to long-term toxicity

    DEFF Research Database (Denmark)

    Barouki, R; Melén, E; Herceg, Z

    2018-01-01

    A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylat......A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA...

  6. Fracture mechanisms in ferroelectric-ferroelastic lead zirconate titanate (Zr:Ti = 0.54:0.46) ceramics

    International Nuclear Information System (INIS)

    Mehta, K.; Virkar, A.V.

    1990-01-01

    Fracture toughness, K IC , of a single-phase commercial lead zirconate titanate (PZT) ceramic of tetragonal structure was measured using the single edge notched beam method above and below the Curie temperature. Domain switching (poling) under electrical and mechanical loading was examined using x-ray diffraction. Surface grinding, electrical poling, and mechanical poling caused crystallographic texture. Similar texture, indicative of domain switching, was also observed on fracture surfaces of some samples fractured at room temperature. At room temperature, the highest K IC measured was 1.85 MPa · m 1/2 , while above the Curie temperature it was about 1.0 MPa · m 1/2 . Cracks emanating from Vickers indents in poled samples were different in the poling and the transverse directions. The difference in crack sizes is explained on the basis of domain switching during crack growth. These results indicate that ferroelastic domain switching (twinning) is a viable toughening mechanism in the PZT materials tested

  7. Transmission electron microscopy investigation of the microstructural mechanisms for the piezoelectricity in lead-free perovskite ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Cheng [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    Lead-free materials with superior piezoelectricity are in increasingly urgent demand in the current century, because the industrial standard Pb(Zr,Ti)O3-based piezoelectrics, which contain over 60 weight% of the toxic element lead, pose severe environmental hazards. Although significant research efforts have been devoted in the past decade, no effective lead-free substitute for Pb(Zr,Ti)O3 has been identified yet. One of the primary hindrances to the development of lead-free piezoelectrics lies in the ignorance of the microstructural mechanism for the electric-field-induced strains in the currently existing compositions. In this dissertation, the microstructural origin for the high piezoelectricity in (1-x)(Bi1/2Na1/2)TiO3-xBaTiO3 [(1-x)BNT-xBT], the most widely studied lead-free piezoelectric system, has been elucidated.

  8. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    Science.gov (United States)

    Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

    2014-01-01

    Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

  9. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Steve P. Crampton

    2014-09-01

    Full Text Available Systemic lupus erythematosus (SLE represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.

  10. Essential Features of Serious Games Design in Higher Education: Linking Learning Attributes to Game Mechanics

    Science.gov (United States)

    Lameras, Petros; Arnab, Sylvester; Dunwell, Ian; Stewart, Craig; Clarke, Samantha; Petridis, Panagiotis

    2017-01-01

    This paper consolidates evidence and material from a range of specialist and disciplinary fields to provide an evidence-based review and synthesis on the design and use of serious games in higher education. Search terms identified 165 papers reporting conceptual and empirical evidence on how learning attributes and game mechanics may be planned,…

  11. 3D mechanical stratigraphy of a deformed multi-layer: Linking sedimentary architecture and strain partitioning

    Science.gov (United States)

    Cawood, Adam J.; Bond, Clare E.

    2018-01-01

    Stratigraphic influence on structural style and strain distribution in deformed sedimentary sequences is well established, in models of 2D mechanical stratigraphy. In this study we attempt to refine existing models of stratigraphic-structure interaction by examining outcrop scale 3D variations in sedimentary architecture and the effects on subsequent deformation. At Monkstone Point, Pembrokeshire, SW Wales, digital mapping and virtual scanline data from a high resolution virtual outcrop have been combined with field observations, sedimentary logs and thin section analysis. Results show that significant variation in strain partitioning is controlled by changes, at a scale of tens of metres, in sedimentary architecture within Upper Carboniferous fluvio-deltaic deposits. Coupled vs uncoupled deformation of the sequence is defined by the composition and lateral continuity of mechanical units and unit interfaces. Where the sedimentary sequence is characterized by gradational changes in composition and grain size, we find that deformation structures are best characterized by patterns of distributed strain. In contrast, distinct compositional changes vertically and in laterally equivalent deposits results in highly partitioned deformation and strain. The mechanical stratigraphy of the study area is inherently 3D in nature, due to lateral and vertical compositional variability. Consideration should be given to 3D variations in mechanical stratigraphy, such as those outlined here, when predicting subsurface deformation in multi-layers.

  12. The Weakest Link : Spatial Variability in the Piping Failure Mechanism of Dikes

    NARCIS (Netherlands)

    Kanning, W.

    2012-01-01

    Piping is an important failure mechanism of flood defense structures. A dike fails due to piping when a head difference causes first the uplift of an inland blanket layer, and subsequently soil erosion due to a ground water flow. Spatial variability of subsoil parameters causes the probability of

  13. Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms.

    Science.gov (United States)

    Gautam, Mukesh; Jara, Javier H; Sekerkova, Gabriella; Yasvoina, Marina V; Martina, Marco; Özdinler, P Hande

    2016-03-15

    Mutations in the ALS2 gene result in early-onset amyotrophic lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia and juvenile primary lateral sclerosis, suggesting prominent upper motor neuron involvement. However, the importance of alsin function for corticospinal motor neuron (CSMN) health and stability remains unknown. To date, four separate alsin knockout (Alsin(KO)) mouse models have been generated, and despite hopes of mimicking human pathology, none displayed profound motor function defects. This, however, does not rule out the possibility of neuronal defects within CSMN, which is not easy to detect in these mice. Detailed cellular analysis of CSMN has been hampered due to their limited numbers and the complex and heterogeneous structure of the cerebral cortex. In an effort to visualize CSMN in vivo and to investigate precise aspects of neuronal abnormalities in the absence of alsin function, we generated Alsin(KO)-UeGFP mice, by crossing Alsin(KO) and UCHL1-eGFP mice, a CSMN reporter line. We find that CSMN display vacuolated apical dendrites with increased autophagy, shrinkage of soma size and axonal pathology even in the pons region. Immunocytochemistry coupled with electron microscopy reveal that alsin is important for maintaining cellular cytoarchitecture and integrity of cellular organelles. In its absence, CSMN displays selective defects both in mitochondria and Golgi apparatus. UCHL1-eGFP mice help understand the underlying cellular factors that lead to CSMN vulnerability in diseases, and our findings reveal unique importance of alsin function for CSMN health and stability. © The Author 2016. Published by Oxford University Press.

  14. [Adsorption kinetics and mechanism of lead (II) on polyamine-functionalized mesoporous activated carbon].

    Science.gov (United States)

    Li, Kun-Quan; Wang, Yan-Jin; Yang, Mei-Rong; Zhu, Zhi-Qiang; Zheng, Zheng

    2014-08-01

    Bagasse mesoporous carbon was prepared by microwave assisted H3 PO4 activation. Amido and imido groups were modified with ethanediamine on the channels' surface of mesoporous carbon through nitric oxidation and amide reaction. The influence of Pb(II) concentration, adsorption time on Pb(II) adsorption on the ethanediamine-modified mesoporous carbon (AC-EDA) was investigated. The adsorption kinetics and mechanism were also discussed. The results showed that AC-EDA had a great performance for Pb(II) adsorption, and more than 70% of Pb(II) was adsorbed in 5 minutes. The adsorption amount of Pb(II) on the carbon increased with the increase of solution pH in acidic conditions. It was found that AC-EDA had different binding energies on different adsorption sites for Pb(II) separation. The Pb(II) adsorption process on AC-EDA was controlled by intra-particle diffusion in the first 3 min, and then film diffusion played the important pole on the adsorption. The adsorption amount increased with the increase of temperature, indicating the adsorption was an endothermic reaction. The high adsorption energy (> 11 kJ x mol(-1)) implied that the) adsorption was a chemical adsorption. The XPS of AC-EDA before and after Pb(II) adsorption showed that the polyamine group was involved in the adsorption, and should be a main factor of the high efficient adsorption.

  15. Ferroelectric behavior of a lead titanate nanosphere due to depolarization fields and mechanical stresses

    Energy Technology Data Exchange (ETDEWEB)

    Andrade Landeta, J.; Lascano, I.

    2017-07-01

    A theorical model has been developed based on the theory of Ginzburg-Landau-Devonshire to study and predict the effects the decreasing of size particle in a nanosphere of PbTiO3 subjected to the action of depolarization fields and mechanical stress. It was considered that the nanosphere is surrounded by a layer of space charges on its surface, and containing 180° domains generated by minimizing free energy of depolarization. Energy density of depolarization, wall domain and electro-elastic energy have been incorporated into the free energy of the theory Ginzburg-Landau-Devonshire. Free energy minimization was performed to determine the spontaneous polarization and transition temperature system. These results show that the transition temperature for nanosphere is substantially smaller than the corresponding bulk material. Also, it has been obtained that the stability of the ferroelectric phase of nanosphere is favored for configurations with a large number of 180° domains, with the decreasing of thickness space charge layer, and the application of tensile stress and decreases with compressive stress. (Author)

  16. Mechanism of Supercooled Water Droplet Breakup near the Leading Edge of an Airfoil

    Science.gov (United States)

    Veras-Alba, Belen; Palacios, Jose; Vargas, Mario; Ruggeri, Charles; Bartkus, Tadas P.

    2017-01-01

    This work presents the results of an experimental study on supercooled droplet deformation and breakup near the leading edge of an airfoil. The results are compared to prior room temperature droplet deformation results to explore the effects of droplet supercooling. The experiments were conducted in the Adverse Environment Rotor Test Stand (AERTS) at The Pennsylvania State University. An airfoil model placed at the end of the rotor blades mounted onto the hub in the AERTS chamber was moved at speeds ranging between 50 and 80 m/sec. The temperature of the chamber was set at -20°C. A monotonic droplet generator was used to produce droplets that fell from above, perpendicular to the path of the airfoil. The supercooled state of the droplets was determined by measurement of the temperature of the drops at various locations below the droplet generator exit. A temperature prediction code was also used to estimate the temperature of the droplets based on vertical velocity and the distance traveled by droplets from the droplet generator to the airfoil stagnation line. High speed imaging was employed to observe the interaction between the droplets and the airfoil. The high speed imaging provided droplet deformation information as the droplet approached the airfoil near the stagnation line. A tracking software program was used to measure the horizontal and vertical displacement of the droplet against time. It was demonstrated that to compare the effects of water supercooling on droplet deformation, the ratio of the slip velocity and the initial droplet velocity must be equal. A case with equal slip velocity to initial velocity ratios was selected for room temperature and supercooled droplet conditions. The airfoil velocity was 60 m/s and the slip velocity for both sets of data was 40 m/s. In these cases, the deformation of the weakly supercooled and warm droplets did not present different trends. The similar behavior for both environmental conditions indicates that water

  17. Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

    Directory of Open Access Journals (Sweden)

    Benedikt Frieg

    2016-02-01

    Full Text Available Glutamine synthetase (GS catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

  18. Effects and mechanisms of meta-sodium silicate amendments on lead uptake and accumulation by rice.

    Science.gov (United States)

    Zhao, Mingliu; Liu, Yuting; Li, Honghong; Cai, Yifan; Wang, Ming Kuang; Chen, Yanhui; Xie, Tuanhui; Wang, Guo

    2017-09-01

    The objectives of this research were to study the effects of Na 2 SiO 3 application on the uptake, translocation, and accumulation of Pb in rice and to investigate the mechanisms of Pb immobilization by Na 2 SiO 3 in paddy rice soils and rice plants. Pot experiments were conducted using a Cd-Pb-Zn-polluted soil and Oryza sativa L. ssp. indica cv. Donglian 5. L 3 -edge X-ray absorption spectroscopy was used to identify Pb species in soils and roots. The results showed that the application of Na 2 SiO 3 increased soil pH and available soil Si but decreased DTPA-extractable Pb in the soil. High dose of Na 2 SiO 3 (12.5 g/kg) reduced the Pb level in brown rice as it inhibited Pb transfer from soil to rice grains, especially Pb transfer from the root to the stem. The Pb X-ray absorption near-edge spectroscopic analysis revealed that application of high dose of Na 2 SiO 3 increased Pb-ferrihydrite and PbSiO 3 precipitates in the soil and in the root while it reduced Pb-humic acids (Pb-HAs) in the soil and Pb-pectin in the root. The decrease in Pb availability in the soil can be partly attributed to increase the precipitation of PbSiO 3 and the association of Pb 2+ with Fe oxides in the soil. The inhibition of the root-to-stem translocation of Pb was partially due to the precipitation of PbSiO 3 on the root surfaces or inside the roots.

  19. Migraine, vertigo and migrainous vertigo: Links between vestibular and pain mechanisms.

    Science.gov (United States)

    Balaban, Carey D

    2011-01-01

    This review develops the hypothesis that co-morbid balance disorders and migraine can be understood as additive effects of processing afferent vestibular and pain information in pre-parabrachial and pre-thalamic pathways, that have consequences on cortical mechanisms influencing perception, interoception and affect. There are remarkable parallel neurochemical phenotypes for inner ear and trigeminal ganglion cells and these afferent channels appear to converge in shared central pathways for vestibular and nociceptive information processing. These pathways share expression of receptors targeted by anti-migraine drugs. New evidence is also presented regarding the distribution of serotonin receptors in the planum semilunatum of the primate cristae ampullaris, which may indicate involvement of inner ear ionic homeostatic mechanisms in audiovestibular symptoms that can accompany migraine.

  20. 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

  1. Barrier and mechanical properties of plasticized and cross-linked nanocellulose coatings for paper packaging applications

    OpenAIRE

    Herrera, M. A. (Martha A.); Mathew, A. P. (Aji P.); Oksman, K. (Kristiina)

    2017-01-01

    Abstract Barrier, mechanical and thermal properties of porous paper substrates dip-coated with nanocellulose (NC) were studied. Sorbitol plasticizer was used to improve the toughness, and citric acid cross-linker to improve the moisture stability of the coatings. In general, the addition of sorbitol increased the barrier properties, maximum strength and toughness as well as the thermal stability of the samples when compared to the non-modified NC coatings. The barrier properties significan...

  2. Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction

    OpenAIRE

    Morino, Katsutaro; Petersen, Kitt Falk; Shulman, Gerald I.

    2006-01-01

    Recent studies using magnetic resonance spectroscopy have shown that decreased insulin-stimulated muscle glycogen synthesis due to a defect in insulin-stimulated glucose transport activity is a major factor in the pathogenesis of type 2 diabetes. The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to increases in intramyocellular lipid metabolites such as fatty acyl CoAs and diacylglycerol, which in turn activate a serine/threonine kina...

  3. Plantar Fasciitis and the Windlass Mechanism: A Biomechanical Link to Clinical Practice

    Science.gov (United States)

    Malone, Terry R.

    2004-01-01

    Objective: Plantar fasciitis is a prevalent problem, with limited consensus among clinicians regarding the most effective treatment. The purpose of this literature review is to provide a systematic approach to the treatment of plantar fasciitis based on the windlass mechanism model. Data Sources: We searched MEDLINE, SPORT Discus, and CINAHL from 1966 to 2003 using the key words plantar fasciitis, windlass mechanism, pronation, heel pain, and heel spur. Data Synthesis: We offer a biomechanical application for the evaluation and treatment of plantar fasciitis based on a review of the literature for the windlass mechanism model. This model provides a means for describing plantar fasciitis conditions such that clinicians can formulate a potential causal relationship between the conditions and their treatments. Conclusions/Recommendations: Clinicians' understanding of the biomechanical causes of plantar fasciitis should guide the decision-making process concerning the evaluation and treatment of heel pain. Use of this approach may improve clinical outcomes because intervention does not merely treat physical symptoms but actively addresses the influences that resulted in the condition. Principles from this approach might also provide a basis for future research investigating the efficacy of plantar fascia treatment. PMID:16558682

  4. Elevated-Temperature Mechanical Properties of Lead-Free Sn-0.7Cu- xSiC Nanocomposite Solders

    Science.gov (United States)

    Mohammadi, A.; Mahmudi, R.

    2018-02-01

    Mechanical properties of Sn-0.7 wt.%Cu lead-free solder alloy reinforced with 0 vol.%, 1 vol.%, 2 vol.%, and 3 vol.% 100-nm SiC particles have been assessed using the shear punch testing technique in the temperature range from 25°C to 125°C. The composite materials were fabricated by the powder metallurgy route by blending, compacting, sintering, and finally extrusion. The 2 vol.% SiC-containing composite showed superior mechanical properties. In all conditions, the shear strength was adversely affected by increasing test temperature, and the 2 vol.% SiC-containing composite showed superior mechanical properties. Depending on the test temperature, the shear yield stress and ultimate shear strength increased, respectively, by 3 MPa to 4 MPa and 4 MPa to 5.5 MPa, in the composite materials. The strength enhancement was mostly attributed to the Orowan particle strengthening mechanism due to the SiC nanoparticles, and to a lesser extent to the coefficient of thermal expansion mismatch between the particles and matrix in the composite solder. A modified shear lag model was used to predict the total strengthening achieved by particle addition, based on the contribution of each of the above mechanisms.

  5. Molecular binding mechanisms of aqueous cadmium and lead to siderophores, bacteria and mineral surfaces

    Science.gov (United States)

    Mishra, Bhoopesh

    Recent studies have shown that diverse groups of bacteria adsorb metals to similar extents and uptake can be modeled using a universal adsorption model. In this study, XAFS has been used to resolve whether binding sites determined for single species systems are responsible for adsorption in more complex natural bacterial assemblages. Results obtained from a series of XAFS experiments on pure Gram positive and Gram negative bacterial strains and consortia of bacteria as a function of pH and Cd loading suggests that every bacterial strain has a complex physiology and they are all slightly different from each other. Nevertheless from the metal adsorption chemistry point of view, the main difference between them lies in the site ratio of three fundamental sites only - carboxyl, phosphoryl and sulfide. Two completely different consortia of bacteria (obtained from natural river water, and soil system with severe organic contamination) were successfully modeled in the pH range 3.4--7.8 using the EXAFS models developed for single species systems. Results thus obtained can potentially have very high impact on the modeling of the complex bacterial systems in realistic geological settings, leading to further refinement and development of robust remediation strategies for metal contamination at macroscopic level. In another study, solution speciation of Pb and Cd with DFO-B has been examined using a combination of techniques (ICP, TOC, thermodynamic modeling and XAFS). Results indicate that Pb does not complex with DFO-B at all until about pH 3.5, but forms a totally caged structure at pH 7.5. At intermediate pH conditions, mixture of species (one and two hydroxamate groups complexed) is formed. Cd on the other hand, does not complex until pH 5, forms intermediate complexes at pH 8 and is totally chelated at pH 9. Further studies were conducted for Pb sorption to mineral surface kaolinite with and without DFO-B. In the absence of DFO-B, results suggest outer sphere and inner

  6. Conduction mechanism in assemblies of metal nanoparticles linked by organic molecules

    International Nuclear Information System (INIS)

    Mueller, K.-H.; Herrmann, J.; Raguse, B.; Baxter, G.; Reda, T.

    2002-01-01

    Full text: We have investigated theoretically and experimentally electron transport through thin films of gold nanoparticles which are linked by alkanedithiol molecules of different chain lengths. We find that conduction between neighbouring nanoparticles takes place by electron tunnelling along weakly conducting organic linker molecules. Using a tight binding model for the alkanedithiol molecules to describe the tunnelling process we predict the conductivity to decrease exponentially with the length of the molecules. During tunnelling the electron has to overcome a charging energy due to the electron-hole interaction between tunnelling electrons and the corresponding holes left behind on the donor nanoparticle. Experimentally we find that large applied voltages cause nonlinear I-V characteristics and that the temperature dependence of the conductivity does not show Arrhenius behaviour but instead is of the form exp[-(E o /kT) 1/2 ]. Using percolation theory for a network of metal nanoparticles separated by barriers we show that strong disorder caused by variations in nanoparticle size and linker length as well as randomly trapped electric charges on the linker molecules can well explain our experimental data

  7. Epigenetics as a mechanism linking developmental exposures to long-term toxicity.

    Science.gov (United States)

    Barouki, R; Melén, E; Herceg, Z; Beckers, J; Chen, J; Karagas, M; Puga, A; Xia, Y; Chadwick, L; Yan, W; Audouze, K; Slama, R; Heindel, J; Grandjean, P; Kawamoto, T; Nohara, K

    2018-05-01

    A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Dynamic processes of domain switching in lead zirconate titanate under cyclic mechanical loading by in situ neutron diffraction

    International Nuclear Information System (INIS)

    Pojprapai, Soodkhet; Luo, Zhenhua; Clausen, Bjorn; Vogel, Sven C.; Brown, Donald W.; Russel, Jennifer; Hoffman, Mark

    2010-01-01

    The performance of ferroelectric ceramics is governed by the ability of domains to switch. A decrease in the switching ability can lead to degradation of the materials and failure of ferroelectric devices. In this work the dynamic properties of domain reorientation are studied. In situ time-of-flight neutron diffraction is used to probe the evolution of ferroelastic domain texture under mechanical cyclic loading in bulk lead zirconate titanate ceramics. The high sensitivity of neutron diffraction to lattice strain is exploited to precisely analyze the change of domain texture and strain through a full-pattern Rietveld method. These results are then used to construct a viscoelastic model, which explains the correlation between macroscopic phenomena (i.e. creep and recovered deformation) and microscopic dynamic behavior (i.e. ferroelastic switching, lattice strain).

  9. Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and Cholesterol Gallstone Formation

    Directory of Open Access Journals (Sweden)

    Mary Carmen Vázquez

    2012-01-01

    Full Text Available Cholesterol gallstone disease is highly prevalent in western countries, particularly in women and some specific ethnic groups. The formation of water-insoluble cholesterol crystals is due to a misbalance between the three major lipids present in the bile: cholesterol, bile salts, and phospholipids. Many proteins implicated in biliary lipid secretion in the liver are regulated by several transcription factors, including nuclear receptors LXR and FXR. Human and murine genetic, physiological, pathophysiological, and pharmacological evidence is consistent with the relevance of these nuclear receptors in gallstone formation. In addition, there is emerging data that also suggests a role for estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone disease. A better comprehension of the role of nuclear receptor function in gallstone formation may help to design new and more effective therapeutic strategies for this highly prevalent disease condition.

  10. Mechanisms of migration development at the community level: Migrant networks and types of links

    Directory of Open Access Journals (Sweden)

    Mónica Serban

    2014-11-01

    Full Text Available The paper approaches the problem of the development mechanism of international migration at community level.Some empirical observations cumulated during several researches,at origin and destination area, regarding Romanian migration to Spain constitute the starting points. Appealing to the distinction introduced by Mark Granovetter in 1976 between weak and strongties, we find that, if initially migration develops almost exclusively based on social relations that could be assimilated to strong ties,there is a moment in the process of development when the departures on the base of weak ties, with important consequences on the migrant’s situation at destination, increase.The paper tries to clarify, preponderantly invoking theoretical arguments,in what measure the departures based on weak ties between migrant and non migrant are normal in the process of international migration development at community level. The study concludes that, because of cumulative effects, migration evolution to a phase when the departure is possible based on weak ties is explainable.Two mechanisms mainly contribute to this result: enhancement of incentives to migrate (because of quantitative and qualitative information increase; visibility of migration effects in the origin area;changes of relative deprivation at community level and migration costs and risk lowering, with the consequence of reduction of effective support that a non-migrant needs from one migrant in order to migrate.

  11. The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms.

    Science.gov (United States)

    Zhang, Feng; Zhong, Rujia; Li, Song; Chang, Raymond Chuen-Chung; Le, Weidong

    2017-05-01

    Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.

  12. Linking the mechanics and energetics of hopping with elastic ankle exoskeletons.

    Science.gov (United States)

    Farris, Dominic James; Sawicki, Gregory S

    2012-12-15

    The springlike mechanics of the human leg during bouncing gaits has inspired the design of passive assistive devices that use springs to aid locomotion. The purpose of this study was to test whether a passive spring-loaded ankle exoskeleton could reduce the mechanical and energetic demands of bilateral hopping on the musculoskeletal system. Joint level kinematics and kinetics were collected with electromyographic and metabolic energy consumption data for seven participants hopping at four frequencies (2.2, 2.5, 2.8, and 3.2 Hz). Hopping was performed without an exoskeleton; with an springless exoskeleton; and with a spring-loaded exoskeleton. Spring-loaded ankle exoskeletons reduced plantar flexor muscle activity and the biological contribution to ankle joint moment (15-25%) and average positive power (20-40%). They also facilitated reductions in metabolic power (15-20%) across frequencies from 2.2 to 2.8 Hz compared with hopping with a springless exoskeleton. Reductions in metabolic power compared with hopping with no exoskeleton were restricted to hopping at 2.5 Hz only (12%). These results highlighted the importance of reducing the rate of muscular force production and work to achieve metabolic reductions. They also highlighted the importance of assisting muscles acting at the knee joint. Exoskeleton designs may need to be tuned to optimize exoskeleton mass, spring stiffness, and spring slack length to achieve greater metabolic reductions.

  13. Moist Orographic Convection: Physical Mechanisms and Links to Surface-Exchange Processes

    Directory of Open Access Journals (Sweden)

    Daniel J. Kirshbaum

    2018-02-01

    Full Text Available This paper reviews the current understanding of moist orographic convection and its regulation by surface-exchange processes. Such convection tends to develop when and where moist instability coincides with sufficient terrain-induced ascent to locally overcome convective inhibition. The terrain-induced ascent can be owing to mechanical (airflow over or around an obstacle and/or thermal (differential heating over sloping terrain forcing. For the former, the location of convective initiation depends on the dynamical flow regime. In “unblocked” flows that ascend the barrier, the convection tends to initiate over the windward slopes, while in “blocked” flows that detour around the barrier, the convection tends to initiate upstream and/or downstream of the high terrain where impinging flows split and rejoin, respectively. Processes that destabilize the upstream flow for mechanically forced moist convection include large-scale moistening and ascent, positive surface sensible and latent heat fluxes, and differential advection in baroclinic zones. For thermally forced flows, convective initiation is driven by thermally direct circulations with sharp updrafts over or downwind of the mountain crest (daytime or foot (nighttime. Along with the larger-scale background flow, local evapotranspiration and transport of moisture, as well as thermodynamic heterogeneities over the complex terrain, regulate moist instability in such events. Longstanding limitations in the quantitative understanding of related processes, including both convective preconditioning and initiation, must be overcome to improve the prediction of this convection, and its collective effects, in weather and climate models.

  14. A polypeptide-DNA hybrid with selective linking capability applied to single molecule nano-mechanical measurements using optical tweezers.

    Directory of Open Access Journals (Sweden)

    Fatemeh Moayed

    Full Text Available Many applications in biosensing, biomaterial engineering and single molecule biophysics require multiple non-covalent linkages between DNA, protein molecules, and surfaces that are specific yet strong. Here, we present a novel method to join proteins and dsDNA molecule at their ends, in an efficient, rapid and specific manner, based on the recently developed linkage between the protein StrepTactin (STN and the peptide StrepTag II (ST. We introduce a two-step approach, in which we first construct a hybrid between DNA and a tandem of two STs peptides (tST. In a second step, this hybrid is linked to polystyrene bead surfaces and Maltose Binding Protein (MBP using STN. Furthermore, we show the STN-tST linkage is more stable against forces applied by optical tweezers than the commonly used biotin-Streptavidin (STV linkage. It can be used in conjunction with Neutravidin (NTV-biotin linkages to form DNA tethers that can sustain applied forces above 65 pN for tens of minutes in a quarter of the cases. The method is general and can be applied to construct other surface-DNA and protein-DNA hybrids. The reversibility, high mechanical stability and specificity provided by this linking procedure make it highly suitable for single molecule mechanical studies, as well as biosensing and lab on chip applications.

  15. 5-HTTLPR polymorphism is linked to neural mechanisms of selective attention in preschoolers from lower socioeconomic status backgrounds

    Directory of Open Access Journals (Sweden)

    Elif Isbell

    2016-12-01

    Full Text Available While a growing body of research has identified experiential factors associated with differences in selective attention, relatively little is known about the contribution of genetic factors to the skill of sustained selective attention, especially in early childhood. Here, we assessed the association between the serotonin transporter linked polymorphic region (5-HTTLPR genotypes and the neural mechanisms of selective attention in young children from lower socioeconomic status (SES backgrounds. Event-related potentials (ERPs were recorded during a dichotic listening task from 121 children (76 females, aged 40–67 months, who were also genotyped for the short and long allele of 5-HTTLPR. The effect of selective attention was measured as the difference in ERP mean amplitudes elicited by identical probe stimuli embedded in stories when they were attended versus unattended. Compared to children homozygous for the long allele, children who carried at least one copy of the short allele showed larger effects of selective attention on neural processing. These findings link the short allele of the 5-HTTLPR to enhanced neural mechanisms of selective attention and lay the groundwork for future studies of gene-by-environment interactions in the context of key cognitive skills.

  16. 5-HTTLPR polymorphism is linked to neural mechanisms of selective attention in preschoolers from lower socioeconomic status backgrounds.

    Science.gov (United States)

    Isbell, Elif; Stevens, Courtney; Hampton Wray, Amanda; Bell, Theodore; Neville, Helen J

    2016-12-01

    While a growing body of research has identified experiential factors associated with differences in selective attention, relatively little is known about the contribution of genetic factors to the skill of sustained selective attention, especially in early childhood. Here, we assessed the association between the serotonin transporter linked polymorphic region (5-HTTLPR) genotypes and the neural mechanisms of selective attention in young children from lower socioeconomic status (SES) backgrounds. Event-related potentials (ERPs) were recorded during a dichotic listening task from 121 children (76 females, aged 40-67 months), who were also genotyped for the short and long allele of 5-HTTLPR. The effect of selective attention was measured as the difference in ERP mean amplitudes elicited by identical probe stimuli embedded in stories when they were attended versus unattended. Compared to children homozygous for the long allele, children who carried at least one copy of the short allele showed larger effects of selective attention on neural processing. These findings link the short allele of the 5-HTTLPR to enhanced neural mechanisms of selective attention and lay the groundwork for future studies of gene-by-environment interactions in the context of key cognitive skills. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Improvement of fatigue resistance for multilayer lead zirconate titanate (PZT)-based ceramic actuators by external mechanical loads

    Science.gov (United States)

    Yang, Gang; Yue, Zhenxing; Ji, Ye; Chu, Xiangcheng; Li, Longtu

    2008-12-01

    The influence of external compressive loads, applied along a direction perpendicular to polarization, on fatigue behaviors of multilayer lead zirconate titanate (PZT)-based ceramic actuators was investigated. Under no external mechanical load, a normal fatigue behavior was observed, demonstrating that both switching polarization (Pswitching) and remnant polarization (Pr) progressively decreased with increasing switching cycles due to domain pinning by charge point defects. However, an anomalous enhancement in both switching and remnant polarizations was observed upon application of the external compressive loads. After 5×106 cycles of polarization switching, Pswitching and Pr increase by about 13% and 6% at 40 MPa, respectively, while Pswitching and Pr increase by about 11% and 21% at 60 MPa, respectively. The improvement of fatigue resistance can be attributed to non-180° domain switching and suppression of microcracking, triggered by external mechanical loads.

  18. Student-Centered Instruction and Academic Achievement: Linking Mechanisms of Educational Inequality to Schools’ Instructional Strategy

    DEFF Research Database (Denmark)

    Andersen, Ida Gran; Andersen, Simon Calmar

    2017-01-01

    educational inequality. We analyze whether the impact of student-centered instructional strategies on academic achievement differs for students with different socioeconomic backgrounds. Results suggest that a student-centered instructional strategy has a negative impact on academic achievement in general......, and for students with low parental education in particular. Our findings support the argument that the instructional strategy of schools is an important mechanism in generating educational inequality through the stratification of learning opportunities.......Research in the sociology of education argues that the educational system provides different learning opportunities for students with different socioeconomic backgrounds and that this circumstance makes the educational process an important institutional context for the reproduction of educational...

  19. Linking definitions, mechanisms, and modeling of drought-induced tree death.

    Science.gov (United States)

    Anderegg, William R L; Berry, Joseph A; Field, Christopher B

    2012-12-01

    Tree death from drought and heat stress is a critical and uncertain component in forest ecosystem responses to a changing climate. Recent research has illuminated how tree mortality is a complex cascade of changes involving interconnected plant systems over multiple timescales. Explicit consideration of the definitions, dynamics, and temporal and biological scales of tree mortality research can guide experimental and modeling approaches. In this review, we draw on the medical literature concerning human death to propose a water resource-based approach to tree mortality that considers the tree as a complex organism with a distinct growth strategy. This approach provides insight into mortality mechanisms at the tree and landscape scales and presents promising avenues into modeling tree death from drought and temperature stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Spared behavioral repetition effects in Alzheimer's disease linked to an altered neural mechanism at posterior cortex.

    Science.gov (United States)

    Broster, Lucas S; Li, Juan; Wagner, Benjamin; Smith, Charles D; Jicha, Gregory A; Schmitt, Frederick A; Munro, Nancy; Haney, Ryan H; Jiang, Yang

    2018-02-20

    Individuals with dementia of the Alzheimer type (AD) classically show disproportionate impairment in measures of working memory, but repetition learning effects are relatively preserved. As AD affects brain regions implicated in both working memory and repetition effects, the neural basis of this discrepancy is poorly understood. We hypothesized that the posterior repetition effect could account for this discrepancy due to the milder effects of AD at visual cortex. Participants with early AD, amnestic mild cognitive impairment (MCI), and healthy controls performed a working memory task with superimposed repetition effects while electroencephalography was collected to identify possible neural mechanisms of preserved repetition effects. Participants with AD showed preserved behavioral repetition effects and a change in the posterior repetition effect. Visual cortex may play a role in maintained repetition effects in persons with early AD.

  1. Linking governance mechanisms to health outcomes: a review of the literature in low- and middle-income countries.

    Science.gov (United States)

    Ciccone, Dana Karen; Vian, Taryn; Maurer, Lydia; Bradley, Elizabeth H

    2014-09-01

    We conducted a synthesis of peer-reviewed literature to shed light on links between governance mechanisms and health outcomes in low- and middle-income countries. Our review yielded 30 studies, highlighting four key governance mechanisms by which governance may influence health outcomes in these settings: Health system decentralization that enables responsiveness to local needs and values; health policymaking that aligns and empowers diverse stakeholders; enhanced community engagement; and strengthened social capital. Most, but not all, studies found a positive association between governance and health. Additionally, the nature of the association between governance mechanisms and health differed across studies. In some studies (N = 9), the governance effect was direct and positive, while in others (N = 5), the effect was indirect or modified by contextual factors. In still other studies (N = 4), governance was found to have a moderating effect, indicating that governance mechanisms influenced other system processes or structures that improved health. The remaining studies reported mixed findings about the association between governance and health (N = 6), no association between governance and health (N = 4), or had inconclusive results (N = 2). Further exploration is needed to fully understand the relationship between governance and health and to inform the design and delivery of evidence-based, effective governance interventions around the world. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Linking morphology and motion: a test of a four-bar mechanism in seahorses.

    Science.gov (United States)

    Roos, Gert; Leysen, Heleen; Van Wassenbergh, Sam; Herrel, Anthony; Jacobs, Patric; Dierick, Manuel; Aerts, Peter; Adriaens, Dominique

    2009-01-01

    Syngnathid fishes (seahorses, pipefish, and sea dragons) possess a highly modified cranium characterized by a long and tubular snout with minute jaws at its end. Previous studies indicated that these species are extremely fast suction feeders with their feeding strike characterized by a rapid elevation of the head accompanied by rotation of the hyoid. A planar four-bar model is proposed to explain the coupled motion of the neurocranium and the hyoid. Because neurocranial elevation as well as hyoid rotation are crucial for the feeding mechanism in previously studied Syngnathidae, a detailed evaluation of this model is needed. In this study, we present kinematic data of the feeding strike in the seahorse Hippocampus reidi. We combined these data with a detailed morphological analysis of the important linkages and joints involved in rotation of the neurocranium and the hyoid, and we compared the kinematic measurements with output of a theoretical four-bar model. The kinematic analysis shows that neurocranial rotation never preceded hyoid rotation, thus indicating that hyoid rotation triggers the explosive feeding strike. Our data suggest that while neurocranium and hyoid initially (first 1.5 ms) behave as predicted by the four-bar model, eventually, the hyoid rotation is underestimated by the model. Shortening, or a posterior displacement of the sternohyoid muscle (of which the posterior end is confluent with the hypaxial muscles in H. reidi), probably explains the discrepancy between the model and our kinematic measurements. As a result, while four-bar modeling indicates a clear coupling between hyoid rotation and neurocranial elevation, the detailed morphological determination of the linkages and joints of this four-bar model remain crucial in order to fully understand this mechanism in seahorse feeding.

  3. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

    Directory of Open Access Journals (Sweden)

    Joo Ho Lee

    2014-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

  4. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.

    Science.gov (United States)

    Lindqvist, Daniel; Epel, Elissa S; Mellon, Synthia H; Penninx, Brenda W; Révész, Dóra; Verhoeven, Josine E; Reus, Victor I; Lin, Jue; Mahan, Laura; Hough, Christina M; Rosser, Rebecca; Bersani, F Saverio; Blackburn, Elizabeth H; Wolkowitz, Owen M

    2015-08-01

    Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. A Summary of Pathways or Mechanisms Linking Preconception Maternal Nutrition with Birth Outcomes.

    Science.gov (United States)

    King, Janet C

    2016-07-01

    Population, human, animal, tissue, and molecular studies show collectively and consistently that maternal nutrition in the pre- or periconception period influences fetal growth and development, which subsequently affects the individual's long-term health. It is known that nutrition during pregnancy is an important determinant of the offspring's growth and health. However, now there is evidence that the mother's nutritional status at conception also influences pregnancy outcome and long-term health. For example, the mother's nutritional status at conception influences the way energy is partitioned between maternal and fetal needs. Furthermore, placental development during the first weeks of gestation reflects maternal nutrition and establishes mechanisms for balancing maternal and fetal nutritional needs. Also, maternal nutritional signals at fertilization influence epigenetic remodeling of fetal genes. These findings all indicate that maternal parenting begins before conception. The following papers from a symposium on preconception nutrition presented at the 2015 Scientific Sessions and Annual Meeting of the ASN emphasize the importance of maternal nutrition at conception on the growth and long-term health of the child. © 2016 American Society for Nutrition.

  6. The grand unified link between the Peccei-Quinn mechanism and the generation puzzle

    International Nuclear Information System (INIS)

    Davidson, A.; Wali, K.C.

    1982-03-01

    The essential ingredients of the Peccei-Quinn mechanism are shown to be dictated by a proper choice of a grand unification scheme. The presence of U(1)sub(PQ) gives rise to the possibility that the same physics which resolves the strong CP-violation problem may decode the generation puzzle with no extra cost. Multigenerational signatures of the invisible axion scenario, such as the canonical fermion mass matrix, are discussed. The uniqueness and the special values of the quantized PQ-assignments, namely 1,-3,5-7,... for successive generations, acquire an automatic explanation once the idea of ''horizontal compositeness'' is invoked. A characteristic feature then is that the muon appears to have a less complicated structure than the electron. Furthermore, U(1)sub(PQ) chooses SO(10) to be its only tenable gauge symmetry partner, and at the same time crucially restricts the associated Higgs system. All this finally results in a consistent fermion mass hierarchy with log m, to the crudest estimation, varying linearly with respect to the generation index. (author)

  7. Broken English, broken bones? Mechanisms linking language proficiency and occupational health in a Montreal garment factory.

    Science.gov (United States)

    Premji, Stéphanie; Messing, Karen; Lippel, Katherine

    2008-01-01

    Language barriers are often cited as a factor contributing to ethnic inequalities in occupational health; however, little information is available about the mechanisms at play. The authors describe the multiple ways in which language influences occupational health in a large garment factory employing many immigrants in Montreal. Between 2004 and 2006, individual, semi-structured interviews were conducted with 15 women and 10 men from 14 countries of birth. Interviews were conducted in French and English, Canada's official languages, as well as in non-official languages with the help of colleague-interpreters. Observation within the workplace was also carried out at various times during the project. The authors describe how proficiency in the official languages influences occupational health by affecting workers' ability to understand and communicate information, and supporting relationships that can affect work-related health. They also describe workers' strategies to address communication barriers and discuss the implications of these strategies from an occupational health standpoint. Along with the longer-term objectives of integrating immigrants into the linguistic majority and addressing structural conditions that can affect health, policies and practices need to be put in place to protect the health and well-being of those who face language barriers in the short term.

  8. Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

    Science.gov (United States)

    Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

    2013-01-01

    The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

  9. A case of hypoglycemiainduced QT prolongation leading to torsade de pointes and a review of pathophysiological mechanisms

    Directory of Open Access Journals (Sweden)

    Faris Hannoodi

    2017-06-01

    Full Text Available Torsades de pointes is a life-threatening cardiac arrhythmia. Occurrence of this arrhythmia as a result of hypoglycemia has not been reported in the literature. We describe an interesting case of an insulindependent diabetic patient presenting with torsades de pointes resulting from hypoglycemia. A 62-year-old male was admitted to the hospital following an episode of severe insulin-induced hypoglycemia and a cardiac arrest. He was found to unresponsive at home after taking insulin. His serum glucose was found to be 18. He was given juice initially to normalize his glucose and was then transferred by EMS to ER where he was given 5% dextrose infusion. Analysis of the LifeVest rhythm recording showed torsades de pointes that was terminated by defibrillation of the LifeVest. Several mechanisms are responsible for torsade, including QT interval prolongation, adrenalin secretion and calcium overload leading to intracellular calcium oscillations. These mechanisms are a trigger to torsade de pointes. Predisposing factors were present leading torsade to occur.

  10. Investigation of reaction mechanisms during electroreduction of carbon dioxide on lead electrode for the production of organic compounds

    International Nuclear Information System (INIS)

    Innocent, B.

    2008-09-01

    The aim of this work was to promote the reduction of CO 2 through its electrochemical conversion (electro-synthesis) on a lead electrode into high added value products. Depending on the nature of electrolyte, the electro-reduction of carbon dioxide leads to different products. Various electrolytes (aqueous or organic, protic or aprotic) were used to study two mechanisms: hydrogenation (formation of formate) and electro-dimerization (synthesis of oxalate). Cyclic voltammetry studies have been carried out for electrochemically characterizing CO 2 reduction on Pb. The electrochemical investigation of the electrode electrolyte interface has shown that the process of CO 2 electro-reduction is a mass transfer control both in the organic and aqueous media. Electrochemical experiments (cyclic voltammetry, chrono-amperometry) coupled with in situ infrared reflectance spectroscopic techniques (SPAIRS, SNIFTIRS) have also shown that in aqueous medium (7 ≤pH≤9) hydrogeno-carbonate ions were reduced to formate. The modification of solvent (propylene carbonate) leads selectively to oxalate as the main reaction product. Long-term electrolyses were performed in a filter-press cell to deal large volumes. In aqueous medium, the reduction of HCO 3 - to HCOO - (R F = 89% at -2.5 mA cm -2 and 4 C) is always accompanied by the production of H 2 . (author)

  11. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

    Science.gov (United States)

    Senba, Masachika; Mori, Naoki

    2012-10-02

    Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  12. Mechanisms of Staphylococcus epidermidis adhesion to model biomaterial surfaces: Establising a link between thrombosis and infection

    Science.gov (United States)

    Higashi, Julie Miyo

    Infections involving Staphylococcus epidermidis remain a life threatening complication associated with the use of polymer based cardiovascular devices. One of the critical steps in infection pathogenesis is the adhesion of the bacteria to the device surface. Currently, mechanisms of S. epidermidis adhesion are incompletely understood, but are thought to involve interactions between bacteria, device surface, and host blood elements in the form of adsorbed plasma proteins and surface adherent platelets. Our central hypothesis is that elements participating in thrombosis also promote S. epidermidis adhesion by specifically binding to the bacterial surface. The adhesion kinetics of S. epidermidis RP62A to host modified model biomaterial surface octadecyltrichlorosilane (OTS) under hydrodynamic shear conditions were characterized. Steady state adhesion to adsorbed proteins and surface adherent platelets was achieved at 90-120 minutes and 60-90 minutes, respectively. A dose response curve of S. epidermidis adhesion in the concentration range of 10sp7{-}10sp9 bac/mL resembled a multilayer adsorption isotherm. Increasing shear stress was found to LTA, and other LTA blocking agents significantly decreased S. epidermidis adhesion to the fibrin-platelet clots, suggesting that this interaction between S. epidermidis and fibrin-platelet clots is specific. Studies evaluated the adhesion of S. epidermidis to polymer immobilized heparin report conflicting results. Paulsson et al., showed that coagulase negative staphylococci adhered in comparable numbers to both immobilized heparin and nonheparinized surfaces, while exhibiting significantly greater adhesion to both surfaces than S. aureus. Preadsorption of the surfaces with specific heparin binding plasma proteins vitronectin, fibronectin, laminin, and collagen significantly increased adhesion. It was postulated that immobilized heparin contained binding sites for the plasma proteins, exposing bacteria binding domains of the

  13. Linking rapid magma reservoir assembly and eruption trigger mechanisms at evolved Yellowstone-type supervolcanoes

    Science.gov (United States)

    Wotzlaw, J.F.; Bindeman, I.N.; Watts, Kathryn E.; Schmitt, A.K.; Caricchi, L.; Schaltegger, U.

    2014-01-01

    reservoir configurations inferred from seismic data at active supervolcanoes. The connection of magma batches vertically distributed over several kilometers in the upper crust would cause a substantial increase of buoyancy overpressure, providing an eruption trigger mechanism that is the direct consequence of the reservoir assembly process.

  14. miR-199a Links MeCP2 with mTOR Signaling and Its Dysregulation Leads to Rett Syndrome Phenotypes

    Directory of Open Access Journals (Sweden)

    Keita Tsujimura

    2015-09-01

    Full Text Available Rett syndrome (RTT is a neurodevelopmental disorder caused by MECP2 mutations. Although emerging evidence suggests that MeCP2 deficiency is associated with dysregulation of mechanistic target of rapamycin (mTOR, which functions as a hub for various signaling pathways, the mechanism underlying this association and the molecular pathophysiology of RTT remain elusive. We show here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs as a component of the microprocessor Drosha complex. Among the MeCP2-regulated miRNAs, we found that miR-199a positively controls mTOR signaling by targeting inhibitors for mTOR signaling. miR-199a and its targets have opposite effects on mTOR activity, ameliorating and inducing RTT neuronal phenotypes, respectively. Furthermore, genetic deletion of miR-199a-2 led to a reduction of mTOR activity in the brain and recapitulated numerous RTT phenotypes in mice. Together, these findings establish miR-199a as a critical downstream target of MeCP2 in RTT pathogenesis by linking MeCP2 with mTOR signaling.

  15. Aging Mechanisms and Nondestructive Aging Indicator of Filled Cross-linked Polyethylene (XLPE) Exposed to Simultaneous Thermal and Gamma Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shuaishuai; Fifield, Leonard S.; Bowler, Nicola

    2018-04-11

    Aging mechanisms and a nondestructive aging indicator of filled cross-linked polyethylene (XLPE) cable insulation material used in nuclear power plants (NPPs) are studied. Using various material characterization techniques, likely candidates and functions for the main additives in a commercial filled-XLPE insulation material have been identified. These include decabromodiphenyl ether and Sb2O3 as flame retardants, ZnS as white pigment and polymerized 1,2-dihydro-2,2,4-trimethylquinoline as antioxidant. Gas chromatography-mass spectrometry, differential scanning calorimetry, oxidation induction time and measurements of dielectric loss tangent are utilized to monitor property changes as a function of thermal and radiation exposure of the cable material. Small-molecular-weight hydrocarbons are evolve with gamma radiation aging at 90 °C. The level of antioxidant decreases with aging by volatilization and chemical reaction with free radicals. Thermal aging at 90 °C for 25 days or less causes no observable change to the cross-linked polymer structure. Gamma radiation causes damage to crystalline polymer regions and introduces defects. Dielectric loss tangent is shown to be an effective and reliable nondestructive indicator of the aging severity of the filled-XLPE insulation material.

  16. Theory of the multiphoton cascade transitions with two photon links: comparison of quantum electrodynamical and quantum mechanical approaches

    International Nuclear Information System (INIS)

    Zalialiutdinov, T; Baukina, Yu; Solovyev, D; Labzowsky, L

    2014-01-01

    The theory of multiphoton cascade transitions with two-photon links is considered within two different approaches: quantum electrodynamical (QED) and phenomenological quantum mechanical (QM). A problem of regularization of the cascade contributions is investigated in detail. It is argued that the correct regularization should include both initial and intermediate level widths in the singular energy denominators. This result follows both from the QED and from the QM approach. Particular transitions nl → 1s + 2γ with nl = 3s, 4s, 3d, 4d and nl → 1s + 3γ with nl = 3p, 4p are considered as examples. The importance of the proper cascade regularization is also demonstrated. (paper)

  17. Does the concept of "sensitization" provide a plausible mechanism for the putative link between the environment and schizophrenia?

    Science.gov (United States)

    Collip, Dina; Myin-Germeys, Inez; Van Os, Jim

    2008-03-01

    Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as "sensitization," facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder.

  18. Effect of modified starch and nanoclay particles on biodegradability and mechanical properties of cross-linked poly lactic acid.

    Science.gov (United States)

    Shayan, M; Azizi, H; Ghasemi, I; Karrabi, M

    2015-06-25

    Mechanical properties and biodegradation of cross-linked poly(lactic acid) (PLA)/maleated thermoplastic starch (MTPS)/montmorillonite (MMT) nanocomposite were studied. Crosslinking was carried out by adding di-cumyl peroxide (DCP) in the presence of triallyl isocyanurate (TAIC) as coagent. At first, MTPS was prepared by grafting maleic anhydride (MA) to thermoplastic starch in internal mixer. Experimental design was performed by using Box-Behnken method at three variables: MTPS, nanoclay and TAIC at three levels. Results showed that increasing TAIC amount substantially increased the gel fraction, enhanced tensile strength, and caused a decrease in elongation at break. Biodegradation was prevented by increasing TAIC amount in nanocomposite. Increasing MTPS amount caused a slight increase in gel fraction and decreased the tensile strength of nanocomposite. Also, MTPS could increase the elongation at break of nanocomposite and improve the biodegradation. Nanoclay had no effect on the gel fraction, but it improved tensile strength. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Warfarin resistance associated with genetic polymorphism of VKORC1: linking clinical response to molecular mechanism using computational modeling.

    Science.gov (United States)

    Lewis, Benjamin C; Nair, Pramod C; Heran, Subash S; Somogyi, Andrew A; Bowden, Jeffrey J; Doogue, Matthew P; Miners, John O

    2016-01-01

    The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.

  20. Study of a Car Body Tilting System Using a Variable Link Mechanism: Fundamental Characteristics of Pendulum Motion and Strategy for Perfect Tilting

    Science.gov (United States)

    Yoshida, Hidehisa; Nagai, Masao

    This paper analyzes the fundamental dynamic characteristics of a tilting railway vehicle using a variable link mechanism for compensating both the lateral acceleration experienced by passengers and the wheel load imbalance between the inner and outer rails. The geometric relations between the center of rotation, the center of gravity, and the positions of all four links of the tilting system are analyzed. Then, equations of the pendulum motions of the railway vehicle body with a four-link mechanism are derived. A theoretically discussion is given on the geometrical shapes employed in the link mechanism that can simultaneously provide zero lateral acceleration and zero wheel load fluctuation. Then, the perfect tilting condition, which is the control target of the feedforward tilting control, is derived from the linear equation of tilting motion.

  1. Application of the IEUBK model for linking Children's blood lead with environmental exposure in a mining site, south China

    International Nuclear Information System (INIS)

    Zhang, Xin-Ying; Carpenter, David O.; Song, Yong-Jin; Chen, Ping; Qin, Yaoming; Wei, Ni-Yu; Lin, Shan-Chun

    2017-01-01

    This study consisted of a site- and age-specific investigation linking children's blood lead level (BLL) to environmental exposures in a historic mining site in south China. A total of 151 children, aged 3–7 years, were included in this study. The geometric mean (GM) BLL was 8.22 μg/dl, indicating an elevated BLL. The Integrated Exposure Uptake Bio-Kinetic (IEUBK) model has proven useful at many sites for study of routes of exposure. Application of the IEUBK model to these children indicated that the GM difference between observed and predicted BLL levels was only 1.07 μg/dl. It was found that the key environmental exposure pathway was soil/dust intake, which contributed 86.3% to the total risk. Younger children had higher BLL than did older children. Therefore, of the various low risk-high benefit solutions, interventions for the children living near the site should be focused on the dust removal and soil remediation. Implementation of the China Eco-village Construction Plan and China New Rural Reconstruction Movement of the government may be a better solution. - Highlights: • BLLs were measured in 151 children aged 3–7 years in a Chinese mining town. • Pb was measured in soil, dust, air, drinking water, home grown vegetables and meat. • IEUBK model predicted BLL was 9.29 μg/dL and observed BLL was 8.22 μg/dL. • Most important exposure pathway was soil/dust which contributed 86.3% of the risk. • Soil and dust remediation is recommended to reduce children's BLLs.

  2. Neuron-specific chromatin remodeling: a missing link in epigenetic mechanisms underlying synaptic plasticity, memory, and intellectual disability disorders.

    Science.gov (United States)

    Vogel-Ciernia, Annie; Wood, Marcelo A

    2014-05-01

    Long-term memory formation requires the coordinated regulation of gene expression. Until recently nucleosome remodeling, one of the major epigenetic mechanisms for controlling gene expression, had been largely unexplored in the field of neuroscience. Nucleosome remodeling is carried out by chromatin remodeling complexes (CRCs) that interact with DNA and histones to physically alter chromatin structure and ultimately regulate gene expression. Human exome sequencing and gene wide association studies have linked mutations in CRC subunits to intellectual disability disorders, autism spectrum disorder and schizophrenia. However, how mutations in CRC subunits were related to human cognitive disorders was unknown. There appears to be both developmental and adult specific roles for the neuron specific CRC nBAF (neuronal Brg1/hBrm Associated Factor). nBAF regulates gene expression required for dendritic arborization during development, and in the adult, contributes to long-term potentiation, a form of synaptic plasticity, and long-term memory. We propose that the nBAF complex is a novel epigenetic mechanism for regulating transcription required for long-lasting forms of synaptic plasticity and memory processes and that impaired nBAF function may result in human cognitive disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Ultra-high mechanical properties of porous composites based on regenerated cellulose and cross-linked poly(ethylene glycol).

    Science.gov (United States)

    Teng, Jian; Yang, Biao; Zhang, Liang-Qing; Lin, Sheng-Qiang; Xu, Ling; Zhong, Gan-Ji; Tang, Jian-Hua; Li, Zhong-Ming

    2018-01-01

    The ultra-high mechanical, biocompatible and biodegradable porous regenerated cellulose/poly(ethylene glycol) (RC/PEG) composites with double network structure were fabricated via an simple method to dissolve cellulose followed by UV irradiation. The porous structure of RC/PEG was sensitively altered by PEG contents, which led to the porous structure morphology transition from 3D fibrillar network to close-grained sheet-like-network with the loading of cross-linked PEG. The porous RC/PEG showed excellent mechanical properties, i.e., the compressive strength can reach 33 times higher than that of neat RC (0.07MPa) at the compressive strain of 30%. Porous RC/PEG also displayed outstanding properties with openly porous structure and structural stabilization. Besides, porous RC/PEG exhibited good water absorbency, which the water absorbency ratio at equilibrium state was 83% higher than that of porous RC. This work provides an environmentally friendly and simple pathway to prepare non-toxic and biocompatible porous regenerated cellulose-based composites with high strength, structural stabilization and good water absorbency, which could be useful for packaging, biomedical applications, sewage purification, etc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Social thermoregulation as a potential mechanism linking sociality and fitness: Barbary macaques with more social partners form larger huddles.

    Science.gov (United States)

    Campbell, Liz A D; Tkaczynski, Patrick J; Lehmann, Julia; Mouna, Mohamed; Majolo, Bonaventura

    2018-04-17

    Individuals with more or stronger social bonds experience enhanced survival and reproduction in various species, though the mechanisms mediating these effects are unclear. Social thermoregulation is a common behaviour across many species which reduces cold stress exposure, body heat loss, and homeostatic energy costs, allowing greater energetic investment in growth, reproduction, and survival, with larger aggregations providing greater benefits. If more social individuals form larger thermoregulation aggregations due to having more potential partners, this would provide a direct link between sociality and fitness. We conducted the first test of this hypothesis by studying social relationships and winter sleeping huddles in wild Barbary macaques (Macaca sylvanus), wherein individuals with more social partners experience greater probability of winter survival. Precipitation and low temperature increased huddle sizes, supporting previous research that huddle size influences thermoregulation and energetics. Huddling relationships were predicted by social (grooming) relationships. Individuals with more social partners therefore formed larger huddles, suggesting reduced energy expenditure and exposure to environmental stressors than less social individuals, potentially explaining how sociality affects survival in this population. This is the first evidence that social thermoregulation may be a direct proximate mechanism by which increased sociality enhances fitness, which may be widely applicable across taxa.

  5. In and out of control: brain mechanisms linking fluency of action selection to self-agency in patients with schizophrenia.

    Science.gov (United States)

    Voss, Martin; Chambon, Valérian; Wenke, Dorit; Kühn, Simone; Haggard, Patrick

    2017-08-01

    Sense of agency refers to the feeling of control over one's actions, and their consequences. It involves both predictive processes linked to action control, and retrospective 'sense-making' causal inferences. Schizophrenia has been associated with impaired predictive processing, but the underlying mechanisms that impair patients' sense of agency remain unclear. We introduce a new 'prospective' aspect of agency and show that subliminally priming an action not only influences response times, but also influences reported sense of agency over subsequent action outcomes. This effect of priming was associated with altered connectivity between frontal areas and the angular gyrus. The effects on response times and on frontal action selection mechanisms were similar in patients with schizophrenia and in healthy volunteers. However, patients showed no effects of priming on sense of agency, no priming-related activation of angular gyrus, and no priming-related changes in fronto-parietal connectivity. We suggest angular gyrus activation reflects the experiences of agency, or non-agency, in part by processing action selection signals generated in the frontal lobes. The altered action awareness that characterizes schizophrenia may be due to impaired communication between these areas. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Converging evolution leads to near maximal junction diversity through parallel mechanisms in B and T cell receptors

    Science.gov (United States)

    Benichou, Jennifer I. C.; van Heijst, Jeroen W. J.; Glanville, Jacob; Louzoun, Yoram

    2017-08-01

    T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question emerges as to whether they can produce a diverse CDR3 repertoire. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large-scale sequencing are required. Such a diversity method should incorporate the complex diversification mechanisms of the adaptive immune response and the BCR and TCR loci structure. We combined large-scale sequencing and diversity measures to show that TCRs have a near maximal CDR3 genetic diversity. Specifically, TCR have a larger junctional and V germline diversity, which starts more 5‧ in Vβ than BCRs. Selection decreases the TCR repertoire diversity, but does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire, with a biased CDR3 length toward short TCRs and long BCRs. These differences suggest parallel converging evolutionary tracks to reach the required diversity to avoid holes in the CDR3 repertoire.

  7. The cytotoxicity of the α1-adrenoceptor antagonist prazosin is linked to an endocytotic mechanism equivalent to transport-P

    International Nuclear Information System (INIS)

    Fuchs, Robert; Stracke, Anika; Ebner, Nadine; Zeller, Christian Wolfgang; Raninger, Anna Maria; Schittmayer, Matthias; Kueznik, Tatjana; Absenger-Novak, Markus; Birner-Gruenberger, Ruth

    2015-01-01

    Since the α1-adrenergic antagonist prazosin (PRZ) was introduced into medicine as a treatment for hypertension and benign prostate hyperplasia, several studies have shown that PRZ induces apoptosis in various cell types and interferes with endocytotic trafficking. Because PRZ is also able to induce apoptosis in malignant cells, its cytotoxicity is a focus of interest in cancer research. Besides inducing apoptosis, PRZ was shown to serve as a substrate for an amine uptake mechanism originally discovered in neurones called transport-P. In line with our hypothesis that transport-P is an endocytotic mechanism also present in non-neuronal tissue and linked to the cytotoxicity of PRZ, we tested the uptake of QAPB, a fluorescent derivative of PRZ, in cancer cell lines in the presence of inhibitors of transport-P and endocytosis. Early endosomes and lysosomes were visualised by expression of RAB5-RFP and LAMP1-RFP, respectively; growth and viability of cells in the presence of PRZ and uptake inhibitors were also tested. Cancer cells showed co-localisation of QAPB with RAB5 and LAMP1 positive vesicles as well as tubulation of lysosomes. The uptake of QAPB was sensitive to transport-P inhibitors bafilomycin A1 (inhibits v-ATPase) and the antidepressant desipramine. Endocytosis inhibitors pitstop ® 2 (general inhibitor of endocytosis), dynasore (dynamin inhibitor) and methyl-β-cyclodextrin (cholesterol chelator) inhibited the uptake of QAPB. Bafilomycin A1 and methyl-β-cyclodextrin but not desipramine were able to preserve growth and viability of cells in the presence of PRZ. In summary, we confirmed the hypothesis that the cellular uptake of QAPB/PRZ represents an endocytotic mechanism equivalent to transport-P. Endocytosis of QAPB/PRZ depends on a proton gradient, dynamin and cholesterol, and results in reorganisation of the LAMP1 positive endolysosomal system. Finally, the link seen between the cellular uptake of PRZ and cell death implies a still unknown pro

  8. Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome

    Science.gov (United States)

    Quartier, Angélique; Poquet, Hélène; Gilbert-Dussardier, Brigitte; Rossi, Massimiliano; Casteleyn, Anne-Sophie; Portes, Vincent des; Feger, Claire; Nourisson, Elsa; Kuentz, Paul; Redin, Claire; Thevenon, Julien; Mosca-Boidron, Anne-Laure; Callier, Patrick; Muller, Jean; Lesca, Gaetan; Huet, Frédéric; Geoffroy, Véronique; El Chehadeh, Salima; Jung, Matthieu; Trojak, Benoit; Le Gras, Stéphanie; Lehalle, Daphné; Jost, Bernard; Maury, Stéphanie; Masurel, Alice; Edery, Patrick; Thauvin-Robinet, Christel; Gérard, Bénédicte; Mandel, Jean-Louis; Faivre, Laurence; Piton, Amélie

    2017-01-01

    Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5′-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman's scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up. PMID:28176767

  9. A Poroelasticity Theory Approach to Study the Mechanisms Leading to Elevated Interstitial Fluid Pressure in Solid Tumours.

    Science.gov (United States)

    Burazin, Andrijana; Drapaca, Corina S; Tenti, Giuseppe; Sivaloganathan, Siv

    2018-05-01

    Although the mechanisms responsible for elevated interstitial fluid pressure (IFP) in tumours remain obscure, it seems clear that high IFP represents a barrier to drug delivery (since the resulting adverse pressure gradient implies a reduction in the driving force for transvascular exchange of both fluid and macromolecules). R. Jain and co-workers studied this problem, and although the conclusions drawn from their idealized mathematical models offered useful insights into the causes of elevated IFP, they by no means gave a definitive explanation for this phenomenon. In this paper, we use poroelasticity theory to also develop a macroscopic mathematical model to describe the time evolution of a solid tumour, but focus our attention on the mechanisms responsible for the rise of the IFP, from that for a healthy interstitium to that measured in malignant tumours. In particular, we discuss a number of possible time scales suggested by our mathematical model and propose a tumour-dependent time scale that leads to results in agreement with experimental observations. We apply our mathematical model to simulate the effect of "vascular normalization" (as proposed by Jain in Nat Med 7:987-989, 2001) on the IFP profile and discuss and contrast our conclusions with those of previous work in the literature.

  10. Mechanisms of plastic deformation in highly cross-linked UHMWPE for total hip components--the molecular physics viewpoint.

    Science.gov (United States)

    Takahashi, Yasuhito; Shishido, Takaaki; Yamamoto, Kengo; Masaoka, Toshinori; Kubo, Kosuke; Tateiwa, Toshiyuki; Pezzotti, Giuseppe

    2015-02-01

    Plastic deformation is an unavoidable event in biomedical polymeric implants for load-bearing application during long-term in-vivo service life, which involves a mass transfer process, irreversible chain motion, and molecular reorganization. Deformation-induced microstructural alterations greatly affect mechanical properties and durability of implant devices. The present research focused on evaluating, from a molecular physics viewpoint, the impact of externally applied strain (or stress) in ultra-high molecular weight polyethylene (UHMWPE) prostheses, subjected to radiation cross-linking and subsequent remelting for application in total hip arthroplasty (THA). Two different types of commercial acetabular liners, which belong to the first-generation highly cross-linked UHMWPE (HXLPE), were investigated by means of confocal/polarized Raman microprobe spectroscopy. The amount of crystalline region and the spatial distribution of molecular chain orientation were quantitatively analyzed according to a combined theory including Raman selection rules for the polyethylene orthorhombic structure and the orientation distribution function (ODF) statistical approach. The structurally important finding was that pronounced recrystallization and molecular reorientation increasingly appeared in the near-surface regions of HXLPE liners with increasing the amount of plastic (compressive) deformation stored in the microstructure. Such molecular rearrangements, occurred in response to external strains, locally increase surface cross-shear (CS) stresses, which in turn trigger microscopic wear processes in HXLPE acetabular liners. Thus, on the basis of the results obtained at the molecular scale, we emphasize here the importance of minimizing the development of irrecoverable deformation strain in order to retain the pristine and intrinsically high wear performance of HXLPE components. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Insights into the Mechanism of a Covalently Linked Organic Dye-Cobaloxime Catalyst System for Dye-Sensitized Solar Fuel Devices.

    Science.gov (United States)

    Pati, Palas Baran; Zhang, Lei; Philippe, Bertrand; Fernández-Terán, Ricardo; Ahmadi, Sareh; Tian, Lei; Rensmo, Håkan; Hammarström, Leif; Tian, Haining

    2017-06-09

    A covalently linked organic dye-cobaloxime catalyst system based on mesoporous NiO is synthesized by a facile click reaction for mechanistic studies and application in a dye-sensitized solar fuel device. The system is systematically investigated by photoelectrochemical measurements, density functional theory, time-resolved fluorescence, transient absorption spectroscopy, and photoelectron spectroscopy. The results show that irradiation of the dye-catalyst on NiO leads to ultrafast hole injection into NiO from the excited dye, followed by a fast electron transfer process to reduce the catalyst. Moreover, the dye adopts different structures with different excited state energies, and excitation energy transfer occurs between neighboring molecules on the semiconductor surface. The photoelectrochemical experiments also show hydrogen production by this system. The axial chloride ligands of the catalyst are released during photocatalysis to create the active sites for proton reduction. A working mechanism of the dye-catalyst system on the photocathode is proposed on the basis of this study. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  12. Interconnection of thermal parameters, microstructure and mechanical properties in directionally solidified Sn–Sb lead-free solder alloys

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Marcelino; Costa, Thiago [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil); Rocha, Otávio [Federal Institute of Education, Science and Technology of Pará — IFPA, 66093-020 Belém, PA (Brazil); Spinelli, José E. [Department of Materials Engineering, Federal University of São Carlos — UFSCar, 13565-905 São Carlos, SP (Brazil); Cheung, Noé, E-mail: cheung@fem.unicamp.br [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil); Garcia, Amauri [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil)

    2015-08-15

    Considerable effort is being made to develop lead-free solders for assembling in environmental-conscious electronics, due to the inherent toxicity of Pb. The search for substitute alloys of Pb–Sn solders has increased in order to comply with different soldering purposes. The solder must not only meet the expected levels of electrical performance but may also have appropriate mechanical strength, with the absence of cracks in the solder joints. The Sn–Sb alloy system has a range of compositions that can be potentially included in the class of high temperature solders. This study aims to establish interrelations of solidification thermal parameters, microstructure and mechanical properties of Sn–Sb alloys (2 wt.%Sb and 5.5 wt.%Sb) samples, which were directionally solidified under cooling rates similar to those of reflow procedures in industrial practice. A complete high-cooling rate cellular growth is shown to be associated with the Sn–2.0 wt.%Sb alloy and a reverse dendrite-to-cell transition is observed for the Sn–5.5 wt.%Sb alloy. Strength and ductility of the Sn–2.0 wt.%Sb alloy are shown not to be affected by the cellular spacing. On the other hand, a considerable variation in these properties is associated with the cellular region of the Sn–5.5 wt.%Sb alloy casting. - Graphical abstract: Display Omitted - Highlights: • The microstructure of the Sn–2 wt.%Sb alloy is characterized by high-cooling rates cells. • Reverse dendrite > cell transition occurs for Sn–5.5 wt.%Sb alloy: cells prevail for cooling rates > 1.2 K/s. • Sn–5.5 wt.%Sb alloy: the dendritic region occurs for cooling rates < 0.9 K/s. • Sn–5.5 wt.%Sb alloy: tensile properties are improved with decreasing cellular spacing.

  13. Preliminary treatment of chlorinated streams containing fission products: mechanisms leading to crystalline phases in molten chloride media

    International Nuclear Information System (INIS)

    Hudry, D.

    2008-10-01

    The world of the nuclear power gets ready for profound modifications so that 'the atom' can aspire in conformance with long-lasting energy: it is what we call the development of generation IV nuclear systems. So, the new pyrochemical separation processes for the spent fuel reprocessing are currently being investigated. Techniques in molten chloride media generate an ultimate flow (with high chlorine content) which cannot be incorporated in conventional glass matrices. This flow is entirely water-soluble and must be conditioned in a chemical form which is compatible with a long-term disposal. This work of thesis consists in studying new ways for the management of the chlorinated streams loaded with fission products (FP). To do it, a strategy of selective FP extraction via the in situ formation of crystalline phases was retained. The possibility of extracting rare earths in the eutectic LiCl-KCl was demonstrated via the development of a new way of synthesis of rare earth phosphates (TRPO 4 ). As regards alkaline earths, the conversion of strontium and barium chlorides to the corresponding tungstates or molybdates was studied in different solvents. Mechanisms leading to the crystalline phases in molten chloride media were studied via the coupling of NMR and XRD techniques. First of all, it has been shown that these mechanisms are dependent on the stability of the used precursors. So in the case of the formation of rare earth phosphates the solvent is chemically active. On the other hand, in the case of the formation of alkaline earth tungstates it would seem that the solvent plays the role of structuring agent which can control the ability to react of chlorides. (author)

  14. A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    O Schätti

    2011-10-01

    Full Text Available ere is great interest in how bone marrow derived stem cells make fate decisions. Numerous studies have investigated the role of individual growth factors on mesenchymal stem cell differentiation, leading to protocols for cartilage, bone and adipose tissue. However, these protocols overlook the role of biomechanics on stem cell differentiation. There have been various studies that have applied mechanical stimulation to constructs containing mesenchymal stem cells, with varying degrees of success. One critical fate decision is that between cartilage and bone. Articular motion is a combination of compressive, tensile and shear deformations; therefore, one can presume that compression alone is unlikely to be a sufficient mechanical signal to generate a cartilage-like tissue in vitro. Within this study, we aimed to determine the role of shear on the fate of stem cell differentiation. Specifically, we investigated the potential enhancing effect of surface shear, superimposed on cyclic axial compression, on chondrogenic differentiation of human bone marrow-derived stem cells. Using a custom built loading device we applied compression, shear or a combination of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded, while no exogenous growth-factors were added to the culture medium. Both compression or shear alone was insufficient for the chondrogenic induction of human mesenchymal stem cells. However, the application of shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression. Histological analysis detected sulphated glycosaminoglycan and collagen II only in the compression and shear group. The results obtained may provide insight into post-operative care after cell therapy involving mesenchymal stromal cells.

  15. SO2 photoexcitation mechanism links mass-independent sulfur isotopic fractionation in cryospheric sulfate to climate impacting volcanism

    Science.gov (United States)

    Hattori, Shohei; Schmidt, Johan A.; Johnson, Matthew S.; Danielache, Sebastian O.; Yamada, Akinori; Ueno, Yuichiro; Yoshida, Naohiro

    2013-01-01

    Natural climate variation, such as that caused by volcanoes, is the basis for identifying anthropogenic climate change. However, knowledge of the history of volcanic activity is inadequate, particularly concerning the explosivity of specific events. Some material is deposited in ice cores, but the concentration of glacial sulfate does not distinguish between tropospheric and stratospheric eruptions. Stable sulfur isotope abundances contain additional information, and recent studies show a correlation between volcanic plumes that reach the stratosphere and mass-independent anomalies in sulfur isotopes in glacial sulfate. We describe a mechanism, photoexcitation of SO2, that links the two, yielding a useful metric of the explosivity of historic volcanic events. A plume model of S(IV) to S(VI) conversion was constructed including photochemistry, entrainment of background air, and sulfate deposition. Isotopologue-specific photoexcitation rates were calculated based on the UV absorption cross-sections of 32SO2, 33SO2, 34SO2, and 36SO2 from 250 to 320 nm. The model shows that UV photoexcitation is enhanced with altitude, whereas mass-dependent oxidation, such as SO2 + OH, is suppressed by in situ plume chemistry, allowing the production and preservation of a mass-independent sulfur isotope anomaly in the sulfate product. The model accounts for the amplitude, phases, and time development of Δ33S/δ34S and Δ36S/Δ33S found in glacial samples. We are able to identify the process controlling mass-independent sulfur isotope anomalies in the modern atmosphere. This mechanism is the basis of identifying the magnitude of historic volcanic events. PMID:23417298

  16. Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

    Science.gov (United States)

    Hasan, Djo; Blankman, Paul; Nieman, Gary F

    2017-09-01

    Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis.

  17. Characterization of Mechanical Properties of MgB$_2$ Conductor for the Superconducting Link Project at CERN

    CERN Document Server

    Sugano, M; Bartova, B; Bjoerstad, R; Scheuerlein, C; Grasso, G

    2015-01-01

    In the framework of high luminosity upgrade of Large Hadron Collider at CERN, superconducting links are being developed. MgB2 wire is a candidate conductor for use in high-current cables. Mechanical properties of this material are of key importance for the definition of the cable design and operating conditions. In this study, we evaluated the Young's modulus of MgB2 filaments extracted from ex situ processed composite wires. The wires were produced in unit lengths of about 1 km and used in high-current cables. Single fiber tensile test was carried out on filaments composed of MgB2, Nb barrier, and Nb-Ni reaction layer. From the unloading modulus of filament specimens measured with different gauge lengths, the Young's modulus of composite filaments extracted from two different strands was determined to be 114 and 122 GPa at room temperature, respectively. By using the rule-of-mixture, the Young's modulus of MgB2 was estimated to be lower than that reported for highly dense MgB2 bulks. The reason for such diff...

  18. Plant polyphenols mobilize nuclear copper in human peripheral lymphocytes leading to oxidatively generated DNA breakage: implications for an anticancer mechanism.

    Science.gov (United States)

    Shamim, Uzma; Hanif, Sarmad; Ullah, M F; Azmi, Asfar S; Bhat, Showket H; Hadi, S M

    2008-08-01

    It was earlier proposed that an important anti-cancer mechanism of plant polyphenols may involve mobilization of endogenous copper ions, possibly chromatin-bound copper and the consequent pro-oxidant action. This paper shows that plant polyphenols are able to mobilize nuclear copper in human lymphocytes, leading to degradation of cellular DNA. A cellular system of lymphocytes isolated from human peripheral blood and comet assay was used for this purpose. Incubation of lymphocytes with neocuproine (a cell membrane permeable copper chelator) inhibited DNA degradation in intact lymphocytes. Bathocuproine, which is unable to permeate through the cell membrane, did not cause such inhibition. This study has further shown that polyphenols are able to degrade DNA in cell nuclei and that such DNA degradation is inhibited by neocuproine as well as bathocuproine (both of which are able to permeate the nuclear pore complex), suggesting that nuclear copper is mobilized in this reaction. Pre-incubation of lymphocyte nuclei with polyphenols indicates that it is capable of traversing the nuclear membrane. This study has also shown that polyphenols generate oxidative stress in lymphocyte nuclei which is inhibited by scavengers of reactive oxygen species (ROS) and neocuproine. These results indicate that the generation of ROS occurs through mobilization of nuclear copper resulting in oxidatively generated DNA breakage.

  19. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    Directory of Open Access Journals (Sweden)

    Spanswick Victoria J

    2012-09-01

    Full Text Available Abstract Background DNA interstrand cross-links (ICLs are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma and solid tumours (ovarian cancer that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Methods Using a modification of the single cell gel electrophoresis (Comet assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Results Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The

  20. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    International Nuclear Information System (INIS)

    Spanswick, Victoria J; Hartley, John A; Lowe, Helen L; Newton, Claire; Bingham, John P; Bagnobianchi, Alessia; Kiakos, Konstantinos; Craddock, Charles; Ledermann, Jonathan A; Hochhauser, Daniel

    2012-01-01

    DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line

  1. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    OpenAIRE

    McMahon, Laura W.; Zhang, Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellu...

  2. Structure and mechanism leading to formation of the cysteine sulfinate product complex of a biomimetic cysteine dioxygenase model.

    Science.gov (United States)

    Sallmann, Madleen; Kumar, Suresh; Chernev, Petko; Nehrkorn, Joscha; Schnegg, Alexander; Kumar, Devesh; Dau, Holger; Limberg, Christian; de Visser, Sam P

    2015-05-11

    Cysteine dioxygenase is a unique nonheme iron enzyme that is involved in the metabolism of cysteine in the body. It contains an iron active site with an unusual 3-His ligation to the protein, which contrasts with the structural features of common nonheme iron dioxygenases. Recently, some of us reported a truly biomimetic model for this enzyme, namely a trispyrazolylborato iron(II) cysteinato complex, which not only has a structure very similar to the enzyme-substrate complex but also represents a functional model: Treatment of the model with dioxygen leads to cysteine dioxygenation, as shown by isolating the cysteine part of the product in the course of the work-up. However, little is known on the conversion mechanism and, so far, not even the structure of the actual product complex had been characterised, which is also unknown in case of the enzyme. In a multidisciplinary approach including density functional theory calculations and X-ray absorption spectroscopy, we have now determined the structure of the actual sulfinato complex for the first time. The Cys-SO2 (-) functional group was found to be bound in an η(2) -O,O-coordination mode, which, based on the excellent resemblance between model and enzyme, also provides the first support for a corresponding binding mode within the enzymatic product complex. Indeed, this is again confirmed by theory, which had predicted a η(2) -O,O-binding mode for synthetic as well as the natural enzyme. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Diminished alternative reinforcement as a mechanism linking conduct problems and substance use in adolescence: a longitudinal examination.

    Science.gov (United States)

    Khoddam, Rubin; Cho, Junhan; Jackson, Nicholas J; Leventhal, Adam M

    2018-06-01

    To determine whether diminished alternative reinforcement (i.e. engagement and enjoyment from substance-free activities) mediated the longitudinal association of conduct problems with substance use in early-mid-adolescence. Structural equation modeling tested whether the association between wave 1 (baseline) conduct problems and wave 3 (24-month follow-up) substance use outcomes was mediated by diminished alternative reinforcement at wave 2 (12-month follow-up). Additional analyses tested whether sex and socio-economic status moderated this association. Ten high schools in Los Angeles, CA, USA, 2013-15. Students (n = 3396, 53.5% female, mean [standard deviation (SD)] age at wave 1 baseline = 14.1 (0.42) years). Self-reported conduct problems (11-item questionnaire), alternative reinforcement (44-item questionnaire) and use of alcohol, marijuana and combustible cigarettes during the past 6 months (yes/no) and the past 30 days (nine-level ordinal response based on days used in past 30 days). Significant associations of wave 1 conduct problems with wave 3 marijuana use during the past 6 months (β = 0.25) and past 30 days (β = 0.26) were mediated by wave 2 diminished alternative reinforcement (β indirect effect : 6 months = 0.013, 30 days = 0.017, Ps alternative reinforcement. All associations did not differ by sex and socio-economic status. Diminished alternative reinforcement may be a modifiable mechanism linking early adolescent conduct problems and subsequent marijuana use that could be targeted in prevention programs to offset the adverse health and social sequelae associated with comorbid conduct problems and marijuana use in early-mid adolescence. © 2018 Society for the Study of Addiction.

  4. Synthetic Biodegradable Hydrogels with Excellent Mechanical Properties and Good Cell Adhesion Characteristics Obtained by the Combinatorial Synthesis of Photo-Cross-Linked Networks

    NARCIS (Netherlands)

    Zant, Erwin; Grijpma, Dirk W.

    Major drawbacks of synthetic hydrogels are their poor mechanical properties and their limited ability to allow cell attachment and proliferation. By photo-cross-linking mixtures of dimethacrylate-functionalized oligomers (macromers) in a combinatorial manner in solution, synthetic hydrogels with

  5. Microscale failure mechanisms leading to internal short circuit in Li-ion batteries under complex loading scenarios

    NARCIS (Netherlands)

    Sahraei, E.; Bosco, E.; Dixon, B.; Lai, B.

    2016-01-01

    One of the least understood mechanisms of Li-ion batteries is the development of internal short circuits under mechanical loads. In this study, a micro mechanical model is developed and subjected to various loading scenarios to understand the sequence of failure in the multi-layer, multi-material

  6. Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait.

    Science.gov (United States)

    Goji, Katsumi; Ozaki, Kayo; Sadewa, Ahmad H; Nishio, Hisahide; Matsuo, Masafumi

    2006-02-01

    Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively. The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance. We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait. Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation. Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.

  7. Researchers Find a Mechanism for Schizophrenia

    Science.gov (United States)

    ... issue Health Capsule Researchers Find a Mechanism for Schizophrenia En español Send us your comments Scientists uncovered a mechanism behind genetic variations previously linked to schizophrenia. The findings may lead to new clinical approaches. ...

  8. Thermal optimum analyses and mechanical design of 10-kA, vapor-cooled power leads for SSC superconducting magnet tests at MTL

    International Nuclear Information System (INIS)

    Shu, Q.S.; Demko, J.; Dorman, R.; Finan, D.; Hatfield, D.; Syromyatnikov, I.; Zolotov, A.; Mazur, P.; Peterson, T.

    1992-08-01

    The spiral-fin, 10-kA, helium vapor-cooled power leads have been designed for Superconducting Super Collider superconducting magnet tests at the Magnet Test Laboratory. In order to thermally optimize the parameters of the power leads, the lead diameters-which minimize the Carnot work for several different lengths, two different fin geometries, and two RRR values of the lead materials-were determined. The cryogenic refrigeration and liquefaction loads for supporting the leads have also been calculated. The optimum operational condition with different currents is discussed. An improved mechanical design of the 10-kA power leads was undertaken, with careful consideration of the cryogenic and mechanical performance. In the design, a new thermal barrier device to reduce heat conduction from the vacuum and gas seal area was employed. Therefore, the electric insulation assembly, which isolates the ground potential parts of the lead from the high-power parts, was moved into a warm region in order to prevent vacuum and helium leakage in the 0-ring seals due to transient cold temperature. The instrumentation for testing the power leads is also discussed

  9. Increased extracellular and intracellular Ca{sup 2+} lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp [Juntendo University Faculty of International Liberal Arts, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Miyamoto, Yuki [Juntendo University Faculty of Health Care and Nursing, Takasu 2-5-1, Urayasu-shi, Chiba 279-0023 (Japan); Itoh, Seigo; Daida, Hiroyuki [Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Nakazato, Yuji [Center for Environmental Research, Department of Cardiology, Juntendo University Faculty of Medicine Urayasu Hospital, Tomioka 2-1-1, Urayasu-shi, Chiba 279-0022 (Japan); Okada, Takao [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2015-02-20

    Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub o} and [Ca{sup 2+}]{sub i}) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation, which suggested that increases in [Ca{sup 2+}]{sub o} caused by bone resorption may accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca{sup 2+}]{sub i} (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca{sup 2+}]{sub o} (addition of CaCl{sub 2}) leads to increases in [Ca{sup 2+}]{sub i}. Flow cytometric methods revealed that high [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK independently of intracellular Ca{sup 2+}. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca{sup 2+} provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca{sup 2+}, which results in BMSC proliferation. - Highlights:

  10. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    OpenAIRE

    Ming W. Chou; Ge Lin; Qingsu Xia; Peter P. Fu

    2002-01-01

    Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP)-derived DNA adduct formation. This mechanism may ...

  11. Why Seedlings Die: Linking Carbon and Water Limitations to Mechanisms of Mortality During Establishment in Conifer Seedlings

    Science.gov (United States)

    Reinhardt, K.; Germino, M. J.; Kueppers, L. M.; Mitton, J.; Castanha, C.

    2012-12-01

    BACKGROUND Recent ecophysiological studies aimed at explaining adult tree mortality during drought have examined the carbon (C)-exhaustion compared to the hydraulic-failure hypotheses for death. Prolonged drought leads to durations of stomatal closure (and thus limited C gain), which could result in long periods of negative C balance and fatal reductions in whole-plant C reserves (i.e., available non-structural carbohydrates ["NSC"]). Alternatively, C reserves may not decrease much but could become increasingly inaccessible to sink tissues in long dry-periods due to impediments to translocation of photosynthate (e.g., through disruption of hydrostatic pressure flow in phloem). As C reserves decline or become inaccessible, continued maintenance respiration has been hypothesized to lead to exhaustion of NSC after extended durations of drought, especially in isohydric plant species. On the other hand, hydraulic failure (e.g., catastrophic xylem embolisms) during drought may be the proximate cause of death, occurring before true C starvation occurs. Few studies have investigated specifically the mechanism(s) of tree death, and no published studies that we know of have quantified changes in NSC during mortality. EXPERIMENTAL DESIGN AND HYPOTHESES We conducted two studies that investigated whole-tree and tissue-specific C relations (photosynthetic C gain, respiration, dry-mass gain, and NSC pools) in Pinus flexilis seedlings during the initial establishment phase, which is characterized by progressive drought during summer. We measured survival, growth and biomass allocation, and C-balance physiology (photosynthetic C-gain and chlorophyll fluorescence, respiration C-use, and NSC concentrations) from germination to mortality. We hypothesized that 1) stomatal and biochemical limitations to C gain would constrain seedling survival (through inadequate seasonal C-balance), as has been shown for conifer seedlings near alpine treeline; 2) hydraulic constraints (embolisms and

  12. Understanding the mechanisms of zinc bacitracin and avilamycin on animal production: linking gut microbiota and growth performance in chickens.

    Science.gov (United States)

    Crisol-Martínez, Eduardo; Stanley, Dragana; Geier, Mark S; Hughes, Robert J; Moore, Robert J

    2017-06-01

    Unravelling the mechanisms of how antibiotics influence growth performance through changes in gut microbiota can lead to the identification of highly productive microbiota in animal production. Here we investigated the effect of zinc bacitracin and avilamycin on growth performance and caecal microbiota in chickens and analysed associations between individual bacteria and growth performance. Two trials were undertaken; each used 96 individually caged 15-day-old Cobb broilers. Trial 1 had a control group (n = 48) and a zinc bacitracin (50 ppm) treatment group (n = 48). Trial 2 had a control group (n = 48) and an avilamycin (15 ppm) treatment group (n = 48). Chicken growth performance was evaluated over a 10-day period, and caecal microbiota was characterised by sequencing of bacterial 16S rRNA gene amplicons. Avilamycin produced no effect on growth performance and exhibited little significant disturbance of the microbiota structure. However, zinc bacitracin reduced the feed conversion ratio (FCR) in treated birds, changed the composition and increased the diversity of their caecal microbiota by reducing dominant species. Avilamycin only produced minor reductions in the abundance of two microbial taxa, whereas zinc bacitracin produced relatively large shifts in a number of taxa, primarily Lactobacillus species. Also, a number of phylotypes closely related to lactobacilli species were positively or negatively correlated with FCR values, suggesting contrasting effects of Lactobacillus spp. on chicken growth performance. By harnessing such bacteria, it may be possible to develop high-productivity strategies in poultry that rely on the use of probiotics and less on in-feed antibiotics.

  13. Lead transport in intra-oceanic subduction zones: 2D geochemical-thermo-mechanical modeling of isotopic signatures

    NARCIS (Netherlands)

    Baitsch-Ghirardello, B.; Stracke, A.; Connolly, J.A.D.; Nikolaeva, K.M.; Gerya, T.V.

    2014-01-01

    Understanding the physical-chemical mechanisms and pathways of geochemical transport in subduction zones remains a long-standing goal of subduction-related research. In this study, we perform fully coupled geochemical-thermo-mechanical (GcTM) numerical simulations to investigate Pb isotopic

  14. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury.

    Science.gov (United States)

    Saghazadeh, Amene; Rezaei, Nima

    2017-10-03

    Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals. Therefore the objective of this study was to investigate the difference in heavy metal measures between patients with ASD and control subjects. We included observational studies that measured levels of toxic metals (antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium) in different specimens (whole blood, plasma, serum, red cells, hair and urine) for patients with ASD and for controls. The main electronic medical database (PubMed and Scopus) were searched from inception through October 2016. 52 studies were eligible to be included in the present systematic review, of which 48 studies were included in the meta-analyses. The hair concentrations of antimony (standardized mean difference (SMD)=0.24; 95% confidence interval (CI): 0.03 to 0.45) and lead (SMD=0.60; 95% confidence interval (CI): 0.17 to 1.03) in ASD patients were significantly higher than those of control subjects. ASD patients had higher erythrocyte levels of lead (SMD=1.55, CI: 0.2 to 2.89) and mercury (SMD=1.56, CI: 0.42 to 2.70). There were significantly higher blood lead levels in ASD patients (SMD=0.43, CI: 0.02 to 0.85). Sensitivity analyses showed that ASD patients in developed but not in developing countries have lower hair concentrations of cadmium (SMD=-0.29, CI: -0.46 to -0.12). Also, such analyses indicated that ASD patients in developing but not in developed lands have higher hair concentrations of lead (SMD=1.58, CI: 0.80 to 2.36) and mercury (SMD=0

  15. Investigation of the effect of mechanical pressure on the performance of negative lead accumulator electrodes during partial state of charge operation

    Czech Academy of Sciences Publication Activity Database

    Bača, P.; Micka, Karel; Křivík, P.; Tonar, K.; Tošer, P.

    2012-01-01

    Roč. 207, JUN 1 2012 (2012), s. 37-44 ISSN 0378-7753 Institutional research plan: CEZ:AV0Z40400503 Keywords : Lead battery electrodes * Doping with carbon or titanium dioxide * Effect of mechanical pressure Subject RIV: CG - Electrochemistry Impact factor: 4.675, year: 2012

  16. The environmental agreement may lead to large losses for the oil producers. The Kyoto mechanisms are very important to Norway

    International Nuclear Information System (INIS)

    1999-01-01

    The article presents an economic model study of the implications of an climatic agreement. Two main scenarios are presented: 1) The Kyoto protocol is extended to 2020. 2) All counties ratify a climatic agreement. The conclusions are that the Kyoto protocol may have great effects on the oil and gas markets and large economic consequences for Norway. It is therefore mandatory to extensively use the Kyoto mechanisms such as trade with quotas, common implementation and the green development mechanism

  17. Bacteriophage Resistance Mechanisms in the Fish Pathogen Flavobacterium psychrophilum: Linking Genomic Mutations to Changes in Bacterial Virulence Factors

    DEFF Research Database (Denmark)

    Castillo, Daniel; Christiansen, Rói Hammershaimb; Dalsgaard, Inger

    2015-01-01

    -resistant strains had all obtained unique insertions and/or deletions and point mutations distributed among intergenic and genic regions. Mutations in genes related to cell surface properties, gliding motility, and biosynthesis of lipopolysaccharides and cell wall were found. The observed links between phage...

  18. Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

    Science.gov (United States)

    Powell, Joshua; Luh, Jeanne; Coronell, Orlando

    2015-10-20

    The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur.

  19. Liver and Renal Function Tests in Artisans Occupationally Exposed to Lead in Mechanic Village in Nnewi, Nigeria

    Directory of Open Access Journals (Sweden)

    S. C. Meludu

    2004-02-01

    Full Text Available Additives in petroleum solvents have been reported to have adverse health implications. An evaluation study on some toxicological effects of occupational exposure to petroleum products (especially petrol which contains tetraethyl lead amongst twenty five occupationally exposed artisans and twenty five graduate students of College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria as controls, was carried out using the following biochemical markers: electrolytes, urea, uric acid, inorganic phosphorus, creatinine, zinc and blood lead, as well as the activities of alanine and aspartate aminotransferases, and alkaline phosphatase. The results showed that occupational exposure of human subjects to lead in petrol increases the concentrations of uric acid (357 ± 123μ mol/L and phosphate (1.5 ± 0.5m mol/L in exposed subjects compared with unexposed subjects (uric acid 228 ± 105μ mol/L, phosphate 1.2 ± 0.41m mol/L; p < 0.01 in both cases. Significantly lower activities were observed for alkaline phosphatase (66 ± 18.9 iu/L. The activities of alanine aminotransferase (11.4 ± 4.0 iu/L and aspartate aminotransferase (15.8 ± 4.4 iu/L in occupationally exposed artisans were higher compared with unexposed subjects (alkaline phosphatase = 78 ± 22.4 iu/L alanine aminotranferase = 6.8 ± 2.7 iu/L, aspartate aminotranferase = 9.6 ± 3.5i u/L; p < 0.01 in all cases. Occupational exposure of human subjects to lead significantly increased blood lead (59.6 ± 15.9 μg/dL and decreased plasma zinc (71.3 ± 14.4 μg/L in exposed compared with unexposed subjects (blood lead = 35 ± 7 μg/dL, zinc = 108.4 ± 16.9 μg/dL; p < 0.01. The results indicate that occupational exposure to lead in petrol may compromise liver and renal function.

  20. Lead-Cooled Fast Reactor (LFR) Design: Safety, Neutronics, Thermal Hydraulics, Structural Mechanics, Fuel, Core, and Plant Design

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C

    2010-02-22

    The idea of developing fast spectrum reactors with molten lead (or lead alloy) as a coolant is not a new one. Although initially considered in the West in the 1950s, such technology was not pursued to completion because of anticipated difficulties associated with the corrosive nature of these coolant materials. However, in the Soviet Union, such technology was actively pursued during the same time frame (1950s through the 1980s) for the specialized role of submarine propulsion. More recently, there has been a renewal of interest in the West for such technology, both for critical systems as well as for Accelerator Driven Subcritical (ADS) systems. Meanwhile, interest in the former Soviet Union, primarily Russia, has remained strong and has expanded well beyond the original limited mission of submarine propulsion. This section reviews the past and current status of LFR development.

  1. Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

    Directory of Open Access Journals (Sweden)

    Hironori Tsuchiya

    2015-10-01

    Full Text Available In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies.

  2. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix.

    Science.gov (United States)

    Barnes, Aileen M; Cabral, Wayne A; Weis, MaryAnn; Makareeva, Elena; Mertz, Edward L; Leikin, Sergey; Eyre, David; Trujillo, Carlos; Marini, Joan C

    2012-11-01

    Recessive osteogenesis imperfecta (OI) is caused by defects in genes whose products interact with type I collagen for modification and/or folding. We identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in FKBP10 or PPIB, which encode endoplasmic reticulum resident chaperone/isomerases FKBP65 and CyPB, respectively. In one pedigree branch, both parents carry a deletion in PPIB (c.563_566delACAG), causing lethal type IX OI in their two children. In another branch, a child with moderate type XI OI has a homozygous FKBP10 mutation (c.1271_1272delCCinsA). Proband FKBP10 transcripts are 4% of control and FKBP65 protein is absent from proband cells. Proband collagen electrophoresis reveals slight band broadening, compatible with ≈10% over-modification. Normal chain incorporation, helix folding, and collagen T(m) support a minimal general collagen chaperone role for FKBP65. However, there is a dramatic decrease in collagen deposited in culture despite normal collagen secretion. Mass spectrometry reveals absence of hydroxylation of the collagen telopeptide lysine involved in cross-linking, suggesting that FKBP65 is required for lysyl hydroxylase activity or access to type I collagen telopeptide lysines, perhaps through its function as a peptidylprolyl isomerase. Proband collagen to organics ratio in matrix is approximately 30% of normal in Raman spectra. Immunofluorescence shows sparse, disorganized collagen fibrils in proband matrix. Published 2012 Wiley Periodicals, Inc.*This article is a US Government work and, as such, is in the public domain of the United States of America.

  3. Heat shrinkable behavior, physico-mechanical and structure properties of electron beam cross-linked blends of high-density polyethylene with acrylonitrile-butadiene rubber

    International Nuclear Information System (INIS)

    Reinholds, Ingars; Kalkis, Valdis; Merijs-Meri, Remo; Zicans, Janis; Grigalovica, Agnese

    2016-01-01

    In this study, heat-shrinkable composites of electron beam irradiated high-density polyethylene (HDPE) composites with acrylonitrile-butadiene rubber (NBR) were investigated. HDPE/NBR blends at a ratio of components 100/0, 90/10, 80/20, 50/50 and 20/80 wt% were prepared using a two-roll mill. The compression molded films were irradiated high-energy (5 MeV) accelerated electrons up to irradiation absorbed doses of 100–300 kGy. The effect of electron beam induced cross-linking was evaluated by the changes of mechanical properties, gel content and by the differences of thermal properties, detected by differential scanning calorimetry. The thermo-shrinkage forces were determined as the kinetics of thermorelaxation and the residual shrinkage stresses of previously oriented (stretched up to 100% at above melting temperature of HDPE and followed by cooling to room temperature) specimens of irradiated HDPE/NBR blends under isometric heating–cooling mode. The compatibility between the both components was enhanced due to the formation of cross-linked sites at amorphous interphase. The results showed increase of mechanical stiffness of composites with increase of irradiation dose. The values of gel fraction compared to thermorelaxation stresses increased with the growth of irradiation dose level, as a result of formation cross-linked sites in amorphous PP/NBR interphase. - Highlights: • Binary blends of HDPE/NBR have been irradiated with 5 MeV accelerated electrons. • Increase of NBR content and irradiation dose improves cross-linking efficiency. • Thermo-shrinkage and residual stresses are investigated for oriented specimens. • Cross-linked HDPE/NBR composites can be successfully used as thermos-shrinkable materials.

  4. Effect of carbon nanotube functionalization on mechanical and thermal properties of cross-linked epoxy-carbon nanotube nanocomposites: role of strengthening the interfacial interactions.

    Science.gov (United States)

    Khare, Ketan S; Khabaz, Fardin; Khare, Rajesh

    2014-05-14

    We have used amido-amine functionalized carbon nanotubes (CNTs) that form covalent bonds with cross-linked epoxy matrices to elucidate the role of the matrix-filler interphase in the enhancement of mechanical and thermal properties in these nanocomposites. For the base case of nanocomposites of cross-linked epoxy and pristine single-walled CNTs, our previous work (Khare, K. S.; Khare, R. J. Phys. Chem. B 2013, 117, 7444-7454) has shown that weak matrix-filler interactions cause the interphase region in the nanocomposite to be more compressible. Furthermore, because of the weak matrix-filler interactions, the nanocomposite containing dispersed pristine CNTs has a glass transition temperature (Tg) that is ∼66 K lower than the neat polymer. In this work, we demonstrate that in spite of the presence of stiff CNTs in the nanocomposite, the Young's modulus of the nanocomposite containing dispersed pristine CNTs is virtually unchanged compared to the neat cross-linked epoxy. This observation suggests that the compressibility of the matrix-filler interphase interferes with the ability of the CNTs to reinforce the matrix. Furthermore, when the compressibility of the interphase is reduced by the use of amido-amine functionalized CNTs, the mechanical reinforcement due to the filler is more effective, resulting in a ∼50% increase in the Young's modulus compared to the neat cross-linked epoxy. Correspondingly, the functionalization of the CNTs also led to a recovery in the Tg making it effectively the same as the neat polymer and also resulted in a ∼12% increase in the thermal conductivity of the nanocomposite containing functionalized CNTs compared to that containing pristine CNTs. These results demonstrate that the functionalization of the CNTs facilitates the transfer of both mechanical load and thermal energy across the matrix-filler interface.

  5. The testing of batteries linked to supercapacitors with electrochemical impedance spectroscopy: A comparison between Li-ion and valve regulated lead acid batteries

    Science.gov (United States)

    Ferg, Ernst; Rossouw, Claire; Loyson, Peter

    2013-03-01

    For electric vehicles, a supercapacitor can be coupled to the electrical system in order to increase and optimize the energy and power densities of the drive system during acceleration and regenerative breaking. This study looked at the charge acceptance and maximum discharge ability of a valve regulated lead acid (VRLA) and a Li-ion battery connected in parallel to supercapacitors. The test procedure evaluated the advantage of using a supercapacitor at a 2 F:1 Ah ratio with the battery types at various states of charge (SoC). The results showed that about 7% of extra charge was achieved over a 5-s test time for a Li-ion hybrid system at 20% SoC, whereas at the 80% SoC the additional capacity was approximately 16%. While for the VRLA battery hybrid system, an additional charge of up to 20% was achieved when the battery was at 80% SoC, with little or no benefit at the 20% SoC. The advantage of the supercapacitor in parallel with a VRLA battery was noticeable on its discharge ability, where significant extra capacity was achieved for short periods of time for a battery at the 60% and 40% SoC when compared to the Li-ion hybrid system. The study also made use of Electrochemical Impedance Spectroscopy (EIS) with a suitable equivalent circuit model to explain, in particular, the internal resistance and capacitance differences observed between the different battery chemistries with and without a supercapacitor.

  6. Grain interaction mechanisms leading to intragranular orientation spread in tensile deformed bulk grains of interstitial-free steel

    DEFF Research Database (Denmark)

    Winther, Grethe; Wright, Jonathan P.; Schmidt, Søren

    2017-01-01

    environments representing the bulk texture, yet their deformation-induced rotations are very different. The ALAMEL model is employed to analyse the grain interaction mechanisms. Predictions of this model qualitatively agree with the directionality and magnitude of the experimental orientation spread. However......, quantitative agreement requires fine-tuning of the boundary conditions. The majority of the modelled slip is accounted for by four slip systems also predicted to be active by the classical Taylor model in uniaxial tension, and most of the orientation spread along the grain boundaries is caused by relative...... variations in the activities of these. Although limited to two grains, the findings prove that shear at the grain boundaries as accounted for by the ALAMEL model is a dominant grain interaction mechanism....

  7. Enhanced Mechanical Properties in Cellulose Nanocrystal-Poly(oligoethylene glycol methacrylate) Injectable Nanocomposite Hydrogels through Control of Physical and Chemical Cross-Linking.

    Science.gov (United States)

    De France, Kevin J; Chan, Katelyn J W; Cranston, Emily D; Hoare, Todd

    2016-02-08

    While injectable hydrogels have several advantages in the context of biomedical use, their generally weak mechanical properties often limit their applications. Herein, we describe in situ-gelling nanocomposite hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA) and rigid rod-like cellulose nanocrystals (CNCs) that can overcome this challenge. By physically incorporating CNCs into hydrazone cross-linked POEGMA hydrogels, macroscopic properties including gelation rate, swelling kinetics, mechanical properties, and hydrogel stability can be readily tailored. Strong adsorption of aldehyde- and hydrazide-modified POEGMA precursor polymers onto the surface of CNCs promotes uniform dispersion of CNCs within the hydrogel, imparts physical cross-links throughout the network, and significantly improves mechanical strength overall, as demonstrated by quartz crystal microbalance gravimetry and rheometry. When POEGMA hydrogels containing mixtures of long and short ethylene oxide side chain precursor polymers were prepared, transmission electron microscopy reveals that phase segregation occurs with CNCs hypothesized to preferentially locate within the stronger adsorbing short side chain polymer domains. Incorporating as little as 5 wt % CNCs results in dramatic enhancements in mechanical properties (up to 35-fold increases in storage modulus) coupled with faster gelation rates, decreased swelling ratios, and increased stability versus hydrolysis. Furthermore, cell viability can be maintained within 3D culture using these hydrogels independent of the CNC content. These properties collectively make POEGMA-CNC nanocomposite hydrogels of potential interest for various biomedical applications including tissue engineering scaffolds for stiffer tissues or platforms for cell growth.

  8. Mechanical properties and microstructure of model lead-free joints for electronics made with use of nanopowders

    Czech Academy of Sciences Publication Activity Database

    Buršík, Jiří; Buršíková, V.; Pešina, Z.; Sopoušek, J.

    2012-01-01

    Roč. 106, SI (2012), s390-s392 ISSN 0009-2770. [Local Mechanical Properties 2011. Olomouc, 09.11.2011-11.11.2011] R&D Projects: GA ČR(CZ) GA106/09/0700 Institutional research plan: CEZ:AV0Z20410507 Keywords : solder * silver nanopowdwer * nanoindentation Subject RIV: JG - Metallurgy Impact factor: 0.453, year: 2012

  9. Development of a Focused Library of Triazole-Linked Privileged-Structure-Based Conjugates Leading to the Discovery of Novel Phenotypic Hits against Protozoan Parasitic Infections.

    Science.gov (United States)

    Uliassi, Elisa; Piazzi, Lorna; Belluti, Federica; Mazzanti, Andrea; Kaiser, Marcel; Brun, Reto; Moraes, Carolina B; Freitas-Junior, Lucio H; Gul, Sheraz; Kuzikov, Maria; Ellinger, Bernhard; Borsari, Chiara; Costi, Maria Paola; Bolognesi, Maria Laura

    2018-04-06

    Protozoan infections caused by Plasmodium, Leishmania, and Trypanosoma spp. contribute significantly to the burden of infectious diseases worldwide, causing severe morbidity and mortality. The inadequacy of available treatments calls for cost- and time-effective drug discovery endeavors. To this end, we envisaged the triazole linkage of privileged structures as an effective drug design strategy to generate a focused library of high-quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME-tox profiling. Thus, an 18-membered library was efficiently assembled via Huisgen cycloaddition of phenothiazine, biphenyl, and phenylpiperazine scaffolds. The resulting 18 compounds were then tested against seven parasite strains, and counter-screened for selectivity against two mammalian cell lines. In parallel, hERG and cytochrome P450 (CYP) inhibition, and mitochondrial toxicity were assessed. Remarkably, 10-((1-(3-([1,1'-biphenyl]-3-yloxy)propyl)-1H-1,2,3-triazol-5-yl)methyl)-10H-phenothiazine (7) and 10-(3-(1-(3-([1,1'-biphenyl]-3-yloxy)propyl)-1H-1,2,3-triazol-4-yl)propyl)-10H-phenothiazine (12) showed respective IC 50 values of 1.8 and 1.9 μg mL -1 against T. cruzi, together with optimal selectivity. In particular, compound 7 showed a promising ADME-tox profile. Thus, hit 7 might be progressed as an antichagasic lead. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Heat shrinkable behavior, physico-mechanical and structure properties of electron beam cross-linked blends of high-density polyethylene with acrylonitrile-butadiene rubber

    Science.gov (United States)

    Reinholds, Ingars; Kalkis, Valdis; Merijs-Meri, Remo; Zicans, Janis; Grigalovica, Agnese

    2016-03-01

    In this study, heat-shrinkable composites of electron beam irradiated high-density polyethylene (HDPE) composites with acrylonitrile-butadiene rubber (NBR) were investigated. HDPE/NBR blends at a ratio of components 100/0, 90/10, 80/20, 50/50 and 20/80 wt% were prepared using a two-roll mill. The compression molded films were irradiated high-energy (5 MeV) accelerated electrons up to irradiation absorbed doses of 100-300 kGy. The effect of electron beam induced cross-linking was evaluated by the changes of mechanical properties, gel content and by the differences of thermal properties, detected by differential scanning calorimetry. The thermo-shrinkage forces were determined as the kinetics of thermorelaxation and the residual shrinkage stresses of previously oriented (stretched up to 100% at above melting temperature of HDPE and followed by cooling to room temperature) specimens of irradiated HDPE/NBR blends under isometric heating-cooling mode. The compatibility between the both components was enhanced due to the formation of cross-linked sites at amorphous interphase. The results showed increase of mechanical stiffness of composites with increase of irradiation dose. The values of gel fraction compared to thermorelaxation stresses increased with the growth of irradiation dose level, as a result of formation cross-linked sites in amorphous PP/NBR interphase.

  11. Proposal of measuring the mechanisms of nuclear excitation leading to fission with the ADONE jet-target tagged photon beam

    International Nuclear Information System (INIS)

    Lucherini, V.; Bianchi, N.; De Sanctis, E.; Guaraldo, C.; Levi Sandri, P.; Muccifora, V.; Polli, E.; Reolon, A.R.; Aiello, S.; De Filippo, E.; Lanzano', G.; Lo Nigro, S.; Milone, C.; Pagano, A.; Botvina, A.S.; Iljinov, A.S.; Mebel, M.V.

    1990-01-01

    The mechanisms of excitation with subsequent fission of heavy nuclei can be conveniently studied by means of photons, since this probe is able to interact deeply inside the nucleus. We propose the use of the (200-1200 MeV) tagged photon beam from the ADONE Jet Target in order to study the mass-energy and total momentum distributions of fission fragments, to obtain experimental information on the configurations (excitation energy and nucleonic composition) of produced compound nuclei and on their decay channels

  12. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc, and copper. Progress report, January 1, 1979-December 31, 1979

    International Nuclear Information System (INIS)

    Wasserman, R.H.

    1979-01-01

    The mechanism of lead transport is presented, and especially the particular similarities or dissimilarities between lead and calcium in this process. The absorption of these metals was determined cockerels, raised on a commercial diet or on a specified diet, using in vivo ligated loop procedure. The dose administered into the loop contained 0.5 μCi 203 Pb (and/or 0.1 μCi 47 Ca), and 0.01 mM lead acetate (and/or mM CaCl 2 ) in 0.5 ml 0.15 M NaCl,pH 6.5. It was shown that lead is rapidly taken up by the mucosal tissue, and slowly transferred into the body, whereas less calcium is retained by the tissue and the transfer of calcium is many times as effective as that for lead. They appear to respond in a similar manner to a low calcium intake and vitamin D treatment. Increasing luminal stable lead concentration significantly reduced the percentage of radiolead significantly reduced the percentage of radiolead absorbed, but did not affect the absorption of calcium. Also, vitamin D enhanced the transfer of plasma 47 Ca into the lumen but did not affect the transfer of plasma 203 Pb. Intravenous administration of 1,25(OH) 2 CC to rachitic chicks enhanced calcium and lead absorption, but the maximal absorption of these metals occurred at slightly different times after administering this metabolite, indicating that two different transport systems may be involved. It was concluded that lead is transported across the epithelial wall by a passive diffusion and this process is affected by vitamin D in a similar manner as this vitamin affects the diffusional component of calcium transport

  13. Mechanical and dielectric characterization of lead zirconate titanate(PZT)/polyurethane(PU) thin film composite for energy harvesting

    Science.gov (United States)

    Aboubakr, S.; Rguiti, M.; Hajjaji, A.; Eddiai, A.; Courtois, C.; d'Astorg, S.

    2014-04-01

    The Lead Zirconate titanate (PZT) ceramic is known by its piezoelectric feature, but also by its stiffness, the use of a composite based on a polyurethane (PU) matrix charged by a piezoelectric material, enable to generate a large deformation of the material, therefore harvesting more energy. This new material will provide a competitive alternative and low cost manufacturing technology of autonomous systems (smart clothes, car seat, boat sail, flag ...). A thin film of the PZT/PU composite was prepared using up to 80 vol. % of ceramic. Due to the dielectric nature of the PZT, inclusions of this one in a PU matrix raises the permittivity of the composite, on other hand this latter seems to decline at high frequencies.

  14. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength

    DEFF Research Database (Denmark)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X......-ray absorptiometry (DEXA), compression testing, ashing, and bone histomorphometry were performed. Individuals with CAA had significantly lower bone mineral density (BMD) in the femoral neck and significantly lower bone volume demonstrated by thinner trabeculae, decreased extent of osteoid surfaces, and lower mean...... wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. Conclusion: CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone...

  15. X-ray-mediated cross linking of protein and DNA

    International Nuclear Information System (INIS)

    Minsky, B.D.; Braun, A.

    1977-01-01

    Using a simple filter assay for the binding of BSA or lysozyme to DNA, two mechanisms of x-ray-mediated cross linking are shown to occur. One, a fast reaction, appears to involve a radical intermediate, is inhibited by high pH and salt, and seems to be enhanced by deoxygenation. The second mechanism, a slow time-dependent component, differs from the fast reaction in its stimulation by histidine, its inhibition by catalase, and the lack of an oxygen effect. Separate irradiation of DNA or water does not lead to cross linking. However, separate irradiation of protein leads to cross linking which proceeds with slow-component kinetics

  16. Mechanical confinement for improved energy storage density in BNT-BT-KNN lead-free ceramic capacitors

    Energy Technology Data Exchange (ETDEWEB)

    Chauhan, Aditya; Patel, Satyanarayan; Vaish, Rahul, E-mail: rahul@iitmandi.ac.in [School of Engineering, Indian Institute of Technology Mandi, 175 001 (India)

    2014-08-15

    With the advent of modern power electronics, embedded circuits and non-conventional energy harvesting, the need for high performance capacitors is bound to become indispensible. The current state-of-art employs ferroelectric ceramics and linear dielectrics for solid state capacitance. However, lead-free ferroelectric ceramics propose to offer significant improvement in the field of electrical energy storage owing to their high discharge efficiency and energy storage density. In this regards, the authors have investigated the effects of compressive stress as a means of improving the energy storage density of lead-free ferroelectric ceramics. The energy storage density of 0.91(Bi{sub 0.5}Na{sub 0.5})TiO{sub 3}-0.07BaTiO{sub 3}-0.02(K{sub 0.5}Na{sub 0.5})NbO{sub 3} ferroelectric bulk ceramic was analyzed as a function of varying levels of compressive stress and operational temperature .It was observed that a peak energy density of 387 mJ.cm{sup -3} was obtained at 100 MPa applied stress (25{sup o}C). While a maximum energy density of 568 mJ.cm{sup -3} was obtained for the same stress at 80{sup o}C. These values are indicative of a significant, 25% and 84%, improvement in the value of stored energy compared to an unloaded material. Additionally, material's discharge efficiency has also been discussed as a function of operational parameters. The observed phenomenon has been explained on the basis of field induced structural transition and competitive domain switching theory.

  17. Lead (Pb) Toxicity; Physio-Biochemical Mechanisms, Grain Yield, Quality, and Pb Distribution Proportions in Scented Rice.

    Science.gov (United States)

    Ashraf, Umair; Kanu, Adam S; Deng, Quanquan; Mo, Zhaowen; Pan, Shenggang; Tian, Hua; Tang, Xiangru

    2017-01-01

    Lead (Pb) caused interruptions with normal plant metabolism, crop yield losses and quality issues are of great concern. This study assessed the physio-biochemical responses, yield and grain quality traits and Pb distribution proportions in three different fragrant rice cultivars i.e., Meixiangzhan-2, Xinagyaxiangzhan and Basmati-385. Plants were exposed to 400, 800, and 1,200 ppm of Pb while pots without Pb were taken as control (0 ppm). Our results showed that Pb toxicity significantly ( P production of hydrogen peroxide (H 2 O 2 ), malanodialdehyde (MDA) and leaves leachates; while such effects were more apparent in Xinagyaxiangzhan than other two rice cultivars. Pb stress differentially affected the production protein, proline and soluble sugars; however the production rates were higher at heading stage (HS) than maturity stage (MS). Furthermore, Pb stress altered superoxide dismutase (SOD), peroxidases (POD), catalases (CAT) and ascorbate peroxidases (APX) activities and glutathione (GSH) and oxidized glutathione (GSSG) production in all rice cultivars at both HS and MS. All Pb levels reduced the yield and yield components of all rice cultivars; nonetheless such reductions were observed highest in Xinagyaxiangzhan (69.12%) than Meixiangzhan-2 (58.05%) and Basmati-385 (46.27%) and resulted in grain quality deterioration. Significant and positive correlations among rice yields with productive tillers/pot and grains per panicle while negative with sterility percentage were also observed. In addition, all rice cultivars readily taken up the Pb contents from soil to roots and transported upward in different proportions with maximum in roots followed by stemss, leaves, ears and grains. Higher proportions of Pb contents in above ground plant parts in Xinagyaxiangzhan possibly lead to maximum losses in this cultivar than other two cultivars; while less damage in Basmati-385 might be related to strong anti-oxidative defense system and lower proportions of Pb contents in

  18. Mechanical confinement for improved energy storage density in BNT-BT-KNN lead-free ceramic capacitors

    Directory of Open Access Journals (Sweden)

    Aditya Chauhan

    2014-08-01

    Full Text Available With the advent of modern power electronics, embedded circuits and non-conventional energy harvesting, the need for high performance capacitors is bound to become indispensible. The current state-of-art employs ferroelectric ceramics and linear dielectrics for solid state capacitance. However, lead-free ferroelectric ceramics propose to offer significant improvement in the field of electrical energy storage owing to their high discharge efficiency and energy storage density. In this regards, the authors have investigated the effects of compressive stress as a means of improving the energy storage density of lead-free ferroelectric ceramics. The energy storage density of 0.91(Bi0.5Na0.5TiO3-0.07BaTiO3-0.02(K0.5Na0.5NbO3 ferroelectric bulk ceramic was analyzed as a function of varying levels of compressive stress and operational temperature .It was observed that a peak energy density of 387 mJ.cm-3 was obtained at 100 MPa applied stress (25oC. While a maximum energy density of 568 mJ.cm-3 was obtained for the same stress at 80oC. These values are indicative of a significant, 25% and 84%, improvement in the value of stored energy compared to an unloaded material. Additionally, material's discharge efficiency has also been discussed as a function of operational parameters. The observed phenomenon has been explained on the basis of field induced structural transition and competitive domain switching theory.

  19. Size effects in tin-based lead-free solder joints: Kinetics of bond formation and mechanical characteristics

    Science.gov (United States)

    Abdelhadi, Ousama Mohamed Omer

    Continuous miniaturization of microelectronic interconnects demands smaller joints with comparable microstructural and structural sizes. As the size of joints become smaller, the volume of intermetallics (IMCs) becomes comparable with the joint size. As a result, the kinetics of bond formation changes and the types and thicknesses of IMC phases that form within the constrained region of the bond varies. This dissertation focuses on investigating combination effects of process parameters and size on kinetics of bond formation, resulting microstructure and the mechanical properties of joints that are formed under structurally constrained conditions. An experiment is designed where several process parameters such as time of bonding, temperature, and pressure, and bond thickness as structural chracteristic, are varied at multiple levels. The experiment is then implemented on the process. Scanning electron microscope (SEM) is then utilized to determine the bond thickness, IMC phases and their thicknesses, and morphology of the bonds. Electron backscatter diffraction (EBSD) is used to determine the grain size in different regions, including the bulk solder, and different IMC phases. Physics-based analytical models have been developed for growth kinetics of IMC compounds and are verified using the experimental results. Nanoindentation is used to determine the mechanical behavior of IMC phases in joints in different scales. Four-point bending notched multilayer specimen and four-point bending technique were used to determine fracture toughness of the bonds containing IMCs. Analytical modeling of peeling and shear stresses and fracture toughness in tri-layer four-point bend specimen containing intermetallic layer was developed and was verified and validated using finite element simulation and experimental results. The experiment is used in conjunction with the model to calculate and verify the fracture toughness of Cu6Sn5 IMC materials. As expected two different IMC phases

  20. Adsorption of aluminum and lead from wastewater by chitosan-tannic acid modified biopolymers: Isotherms, kinetics, thermodynamics and process mechanism.

    Science.gov (United States)

    Badawi, M A; Negm, N A; Abou Kana, M T H; Hefni, H H; Abdel Moneem, M M

    2017-06-01

    Chitosan was reacted by tannic acid to obtain three modified chitosan biopolymer. Their chemical structures were characterized by FTIR and elemental analysis. The prepared biopolymers were used to adsorb Al(III) and Pb(II) metal ions from industrial wastewater. The factors affecting the adsorption process were biosorbent amount, initial concentration of metal ion and pH of the medium. The adsorption efficiency increased considerably with the increase of the biosorbent amount and pH of the medium. The adsorption process of biosorbent on different metal ions was fitted by Freundlich adsorption model. The adsorption kinetics was followed Pseudo-second-order kinetic model. The adsorption process occurred according to diffusion mechanism which was confirmed by the interparticle diffusion model. The modified biopolymers were efficient biosorbents for removal of Pb(II) and Al(III) metal ions from the medium. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

    Directory of Open Access Journals (Sweden)

    Danielle Botelho

    2018-03-01

    Full Text Available Here we examine the organ level toxicology of both carbon black (CB and silver nanoparticles (AgNP. We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF. C57Bl6/J male mice were intratracheally instilled with saline (control, low (0.05 μg/g or high (0.5 μg/g doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

  2. Leading global energy and environmental transformation: Unified ASEAN biomass-based bio-energy system incorporating the clean development mechanism

    International Nuclear Information System (INIS)

    Lim, Steven; Lee, Keat Teong

    2011-01-01

    In recent years, the ten member countries in the Association of Southeast Asia Nations (ASEAN) have experienced high economic growth and, in tandem, a substantial increment in energy usage and demand. Consequently, they are now under intense pressure to secure reliable energy supplies to keep up with their growth rate. Fossil fuels remain the primary source of energy for the ASEAN countries, due to economic and physical considerations. This situation has led to unrestrained emissions of greenhouse gases to the environment and thus effectively contributes to global climate change. The abundant supply of biomass from their tropical environmental conditions offers great potential for ASEAN countries to achieve self-reliance in energy supplies. This fact can simultaneously transform into the main driving force behind combating global climate change, which is associated with the usage of fossil fuels. This research article explores the potential and advantages for ASEAN investment in biomass-based bio-energy supply, processing and distribution network with an emphasis on regional collaborations. It also investigates the implementation and operational challenges in terms of political, economic and technical factors for the cross-border energy scheme. Reliance of ASEAN countries on the clean development mechanism (CDM) to address most of the impediments in developing the project is also under scrutiny. Unified co-operation among ASEAN countries in integrating biomass-based bio-energy systems and utilising the clean development mechanism (CDM) as the common effort could serve as the prime example for regional partnerships in achieving sustainable development for the energy and environmental sector in the future. -- Highlights: →A study that explores feasibility for ASEAN investment in biomass-based bio-energy. →Focus is given on regional supply, processing and distribution network. →Cross-border implementation and operational challenges are discussed thoroughly.

  3. Studies of the thermal and mechanical properties of poly(urethane-siloxane)s cross-linked by hyperbranched polyesters

    Czech Academy of Sciences Publication Activity Database

    Džunuzović, J. V.; Pergal, M. V.; Poreba, Rafal; Ostojić, S.; Lazić, N.; Špírková, Milena; Jovanović, S.

    2012-01-01

    Roč. 51, č. 33 (2012), s. 10824-10832 ISSN 0888-5885 R&D Projects: GA ČR GAP108/10/0195 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : poly urethane * mechanical properties * thermal properties Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.206, year: 2012

  4. Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism

    Directory of Open Access Journals (Sweden)

    Haseeb Zubair

    2016-06-01

    Full Text Available There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.

  5. Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?

    Science.gov (United States)

    Chui, A; Murthi, P; Gunatillake, T; Brennecke, S P; Ignjatovic, V; Monagle, P T; Whitelock, J M; Said, J M

    2014-08-01

    Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Mechanism of action of electrochemically active carbons on the processes that take place at the negative plates of lead-acid batteries

    Energy Technology Data Exchange (ETDEWEB)

    Pavlov, D.; Rogachev, T.; Nikolov, P.; Petkova, G. [Institute of Electrochemistry and Energy Systems, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, bl. 10, Sofia 1113 (Bulgaria)

    2009-06-01

    It is known that negative plates of lead-acid batteries have low charge acceptance when cycled at high rates and progressively accumulate lead sulphate on high-rate partial-state-of-charge (HRPSoC) operation in hybrid-electric vehicle (HEV) applications. Addition of some carbon or graphite forms to the negative paste mix improves the charge efficiency and slows down sulfation of the negative plates. The present investigation aims to elucidate the contribution of electrochemically active carbon (EAC) additives to the mechanism of the electrochemical reactions of charge of the negative plates. Test cells are assembled with four types of EAC added to the negative paste mix in five different concentrations. Through analysis of the structure of NAM (including specific surface and pore radius measurements) and of the electrochemical parameters of the test cells on HRPSoC cycling, it is established that the electrochemical reaction of charge Pb{sup 2+} + 2e{sup -} {yields} Pb proceeds at 300-400 mV lower over-potentials on negative plates doped with EAC additives as compared to the charge potentials of cells with no carbon additives. Hence, electrochemically active carbons have a highly catalytic effect on the charge reaction and are directly involved in it. Consequently, the reversibility of the charge/discharge processes is improved, which eventually leads to longer battery cycle life. Thus, charging of the negative plates proceeds via a parallel mechanism on the surfaces of both Pb and EAC particles, at a higher rate on the EAC phase. Cells with EAC in NAM have the longest cycle life when their NAM specific surface is up to 4 m{sup 2} g{sup -1} against 0.5 m{sup 2} g{sup -1} for the lead surface. The proposed parallel mechanism of charge is verified experimentally on model Pb/EAC/PbSO{sub 4} and Pb/EAC electrodes. During the charge and discharge cycles of the HRPSoC test, the EAC particles are involved in dynamic adsorption/desorption on the lead sulfate and lead

  7. Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships.

    Science.gov (United States)

    Sanabria-DeLong, Naomi; Crosby, Alfred J; Tew, Gregory N

    2008-10-01

    Poly(lactide)-block-poly(ethylene oxide)-block-poly(lactide) (PLA-PEO-PLA) triblock copolymers are known to form physical hydrogels in water as a result of the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently cross-linked, and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the designed mechanical properties. In this article, a hydrogel was formed by the use of a novel two-step approach. In the first step, the end-functionalized PLA-PEO-PLA triblock was self-assembled into a physical hydrogel through hydrophobic micelle network junctions, and in the second step, this self-assembled physical network structure was locked into place by photo-cross-linking the terminal acrylate groups. In contrast with physical hydrogels, the photo-cross-linked gels remained intact in phosphate-buffered solution at body temperature. The swelling, degradation, and mechanical properties were characterized, and they demonstrated an extended degradation time (approximately 65 days), an exponential decrease in modulus with degradation time, and a tunable shear modulus (1.6-133 kPa). We also discuss the various constitutive relationships (Hookean, neo-Hookean, and Mooney-Rivlin) that can be used to describe the stress-strain behavior of these hydrogels. The chosen model and assumptions used for data fitting influenced the obtained modulus values by as much as a factor of 3.5, which demonstrates the importance of clearly stating one's data fitting parameters so that accurate comparisons can be made within the literature.

  8. Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

    Science.gov (United States)

    Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

    2012-01-01

    Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

  9. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid and methylglyoxal

    Directory of Open Access Journals (Sweden)

    Y. Tan

    2012-01-01

    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including pyruvate, oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid plays a central role in the aqueous oxidation of methylglyoxal and it is a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid (20 μM–10 mM was oxidized by OH radicals, and pyruvic acid and methylglyoxal experimental samples were analyzed using new analytical methods, in order to better understand the formation of SOA from acetic acid and methylglyoxal. Glyoxylic, glycolic, and oxalic acids formed from acetic acid and OH radicals. In contrast to the aqueous OH radical oxidation of methylglyoxal, the aqueous OH radical oxidation of acetic acid did not produce succinic acid and oligomers. This suggests that the methylgloxal-derived oligomers do not form through the acid catalyzed esterification pathway proposed previously. Using results from these experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  10. Studies of the pulse charge of lead-acid batteries for PV applications. Part I. Factors influencing the mechanism of the pulse charge of the positive plate

    Energy Technology Data Exchange (ETDEWEB)

    Kirchev, A.; Perrin, M.; Lemaire, E.; Karoui, F.; Mattera, F. [Commissariat de l' Energie Atomique, Institut National de l' Energie Solaire, INES-RDI, Parc Technologique de Savoie Technolac, 50 Avenue du Lac Leman, 73377 Le Bourget du Lac Cedex (France)

    2008-02-15

    The mechanism of the positive plate charge in pulse regime was studied in model lead-acid cells with one positive and two negative plates (8 Ah each) and Ag/Ag{sub 2}SO{sub 4} reference electrodes. The results showed that the evolution of the electrode potential is much slower on the positive plate than on the negative plate. Regardless of this fact, the calculated capacitive current of charge and self-discharge of the electrochemical double layer (EDL) during the 'ON' and 'OFF' half-periods of the pulse current square waves is comparable with the charge current amplitude. The result is due to the high values of the EDL on the surface of the lead dioxide active material. The influence of different factors like state of charge, state of health, pulse frequency, current amplitude and open circuit stay before the polarization was discussed. The previously determined optimal frequency of 1 Hz was associated with a maximum in the average double layer current on frequency dependence. The average double layer current is also maximal at SOC between 75 and 100%. The exchange of the constant current polarization with pulse polarization does not change substantially the mechanism and the overvoltage of the oxygen evolution reaction on the positive plate. The mechanism of the self-discharge of the EDL was also estimated analyzing long-time PPP transients (up to 2 h). It was found that when the PPP is lower than 1.2 V the preferred mechanism of EDL self-discharge is by coupling with the lead sulphate oxidation reaction. At higher values of PPP the EDL self-discharge happens via oxygen evolution. The high faradic efficiency of the pulse charge is due to the chemical oxidation of the Pb(II) ions by the O atoms and OH radicals formed at the oxygen evolution both during the 'ON' and 'OFF' periods. (author)

  11. Mechanical behaviour of a fuel cell stack under vibrating conditions linked to aircraft applications part II: Three-dimensional modelling

    Energy Technology Data Exchange (ETDEWEB)

    Rouss, Vicky; Charon, Willy [M3M, University of Technology Belfort - Montbeliard (France); FCLAB, Rue Thierry Mieg, F 90010 Belfort, Cedex (France); Candusso, Denis [INRETS, The French National Institute for Transport and Safety Research (France); FCLAB, Rue Thierry Mieg, F 90010 Belfort, Cedex (France)

    2008-11-15

    The implementation of fuel cells (FC) in transportation systems such as airplanes requires better understanding of their mechanical behaviour in vibrating environment. To this end, a FC stack was tested on a vibrating platform for all three orthogonal axes. The experimental procedure is described in the first part of the paper. This second part of the paper demonstrates how the experimental data collected can be used to create a three-dimensional, multi-input and multi-output model based on the Artificial Neural Network (ANN) approach. Indeed FCs are nonlinear mechanical systems, difficult to be physically modelled. The ANN methodology which depends strictly on raw data is a particularly interesting alternative solution to model FCs, for example, for monitoring purpose. The ANN model is described along with the training, pruning and validation stages. The results are exposed and commented. (author)

  12. A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology

    Directory of Open Access Journals (Sweden)

    Michelle T. Burstein

    2014-01-01

    Full Text Available A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.

  13. Electro-mechanical characterization of MgB2 wires for the Superconducting Link Project at CERN

    Science.gov (United States)

    Konstantopoulou, K.; Ballarino, A.; Gharib, A.; Stimac, A.; Garcia Gonzalez, M.; Perez Fontenla, A. T.; Sugano, M.

    2016-08-01

    In previous years, the R & D program between CERN and Columbus Superconductors SpA led to the development of several configurations of MgB2 wires. The aim was to achieve excellent superconducting properties in high-current MgB2 cables for the HL-LHC upgrade. In addition to good electrical performance, the superconductor shall have good mechanical strength in view of the stresses during operation (Lorenz forces and thermal contraction) and handling (tension and bending) during cabling and installation at room temperature. Thus, the study of the mechanical properties of MgB2 wires is crucial for the cable design and its functional use. In the present work we report on the electro-mechanical characterization of ex situ processed composite MgB2 wires. Tensile tests (critical current versus strain) were carried out at 4.2 K and in a 3 T external field by means of a purpose-built bespoke device to determine the irreversible strain limit of the wire. The minimum bending radius of the wire was calculated taking into account the dependence of the critical current with the strain and it was then used to obtain the minimum twist pitch of MgB2 wires in the cable. Strands extracted from cables having different configurations were tested to quantify the critical current degradation. The Young’s modulus of the composite wire was measured at room temperature. Finally, all measured mechanical parameters will be used to optimize an 18-strand MgB2 cable configuration.

  14. Electro-mechanical energy conversion system having a permanent magnet machine with stator, resonant transfer link and energy converter controls

    Science.gov (United States)

    Skeist, S. Merrill; Baker, Richard H.

    2006-01-10

    An electro-mechanical energy conversion system coupled between an energy source and an energy load comprising an energy converter device including a permanent magnet induction machine coupled between the energy source and the energy load to convert the energy from the energy source and to transfer the converted energy to the energy load and an energy transfer multiplexer to control the flow of power or energy through the permanent magnetic induction machine.

  15. LEADING WITH LEADING INDICATORS

    International Nuclear Information System (INIS)

    PREVETTE, S.S.

    2005-01-01

    This paper documents Fluor Hanford's use of Leading Indicators, management leadership, and statistical methodology in order to improve safe performance of work. By applying these methods, Fluor Hanford achieved a significant reduction in injury rates in 2003 and 2004, and the improvement continues today. The integration of data, leadership, and teamwork pays off with improved safety performance and credibility with the customer. The use of Statistical Process Control, Pareto Charts, and Systems Thinking and their effect on management decisions and employee involvement are discussed. Included are practical examples of choosing leading indicators. A statistically based color coded dashboard presentation system methodology is provided. These tools, management theories and methods, coupled with involved leadership and employee efforts, directly led to significant improvements in worker safety and health, and environmental protection and restoration at one of the nation's largest nuclear cleanup sites

  16. A facile strategy for fabrication of nano-ZnO/yeast composites and their adsorption mechanism towards lead (II) ions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei; Meng, Lingyin [College of Science, Sichuan Agricultural University, Yaan 625014 (China); Mu, Guiqin [Maize Research Institute of Sichuan Agricultural University, Wenjiang 611130 (China); Zhao, Maojun; Zou, Ping [College of Science, Sichuan Agricultural University, Yaan 625014 (China); Zhang, Yunsong, E-mail: yaanyunsong@126.com [College of Science, Sichuan Agricultural University, Yaan 625014 (China)

    2016-08-15

    Highlights: • Nano-ZnO/yeast composites were fabricated by alkali hydrothermal method. • Nano-ZnO was in-situ achieved and anchored on the yeast surface. • Alkali and hydrothermal process cause more exposed funcitional groups on yeast. • Nano-ZnO/yeast composites show higher Pb{sup 2+} adsorption ability than pristine yeast. • Nano-ZnO and exposed functional groups synergistically participate in adsorption. - Abstract: Nano-ZnO/yeast composites were successfully fabricated by one-step alkali hydrothermal method, and their adsorption properties for Pb{sup 2+} ions were also evaluated. Various influencing parameters of nano-ZnO/yeast composites, such as initial pH, contact time and initial Pb{sup 2+} concentration were investigated, respectively. The maximum adsorption capacity of nano-ZnO/yeast composites for Pb{sup 2+} (31.72 mg g{sup −1}) is 2.03 times higher than that of pristine yeast (15.63 mg g{sup −1}). The adsorption mechanism of nano-ZnO/yeast composites was studied by a series of techniques. Scanning electron microscopy (SEM) showed that nano-ZnO is evenly deposited on yeast surface. Atomic force microscopy (AFM) analysis exhibited that the yeast surface is rougher than that of pristine yeast. Energy dispersive X-ray detector (EDX) and X-ray diffraction (XRD) indicated the existence of nano-ZnO on yeast surface. Additionally, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) measurements further illustrated that alkali hydrothermal method causes not only the generation and anchorage of nano-ZnO on yeast surface but also the exposure of more functional groups (such as amino, carboxyl groups etc.) on yeast surface, both of which could adsorb Pb{sup 2+} via synergistic effect.

  17. A facile strategy for fabrication of nano-ZnO/yeast composites and their adsorption mechanism towards lead (II) ions

    International Nuclear Information System (INIS)

    Zhang, Wei; Meng, Lingyin; Mu, Guiqin; Zhao, Maojun; Zou, Ping; Zhang, Yunsong

    2016-01-01

    Highlights: • Nano-ZnO/yeast composites were fabricated by alkali hydrothermal method. • Nano-ZnO was in-situ achieved and anchored on the yeast surface. • Alkali and hydrothermal process cause more exposed funcitional groups on yeast. • Nano-ZnO/yeast composites show higher Pb"2"+ adsorption ability than pristine yeast. • Nano-ZnO and exposed functional groups synergistically participate in adsorption. - Abstract: Nano-ZnO/yeast composites were successfully fabricated by one-step alkali hydrothermal method, and their adsorption properties for Pb"2"+ ions were also evaluated. Various influencing parameters of nano-ZnO/yeast composites, such as initial pH, contact time and initial Pb"2"+ concentration were investigated, respectively. The maximum adsorption capacity of nano-ZnO/yeast composites for Pb"2"+ (31.72 mg g"−"1) is 2.03 times higher than that of pristine yeast (15.63 mg g"−"1). The adsorption mechanism of nano-ZnO/yeast composites was studied by a series of techniques. Scanning electron microscopy (SEM) showed that nano-ZnO is evenly deposited on yeast surface. Atomic force microscopy (AFM) analysis exhibited that the yeast surface is rougher than that of pristine yeast. Energy dispersive X-ray detector (EDX) and X-ray diffraction (XRD) indicated the existence of nano-ZnO on yeast surface. Additionally, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) measurements further illustrated that alkali hydrothermal method causes not only the generation and anchorage of nano-ZnO on yeast surface but also the exposure of more functional groups (such as amino, carboxyl groups etc.) on yeast surface, both of which could adsorb Pb"2"+ via synergistic effect.

  18. Muscle co-contraction modulates damping and joint stability in a three-link bio mechanical limb

    Directory of Open Access Journals (Sweden)

    Stewart eHeitmann

    2012-01-01

    Full Text Available Computational models of neuromotor control require forward models of limb movement that can replicate the natural relationships between muscle activation and joint dynamics without the burdens of excessive anatomical detail. We present a model of a three-link biomechanical limb that emphasizes the dynamics of limb movement within a simplified two-dimensional framework. Muscle co-contraction effects were incorporated into the model by flanking each joint with a pair of antagonist muscles that may be activated independently. Muscle co-contraction is known to alter the damping and stiffness of limb joints without altering net joint torque. Idealized muscle actuators were implemented using the Voigt muscle model which incorporates the parallel elasticity of muscle and tendon but omits series elasticity. The natural force-length-velocity relationships of contractile muscle tissue were incorporated into the actuators using ideal mathematical forms. Numerical stability analysis confirmed that co-contraction of these simplified actuators increased damping in the biomechanical limb consistent with observations of human motor control. Dynamic changes in joint stiffness were excluded by the omission of series elasticity. The analysis also revealed the unexpected finding that distinct stable (bistable equilibrium positions can co-exist under identical levels of muscle co-contraction. We map the conditions under which bistability arises and prove analytically that monostability (equifinality is guaranteed when the antagonist muscles are identical. Lastly we verify these analytic findings in the full biomechanical limb model.

  19. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

    Science.gov (United States)

    Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

    2006-11-01

    A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

  20. Can the dopaminergic-related effects of general anesthetics be linked to mechanisms involved in drug abuse and addiction?

    Science.gov (United States)

    Melo, A; Tavares, I; Sousa, N; Pêgo, J M

    2015-08-01

    General anesthetics (GA) are well known for the ability to induce a state of reversible loss of consciousness and unresponsiveness to painful stimuli. However, evidence from animal models and clinical studies show that GA exposure may induce behavioral changes beyond acute effects. Most research and concerns are focused on changes in cognition and memory. We will look at effects of GA on behavior that is mediated by the dopaminergic system. Pharmacological resemblance of GA with drugs of abuse, and the complexity and importance of dopaminergic systems in both reward seeking and addictive illnesses make us believe that it deserves an overview about what is already known and what matters to us as healthcare workers and specifically as anesthesiologists. A review of available evidence strongly suggests that there may be a link between the effects of GA on the brain and substance abuse, partly explained by their influence on the dopaminergic system. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Park Stephen DE

    2009-12-01

    . These findings suggest that protein synthesis, mechanosensation and muscle remodeling contribute to skeletal muscle adaptation towards improved integrity and hypertrophy. Conclusions This is the first study to characterize global mRNA expression profiles in equine skeletal muscle using an equine-specific microarray platform. Here we reveal novel genes and mechanisms that are temporally expressed following exercise providing new knowledge about the early and late molecular responses to exercise in the equine skeletal muscle transcriptome.

  2. Linking carbon supply to root cell-wall chemistry and mechanics at high altitudes in Abies georgei

    Science.gov (United States)

    Genet, Marie; Li, Mingcai; Luo, Tianxiang; Fourcaud, Thierry; Clément-Vidal, Anne; Stokes, Alexia

    2011-01-01

    Background and Aims The mobile carbon supply to different compartments of a tree is affected by climate, but its impact on cell-wall chemistry and mechanics remains unknown. To understand better the variability in root growth and biomechanics in mountain forests subjected to substrate mass movement, we investigated root chemical and mechanical properties of mature Abies georgei var. smithii (Smith fir) growing at different elevations on the Tibet–Qinghai Plateau. Methods Thin and fine roots (0·1–4·0 mm in diameter) were sampled at three different elevations (3480, 3900 and 4330 m, the last corresponding to the treeline). Tensile resistance of roots of different diameter classes was measured along with holocellulose and non-structural carbon (NSC) content. Key Results The mean force necessary to break roots in tension decreased significantly with increasing altitude and was attributed to a decrease in holocellulose content. Holocellulose was significantly lower in roots at the treeline (29·5 ± 1·3 %) compared with those at 3480 m (39·1 ± 1·0 %). Roots also differed significantly in NSC, with 35·6 ± 4·1 mg g−1 dry mass of mean total soluble sugars in roots at 3480 m and 18·8 ± 2·1 mg g−1 dry mass in roots at the treeline. Conclusions Root mechanical resistance, holocellulose and NSC content all decreased with increasing altitude. Holocellulose is made up principally of cellulose, the biosynthesis of which depends largely on NSC supply. Plants synthesize cellulose when conditions are optimal and NSC is not limiting. Thus, cellulose synthesis in the thin and fine roots measured in our study is probably not a priority in mature trees growing at very high altitudes, where climatic factors will be limiting for growth. Root NSC stocks at the treeline may be depleted through over-demand for carbon supply due to increased fine root production or winter root growth. PMID:21186240

  3. Potential climatic mechanisms associated with the mega drought at 4200 cal yr BP: linking proxy data with modern climate analogues

    Science.gov (United States)

    Carter, V.; Shinker, J. J.

    2017-12-01

    Roughly 4200 years ago, a 150-year long mega drought occurred in the central Rocky Mountains, as indicated by pollen evidence from lake sediments from Long Lake, south-eastern Wyoming. However, pollen evidence does not record the climate mechanisms that caused the drought; they only provide evidence that the drought occurred. A modern climate analogue technique using North American Regional Reanalysis data was applied to the sedimentary data in order to identify possible synoptic and dynamic patterns that may have caused the mega drought at 4200 cal yr BP. Our results suggest warm and dry conditions were a result of anomalously higher-than-normal geopotential heights that were centred over the Great Plains beginning in the spring and persisting through the fall. Drought conditions during the growing seasons was the result of the anomalous high-pressure ridge, which suppressed moisture transport via the low level jet from the Gulf of Mexico, as well as brought in dry continental air from in the interior region of North America. The conditions associated with modern analogues offer a potential climate mechanism that caused the mega drought 4200 years ago, and likely led to the changes in vegetation composition as evidenced by the pollen record from Long Lake, Wyoming.

  4. Variability of filtration and food assimilation rates, respiratory activity and multixenobiotic resistance (MXR mechanism in the mussel Perna perna under lead influence

    Directory of Open Access Journals (Sweden)

    M. L. PESSATTI

    Full Text Available The economic importance that myticulture is conquering in Santa Catarina State (South of Brazil explains the crescent search for new coastal sites for farming. Physiological and biochemical studies of the mussel Perna perna are important to the establishment of methodologies for program assessment and environmental monitoring, allowing to infer about site quality and possible influences of xenobiotic agents on coastal areas. In order to evaluate effects caused by lead poisoning (1.21 mumol.L-1, the mussels were maintained at constant temperature (25ºC and fed with Chaetoceros gracilis for 15 days. The control group was acclimatized in sea water 30‰. At the end of this period time, physiological measurements were carried out along with statistic analysis for filtration rates, lead assimilation and overall respiratory activity. The mechanism of multixenobiotic resistance (MXR was particularly evaluated in standardized gill fragments using rhodamine B accumulation and its quantification under fluorescence optical microscopy. Regarding the control group, results had shown that the mussels maintenance in a lead-poisoned environment caused higher filtration rates (1.04 and 2.3 and L.h-1.g-1; p < 0.05 and lower assimilation rates (71.96% and 54.1%, respectively. Also it was confirmed a lesser rhodamine B accumulation in the assays under influence of lead, suggesting that this metal induces the MXR mechanism expression in mussel P. perna. These results indicate that such physiological and biochemical alterations in the mussels can modify the energy fluxes of its metabolism, resulting in possible problems on the coastal systems used as cultivating sites.

  5. Variability of filtration and food assimilation rates, respiratory activity and multixenobiotic resistance (MXR mechanism in the mussel Perna perna under lead influence

    Directory of Open Access Journals (Sweden)

    PESSATTI M. L.

    2002-01-01

    Full Text Available The economic importance that myticulture is conquering in Santa Catarina State (South of Brazil explains the crescent search for new coastal sites for farming. Physiological and biochemical studies of the mussel Perna perna are important to the establishment of methodologies for program assessment and environmental monitoring, allowing to infer about site quality and possible influences of xenobiotic agents on coastal areas. In order to evaluate effects caused by lead poisoning (1.21 mumol.L-1, the mussels were maintained at constant temperature (25ºC and fed with Chaetoceros gracilis for 15 days. The control group was acclimatized in sea water 30?. At the end of this period time, physiological measurements were carried out along with statistic analysis for filtration rates, lead assimilation and overall respiratory activity. The mechanism of multixenobiotic resistance (MXR was particularly evaluated in standardized gill fragments using rhodamine B accumulation and its quantification under fluorescence optical microscopy. Regarding the control group, results had shown that the mussels maintenance in a lead-poisoned environment caused higher filtration rates (1.04 and 2.3 and L.h-1.g-1; p < 0.05 and lower assimilation rates (71.96% and 54.1%, respectively. Also it was confirmed a lesser rhodamine B accumulation in the assays under influence of lead, suggesting that this metal induces the MXR mechanism expression in mussel P. perna. These results indicate that such physiological and biochemical alterations in the mussels can modify the energy fluxes of its metabolism, resulting in possible problems on the coastal systems used as cultivating sites.

  6. Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity.

    Science.gov (United States)

    Ryan, Karen K; Woods, Stephen C; Seeley, Randy J

    2012-02-08

    The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. In the loop: how chromatin topology links genome structure to function in mechanisms underlying learning and memory.

    Science.gov (United States)

    Watson, L Ashley; Tsai, Li-Huei

    2017-04-01

    Different aspects of learning, memory, and cognition are regulated by epigenetic mechanisms such as covalent DNA modifications and histone post-translational modifications. More recently, the modulation of chromatin architecture and nuclear organization is emerging as a key factor in dynamic transcriptional regulation of the post-mitotic neuron. For instance, neuronal activity induces relocalization of gene loci to 'transcription factories', and specific enhancer-promoter looping contacts allow for precise transcriptional regulation. Moreover, neuronal activity-dependent DNA double-strand break formation in the promoter of immediate early genes appears to overcome topological constraints on transcription. Together, these findings point to a critical role for genome topology in integrating dynamic environmental signals to define precise spatiotemporal gene expression programs supporting cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Self-focused and other-focused resiliency: Plausible mechanisms linking early family adversity to health problems in college women.

    Science.gov (United States)

    Coleman, Sulamunn R M; Zawadzki, Matthew J; Heron, Kristin E; Vartanian, Lenny R; Smyth, Joshua M

    2016-01-01

    This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Female students (N = 795) participated between October 2009 and May 2010. Participants completed self-report measures of early family adversity, self-focused (self-esteem, personal growth initiative) and other-focused (perceived social support, gratitude) resiliency, stress, subjective health, and health behaviors. Using structural equation modeling, self-focused resiliency associated with less stress, better subjective health, more sleep, less smoking, and less weekend alcohol consumption. Other-focused resiliency associated with more exercise, greater stress, and more weekend alcohol consumption. Early family adversity was indirectly related to all health outcomes, except smoking, via self-focused and other-focused resiliency. Self-focused and other-focused resiliency represent plausible mechanisms through which early family adversity relates to stress and health in college women. This highlights areas for future research in disease prevention and management.

  9. Mechanisms linking authentic leadership to emotional exhaustion: The role of procedural justice and emotional demands in a moderated mediation approach.

    Science.gov (United States)

    Kampa, Judith; Rigotti, Thomas; Otto, Kathleen

    2017-04-07

    In order to gain more knowledge on how the positive leadership concept of authentic leadership impacts follower strain, this study tries to uncover procedural justice as an underlying mechanism. In contrast to previous work, we exclusively base our theoretical model on justice theories. Specifically, we hypothesize that authentic leadership negatively predicts emotional exhaustion through perceptions of procedural justice. We assume that this indirect effect is conditional on followers' amount of emotional demands, and that the procedural justice-emotional exhaustion relationship is stronger when emotional demands are high. This finally results in a stronger exhaustion-reducing effect of authentic leadership. The proposed moderated mediation model was tested in a sample of N=628 employees nested in 168 teams using lagged data from three waves. Results provide support for all hypotheses. Authentic leadership is critical to employees' well-being as it contributes to an elevated perception of positive work conditions (procedural justice), especially in contexts with high emotional demands. Limitations and practical implications on leadership development are discussed.

  10. Mechanisms linking authentic leadership to emotional exhaustion: The role of procedural justice and emotional demands in a moderated mediation approach

    Science.gov (United States)

    KAMPA, Judith; RIGOTTI, Thomas; OTTO, Kathleen

    2016-01-01

    In order to gain more knowledge on how the positive leadership concept of authentic leadership impacts follower strain, this study tries to uncover procedural justice as an underlying mechanism. In contrast to previous work, we exclusively base our theoretical model on justice theories. Specifically, we hypothesize that authentic leadership negatively predicts emotional exhaustion through perceptions of procedural justice. We assume that this indirect effect is conditional on followers’ amount of emotional demands, and that the procedural justice-emotional exhaustion relationship is stronger when emotional demands are high. This finally results in a stronger exhaustion-reducing effect of authentic leadership. The proposed moderated mediation model was tested in a sample of N=628 employees nested in 168 teams using lagged data from three waves. Results provide support for all hypotheses. Authentic leadership is critical to employees’ well-being as it contributes to an elevated perception of positive work conditions (procedural justice), especially in contexts with high emotional demands. Limitations and practical implications on leadership development are discussed. PMID:27818452

  11. Attachment security as a mechanism linking foster care placement to improved mental health outcomes in previously institutionalized children.

    Science.gov (United States)

    McLaughlin, Katie A; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2012-01-01

    Children reared in institutions experience elevated rates of psychiatric disorders. Inability to form a secure attachment relationship to a primary caregiver is posited to be a central mechanism in this association. We determined whether the ameliorative effect of a foster care (FC) intervention on internalizing disorders in previously institutionalized children was explained by the development of secure attachment among children placed in FC. Second we evaluated the role of lack of attachment in an institutionalized sample on the etiology of internalizing disorders within the context of a randomized trial. A sample of 136 children (aged 6-30 months) residing in institutions was recruited in Bucharest, Romania. Children were randomized to FC (n = 68) or to care as usual (CAU; n = 68). Foster parents were recruited, trained, and overseen by the investigative team. Attachment security at 42 months was assessed using the Strange Situation Procedure, and internalizing disorders at 54 months were assessed using the Preschool Age Psychiatric Assessment. Girls in FC had fewer internalizing disorders than girls in CAU (OR = 0.17, p = .006). The intervention had no effect on internalizing disorders in boys (OR = 0.47, p = .150). At 42 months, girls in FC were more likely to have secure attachment than girls in CAU (OR = 12.5, p security predicted lower rates of internalizing disorders in both sexes. Development of attachment security fully mediated intervention effects on internalizing disorders in girls. Placement into FC facilitated the development of secure attachment and prevented the onset of internalizing disorders in institutionalized girls. The differential effects of FC on attachment security in boys and girls explained gender differences in the intervention effects on psychopathology. Findings provide evidence for the critical role of disrupted attachment in the etiology of internalizing disorders in children exposed to institutionalization. © 2011 The Authors

  12. A linked lake system beneath Thwaites Glacier, West Antarctica reveals an efficient mechanism for subglacial water flow.

    Science.gov (United States)

    Smith, B. E.; Gourmelen, N.; Huth, A.; Joughin, I. R.

    2016-12-01

    In this presentation we show the results of a multi-sensor survey of a system of subglacial lakes beneath Thwaites Glacier, West Antarctica. This is the first substantial active (meaning draining or filling on annual time scales) lake system detected under the fast-flowing glaciers of the Amundsen Coast. Altimetry data show that over the 2013 calendar year, four subglacial lakes drained, essentially simultaneously, with the bulk of the drainage taking place over the course the first three months of the year. The largest of the lakes appears to have drained around 3.7 km3 of water, with the others each draining less than 1 km3. The high-resolution radar surveys conducted in this area by NASA's IceBridge program allow detailed analysis of the subglacial hydrologic potential, which shows that the potential map in this area is characterized by small closed basins that should not, under the common assumption that water flow is directed down the gradient of the hydropotential, allow long-range water transport. The lakes' discharge demonstrates that, at least in some cases, water can flow out of apparently closed hydropotential basins. Combining a basal-flow routing map with a map of basal melt production suggests that the largest drainage event could recur as often as every 22 years, provided that overflow or leakage of mapped hydropotential basins allows melt water transport to refill the lake. An analysis of ice-surface speed records both around the lakes and at the Thwaites grounding line shows small changes in ice speed, but none clearly associated with the drainage event, suggesting that, at least in this area where subglacial melt is abundant, the addition of further water to the subglacial hydrologic system need not have any significant effect on ice flow. It is likely that the main impact of the lake system on the glacier is that as an efficient mechanism to remove meltwater from the system, it drains water that would otherwise flow through less efficient

  13. Inference of the phase-to-mechanical property link via coupled X-ray spectrometry and indentation analysis: Application to cement-based materials

    Energy Technology Data Exchange (ETDEWEB)

    Krakowiak, Konrad J.; Wilson, William [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States); James, Simon [Schlumberger Riboud Product Center, 1 Rue Henri Becquerel, Clamart 92140 (France); Musso, Simone [Schlumberger-Doll Research Center, 1 Hampshire St., Cambridge, MA 02139-1578 (United States); Ulm, Franz-Josef, E-mail: ulm@mit.edu [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307 (United States)

    2015-01-15

    A novel approach for the chemo-mechanical characterization of cement-based materials is presented, which combines the classical grid indentation technique with elemental mapping by scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDS). It is illustrated through application to an oil-well cement system with siliceous filler. The characteristic X-rays of major elements (silicon, calcium and aluminum) are measured over the indentation region and mapped back on the indentation points. Measured intensities together with indentation hardness and modulus are considered in a clustering analysis within the framework of Finite Mixture Models with Gaussian component density function. The method is able to successfully isolate the calcium-silica-hydrate gel at the indentation scale from its mixtures with other products of cement hydration and anhydrous phases; thus providing a convenient means to link mechanical response to the calcium-to-silicon ratio quantified independently via X-ray wavelength dispersive spectroscopy. A discussion of uncertainty quantification of the estimated chemo-mechanical properties and phase volume fractions, as well as the effect of chemical observables on phase assessment is also included.

  14. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

    Science.gov (United States)

    Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

    2016-12-01

    We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The Ecology of Stress: linking life-history traits with physiological control mechanisms in free-living guanacos.

    Science.gov (United States)

    Ovejero Aguilar, Ramiro J A; Jahn, Graciela A; Soto-Gamboa, Mauricio; Novaro, Andrés J; Carmanchahi, Pablo

    2016-01-01

    Providing the context for the evolution of life-history traits, habitat features constrain successful ecological and physiological strategies. In vertebrates, a key response to life's challenges is the activation of the Stress (HPA) and Gonadal (HPG) axes. Much of the interest in stress ecology is motivated by the desire to understand the physiological mechanisms in which the environment affects fitness. As reported in the literature, several intrinsic and extrinsic factors affect variability in hormone levels. In both social and non-social animals, the frequency and type of interaction with conspecifics, as well as the status in social species, can affect HPA axis activity, resulting in changes in the reproductive success of animals. We predicted that a social environment can affect both guanaco axes by increasing the secretion of testosterone (T) and Glucocorticoid (GCs) in response to individual social interactions and the energetic demands of breeding. Assuming that prolonged elevated levels of GCs over time can be harmful to individuals, it is predicted that the HPA axis suppresses the HPG axis and causes T levels to decrease, as GCs increase. All of the data for individuals were collected by non-invasive methods (fecal samples) to address hormonal activities. This is a novel approach in physiological ecology because feces are easily obtained through non-invasive sampling in animal populations. As expected, there was a marked adrenal ( p -value = .3.4e-12) and gonadal ( p -value = 0.002656) response due to seasonal variation in Lama guanicoe . No significant differences were found in fecal GCs metabolites between males/females*season for the entire study period ( p -value = 0.2839). Despite the seasonal activity variation in the hormonal profiles, our results show a positive correlation ( p -value = 1.952e-11, COR = 0.50) between the adrenal and gonadal system. The marked endocrine ( r 2  = 0.806) and gonad ( r 2  = 0.7231) response due to seasonal

  16. The Ecology of Stress: linking life-history traits with physiological control mechanisms in free-living guanacos

    Directory of Open Access Journals (Sweden)

    Ramiro J.A. Ovejero Aguilar

    2016-11-01

    Full Text Available Background Providing the context for the evolution of life-history traits, habitat features constrain successful ecological and physiological strategies. In vertebrates, a key response to life’s challenges is the activation of the Stress (HPA and Gonadal (HPG axes. Much of the interest in stress ecology is motivated by the desire to understand the physiological mechanisms in which the environment affects fitness. As reported in the literature, several intrinsic and extrinsic factors affect variability in hormone levels. In both social and non-social animals, the frequency and type of interaction with conspecifics, as well as the status in social species, can affect HPA axis activity, resulting in changes in the reproductive success of animals. We predicted that a social environment can affect both guanaco axes by increasing the secretion of testosterone (T and Glucocorticoid (GCs in response to individual social interactions and the energetic demands of breeding. Assuming that prolonged elevated levels of GCs over time can be harmful to individuals, it is predicted that the HPA axis suppresses the HPG axis and causes T levels to decrease, as GCs increase. Methods All of the data for individuals were collected by non-invasive methods (fecal samples to address hormonal activities. This is a novel approach in physiological ecology because feces are easily obtained through non-invasive sampling in animal populations. Results As expected, there was a marked adrenal (p-value = .3.4e−12 and gonadal (p-value = 0.002656 response due to seasonal variation in Lama guanicoe. No significant differences were found in fecal GCs metabolites between males/females*season for the entire study period (p-value = 0.2839. Despite the seasonal activity variation in the hormonal profiles, our results show a positive correlation (p-value = 1.952e−11, COR = 0.50 between the adrenal and gonadal system. The marked endocrine (r2 = 0.806 and gonad (r2 = 0

  17. Analysis of the thermo-mechanical behaviour of the DEMO Water-Cooled Lithium Lead breeding blanket module under normal operation steady state conditions

    Energy Technology Data Exchange (ETDEWEB)

    Di Maio, P.A.; Arena, P. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Aubert, J. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Bongiovì, G. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Chiovaro, P., E-mail: pierluigi.chiovaro@unipa.it [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Giammusso, R. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy); Li Puma, A. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Tincani, A. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy)

    2015-10-15

    Highlights: • A DEMO WCLL blanket module thermo-mechanical behaviour has been investigated. • Two models of the WCLL blanket module have been set-up adopting a code based on FEM. • The water flow domain in the module has been considered. • A set of uncoupled steady state thermo-mechanical analyses has been carried out. • Critical temperature is not overcome. Safety verifications are generally satisfied. - Abstract: Within the framework of DEMO R&D activities, a research cooperation has been launched between ENEA, the University of Palermo and CEA to investigate the thermo-mechanical behaviour of the outboard equatorial module of the DEMO1 Water-Cooled Lithium Lead (WCLL) blanket under normal operation steady state scenario. The research campaign has been carried out following a theoretical–computational approach based on the Finite Element Method (FEM) and adopting a qualified commercial FEM code. In particular, two different 3D FEM models (Model 1 and Model 2), reproducing respectively the central and the lateral poloidal–radial slices of the WCLL blanket module, have been set up. A particular attention has been paid to the modelling of water flow domain, within both the segment box channels and the breeder zone tubes, to simulate realistically the coolant-box thermal coupling. Results obtained are herewith reported and critically discussed.

  18. Amino-Functionalized Multiwalled Carbon Nanotubes Lead to Successful Ring-Opening Polymerization of Poly(ε-caprolactone): Enhanced Interfacial Bonding and Optimized Mechanical Properties.

    Science.gov (United States)

    Roumeli, Eleftheria; Papageorgiou, Dimitrios G; Tsanaktsis, Vasilios; Terzopoulou, Zoe; Chrissafis, Konstantinos; Avgeropoulos, Apostolos; Bikiaris, Dimitrios N

    2015-06-03

    In this work, the synthesis, structural characteristics, interfacial bonding, and mechanical properties of poly(ε-caprolactone) (PCL) nanocomposites with small amounts (0.5, 1.0, and 2.5 wt %) of amino-functionalized multiwalled carbon nanotubes (f-MWCNTs) prepared by ring-opening polymerization (ROP) are reported. This method allows the creation of a covalent-bonding zone on the surface of nanotubes, which leads to efficient debundling and therefore satisfactory dispersion and effective load transfer in the nanocomposites. The high covalent grafting extent combined with the higher crystallinity provide the basis for a significant enhancement of the mechanical properties, which was detected in the composites with up to 1 wt % f-MWCNTs. Increasing filler concentration encourages intrinsic aggregation forces, which allow only minor grafting efficiency and poorer dispersion and hence inferior mechanical performance. f-MWCNTs also cause a significant improvement on the polymerization reaction of PCL. Indeed, the in situ polymerization kinetics studies reveal a significant decrease in the reaction temperature, by a factor of 30-40 °C, combined with accelerated the reaction kinetics during initiation and propagation and a drastically reduced effective activation energy.

  19. Loss of covalently linked lipid as the mechanism for radiation-induced release of membrane-bound polysaccharide and exonuclease from Micrococcus radiodurans

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.

    1981-01-01

    The mechanism of γ-radiation-induced release of polysaccharide and exonuclease from the midwall membrane of Micrococcus radiodurans has been examined. These two components appear to be released independently, but by very similar processes. Direct analysis of radiation-released polysaccharide indicated the absence of an alkali-labile neutral lipid normally present in the native material. Radiation-induced release therefore probably results from the radiolytic cleavage of a covalently linked lipid which normally serves to anchor these substances to the membrane. The absence of a natural membrane-bound carotenoid had no effect on the rate of release of these components. Likewise, the absence of exonuclease in an exonuclease minus mutant did not influence the release of polysaccharide. It is suggested that the major pathway of radical transfer from the initiating .OH and culminating in the cleavage of the neutral lipid anchor may not be via the membrane

  20. Linking MedDRA®-coded Clinical Phenotypes to Biological Mechanisms by The Ontology of Adverse Events: A pilot study on Tyrosine Kinase Inhibitors (TKIs)

    Science.gov (United States)

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G.; Zaman, Shadia; Burkhart, Keith K.; Omenn, Gilbert S.; He, Yongqun; Athey, Brian D.; Abernethy, Darrell R.

    2016-01-01

    Introduction A translational bioinformatics challenge lies in connecting population and individual’s clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA®) is the default dictionary for Adverse Event (AE) reporting in the FDA Adverse Event Reporting System (FAERS). The Ontology of Adverse Events (OAE) represents AEs as pathological processes occurring after drug exposures. Objectives The aim is to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA® in FAERS data analysis. We investigated the AEs associated with Tyrosine Kinase Inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The selected 5 TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Results Statistical analysis of FAERS data identified 1,053 distinct MedDRA® terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA®. The data integration to provide insights into molecular mechanisms for drug-associated AEs is performed by including linkages in OAE for all related AE terms to MedDRA® and existing ontologies including Human Phenotype Ontology (HP), Uber Anatomy Ontology (UBERON), and Gene Ontology (GO). Sixteen AEs are shared by all 5 TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed ‘cardiac failure’ using the relations established in OAE with other ontologies, and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. Conclusion By expanding existing OAE ontological design, our TKI use case demonstrates that the combination of OAE and Med

  1. Linking MedDRA(®)-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G; Zaman, Shadia; Burkhart, Keith K; Omenn, Gilbert S; He, Yongqun; Athey, Brian D; Abernethy, Darrell R

    2016-07-01

    A translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA(®)) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures. The aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA(®) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Statistical analysis of FAERS data identified 1053 distinct MedDRA(®) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA(®). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA(®) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination

  2. Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis in Long QT Syndrome Type 8: CACNA1C R858H Mutation Linked to Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Jieyun Bai

    2017-10-01

    Full Text Available Functional analysis of the L-type calcium channel has shown that the CACNA1C R858H mutation associated with severe QT interval prolongation may lead to ventricular fibrillation (VF. This study investigated multiple potential mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF. The Ten Tusscher-Panfilov (TP06 human ventricular cell models incorporating the experimental data on the kinetic properties of L-type calcium channels were integrated into one-dimensional (1D fiber, 2D sheet, and 3D ventricular models to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying changes in intracellular calcium handling, action potential profiles, action potential duration restitution (APDR curves, dispersion of repolarization (DOR, QT interval and spiral wave dynamics. R858H “mutant” L-type calcium current (ICaL augmented sarcoplasmic reticulum calcium content, leading to the development of afterdepolarizations at the single cell level and focal activities at the tissue level. It also produced inhomogeneous APD prolongation, causing QT prolongation and repolarization dispersion amplification, rendering R858H “mutant” tissue more vulnerable to the induction of reentry compared with other conditions. In conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia risk due to afterdepolarizations and increased tissue vulnerability to unidirectional conduction block. However, the observed reentry is not due to afterdepolarizations (not present in our model, but rather to a novel blocking mechanism.

  3. Water-cooled lithium-lead box-shaped blanket concept for Demo: thermo-mechanical optimization and manufacturing sequence proposal

    International Nuclear Information System (INIS)

    Baraer, L.; Dinot, N.; Giancarli, L.; Proust, E.; Salavy, J.F.; Severi, Y.; Quintric-Bossy, J.

    1992-01-01

    The development of the water-cooled lithium-lead box-shaped blanket concept for DEMO has now reached the stage of thermo-mechanical optimization. In the previous design phases the preliminary dimensioning of the cooling circuit has permitted to define the water proportions required in the breeder region and to demonstrate, after a minimization of steel proportion and thicknesses, that this concept could reach tritium breeding self-sufficiency. In the present analysis the location of the coolant pipes has been optimized for the whole equatorial plane cross-section of both inboard and outboard segments in order to maintain the maximum Pb-17Li/steel interface temperature below 480 deg C and to minimize the thermal gradients along the steel structures. The consequent thermo-mechanical analysis has shown that the thermal stresses always remain below the allowable limits. Segment fabricability and removal are the next design issues to be analyzed. Within this strategy, a first manufactury sequence for the outboard segment is proposed

  4. Lead poisoning

    Science.gov (United States)

    ... drinking water in homes containing pipes that were connected with lead solder . Although new building codes require ... lead in their bodies when they put lead objects in their mouths, especially if they swallow those ...

  5. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  6. Activation and Inhibition of Sodium-Hydrogen Exchanger Is a Mechanism That Links the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart Failure.

    Science.gov (United States)

    Packer, Milton

    2017-10-17

    The mechanisms underlying the progression of diabetes mellitus and heart failure are closely intertwined, such that worsening of one condition is frequently accompanied by worsening of the other; the degree of clinical acceleration is marked when the 2 coexist. Activation of the sodium-hydrogen exchanger in the heart and vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links both disorders and may underlie their interplay. Insulin insensitivity and adipokine abnormalities (the hallmarks of type 2 diabetes mellitus) are characteristic features of heart failure; conversely, neurohormonal systems activated in heart failure (norepinephrine, angiotensin II, aldosterone, and neprilysin) impair insulin sensitivity and contribute to microvascular disease in diabetes mellitus. Each of these neurohormonal derangements may act through increased activity of both NHE1 and NHE3. Drugs used to treat diabetes mellitus may favorably affect the pathophysiological mechanisms of heart failure by inhibiting either or both NHE isoforms, and drugs used to treat heart failure may have beneficial effects on glucose tolerance and the complications of diabetes mellitus by interfering with the actions of NHE1 and NHE3. The efficacy of NHE inhibitors on the risk of cardiovascular events may be enhanced when heart failure and glucose intolerance coexist and may be attenuated when drugs with NHE inhibitory actions are given concomitantly. Therefore, the sodium-hydrogen exchanger may play a central role in the interplay of diabetes mellitus and heart failure, contribute to the physiological and clinical progression of both diseases, and explain certain drug-drug and drug-disease interactions that have been reported in large-scale randomized clinical trials. © 2017 American Heart Association, Inc.

  7. A realist evaluation of social prescribing: an exploration into the context and mechanisms underpinning a pathway linking primary care with the voluntary sector.

    Science.gov (United States)

    Bertotti, Marcello; Frostick, Caroline; Hutt, Patrick; Sohanpal, Ratna; Carnes, Dawn

    2018-05-01

    This article adopts a realist approach to evaluate a social prescribing pilot in the areas of Hackney and City in London (United Kingdom). It unpacks the contextual factors and mechanisms that influenced the development of this pilot for the benefits of GPs, commissioners and practitioners, and reflects on the realist approach to evaluation as a tool for the evaluation of health interventions. Primary care faces considerable challenges including the increase in long-term conditions, GP consultation rates, and widening health inequalities. With its emphasis on linking primary care to non-clinical community services via a social prescribing coordinator (SPC), some models of social prescribing could contribute to reduce the burden on primary care, tackle health inequalities and encourage people to make greater use of non-clinical forms of support. This realist analysis was based on qualitative interviews with users, commissioners, a GP survey, focus groups and learning events to explore stakeholders' experience. To enable a detailed analysis, we adapted the realist approach by subdividing the social prescribing pathway into stages, each with contextual factors, mechanisms and outcomes. SPCs were pivotal to the effective functioning of the social prescribing service and responsible for the activation and initial beneficial impact on users. Although social prescribing shows significant potential for the benefit of patients and primary care, several challenges need to be considered and overcome, including 'buy in' from some GPs, branding, and funding for the third sector in a context where social care cuts are severely affecting the delivery of health care. With its emphasis on context and mechanisms, the realist evaluation approach is useful in understanding how to identify and improve health interventions, and analyse in greater detail the contribution of different stakeholders. As the SPC is central to social prescribing, more needs to be done to understand their role

  8. Effect of silver and indium addition on mechanical properties and indentation creep behavior of rapidly solidified Bi–Sn based lead-free solder alloys

    International Nuclear Information System (INIS)

    Shalaby, Rizk Mostafa

    2013-01-01

    Mechanical properties and indentation creep of the melt-spun process Bi–42 wt%Sn, Bi–40 wt%Sn–2 wt%In, Bi–40 wt%Sn–2 wt%Ag and Bi–38 wt%Sn–2 wt%In–2 wt%Ag were studied by dynamic resonance technique and Vickers indentation testing at room temperature and compared to that of the traditional Sn–37 wt%Pb eutectic alloy. The results show that the structure of Bi–42 wt%Sn alloy is characterized by the presence of rhombohedral Bi and body centered tetragonal β-Sn. The two ternary alloys exhibit additional constituent phases of intermetallic compounds SnIn 19 for Bi–40 wt%Sn–2 wt%In and ε-Ag 3 Sn for Bi–40 wt%Sn–2 wt%Ag alloys. Attention has been paid to the role of intermetallic compounds on mechanical and creep behavior. The In and Ag containing solder alloy exhibited a good combination of higher creep resistance, good mechanical properties and lower melting temperature as compared with Pb–Sn eutectic solder alloy. This was attributed to the strengthening effect of Bi as a strong solid solution element in the Sn matrix and formation of intermetallic compounds β-SnBi, ε-Ag 3 Sn and InSn 19 which act as both strengthening agent and grain refiner in the matrix of the material. Addition of In and Ag decreased the melting temperature of Bi–Sn lead-free solder from 143 °C to 133 °C which was possible mainly due to the existence of InSn 19 and Ag 3 Sn intermetallic compounds. Elastic constants, internal friction and thermal properties of Bi–Sn based alloys have been studied and analyzed.

  9. Down-regulation of osmotin (PR5) gene by virus-induced gene silencing (VIGS) leads to susceptibility of resistant Piper colubrinum Link. to the oomycete pathogen Phytophthora capsici Leonian.

    Science.gov (United States)

    Anu, K; Jessymol, K K; Chidambareswaren, M; Gayathri, G S; Manjula, S

    2015-06-01

    Piper colubrinum Link., a distant relative of Piper nigrum L., is immune to the oomycete pathogen Phytophthora capsici Leonian that causes 'quick wilt' in cultivated black pepper (P. nigrum). The osmotin, PR5 gene homologue, earlier identified from P. colubrinum, showed significant overexpression in response to pathogen and defense signalling molecules. The present study focuses on the functional validation of P. colubrinum osmotin (PcOSM) by virus induced gene silencing (VIGS) using Tobacco Rattle Virus (TRV)-based vector. P. colubrinum plants maintained under controlled growth conditions in a growth chamber were infiltrated with Agrobacterium carrying TRV empty vector (control) and TRV vector carrying PcOSM. Three weeks post infiltration, viral movement was confirmed in newly emerged leaves of infiltrated plants by RT-PCR using TRV RNA1 and TRV RNA2 primers. Semi-quantitative RT-PCR confirmed significant down-regulation of PcOSM gene in TRV-PcOSM infiltrated plant compared with the control plants. The control and silenced plants were challenged with Phytophthora capsici which demonstrated that knock-down of PcOSM in P. colubrinum leads to increased fungal mycelial growth in silenced plants compared to control plants, which was accompanied by decreased accumulation of H2O2 as indicated by 3,3'-diaminobenzidine (DAB) staining. Thus, in this study, we demonstrated that Piper colubrinum osmotin gene is required for resisting P. capsici infection and has possible role in hypersensitive cell death response and oxidative burst signaling during infection.

  10. Highly effective removal of mercury and lead ions from wastewater by mercaptoamine-functionalised silica-coated magnetic nano-adsorbents: Behaviours and mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Shuangyou; Li, Kai; Ning, Ping [Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, YunNan, KunMing, 650500 (China); Peng, Jinhui [Faculty of Metallurgical and Energy, Kunming University of Science and Technology, YunNan, KunMing 650500 (China); Jin, Xu [Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, YunNan, KunMing, 650500 (China); Tang, Lihong, E-mail: luckyman@163.com [Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, YunNan, KunMing, 650500 (China)

    2017-01-30

    Highlights: • Highly effective removal of Hg(II) and Pb(II) ions from wastewater. • This adsorbent had multiple adsorption sites (sulfur and amine sites) on the surface. • This adsorbent had better tolerance to low pH for removal of Hg(II). • This new hybrid material was much cheaper and no secondary pollution. • This adsorbent shows notable advantages including easy separation and recyclability. - Abstract: A novel hybrid material was fabricated using mercaptoamine-functionalised silica-coated magnetic nanoparticles (MAF-SCMNPs) and was effective in the extraction and recovery of mercury and lead ions from wastewater. The properties of this new magnetic material were explored using various characterisation and analysis methods. Adsorbent amounts, pH levels and initial concentrations were optimised to improve removal efficiency. Additionally, kinetics, thermodynamics and adsorption isotherms were investigated to determine the mechanism by which the fabricated MAF-SCMNPs adsorb heavy metal ions. The results revealed that MAF-SCMNPs were acid-resistant. Sorption likely occurred by chelation through the amine group and ion exchange between heavy metal ions and thiol functional groups on the nanoadsorbent surface. The equilibrium was attained within 120 min, and the adsorption kinetics showed pseudo-second-order (R{sup 2} > 0.99). The mercury and lead adsorption isotherms were in agreement with the Freundlich model, displaying maximum adsorption capacities of 355 and 292 mg/g, respectively. The maximum adsorptions took place at pH 5–6 and 6–7 for Hg(II) and Pb(II), respectively. The maximum adsorptions were observed at 10 mg and 12 mg adsorbent quantities for Hg(II) and Pb(II), respectively. The adsorption process was endothermic and spontaneous within the temperature range of 298–318 K. This work demonstrates a unique magnetic nano-adsorbent for the removal of Hg(II) and Pb(II) from wastewater.

  11. How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

    2015-03-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  12. Linking Theoretical Decision-making Mechanisms in the Simon Task with Electrophysiological Data: A Model-based Neuroscience Study in Humans.

    Science.gov (United States)

    Servant, Mathieu; White, Corey; Montagnini, Anna; Burle, Borís

    2016-10-01

    A current challenge for decision-making research is in extending models of simple decisions to more complex and ecological choice situations. Conflict tasks (e.g., Simon, Stroop, Eriksen flanker) have been the focus of much interest, because they provide a decision-making context representative of everyday life experiences. Modeling efforts have led to an elaborated drift diffusion model for conflict tasks (DMC), which implements a superimposition of automatic and controlled decision activations. The DMC has proven to capture the diversity of behavioral conflict effects across various task contexts. This study combined DMC predictions with EEG and EMG measurements to test a set of linking propositions that specify the relationship between theoretical decision-making mechanisms involved in the Simon task and brain activity. Our results are consistent with a representation of the superimposed decision variable in the primary motor cortices. The decision variable was also observed in the EMG activity of response agonist muscles. These findings provide new insight into the neurophysiology of human decision-making. In return, they provide support for the DMC model framework.

  13. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  14. How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

    Science.gov (United States)

    Vandervert, Larry

    2015-01-01

    Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models

  15. Study and understanding of the ageing mechanisms in lead-calcium alloys; Etude et comprehension des mecanismes de vieillissement des alliages de plomb-calcium

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, F

    2006-12-15

    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)

  16. Lead poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Beijers, J A

    1952-01-01

    Three cases of acute lead poisoning of cattle herds via ingestion are reported, and reference is made to several other incidents of lead in both humans and animals. The quantity of lead which was found in the livers of the dead cows varied from 6.5 to 19 mg/kg, while 1160 mg/kg of lead in the liver was found for a young cow which was poisoned experimentally with 5 gms of lead acetate per day; hence, there appears to be great variability in the amounts deposited that can lead to intoxication and death. No evidence was found for a lead seam around the teeth, prophyrinuria, or basophil granules in the erythrocytes during acute or chronic lead poisoning of cattle or horses examined. Reference is made to attempts of finding the boundary line between increased lead absorption and lead intoxication in humans, and an examination of 60 laborers in an offset-printing office containing a great deal of inhalable lead (0.16 to 1.9 mg/cu m air) is reviewed. Physical deviation, basophylic granulation of erythrocytes, increased lead content of the urine, and porphyrinuria only indicate an increased absorption of lead; the use of the term intoxication is justified if, in addition, there are complaints of lack of appetite, constipation, fatigue, abdominal pain, and emaciation.

  17. Lead Toxicity

    Science.gov (United States)

    ... o Do not use glazed ceramics, home remedies, cosmetics, or leaded-crystal glassware unless you know that they are lead safe. o If you live near an industry, mine, or waste site that may have contaminated ...

  18. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  19. Lead Test

    Science.gov (United States)

    ... to do renovation and repair projects using lead-safe work practices to avoid creating more lead dust or ... in a dangerous area? Yes. If you are working in a potentially harmful environment with exposure to lead dust or fumes: Wash ...

  20. Interaction of infectious spleen and kidney necrosis virus ORF119L with PINCH leads to dominant-negative inhibition of integrin-linked kinase and cardiovascular defects in zebrafish.

    Science.gov (United States)

    Yuan, Ji-Min; He, Bai-Liang; Yang, Lu-Yun; Guo, Chang-Jun; Weng, Shao-Ping; Li, Shengwen Calvin; He, Jian-Guo

    2015-01-01

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus, Iridoviridae family, causing a severe systemic disease with high mortality in mandarin fish (Siniperca chuatsi) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction in vitro in fathead minnow (FHM) cells. In vivo ORF119L overexpression in zebrafish (Danio rerio) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis. Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly

  1. Effects of aging time on the mechanical properties of Sn–9Zn–1.5Ag–xBi lead-free solder alloys

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chih-Yao [Department of Materials Science and Engineering, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70101, Taiwan (China); Hon, Min-Hsiung [Department of Materials Science and Engineering, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70101, Taiwan (China); Department of Mechanical Engineering, National Kaohsiung University of Applied Sciences, 415 Chien-Kung Road, Kaohsiung 80782, Taiwan (China); Wang, Moo-Chin, E-mail: mcwang@kmu.edu.tw [Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80728, Taiwan (China); Chen, Ying-Ru; Chang, Kuo-Ming; Li, Wang-Long [Institute of Nanotechnology and Microsystems Engineering, National Cheng Kung University, No. 1, University Road, Tainan 70101, Taiwan (China)

    2014-01-05

    Highlights: • The microstructure of these solder alloys are composed of Sn-rich phase and Ag{sub 3}Sn. • The grain size of Sn–9Zn–1.5Ag–xBi solder alloys increases with rose aging time. • The maximum yield strength is 112.7 ± 2.2 MPa for Sn–9Zn–1.5Ag–3Bi solder alloys. • TEM observed that Bi appears as oblong shape fine particles. -- Abstract: The effects of aging time on the mechanical properties of the Sn–9Zn–1.5Ag–xBi lead-free solder alloys are investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive spectrometry (EDS) and a universal testing machine. The experimental results show that the microstructure of Sn–9Zn–1.5Ag–xBi solder alloys is composed of Sn-rich phase and AgZn{sub 3}. No other intermetallic compounds (IMCs) with Bi content was observed in the solder matrix for Sn–9Zn–1.5Ag solder alloys with various Bi contents before and after aging at 150 °C for different durations. The lattice parameter increases significantly with increasing aging time or Bi addition. The size of Sn-rich grain increased gradually with aging time increased, but decreases with Bi content increases. The maximum yield strength is 112.7 ± 2.2 MPa for Sn–9Zn–1.5Ag–3Bi solder alloy before aging.

  2. Effects of aging time on the mechanical properties of Sn–9Zn–1.5Ag–xBi lead-free solder alloys

    International Nuclear Information System (INIS)

    Liu, Chih-Yao; Hon, Min-Hsiung; Wang, Moo-Chin; Chen, Ying-Ru; Chang, Kuo-Ming; Li, Wang-Long

    2014-01-01

    Highlights: • The microstructure of these solder alloys are composed of Sn-rich phase and Ag 3 Sn. • The grain size of Sn–9Zn–1.5Ag–xBi solder alloys increases with rose aging time. • The maximum yield strength is 112.7 ± 2.2 MPa for Sn–9Zn–1.5Ag–3Bi solder alloys. • TEM observed that Bi appears as oblong shape fine particles. -- Abstract: The effects of aging time on the mechanical properties of the Sn–9Zn–1.5Ag–xBi lead-free solder alloys are investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive spectrometry (EDS) and a universal testing machine. The experimental results show that the microstructure of Sn–9Zn–1.5Ag–xBi solder alloys is composed of Sn-rich phase and AgZn 3 . No other intermetallic compounds (IMCs) with Bi content was observed in the solder matrix for Sn–9Zn–1.5Ag solder alloys with various Bi contents before and after aging at 150 °C for different durations. The lattice parameter increases significantly with increasing aging time or Bi addition. The size of Sn-rich grain increased gradually with aging time increased, but decreases with Bi content increases. The maximum yield strength is 112.7 ± 2.2 MPa for Sn–9Zn–1.5Ag–3Bi solder alloy before aging

  3. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  4. The Formation Mechanism of Hydrogels.

    Science.gov (United States)

    Lu, Liyan; Yuan, Shiliang; Wang, Jing; Shen, Yun; Deng, Shuwen; Xie, Luyang; Yang, Qixiang

    2017-06-12

    Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By cross-linking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternate solution for cross-linker toxicity. Both methods will be discussed in this essay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking.

    Science.gov (United States)

    Channar, Pervaiz Ali; Saeed, Aamer; Albericio, Fernando; Larik, Fayaz Ali; Abbas, Qamar; Hassan, Mubashir; Raza, Hussain; Seo, Sung-Yum

    2017-08-16

    Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC 50 = 0.081 ± 0.003 µM), 6a (IC 50 = 0.0022 ± 0.0002 µM), 9e (IC 50 = 0.0250 ± 0.0007 µM) and 12d (IC 50 = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC 50 = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e , 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a , 12b , 12d , 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C.

  6. Leading Democratically

    Science.gov (United States)

    Brookfield, Stephen

    2010-01-01

    Democracy is the most venerated of American ideas, the one for which wars are fought and people die. So most people would probably agree that leaders should be able to lead well in a democratic society. Yet, genuinely democratic leadership is a relative rarity. Leading democratically means viewing leadership as a function or process, rather than…

  7. Disentangling mechanisms involved in collagen pyridinoline cross-linking : The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2

    NARCIS (Netherlands)

    Gjaltema, Rutger A. F.; van der Stoel, Miesje M.; Boersema, Miriam; Bank, Ruud A.

    2016-01-01

    Collagens are subjected to extensive posttranslational modifications, such as lysine hydroxylation. Bruck syndrome (BS) is a connective tissue disorder characterized at the molecular level by a loss of telopeptide lysine hydroxylation, resulting in reduced collagen pyridinoline cross-linking. BS

  8. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  9. Suppression of alpha-tocopherol ether-linked acetic acid in VEGF-induced angiogenesis and the possible mechanisms in human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Chuang, Cheng-Hung; Liu, Chia-Hua; Lu, Ta-Jung; Hu, Miao-Lin

    2014-01-01

    Alpha-tocopherol ether-linked acetic acid (α-TEA) has been reported to exhibit both anti-tumor and anti-metastatic activities in cell culture and animal studies. However, it is unclear whether α-TEA possesses anti-angiogenic effects. In this study, we investigated the effect of α-TEA on vascular endothelial growth factor (VEGF)-induced angiogenesis and matrix metalloproteinase (MMP) expression both in vitro and ex vivo. We found that the α-TEA inhibited tube formation, invasion, and migration in human umbilical vein endothelial cells (HUVECs) and that such actions were accompanied by reduced expression of MMP-2. α-TEA also inhibited ex vivo angiogenesis, as indicated by chicken egg chorioallantoic membrane assay. We further showed that α-TEA attenuated protein expression of VEGF receptor-2 (VEGFR-2)-mediated p38 mitogen-activated protein kinase (p38), phosphorylated p38, and focal adhesion kinase (FAK). Moreover, α-TEA (30 μM) significantly up-regulated protein expression of tissue inhibitors of MMP (TIMP)-2 (by 138%) and the metastasis suppressor gene nm23-H1 (by 54%). These results demonstrate that the anti-angiogenic effect of α-TEA both in vitro and ex vivo and its possible mechanistic action appears to involve the inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways and through up-regulation of TIMP-2 and nm23-H1 expression. - Graphical abstract: Possible mechanisms of α-TEA on inhibited angiogenesis of human umbilical vein endothelial cells. Brief summary In the present study, we have demonstrated that VEGF-mediated angiogenesis is significantly inhibited by α-TEA, and that this effect involves inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways related to invasion and migration. - Highlights: • The anti-angiogenic effect and the mechanistic action of α-TEA were investigated. • α-TEA significantly inhibited VEGF-mediated angiogenesis both in vitro and ex vivo. • α-TEA down

  10. Suppression of alpha-tocopherol ether-linked acetic acid in VEGF-induced angiogenesis and the possible mechanisms in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Cheng-Hung, E-mail: chchuang@hk.edu.tw [Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, 1018 Sec. 6 Taiwan Boulevard, Taichung 43302, Taiwan, ROC (China); Liu, Chia-Hua [Department of Food Science and Biotechnology, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China); Lu, Ta-Jung [Department of Chemistry, Institute of Technology and Innovation Management, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China); Hu, Miao-Lin, E-mail: mlhuhu@dragon.nchu.edu.tw [Department of Food Science and Biotechnology, National Chung-Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan, ROC (China)

    2014-12-15

    Alpha-tocopherol ether-linked acetic acid (α-TEA) has been reported to exhibit both anti-tumor and anti-metastatic activities in cell culture and animal studies. However, it is unclear whether α-TEA possesses anti-angiogenic effects. In this study, we investigated the effect of α-TEA on vascular endothelial growth factor (VEGF)-induced angiogenesis and matrix metalloproteinase (MMP) expression both in vitro and ex vivo. We found that the α-TEA inhibited tube formation, invasion, and migration in human umbilical vein endothelial cells (HUVECs) and that such actions were accompanied by reduced expression of MMP-2. α-TEA also inhibited ex vivo angiogenesis, as indicated by chicken egg chorioallantoic membrane assay. We further showed that α-TEA attenuated protein expression of VEGF receptor-2 (VEGFR-2)-mediated p38 mitogen-activated protein kinase (p38), phosphorylated p38, and focal adhesion kinase (FAK). Moreover, α-TEA (30 μM) significantly up-regulated protein expression of tissue inhibitors of MMP (TIMP)-2 (by 138%) and the metastasis suppressor gene nm23-H1 (by 54%). These results demonstrate that the anti-angiogenic effect of α-TEA both in vitro and ex vivo and its possible mechanistic action appears to involve the inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways and through up-regulation of TIMP-2 and nm23-H1 expression. - Graphical abstract: Possible mechanisms of α-TEA on inhibited angiogenesis of human umbilical vein endothelial cells. Brief summary In the present study, we have demonstrated that VEGF-mediated angiogenesis is significantly inhibited by α-TEA, and that this effect involves inhibition of MMP-2 level through VEGFR-2-mediated FAK and p38 signaling pathways related to invasion and migration. - Highlights: • The anti-angiogenic effect and the mechanistic action of α-TEA were investigated. • α-TEA significantly inhibited VEGF-mediated angiogenesis both in vitro and ex vivo. • α-TEA down

  11. Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H ß-synuclein

    Directory of Open Access Journals (Sweden)

    Sekigawa Akio

    2012-09-01

    Full Text Available Abstract Background Axonopathy is critical in the early pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD and dementia with Lewy bodies (DLB. Axonal swellings such as globules and spheroids are a distinct feature of axonopathy and our recent study showed that transgenic (tg mice expressing DLB-linked P123H β-synuclein (P123H βS were characterized by P123H βS-immunoreactive axonal swellings (P123H βS-globules. Therefore, the objectives of this study were to evaluate α-synuclein (αS-immunoreactive axonal swellings (αS-globules in the brains of tg mice expressing human wild-type αS and to compare them with the globules in P123H βS tg mice. Results In αS tg mice, αS-globules were formed in an age-dependent manner in various brain regions, including the thalamus and basal ganglia. These globules were composed of autophagosome-like membranous structures and were reminiscent of P123H βS-globules in P123H βS tg mice. In the αS-globules, frequent clustering and deformation of mitochondria were observed. These changes were associated with oxidative stress, based on staining of nitrated αS and 4-hydroxy-2-nonenal (4-HNE. In accord with the absence of mitochondria in the P123H βS-globules, staining of nitrated αS and 4-HNE in these globules was weaker than that for αS-globules. Leucine-rich repeat kinase 2 (LRRK2, the PARK8 of familial PD, was detected exclusively in αS-globules, suggesting a specific role of this molecule in these globules. Conclusions Lysosomal pathology was similarly observed for both αS- and P123H βS-globules, while oxidative stress was associated with the αS-globules, and to a lesser extent with the P123H βS-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for αS-globules. Collectively, both αS- and P123H βS-globules were formed through similar but distinct pathogenic mechanisms. Our findings suggest that synuclein

  12. Puzzling Mechanisms

    Science.gov (United States)

    van Deventer, M. Oskar

    2009-01-01

    The basis of a good mechanical puzzle is often a puzzling mechanism. This article will introduce some new puzzling mechanisms, like two knots that engage like gears, a chain whose links can be interchanged, and flat gears that do not come apart. It illustrates how puzzling mechanisms can be transformed into real mechanical puzzles, e.g., by…

  13. Leading change.

    Science.gov (United States)

    2017-02-27

    In response to feedback from nursing, midwifery and other care staff who wanted to understand better how the Leading Change, Adding Value framework applies to them, NHS England has updated its webpage to include practice examples.

  14. Depression And The Link With Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Arup Kumar Dhar

    2016-03-01

    Full Text Available This review provides an outline of the association between major depressive disorder (MDD and coronary heart disease (CHD. Much is known about the two individual clinical conditions; however it is not until recently, that biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors such as major depression and stress are now known as risk factors for developing CHD which is as important and is independent of classic risk factors such as hypertension, diabetes mellitus and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments.

  15. Effect of Cross-Linking on the Mechanical and Thermal Properties of Poly(amidoamine Dendrimer/Poly(vinyl alcohol Hybrid Membranes for CO2 Separation

    Directory of Open Access Journals (Sweden)

    Shuhong Duan

    2014-04-01

    Full Text Available Poly(amidoamine (PAMAM dendrimers were incorporated into cross-linked poly(vinyl alcohol (PVA matrix to improve carbon dioxide (CO2 separation performance at elevated pressures. In our previous studies, PAMAM/PVA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, three types of organic Ti metal compounds were selected as PVA cross-linkers that were used to prepare PAMAM/cross-linked PVA hybrid membranes. Characterization of the PAMAM/cross-linked PVA hybrid membranes was conducted using nanoindentation and thermogravimetric analyses. The effects of the cross-linker and CO2 partial pressure in the feed gas on CO2 separation performance were discussed. H2O and CO2 sorption of the PAMAM/PVA hybrid membranes were investigated to explain the obtained CO2 separation efficiencies.

  16. Effect of Cross-Linking on the Mechanical and Thermal Properties of Poly(amidoamine) Dendrimer/Poly(vinyl alcohol) Hybrid Membranes for CO2 Separation.

    Science.gov (United States)

    Duan, Shuhong; Kai, Teruhiko; Saito, Takashi; Yamazaki, Kota; Ikeda, Kenichi

    2014-04-08

    Poly(amidoamine) (PAMAM) dendrimers were incorporated into cross-linked poly(vinyl alcohol) (PVA) matrix to improve carbon dioxide (CO2) separation performance at elevated pressures. In our previous studies, PAMAM/PVA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, three types of organic Ti metal compounds were selected as PVA cross-linkers that were used to prepare PAMAM/cross-linked PVA hybrid membranes. Characterization of the PAMAM/cross-linked PVA hybrid membranes was conducted using nanoindentation and thermogravimetric analyses. The effects of the cross-linker and CO2 partial pressure in the feed gas on CO2 separation performance were discussed. H2O and CO2 sorption of the PAMAM/PVA hybrid membranes were investigated to explain the obtained CO2 separation efficiencies.

  17. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  18. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  19. Operative Links

    DEFF Research Database (Denmark)

    Wistoft, Karen; Højlund, Holger

    2012-01-01

    and have been the object of great expectations concerning the ability to incorporate health concerns into every welfare area through health promotion strategies. The paper draws on results and analyses of a collective research project funded by the Danish National Research Council and carried out...... links' that indicate cooperative levels which facilitate a creative and innovative effort in disease prevention and health promotion targeted at children and adolescents - across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

  20. Linking GHG Emission Trading Systems and Markets

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    Several different types of links are possible between different GHG-mitigation systems. These include: Linking two or more emission trading schemes so that emissions trading can occur both within and between different schemes ('direct links'); and Linking emission trading systems to registries/mechanisms and systems that generate offsets from project based mechanisms or from direct purchases/transfers of AAUs ('indirect links').

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of many drugs, which can alter judgment and inhibition and lead people to engage in impulsive and ... easily copy and paste to help show your support for Learn the Link . Be sure to check ...

  2. X‐linked retinoschisis: an update

    Science.gov (United States)

    Sikkink, Stephen K; Biswas, Susmito; Parry, Neil R A; Stanga, Paulo E; Trump, Dorothy

    2007-01-01

    X‐linked retinoschisis is the leading cause of macular degeneration in males and leads to splitting within the inner retinal layers leading to visual deterioration. Many missense and protein truncating mutations have now been identified in the causative retinoschisis gene (RS1) which encodes a 224 amino acid secreting retinal protein, retinoschisin. Retinoschisin octamerises is implicated in cell–cell interactions and cell adhesion perhaps by interacting with β2 laminin. Mutations cause loss of retinoschisin function by one of the three mechanisms: by interfering with protein secretion, by preventing its octamerisation or by reducing function in the secreted octamerised protein. The development of retinoschisis mouse models have provided a model system that closely resembles the human disease. Recent reports of RS1 gene transfer to these models and the sustained restoration of some retinal function and morphology suggest gene replacement may be a possible future therapy for patients. PMID:17172462

  3. Scandinavian links

    DEFF Research Database (Denmark)

    Matthiessen, Christian Wichmann; Knowles, Richard D.

    2014-01-01

    are impressive mega structures spanning international waterways. These waterways between the Baltic Sea and the North Sea have played major roles in history. The length of each of the crossings are around 20 km. The fixed links closes gaps between the Scandinavian and European motorway and rail networks...

  4. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  5. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc and copper. Progress report, January 1, 1980-December 31, 1980

    International Nuclear Information System (INIS)

    Wasserman, R.H.

    1980-01-01

    Investigations were continued to elucidate the mode of transepithelial transport of toxic metal ions across the gastrointestinal tract, as well as their interactions with biological processes and other metal ions. All experimental details that are either published, submitted for publication or in press during this report period are included in the Appendix. Primary attention for this report has been given to the intestinal absorption of lead and its interaction with other biological moieties

  6. Underlying mechanisms leading to El Niño-to-La Niña transition are unchanged under global warming

    Science.gov (United States)

    Yun, Kyung-Sook; Yeh, Sang-Wook; Ha, Kyung-Ja

    2018-05-01

    El Niño's transitions play critical roles in modulating severe weather and climate events. Therefore, understanding the dynamic factors leading to El Niño's transitions and its future projection is a great challenge in predicting the diverse socioeconomic influences of El Niño over the globe. This study focuses on two dynamic factors controlling the El Niño-to-La Niña transition from the present climate and to future climate, using the observation, the historical and the RCP8.5 simulations of Coupled Model Intercomparison phase 5 climate models. The first is the inter-basin coupling between the Indian Ocean and the western North Pacific through the subtropical high variability. The second is the enhanced sensitivity between sea surface temperature and a deep tropical convection in the central tropical Pacific during the El Niño's developing phase. We show that the dynamic factors leading to El Niño-to-La Niña transition in the present climate are unchanged in spite of the increase of greenhouse gas concentrations. We argue that the two dynamic factors are strongly constrained by the climatological precipitation distribution over the central tropical Pacific and western North Pacific as little changed from the present climate to future climate. This implies that two dynamical processes leading to El Niño-to-La Niña transitions in the present climate will also play a robust role in global warming.

  7. The recombination mechanisms leading to amplified spontaneous emission at the true-green wavelength in CH3NH3PbBr3 perovskites

    KAUST Repository

    Priante, Davide; Dursun, Ibrahim; Alias, M. S.; Shi, Dong; Melnikov, V. A.; Ng, Tien Khee; Mohammed, Omar F.; Bakr, Osman; Ooi, Boon S.

    2015-01-01

    We investigated the mechanisms of radiative recombination in a CH3NH3PbBr3 hybrid perovskite material using low-temperature, power-dependent (77K), and temperature-dependent photoluminescence (PL) measurements. Two bound-excitonic radiative

  8. Effect of micron size Ni particle addition in Sn–8Zn–3Bi lead-free solder alloy on the microstructure, thermal and mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Billah, Md. Muktadir; Shorowordi, Kazi Mohammad; Sharif, Ahmed, E-mail: asharif@mme.buet.ac.bd

    2014-02-05

    Highlights: • Ni-added Sn-Zn-Bi were characterized metallographically, thermally and mechanically. • The volume fraction of α-Zn phase increased with both Bi and Ni in Sn-Zn-Bi alloys. • Micron-sized Ni particles reacted with neither Sn nor Zn to form intermetallics. • Better combination of thermal and mechanical properties can be achieved with Ni. -- Abstract: Micron-sized Ni particle-reinforced Sn–8Zn–3Bi composite solders were prepared by mechanically dispersing Ni particles into Sn–8Zn–3Bi alloy and the bulk properties of the composite solder alloy were characterized metallographically, thermally and mechanically. Different percentage of Ni particle viz. 0.25, 0.5 and 1 wt.% were added in the liquid Sn–8Zn–3Bi alloy and then cast into the metal molds. Melting behavior was studied by differential thermal analyzer (DTA). Microstructural investigation was carried out by both optical and scanning electron microscope. Tensile properties were determined using an Instron Universal Testing Machine at a strain rate 3.00 mm/min. The results indicated that the Ni addition increased the melting temperature of Sn–8Zn–3Bi alloy. The addition of Ni was also found to increase the solidification range. In the Sn–8Zn–3Bi alloy, needle-shaped α-Zn phase was found to be uniformly distributed in the β-Sn matrix. However, it was found that the small amount of Ni addition in Sn–8Zn–3Bi alloy refined the Zn needles throughout the matrix. Also an enhanced precipitation of Zn in the structure was observed with the addition of Ni. All these structural changes improved the mechanical properties like tensile strength and hardness of the newly developed quaternary alloy.

  9. Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

    Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

  10. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  11. The interrelation between mechanical properties, corrosion resistance and microstructure of Pb-Sn casting alloys for lead-acid battery components

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto, Leandro C.; Osorio, Wislei R.; Garcia, Amauri [Department of Materials Engineering, University of Campinas - UNICAMP, PO Box 6122, 13083-970, Campinas - SP (Brazil)

    2010-01-15

    It is well known that there is a strong influence of thermal processing variables on the solidification structure and as a direct consequence on the casting final properties. The morphological microstructural parameters such as grain size and cellular or dendritic spacings will depend on the heat transfer conditions imposed by the metal/mould system. There is a need to improve the understanding of the interrelation between the microstructure, mechanical properties and corrosion resistance of dilute Pb-Sn casting alloys which are widely used in the manufacture of battery components. The present study has established correlations between cellular microstructure, ultimate tensile strength and corrosion resistance of Pb-1 wt% Sn and Pb-2.5 wt% Sn alloys by providing a combined plot of these properties as a function of cell spacing. It was found that a compromise between good corrosion resistance and good mechanical properties can be attained by choosing an appropriate cell spacing range. (author)

  12. A quantum chemical study of the mechanism for proton-coupled electron transfer leading to proton pumping in cytochrome c oxidase

    Science.gov (United States)

    Blomberg, Margareta R. A.; Siegbahn, Per E. M.

    2010-10-01

    The proton pumping mechanism in cytochrome c oxidase, the terminal enzyme in the respiratory chain, has been investigated using hybrid DFT with large chemical models. In previous studies, a gating mechanism was suggested based on electrostatic interpretations of kinetic experiments. The predictions from that analysis are tested here. The main result is that the suggestion of a positively charged transition state for proton transfer is confirmed, while some other suggestions for the gating are not supported. It is shown that a few critical relative energy values from the earlier studies are reproduced with quite high accuracy using the present model calculations. Examples are the forward barrier for proton transfer from the N-side of the membrane to the pump-loading site when the heme a cofactor is reduced, and the corresponding back leakage barrier when heme a is oxidised. An interesting new finding is an unexpected double-well potential for proton transfer from the N-side to the pump-loading site. In the intermediate between the two transition states found, the proton is bound to PropD on heme a. A possible purpose of this type of potential surface is suggested here. The accuracy of the present values are discussed in terms of their sensitivity to the choice of dielectric constant. Only one energy value, which is not critical for the present mechanism, varies significantly with this choice and is therefore less certain.

  13. Linking climate change to community-level impacts on copepods via a new, trait-based model: Life-history and metabolic mechanisms compared

    DEFF Research Database (Denmark)

    Banas, Neil S.; Møller, Eva Friis; Nielsen, Torkel Gissel

    2017-01-01

    A new, trait-based copepod model ("Coltrane": Copepod Life-history Traits and Adaptation to Novel Environments) has been developed, drawing on past work on both optimal annual routines and trait-based plankton metacommunity models, in order to evaluate climate impacts on copepods via 1) phenology...... and physiology of local populations of C. finmarchicus, C. glacialis, and C. hyperboreus. Futhermore, the model replicates the observed range of stored lipid content of these copepod populations (30–60%, C. finmarchicus–C. hyperboreus), suggesting a means for linking changes in temperature and primary production...

  14. Linking climate change to community-level impacts on copepods via a new, trait-based model: Life-history and metabolic mechanisms compared

    DEFF Research Database (Denmark)

    Banas, Neil S.; Møller, Eva Friis; Nielsen, Torkel Gissel

    A new, trait-based copepod model ("Coltrane": Copepod Life-history Traits and Adaptation to Novel Environments) has been developed, drawing on past work on both optimal annual routines and trait-based plankton metacommunity models, in order to evaluate climate impacts on copepods via 1) phenology...... and physiology of local populations of C. finmarchicus, C. glacialis, and C. hyperboreus. Futhermore, the model replicates the observed range of stored lipid content of these copepod populations (30–60%, C. finmarchicus–C. hyperboreus), suggesting a means for linking changes in temperature and primary production...

  15. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

    2015-01-01

    of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide......, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose...

  16. Intoxication for lead

    International Nuclear Information System (INIS)

    Velez, Ruben Dario; Tamayo, Margarita Maria

    1999-01-01

    We present a case of a hospitalized girl with bronchopneumonia, who needed mechanic ventilation. Also she had a developmental delay and Burtons border in gums. Radiological studies showed dense transverse metaphiseal bands in long bones and hyperdensity in basal ganglia. We found high serum lead levels

  17. Anatomy of lead poisoning

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Results: The primary form of lead toxicity is by oxidative stress mechanisms, apoptosis and necrosis involving ... néfastes sur la reproduction à l'avenir. Résultats:La forme ... prostate cancers, abnormal sexual ..... ensure this work is a success.

  18. F-center mechanism of long-term relaxation in lead zirconate-titanate-based piezoelectric ceramics. 1. After-heating relaxation

    Directory of Open Access Journals (Sweden)

    V. M. Ishchuk

    2015-12-01

    The oxygen vacancies-based model for description of the long-time relaxation processes is suggested. The model takes into account oxygen vacancies on the sample’s surface ends, their conversion into F+- and F0-centers under external effects (due to the liberation of the pyroelectric charge and subsequent relaxation of these centers into the simple oxygen vacancies after the actions termination. The initial sample’s state is electroneutrality one. F-center formation leads to the violation of the original sample’s electroneutrality, and generates DC electric field into the sample. Relaxation of F-centers is accompanied by decreasing of electric field, induced by them, and dielectric constant relaxation as consequent effect.

  19. Specific cerebral heat shock proteins and histamine receptor cross-talking mechanisms promote distinct lead-dependent neurotoxic responses in teleosts

    International Nuclear Information System (INIS)

    Giusi, Giuseppina; Alo, Raffaella; Crudo, Michele; Facciolo, Rosa Maria; Canonaco, Marcello

    2008-01-01

    Recent interests are beginning to be directed towards toxic neurobiological dysfunctions caused by lead (Pb) in aquatic vertebrates. In the present work, treatment with a maximum acceptable toxic concentration of this heavy metal was responsible for highly significant (p 2 R) antagonist cimetidine (Cim), as shown by the very robust (p 3 R) thioperamide (Thio), instead, blocked Pb-dependent up-regulatory trends of both chaperones in mostly hypothalamic areas. Moreover, intense neuronal damages of the above brain regions coincided with altered expressions of HSP70 and HSP90 when treated only with Cim. Overall these first results show that distinct H n R are able to exert a net neuroprotective role arising from their interaction with chaperones in fish exposed to Pb-dependent stressful conditions making this a potentially key interaction especially for T. pavo, aquatic species which plays an important ecological role towards the survival of other commercially vital fishes

  20. Influence of SiO{sub 2} on conduction and relaxation mechanism of Li{sup +} ions in binary network former lead silicate glasses

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Navneet [Department of Physics, Chaudhary Devi Lal University, Sirsa 125055, Haryana (India); Ahlawat, Neetu, E-mail: neetugju@yahoo.co.in [Department of Applied Physics, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana (India); Aghamkar, Praveen [Department of Physics, Chaudhary Devi Lal University, Sirsa 125055, Haryana (India); Agarwal, Ashish; Sanghi, Sujata; Sindhu, Monica [Department of Applied Physics, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana (India)

    2013-04-01

    Ion conducting glasses having composition 30Li{sub 2}O·(70−x)PbO·xSiO{sub 2} were prepared by the normal melt quench technique. The compositional variations in density, molar volume and glass transition temperature confirm the dual role of PbO acting as a network modifying oxide as well as a network forming oxide. Conduction and relaxation mechanisms in these glasses were studied using impedance spectroscopy in the frequency range from 1 Hz to 7 MHz and in a temperature range below glass transition temperature. The ac and dc conductivities, activation energy of the dc conductivity and relaxation frequency were extracted from the impedance spectra. Similar values of activation energy for dc conduction and for conductivity relaxation time indicate that the ions have to overcome the same energy barrier while conducting and relaxing. The increase in dc conductivity for silica rich compositions is attributed to the presence of mixed former effect in the studied glasses. The study of conductivity spectra reveals a transition from non-random to random hopping motion of lithium ions on successive replacement of PbO by SiO{sub 2} in glass matrix. The conduction and relaxation mechanism in the studied glasses are well explained with the concept of mismatch and relaxation (CMR) model.

  1. Children’s Patterns of Emotional Reactivity to Conflict as Explanatory Mechanisms in Links Between Interpartner Aggression and Child Physiological Functioning

    Science.gov (United States)

    Davies, Patrick T.; Sturge-Apple, Melissa L.; Cicchetti, Dante; Manning, Liviah G.; Zale, Emily

    2009-01-01

    Background This paper examined children’s fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Methods Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children’s emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. Conclusions The results are interpreted within conceptualizations of how exposure and reactivity to family risk organizing individual differences in physiological functioning. PMID:19744183

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Visual attention in preterm born adults: specifically impaired attentional sub-mechanisms that link with altered intrinsic brain networks in a compensation-like mode.

    Science.gov (United States)

    Finke, Kathrin; Neitzel, Julia; Bäuml, Josef G; Redel, Petra; Müller, Hermann J; Meng, Chun; Jaekel, Julia; Daamen, Marcel; Scheef, Lukas; Busch, Barbara; Baumann, Nicole; Boecker, Henning; Bartmann, Peter; Habekost, Thomas; Wolke, Dieter; Wohlschläger, Afra; Sorg, Christian

    2015-02-15

    Although pronounced and lasting deficits in selective attention have been observed for preterm born individuals it is unknown which specific attentional sub-mechanisms are affected and how they relate to brain networks. We used the computationally specified 'Theory of Visual Attention' together with whole- and partial-report paradigms to compare attentional sub-mechanisms of pre- (n=33) and full-term (n=32) born adults. Resting-state fMRI was used to evaluate both between-group differences and inter-individual variance in changed functional connectivity of intrinsic brain networks relevant for visual attention. In preterm born adults, we found specific impairments of visual short-term memory (vSTM) storage capacity while other sub-mechanisms such as processing speed or attentional weighting were unchanged. Furthermore, changed functional connectivity was found in unimodal visual and supramodal attention-related intrinsic networks. Among preterm born adults, the individual pattern of changed connectivity in occipital and parietal cortices was systematically associated with vSTM in such a way that the more distinct the connectivity differences, the better the preterm adults' storage capacity. These findings provide first evidence for selectively changed attentional sub-mechanisms in preterm born adults and their relation to altered intrinsic brain networks. In particular, data suggest that cortical changes in intrinsic functional connectivity may compensate adverse developmental consequences of prematurity on visual short-term storage capacity. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Thermal and mechanical properties of lead-free SnZn–xNa casting alloys, and interfacial chemistry on Cu substrates during the soldering process

    Energy Technology Data Exchange (ETDEWEB)

    Gancarz, Tomasz, E-mail: tomasz.gancarz@imim.pl [Institute of Metallurgy and Materials Science, Polish Academy of Sciences, Krakow (Poland); Bobrowski, Piotr; Pstruś, Janusz [Institute of Metallurgy and Materials Science, Polish Academy of Sciences, Krakow (Poland); Pawlak, Sylwia [Wroclaw Research Centre EIT+, Wroclaw (Poland)

    2016-09-15

    The microstructural features, thermal properties and mechanical properties of eutectic Sn–Zn alloys with varying Na content (0.1, 0.2, 0.5, 1.0 3.0 and 5.0 at. %) were examined in this study. In the scanning electron microscopy, transmission electron microscopy, and X-ray diffraction analysis data, precipitates of NaSn were observed. The addition of Na to eutectic Sn–Zn alloy improved the mechanical properties and increased electrical resistivity, and reduced the coefficient of thermal expansion; however, the melting point did not change. Wettability tests carried out using Na-doped Sn–15Zn alloys on Cu substrates showed the formation of Cu–Zn phases at the interfaces. Wettability studies were performed using flux ALU33 after 60, 180, 480, 900, 1800 and 3600 s of contact, at temperatures of 230, 250, 280 and 320 °C. The experiments were designed to demonstrate the effect of Na addition on the formation and growth kinetics of Cu{sub 5}Zn{sub 8} and CuZn{sub 4} phases, which were identified using XRDs and EDS. The addition of Na to SnZn causes a reduction in the thickness of the intermetallic compounds layer created at the interface between the liquid solder and the Cu substrate, and an increase in the activation energy of the Cu{sub 5}Zn{sub 8} phase compared to eutectic SnZn. - Highlights: • Precipitates of NaSn was observed and confirmed using TEM and XRD. • Addition Na to eutectic SnZn cussed increased the mechanical properties. • IMCs of Na–Zn and Na–Sn increased electrical resistivity and reduced the CTE. • IMCs layers CuZn{sub 4} and Cu{sub 5}Zn{sub 8} was found at the interface. • Na content changing the character of growth CuZn{sub 4} layer in SnZnNa alloys.

  5. Mechanism of ({sup 14}N, {sup 12}B) reactions at intermediate energy leading to large spin-polarization of {sup 12}B

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuoka, Shin-ichi [Osaka Univ., Ibaraki (Japan). Research Center for Nuclear Physics; Shimoda, Tadashi; Miyatake, Hiroari [and others

    1996-05-01

    To study mechanisms of the ({sup 14}N, {sup 12}B) reactions at intermediate energies, double differential cross section and nuclear spin-polarization of the {sup 12}B projectile-like fragments have been measured as a function of longitudinal momentum in the angular range of 0deg - 9deg. Large spin-polarization of the reaction products {sup 12}B has been observed in the {sup 9}Be({sup 14}N, {sup 12}B) reaction at 39.3 MeV/u. The momentum distributions at forward angles exhibit characteristic features which can not be understood by the current projectile fragmentation picture. It is shown that by assuming the existence of direct two-proton transfer process in addition to the fragmentation process, both the cross section and polarization of {sup 12}B fragments are successfully explained. The target and incident energy dependence of the momentum distribution are also explained reasonably. (author)

  6. The recombination mechanisms leading to amplified spontaneous emission at the true-green wavelength in CH3NH3PbBr3 perovskites

    Science.gov (United States)

    Priante, D.; Dursun, I.; Alias, M. S.; Shi, D.; Melnikov, V. A.; Ng, T. K.; Mohammed, O. F.; Bakr, O. M.; Ooi, B. S.

    2015-02-01

    We investigated the mechanisms of radiative recombination in a CH3NH3PbBr3 hybrid perovskite material using low-temperature, power-dependent (77 K), and temperature-dependent photoluminescence (PL) measurements. Two bound-excitonic radiative transitions related to grain size inhomogeneity were identified. Both transitions led to PL spectra broadening as a result of concurrent blue and red shifts of these excitonic peaks. The red-shifted bound-excitonic peak dominated at high PL excitation led to a true-green wavelength of 553 nm for CH3NH3PbBr3 powders that are encapsulated in polydimethylsiloxane. Amplified spontaneous emission was eventually achieved for an excitation threshold energy of approximately 350 μJ/cm2. Our results provide a platform for potential extension towards a true-green light-emitting device for solid-state lighting and display applications.

  7. The recombination mechanisms leading to amplified spontaneous emission at the true-green wavelength in CH3NH3PbBr3 perovskites

    KAUST Repository

    Priante, Davide

    2015-02-23

    We investigated the mechanisms of radiative recombination in a CH3NH3PbBr3 hybrid perovskite material using low-temperature, power-dependent (77K), and temperature-dependent photoluminescence (PL) measurements. Two bound-excitonic radiative transitions related to grain size inhomogeneity were identified. Both transitions led to PL spectra broadening as a result of concurrent blue and red shifts of these excitonic peaks. The red-shifted bound-excitonic peak dominated at high PL excitation led to a true-green wavelength of 553nm for CH3NH3PbBr3 powders that are encapsulated in polydimethylsiloxane. Amplified spontaneous emission was eventually achieved for an excitation threshold energy of approximately 350μJ/cm2. Our results provide a platform for potential extension towards a true-green light-emitting device for solid-state lighting and display applications.

  8. Linking Ethics and Economic Growth

    DEFF Research Database (Denmark)

    Foss, Nicolai Juul

    2012-01-01

    Hunt (2012) builds on his work concerning ethics and resource-advantage theory to link personal ethical standards, societal norms, and economic growth but offers few details concerning the precise mechanisms that link ethics and growth. This comment suggests a number of such mechanisms – for exam...... – for example, the influence of prevailing ethical norms on the aggregate elasticity of substitution and, therefore, total factor productivity and growth....

  9. A heuristic model linking yoga philosophy and self-reflection to examine underlying mechanisms of add-on yoga treatment in schizophrenia.

    Science.gov (United States)

    Rao, Naren; Menon, Sangeetha

    2016-06-01

    Preliminary evidence suggests efficacy of yoga as add-on treatment for schizophrenia, but the underlying mechanism by which yoga improves the symptoms of schizophrenia is not completely understood. Yoga improves self-reflection in healthy individuals, and self-reflection abnormalities are typically seen in schizophrenia. However, whether yoga treatment improves impairments in self-reflection typically seen in patients with schizophrenia is not examined. This paper discusses the potential mechanism of yoga in the treatment of schizophrenia and proposes a testable hypothesis for further empirical studies. It is proposed that self-reflection abnormalities in schizophrenia improve with yoga and the neurobiological changes associated with this can be examined using empirical behavioural measures and neuroimaging measures such as magnetic resonance imaging.

  10. Mechanical bending strength of (Bi0.5Na0.5 TiO3-based lead-Free piezoelectric ceramics

    Directory of Open Access Journals (Sweden)

    Hiroaki Takahashi

    2017-09-01

    Full Text Available (Bi0.5Na0.5TiO3 [BNT] is expected as one of candidate lead-free materials because these ceramics show relatively good high-power piezoelectric properties. In this study, we tried to understand the bending strength and fracture behavior of the BNT-based ceramics. To measure the bending strength, a three-point bending test on the basis of JIS was conducted using 12.0 × 4.0 × 1.0 mm3 specimens. An average bending strength, σA, of pure BNT ceramics sintered at 1100 °C for 2, 12 and 24 h were 217, 195 and 187 MPa, respectively. It is cleared that the σA increased with decreasing the sintering time, (grain size and pore size. We also investigated the bending strength of Nb2O5 doped BNT ceramics [BNT-Nb x, x = 0.05 ∼ 1.5 wt%] and MnCO3 doped BNT ceramics [BNT-Mn x, x = 0.5 and 1.0 wt%]. Values of the σA of BNT-Nb 0.5 and BNT-Mn 0.5 were 222, and 188 MPa, respectively. It is clarified that soft dopants (Nb can improve the bending strength of BNT-based ceramics. Additionally, hot-pressed BNT [HP-BNT] were sintered at 1050 °C for 5 h, and the σA of HP-BNT was 245 MPa.

  11. Multiple-layer laser deposition of steel components using gas- and water-atomised powders: the differences and the mechanisms leading to them

    International Nuclear Information System (INIS)

    Pinkerton, Andrew J.; Li Lin

    2005-01-01

    Functionally-graded or composite components have been recognised as having immense potential for many industries. The flexibility of direct metal deposition (DMD) has the potential to expand this to microstructurally graded components, but accurate control of the process is a problem. In this work, the effects of using different powder morphologies as a control mechanism for microstructure and other material properties are investigated experimentally. For the first time, comparison of the characteristics of two different gas-atomised (GA) and water-atomised (WA) materials is undertaken in order to evaluate the significance of the different DMD characteristics originating from the difference in atomisation method. 316L and H13 materials and a 1.2 kW CO 2 DMD system are used. Three primary factors for the differences are identified: increased vaporisation of the powder, a hotter melt pool and less powerful outward Marangoni flow when using water-atomised powder. The reasons for these, the influence they have on process characteristics and final material properties, and the circumstances under which they occur are discussed

  12. Study on accumulation mechanism of lead and copper in metal-hypertolerant fern, Athyrium yokoscense, by micro-XRF analysis utilizing synchrotron radiation

    International Nuclear Information System (INIS)

    Mitsuo, Sakiko; Kashiwabara, Teruhiko; Hokura, Akiko; Nakai, Izumi; Kitajima, Nobuyuki; Goto, Fumiyuki; Yoshihara, Toshihiro; Abe, Tomoko

    2009-01-01

    Athyrium yokoscense is a plant which accumulates high level of heavy metals such as Cu, Zn, Pb and Cd, and is expected to be used for phytoremediation. This paper reports the distribution and the chemical forms of Pb and Cu in underground parts (root and old leaf stalks) of the metal-hypertolerant fern, A. yokoscense, by synchrotron radiation micro-XRF imaging and micro-XANES analyses. The old and new tissues of root and leaf stalks were prepared for micro-XRF analysis. The XRF imaging of the young root revealed that K, Cu and Zn were distributed in whole area of cross-section, whereas Pb was found in a certain part of the epidermal tissue. For the old root, Pb and Cu were mainly distributed in the cell wall of the whole tissue. The distribution of heavy metal in old tissue is different from those of new tissue, and consequently it was assumed that the root at different age have different heavy metal accumulation mechanism. Alternatively, for the old leaf stalks, Cu and Pb were highly accumulated in a specific part located around the vascular tissue. Cu K-edge micro-XANES analysis indicated that the chemical form of Cu at the Cu accumulating point was Cu (II). (author)

  13. FABRICATION AND MECHANICAL PROPERTIES OF Na0.5Bi0.5TiO3–BaTiO3 LEAD-FREE PIEZOELECTRIC CERAMICS

    Directory of Open Access Journals (Sweden)

    PAN YUSONG

    2014-03-01

    Full Text Available Piezoelectric ceramics with 0.94Na0.5Bi0.5TO3–0.06BaTiO3 compositions were fabricated by solid state mixed oxide method and sintered at different temperatures varying from 1050°C to 1150°C to obtain dense ceramics. Phase analysis using X-ray diffraction showed tetragonal perovskite structure of Na0.5Bi0.5TO3 with no BaTiO3 peak detected. The SEM observation revealed that the crystal grain size of the piezoelectric ceramics is on the nano-size dimensions under all the sintering temperature. The study on the compressive mechanical characteristics showed that the compressive strength of the 0.94Na0.5Bi0.5TO3–0.06BaTiO3 piezoelectric ceramics increases with the rise of sintering temperature and sintering time. The change behavior of the compressive strength with the rise of cold pressure presents increasing firstly and then decreases.

  14. [Biophysical principles of collagen cross-linking].

    Science.gov (United States)

    Spörl, E; Raiskup-Wolf, F; Pillunat, L E

    2008-02-01

    The reduced mechanical stability of the cornea in keratoconus or in keratectasia after Lasik may be increased by photooxidative cross-linking of corneal collagen. The biophysical principles are compiled for the safe and effective application of this new treatment method. The setting of the therapy parameters should be elucidated from the absorption behaviour of the cornea. The safety of the method for the endothelium cells and the lens will be discussed. The induced cross-links are shown to be the result of changes in the physico-chemical properties of the cornea. To reach a high absorption of the irradiation energy in the cornea, riboflavin of a concentration of 0.1% and UV light of a wavelength of 370 nm, corresponding to the relative maximum of absorption of riboflavin, were used. An irradiance of 3 mW/cm(2) and an irradiation time of 30 min lead to an increase of the mechanical stiffness. The endothelium cells will be protected due to the high absorption within the cornea, that means the damaging threshold of the endothelium cells will not be reached in a 400 microm thick stroma. As evidence for cross-links we can consider the increase of the biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibres. The therapy parameters were tested experimentally and have been proven clinically in the corneal collagen cross-linking. These parameters should be respected to reach a safe cross-linking effect without damage of the adjacent tissues.

  15. Activation of mas-related G-protein-coupled receptors by the house dust mite cysteine protease Der p1 provides a new mechanism linking allergy and inflammation.

    Science.gov (United States)

    Reddy, Vemuri B; Lerner, Ethan A

    2017-10-20

    Cysteine and serine proteases function via protease-activated and mas-related G-protein-coupled receptors (Mrgprs) to contribute to allergy and inflammation. Der p1 is a cysteine protease and major allergen from the house dust mite and is associated with allergic rhinitis and allergic asthma. Der p1 activates protease-activated receptor 2 and induces the release of the pro-inflammatory cytokine IL-6 from cells. However, the possibility that Der p1 acts on Mrgprs has not been considered. We report here that ratiometric calcium imaging reveals that Der p1 activates the human receptor MRGPRX1 and the mouse homolog MrgprC11, implicated previously in itch. Der p1 cleavage of N-terminal receptor peptides followed by site-directed mutagenesis of the cleavage sites links receptor activation to specific amino acid residues. Der p1 also induced the release of IL-6 from heterologous cells expressing MRGPRX1. In summary, activation of Mrgprs by the allergen Der p1 may contribute to inflammation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Derrick, Jeffrey S.; Kerr, Richard A.; Nam, Younwoo; Oh, Shin Bi; Lee, Hyuck Jin; Earnest, Kaylin G.; Suh, Nayoung; Peck, Kristy L.; Ozbil, Mehmet; Korshavn, Kyle J.; Ramamoorthy, Ayyalusamy; Prabhakar, Rajeev; Merino, Edward J.; Shearer, Jason; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2015-11-25

    Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

  17. How perceptions of community environment influence health behaviours: using the Analysis Grid for Environments Linked to Obesity Framework as a mechanism for exploration.

    Science.gov (United States)

    Nieuwendyk, L M; Belon, A P; Vallianatos, H; Raine, K D; Schopflocher, D; Spence, J C; Plotnikoff, R C; Nykiforuk, C I

    2016-09-01

    Overweight and obesity are influenced by a complex interplay of individual and environmental factors that affect physical activity and healthy eating. Nevertheless, little has been reported on people's perceptions of those factors. Addressing this critical gap and community partner needs, this study explored how people perceived the influence of micro- and macroenvironmental factors on physical activity and healthy eating. Community partners wanted the study results in a format that would be readily and easily used by local decision makers. We used photovoice to engage 35 community members across four municipalities in Alberta, Canada, and to share their narratives about their physical activity and healthy eating. A combination of inductive and deductive analysis categorized data by environmental level (micro vs. macro) and type (physical, political, economic, and sociocultural), guided by the Analysis Grid for Environments Linked to Obesity Framework. Participants conceptualized health-influencing factors more broadly than physical activity and healthy eating to include "community social health." Participants spoke most often about the influence of the microenvironment (n = 792 ANGELO Framework coding tallies) on their physical activity, healthy eating and community social health in comparison to the macroenvironment (n = 93). Photovoice results provided a visual narrative to community partners and decision makers about how people's ability to make healthy choices can be limited by macroenvironmental forces beyond their control. Focussing future research on macro- and microenvironmental influences and localized community social health can inform practice by providing strategies on how to implement healthy changes within communities, while ensuring that research and interventions echo diverse people's perceptions.

  18. Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

    Science.gov (United States)

    Cheng, W-F; Chang, M-C; Sun, W-Z; Lee, C-N; Lin, H-W; Su, Y-N; Hsieh, C-Y; Chen, C-A

    2008-07-01

    A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

  19. Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Sarwar, Tarique [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India); Zafaryab, Md [Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Central University, New Delhi 110025 (India); Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Rehman, Sayeed Ur [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India); Moshahid Alam Rizvi, M. [Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, Central University, New Delhi 110025 (India); Tabish, Mohammad, E-mail: tabish.bcmlab@gmail.com [Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, UP 202002 (India)

    2015-12-01

    Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we have shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS. - Highlights: • Pro-oxidant properties of ferulic acid are enhanced in presence of copper. • Ferulic acid causes oxidative DNA damage in lymphocytes as observed by comet assay. • DNA damage was ameliorated by copper chelating agent neocuproine and ROS scavengers. • Endogenous copper is involved in ROS generation causing DNA damage. • Ferulic acid exerts cancer cell specific cytotoxicity as observed by MTT assay.

  20. Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

    Science.gov (United States)

    Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

    2017-01-01

    Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.