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Sample records for blocking chemically induced

  1. Photo-Induced Micellization of Block Copolymers

    OpenAIRE

    Satoshi Kuwayama; Eri Yoshida

    2010-01-01

    We found novel photo-induced micellizations through photolysis, photoelectron transfer, and photo-Claisen rearrangement. The photolysis-induced micellization was attained using poly(4-tert-butoxystyrene)-block-polystyrene diblock copolymer (PBSt-b-PSt). BSt-b-PSt showed no self-assembly in dichloromethane and existed as isolated copolymers. Dynamic light scattering demonstrated that the copolymer produced spherical micelles in this solvent due to irradiation with a high-pressure mercury lamp ...

  2. Hyperkalemia-induced complete heart block

    Directory of Open Access Journals (Sweden)

    Alireza Baratloo

    2015-05-01

    Full Text Available Background: Potassium, as an extracellular ion, plays an important role in the electrophysiologic function of the myocardium and any change in extracellular concentration of this ion might have a marked impression upon myocyte electrophysiologic gain. High serum potassium levels are thought to impair pulse conduction in Purkinje fibers and ventricles more than that in the Atrioventricular (AV node. Therefore, although complete AV block can occur, it is a rare initial presentation. Case Report: We describe a 62-year-old man with a history of diabetes mellitus, ischemic heart disease and previous Coronary Artery Bypass Graft (CABG, who came to our emergency department due to generalized weakness starting 2 days before admission. The patient also had decreased force in lower limbs, exacerbating from the morning, and was finally diagnosed as a hyperkalemia-induced Complete Heart Block (CHB. It should also be noted that the patient responded dramatically to the administration of 10 mL of 10% calcium gluconate along with external pacing until potassium level correction became effective. Conclusion: In spite of the fact that Hyperkalemia can be associated with frequent Electrocardiogram (ECG abnormality, advanced heart blocks (second- and third-degree AV blocks are usually found only in patients with pre-existing heart failure, conduction abnormalities, or other cardiac diseases. Institution of effective treatment rapidly and forgiveness of traditional non-effective, time consumptive and sometimes risking full-adjustment modalities, such as sodium bicarbonate infusion or exchange resins that prevent their use in the emergent phase, can help minimize patient morbidity and mortality.

  3. Inducible chemical defences in animals

    OpenAIRE

    Heyttyey, Attila; Tóth, Zoltán; Buskirk, Josh

    2014-01-01

    Phenotypic plasticity is extremely widespread in the behaviour, morphology and life-history of animals. However, inducible changes in the production of defensive chemicals are described mostly in plants and surprisingly little is known about similar plasticity in chemical defences of animals. Inducible chemical defences may be common in animals because many are known to produce toxins, the synthesis of toxins is likely to be costly, and there are a few known cases of animals adjusting their t...

  4. Microbial production of building block chemicals and polymers.

    Science.gov (United States)

    Lee, Jeong Wook; Kim, Hyun Uk; Choi, Sol; Yi, Jongho; Lee, Sang Yup

    2011-12-01

    Owing to our increasing concerns on the environment, climate change, and limited natural resources, there has recently been considerable effort exerted to produce chemicals and materials from renewable biomass. Polymers we use everyday can also be produced either by direct fermentation or by polymerization of monomers that are produced by fermentation. Recent advances in metabolic engineering combined with systems biology and synthetic biology are allowing us to more systematically develop superior strains and bioprocesses for the efficient production of polymers and monomers. Here, we review recent trends in microbial production of building block chemicals that can be subsequently used for the synthesis of polymers. Also, recent successful cases of direct one-step production of polymers are reviewed. General strategies for the production of natural and unnatural platform chemicals are described together with representative examples. PMID:21420291

  5. Laser-induced chemical reactions

    International Nuclear Information System (INIS)

    A classical model for the interaction of laser radiation with a molecular system is derived. This model is used to study the enhancement of a chemical reaction via a collision induced absorption. It was found that an infrared laser will in general enhance the rate of a chemical reaction, even if the reactants are infrared inactive. Results for an illustrative analytically solvable model are presented, as well as results from classical trajectory studies on a number of systems. The collision induced absorption spectrum in these systems can be written as the Fourier transform of a particular dipole correlation function. This is used to obtain the collision induced absorption spectrum for a state-selected, mono-energetic reactive collision system. Examples treated are a one-dimensional barrier problem, reactive and nonreactive collisions of H + H2, and a modified H + H2 potential energy surface which leads to a collision intermediate. An extension of the classical model to treat laser-induced electronically nonadiabatic collision processes is constructed. The model treats all degrees of freedom, molecular, electronic and radiation, in a dynamically consistent framework within classical mechanics. Application is made to several systems. Several interesting phenomena are discovered including a Franck-Condon-like effect causing maxima in the reaction probability at energies much below the classical threshold, laser de-enhancement of chemical reactions and an isotope effect. In order to assess the validity of the classical model for electronically nonadiabatic process (without a laser field), a model problem involving energy transfer in a collinear atom-diatom system is studied, and the results compared to the available quantum mechanical calculation. The calculations are in qualitative agreement

  6. A physical model for measuring thermally-induced block displacements

    Science.gov (United States)

    Bakun-Mazor, Dagan; Feldhiem, Aviran; Keissar, Yuval; Hatzor, Yossef H.

    2016-04-01

    A new model for thermally-induced block displacement in discontinuous rock slopes has been recently suggested. The model consists of a discrete block that is separated from the rock mass by a tension crack and rests on an inclined plane. The tension crack is filled with a wedge block or rock fragments. Irreversible block sliding is assumed to develop in response to climatic thermal fluctuations and consequent contraction and expansion of the sliding block material. While a tentative analytical solution for this model is already available, we are exploring here the possibility of obtaining such a permanent, thermally-induced, rock block displacement, under fully controlled conditions at the laboratory, and the sensitivity of the mechanism to geometry, mechanical properties, and temperature fluctuations. A large scale concrete physical model (50x150x60 cm^3) is being examined in a Climate-Controlled Room (CCR). The CCR permits accurate control of ambient temperature from 5 to 45 Celsius degrees. The permanent plastic displacement is being measured using four displacement transducers and a high resolution (29M pixel) visual range camera. A series of thermocouples measure the heating front inside the sliding block, hence thermal diffusivity is evaluated from the measured thermal gradient and heat flow. In order to select the appropriate concrete mixture, the mechanical and thermo-physical properties of concrete samples are determined in the lab. Friction angle and shear stiffness of the sliding interface are determined utilizing a hydraulic, servo-controlled direct shear apparatus. Uniaxial compression tests are performed to determine the uniaxial compressive strength, Young's modulus and Poison's ratio of the intact block material using a stiff triaxial load frame. Thermal conductivity and linear thermal expansion coefficient are determined experimentally using a self-constructed measuring system. Due to the fact that this experiment is still in progress, preliminary

  7. Creating pathways towards aromatic building blocks and fine chemicals.

    Science.gov (United States)

    Thompson, Brian; Machas, Michael; Nielsen, David R

    2015-12-01

    Aromatic compounds represent a broad class of chemicals with a range of industrial applications, all of which are conventionally derived from petroleum feedstocks. However, owing to a diversity of available pathway precursors along with natural and engineered enzyme 'parts', microbial cell factories can be engineered to create alternative, renewable routes to many of the same aromatic products. Drawing from the latest tools and strategies in metabolic engineering and synthetic biology, such efforts are becoming an increasingly systematic practice, while continued efforts promise to open new doors to an ever-expanding range and diversity of renewable chemical and material products. This short review will highlight recent and notable achievements related for the microbial production of aromatic chemicals. PMID:26264997

  8. Understanding Chemical Reaction Kinetics and Equilibrium with Interlocking Building Blocks

    Science.gov (United States)

    Cloonan, Carrie A.; Nichol, Carolyn A.; Hutchinson, John S.

    2011-01-01

    Chemical reaction kinetics and equilibrium are essential core concepts of chemistry but are challenging topics for many students, both at the high school and undergraduate university level. Visualization at the molecular level is valuable to aid understanding of reaction kinetics and equilibrium. This activity provides a discovery-based method to…

  9. ChemCalc: a building block for tomorrow's chemical infrastructure.

    Science.gov (United States)

    Patiny, Luc; Borel, Alain

    2013-05-24

    Web services, as an aspect of cloud computing, are becoming an important part of the general IT infrastructure, and scientific computing is no exception to this trend. We propose a simple approach to develop chemical Web services, through which servers could expose the essential data manipulation functionality that students and researchers need for chemical calculations. These services return their results as JSON (JavaScript Object Notation) objects, which facilitates their use for Web applications. The ChemCalc project http://www.chemcalc.org demonstrates this approach: we present three Web services related with mass spectrometry, namely isotopic distribution simulation, peptide fragmentation simulation, and molecular formula determination. We also developed a complete Web application based on these three Web services, taking advantage of modern HTML5 and JavaScript libraries (ChemDoodle and jQuery). PMID:23480664

  10. Chemical Interactions and Their Role in the Microphase Separation of Block Copolymer Thin Films

    Directory of Open Access Journals (Sweden)

    Richard A. Farrell

    2009-08-01

    Full Text Available The thermodynamics of self-assembling systems are discussed in terms of the chemical interactions and the intermolecular forces between species. It is clear that there are both theoretical and practical limitations on the dimensions and the structural regularity of these systems. These considerations are made with reference to the microphase separation that occurs in block copolymer (BCP systems. BCP systems self-assemble via a thermodynamic driven process where chemical dis-affinity between the blocks driving them part is balanced by a restorative force deriving from the chemical bond between the blocks. These systems are attracting much interest because of their possible role in nanoelectronic fabrication. This form of self-assembly can obtain highly regular nanopatterns in certain circumstances where the orientation and alignment of chemically distinct blocks can be guided through molecular interactions between the polymer and the surrounding interfaces. However, for this to be possible, great care must be taken to properly engineer the interactions between the surfaces and the polymer blocks. The optimum methods of structure directing are chemical pre-patterning (defining regions on the substrate of different chemistry and graphoepitaxy (topographical alignment but both centre on generating alignment through favourable chemical interactions. As in all self-assembling systems, the problems of defect formation must be considered and the origin of defects in these systems is explored. It is argued that in these nanostructures equilibrium defects are relatively few and largely originate from kinetic effects arising during film growth. Many defects also arise from the confinement of the systems when they are ‘directed’ by topography. The potential applications of these materials in electronics are discussed.

  11. Chemical Interactions and Their Role in the Microphase Separation of Block Copolymer Thin Films

    Science.gov (United States)

    Farrell, Richard A.; Fitzgerald, Thomas G.; Borah, Dipu; Holmes, Justin D.; Morris, Michael A.

    2009-01-01

    The thermodynamics of self-assembling systems are discussed in terms of the chemical interactions and the intermolecular forces between species. It is clear that there are both theoretical and practical limitations on the dimensions and the structural regularity of these systems. These considerations are made with reference to the microphase separation that occurs in block copolymer (BCP) systems. BCP systems self-assemble via a thermodynamic driven process where chemical dis-affinity between the blocks driving them part is balanced by a restorative force deriving from the chemical bond between the blocks. These systems are attracting much interest because of their possible role in nanoelectronic fabrication. This form of self-assembly can obtain highly regular nanopatterns in certain circumstances where the orientation and alignment of chemically distinct blocks can be guided through molecular interactions between the polymer and the surrounding interfaces. However, for this to be possible, great care must be taken to properly engineer the interactions between the surfaces and the polymer blocks. The optimum methods of structure directing are chemical pre-patterning (defining regions on the substrate of different chemistry) and graphoepitaxy (topographical alignment) but both centre on generating alignment through favourable chemical interactions. As in all self-assembling systems, the problems of defect formation must be considered and the origin of defects in these systems is explored. It is argued that in these nanostructures equilibrium defects are relatively few and largely originate from kinetic effects arising during film growth. Many defects also arise from the confinement of the systems when they are ‘directed’ by topography. The potential applications of these materials in electronics are discussed. PMID:19865513

  12. Directed self-assembly of block copolymer films on atomically-thin graphene chemical patterns.

    Science.gov (United States)

    Chang, Tzu-Hsuan; Xiong, Shisheng; Jacobberger, Robert M; Mikael, Solomon; Suh, Hyo Seon; Liu, Chi-Chun; Geng, Dalong; Wang, Xudong; Arnold, Michael S; Ma, Zhenqiang; Nealey, Paul F

    2016-01-01

    Directed self-assembly of block copolymers is a scalable method to fabricate well-ordered patterns over the wafer scale with feature sizes below the resolution of conventional lithography. Typically, lithographically-defined prepatterns with varying chemical contrast are used to rationally guide the assembly of block copolymers. The directed self-assembly to obtain accurate registration and alignment is largely influenced by the assembly kinetics. Furthermore, a considerably broad processing window is favored for industrial manufacturing. Using an atomically-thin layer of graphene on germanium, after two simple processing steps, we create a novel chemical pattern to direct the assembly of polystyrene-block-poly(methyl methacrylate). Faster assembly kinetics are observed on graphene/germanium chemical patterns than on conventional chemical patterns based on polymer mats and brushes. This new chemical pattern allows for assembly on a wide range of guiding periods and along designed 90° bending structures. We also achieve density multiplication by a factor of 10, greatly enhancing the pattern resolution. The rapid assembly kinetics, minimal topography, and broad processing window demonstrate the advantages of inorganic chemical patterns composed of hard surfaces. PMID:27528258

  13. Laser Induced Surface Chemical Epitaxy

    Science.gov (United States)

    Stinespring, Charter D.; Freedman, Andrew

    1990-02-01

    Studies of the thermal and photon-induced surface chemistry of dimethyl cadmium (DMCd) and dimethyl tellurium (DMTe) on GaAs(100) substrates under ultrahigh vacuum conditions have been performed for substrate temperatures in the range of 123 K to 473 K. Results indicate that extremely efficient conversion of admixtures of DMTe and DMCd to CdTe can be obtained using low power (5 - 10 mJ cm-2) 193 nm laser pulses at substrate temperatures of 123 K. Subsequent annealing at 473 K produces an epitaxial film.

  14. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody

    Energy Technology Data Exchange (ETDEWEB)

    Eastmond, D.A.; Tucker, J.D.

    1989-01-01

    The identification of agents causing aneuploidy in humans, a condition associated with carcinogenesis and birth defects, is currently limited due to the highly skilled and time-consuming nature of cytogenetic analyses. We report the development of a new simple and rapid assay to identify aneuploidy-inducing agents (aneuploidogens). The assay involves the chemical- or radiation-induced formation of micronuclei in cytokinesis-blocked human lymphocytes and the use of an antikinetochore antibody to determine whether the micronuclei contain centromeres--a condition indicating a high potential for aneuploidy. All agents tested produced dose-related increases in the frequency of micronucleated cells. The micronucleated cells induced by the known aneuploidogens--colchicine, vincristine sulfate, and diethylstilbestrol--contained kinetochore-positive micronuclei 92, 87, and 76% of the time, respectively. In contrast, the micronucleated cells induced by the potent clastogens--ionizing radiation and sodium arsenite--contained kinetochore-positive micronuclei only 3 and 19% of the time, respectively. These results indicate that this relatively simple assay can discriminate between aneuploidogens and clastogens and may allow a more rapid identification of environmental and therapeutic agents with aneuploidy-inducing potential.

  15. The understanding of the R7T7 glass blocks long term behavior: chemical and transport coupling in fractured media

    International Nuclear Information System (INIS)

    The long term behavior of nuclear waste glass blocks depends highly on chemical reactions which occur at the surface in contact with water. Studies carried out on inactive fractured glass blocks show that fracture networks play a significant part in reactive surface area. Nevertheless, the complexity of results interpretation, due to a weak knowledge of fracture networks and local lixiviation conditions, does not allow us to comprehend the physical and chemical mechanisms involved. Model cracks are a key step to study chemical and transport coupling in fractured media. Crack lixiviation in aggressive conditions (pH≥11) show that the crack's position (horizontal or vertical) determines the dominant transport mechanism (respectively diffusion or convection induced by gravity). This gravity driven flow seems to be negligible in lower pH conditions. The convective velocity is estimated by a 1D model of reactive transport. Two other parameters are studied: the influence of thermal gradient and the influence of interconnected cracks on alteration. A strong retroactive effect of convection, due to thermal gradient, on the alteration kinetic is observed inside the crack. These works lead to a complete alteration experiment of a 163 crack network subject to a thermal gradient. The use of the geochemical software, HYTEC, within the framework of this study shows the potential of the software which is however limited by the kinetics law used. (author)

  16. Composite block of magnesium hydroxide – Expanded graphite for chemical heat storage and heat pump

    International Nuclear Information System (INIS)

    The chemical heat storage/chemical heat pump technology (CHS/CHP) based on the reversible gas–solid chemical reactions between magnesium oxide, water, and magnesium hydroxide (MgO/H2O/Mg(OH)2) requires enhanced thermal conductivity for the packed bed reactors. A composite material of expanded graphite (EG) and Mg(OH)2, EM8, was prepared. Mg(OH)2 and EG, used in the preparation of EM8, were mixed at the optimal mass mixing ratio of 8:1. EM8 was then compressed into a cylindrical block with dimensions matching that of the reactor of a CHP apparatus (diameter ϕreactor = 48 mm, height zreactor = 48 mm). The dehydration and hydration reactions, corresponding to the heat storage and heat output mode of the CHP, were carried out using the apparatus by inserting the EM8 block directly into the reactor. The results were compared with those obtained under the same reaction conditions by filling the reactor with a packed bed of Mg(OH)2 pellets. The results show that after 120 min of dehydration at 400 °C, the EM8 block had a volumetric heat storage (qd,v) of 747 MJ mbed−3, while that for the bed of Mg(OH)2 pellets was 502 MJ mbed−3. After 60 min of hydration at water vapor pressure of 361 kPa, the EM8 block had a gross heat output (qh,v) of 911 MJ mbed−3, while that for the bed of Mg(OH)2 pellets was 497 MJ mbed−3. Kinetic analysis for the hydration reaction indicated that in the EM8 block, the hydration rate was controlled by mass transfer for Ph h > 101 kPa. - Highlights: •A composite material of expanded graphite and Mg(OH)2 has been developed (EM8). •Thermal conductivity of EM8 was measured, resulting higher than that of Mg(OH)2. •An EM8 cylindrical block was manufactured for utilization in a packed bed reactor. •EM8 block had superior thermochemical performances than a bed of Mg(OH)2 pellets. •Hydration in EM8 block is controlled by mass transfer for Ph < 101 kPa

  17. Negative-tone block copolymer lithography by in situ surface chemical modification.

    Science.gov (United States)

    Kim, Bong Hoon; Byeon, Kyeong-Jae; Kim, Ju Young; Kim, Jinseung; Jin, Hyeong Min; Cho, Joong-Yeon; Jeong, Seong-Jun; Shin, Jonghwa; Lee, Heon; Kim, Sang Ouk

    2014-10-29

    Negative-tone block copolymer (BCP) lithography based on in situ surface chemical modification is introduced as a highly efficient, versatile self-assembled nanopatterning. BCP blends films consisting of end-functionalized low molecular weight poly(styrene-ran-methyl methacrylate) and polystyrene-block-Poly(methyl methacylate) can produce surface vertical BCP nanodomains on various substrates without prior surface chemical treatment. Simple oxygen plasma treatment is employed to activate surface functional group formation at various substrates, where the end-functionalized polymers can be covalently bonded during the thermal annealing of BCP thin films. The covalently bonded brush layer mediates neutral interfacial condition for vertical BCP nanodomain alignment. This straightforward approach for high aspect ratio, vertical self-assembled nanodomain formation facilitates single step, site-specific BCP nanopatterning widely useful for various substrates. Moreover, this approach is compatible with directed self-assembly approaches to produce device oriented laterally ordered nanopatterns. PMID:24912807

  18. Contribution of orientational effects into radiation-chemical properties of segregated block copolymers

    International Nuclear Information System (INIS)

    Model of radiolysis of microphase-separated block copolymers of PS with PB is proposed. According this scheme the radiation-chemical yields of paramagnetic centres and crosslinks in PB domains differ from those for the PB homopolymer by the value proportional to the fraction of ordered chain segments. This orientational small-scale order arises as a result of the deformation of chains in a domain in the direction perpendicular to the interphase

  19. Ultrasound biomicroscopic analysis of pseudophakic pupillary block glaucoma induced by Soemmering's ring

    OpenAIRE

    Kobayashi, H.; Hirose, M.; Kobayashi, K

    2000-01-01

    AIM—To perform ultrasound biomicroscopic analysis of pseudophakic pupillary block glaucoma induced by lens capsule and a Soemmering's ring and its resolution, and to elucidate the pathophysiology of this glaucoma.
METHODS—A woman with pseudophakic pupillary block glaucoma underwent successful neodymium:YAG (Nd:YAG) laser photodisruption of the lens capsule through a laser iridotomised coloboma with resolution of the pupillary block. The Humphrey ultrasonic biomicroscope model 840 was employed...

  20. Chemical bond cleavage induced by electron heating

    International Nuclear Information System (INIS)

    Gas emissions from titanium-metalloid compounds (titanium nitride and oxide) have been investigated to understand the effects of a microwave field on chemical reactions. We employed a high vacuum system (PO2 = 10−6 Pa) to observe in situ reductions. For titanium oxides, H-field heating significantly differed from conventional one in terms of oxygen emissions. For titanium nitride, the emissions were also induced by microwave heating. These tendencies were observed at temperatures above 1000 °C. A quantum chemical interpretation is provided to explain the emissions of the gases, and the experimental data is in good agreement with results predicted using the electronic energy band structure.

  1. Study of chemical and radiation induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  2. Self-assembled monolayer-modified block copolymers for chemical surface nanopatterning

    International Nuclear Information System (INIS)

    Research highlights: → Self-organizing PS-b-PMMA creates striped nanostructure scaffolds. → These striped nanostructures can be selectively metalized and modified using light. → Metalized stripes can be decorated with SAMs to create functional substrates. → Nanostructured surfaces thus prepared exhibit controlled wetting and recognition. - Abstract: Thin-film poly(styrene-block-methyl methacrylate) diblock copolymer (PS-b-PMMA) is used to create chemically patterned surfaces via metal deposition combined with self-assembled monolayers (SAMs) and UV exposure. We use this method to produce surfaces that are chemically striped on the scale of a few tens of nanometers. Atomic force and transmission electron microscopies are used to verify the spatially localized organization of materials, and contact angle measurements confirm the chemical tunability of these scaffolds. These surfaces may be used for arraying nanoscale objects, such as nanoparticles or biological species, or for electronic, magnetic memory or photovoltaic applications.

  3. Are lesions induced by ionizing radiation direct blocks to DNA chain elongation

    International Nuclear Information System (INIS)

    Ionizing radiation blocks DNA chain elongation in normal diploid fibroblasts but not in fibroblasts from patients with ataxia-telangiectasia, even though there are no differences in the damage induced between the two cell types. This difference suggests that radiation-induced lesions in DNA are not themselves blocks to chain elongation in ataxia cells and raises the possibility that in normal cells a mediator exists between DNA damage and chain termination

  4. Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2013-01-01

    Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective...

  5. High-strain-induced deformation mechanisms in block-graft and multigraft copolymers

    KAUST Repository

    Schlegel, Ralf

    2011-12-13

    The molecular orientation behavior and structural changes of morphology at high strains for multigraft and block-graft copolymers based on polystyrene (PS) and polyisoprene (PI) were investigated during uniaxial monotonic loading via FT-IR and synchrotron SAXS. Results from FT-IR revealed specific orientations of PS and PI segments depending on molecular architecture and on the morphology, while structural investigations revealed a typical decrease in long-range order with increasing strain. This decrease was interpreted as strain-induced dissolution of the glassy blocks in the soft matrix, which is assumed to affect an additional enthalpic contribution (strain-induced mixing of polymer chains) and stronger retracting forces of the network chains during elongation. Our interpretation is supported by FT-IR measurements showing similar orientation of rubbery and glassy segments up to high strains. It also points to highly deformable PS domains. By synchrotron SAXS, we observed in the neo-Hookean region an approach of glassy domains, while at higher elongations the intensity of the primary reflection peak was significantly decreasing. The latter clearly verifies the assumption that the glassy chains are pulled out from the domains and are partly mixed in the PI matrix. Results obtained by applying models of rubber elasticity to stress-strain and hysteresis data revealed similar correlations between the softening behavior and molecular and morphological parameters. Further, an influence of the network modality was observed (random grafted branches). For sphere forming multigraft copolymers the domain functionality was found to be less important to achieve improved mechanical properties but rather size and distribution of the domains. © 2011 American Chemical Society.

  6. Effect of adrenal blocking chemicals on viral and respiratory infections of chickens.

    OpenAIRE

    Gross, W B

    1989-01-01

    In a series of experiments chickens were treated with chemicals which block the production of corticosterone by the adrenal cortex prior to being challenged with respiratory disease (and other) agents in order to determine if the course of the diseases could be altered. Some chickens received a single intramuscular injection (14 mg/kg) of 1,1-dichloro-2,2-bis/p-chlorophenyl/ethane (ABC) dissolved in corn oil (20 mg/mL) at least 12 h before challenge. Other chickens received feed containing 50...

  7. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    OpenAIRE

    Eunsun Jung; Jung-A Lee; Seoungwoo Shin; Kyung-Baeg Roh; Jang-Hyun Kim; Deokhoon Park

    2013-01-01

    Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and mel...

  8. Histone deacetylase inhibitors block IFNγ-induced STAT1 phosphorylation.

    Science.gov (United States)

    Ginter, Torsten; Bier, Carolin; Knauer, Shirley K; Sughra, Kalsoom; Hildebrand, Dagmar; Münz, Tobias; Liebe, Theresa; Heller, Regine; Henke, Andreas; Stauber, Roland H; Reichardt, Werner; Schmid, Johannes A; Kubatzky, Katharina F; Heinzel, Thorsten; Krämer, Oliver H

    2012-07-01

    Signal transducer and activator of transcription 1 (STAT1) is important for innate and adaptive immunity. Histone deacetylase inhibitors (HDACi) antagonize unbalanced immune functions causing chronic inflammation and cancer. Phosphorylation and acetylation regulate STAT1 and different IFNs induce phosphorylated STAT1 homo-/heterodimers, e.g. IFNα activates several STATs whereas IFNγ only induces phosphorylated STAT1 homodimers. In transformed cells HDACi trigger STAT1 acetylation linked to dephosphorylation by the phosphatase TCP45. It is unclear whether acetylation differentially affects STAT1 activated by IFNα or IFNγ, and if cellular responses to both cytokines depend on a phosphatase-dependent inactivation of acetylated STAT1. Here, we report that HDACi counteract IFN-induced phosphorylation of a critical tyrosine residue in the STAT1 C-terminus in primary cells and hematopoietic cells. STAT1 mutants mimicking a functionally inactive DNA binding domain (DBD) reveal that the number of acetylation-mimicking sites in STAT1 determines whether STAT1 is recruited to response elements after stimulation with IFNγ. Furthermore, we show that IFNα-induced STAT1 heterodimers carrying STAT1 molecules mimicking acetylation bind cognate DNA and provide innate anti-viral immunity. IFNγ-induced acetylated STAT1 homodimers are though inactive, suggesting that heterodimerization and complex formation can rescue STAT1 lacking a functional DBD. Apparently, the type of cytokine determines how acetylation affects the nuclear entry and DNA binding of STAT1. Our data contribute to a better understanding of STAT1 regulation by acetylation. PMID:22425562

  9. Processi di biorefining per l'estrazione di secondary chemical building blocks da sottoprotti dell'agro-industria

    OpenAIRE

    Zanichelli, Dario

    2008-01-01

    Phenol and cresols represent a good example of primary chemical building blocks of which 2.8 million tons are currently produced in Europe each year. Currently, these primary phenolic building blocks are produced by refining processes from fossil hydrocarbons: 5% of the world-wide production comes from coal (which contains 0.2% of phenols) through the distillation of the tar residue after the production of coke, while 95% of current world production of phenol is produced by the...

  10. Probing the bioactivity-relevant chemical space of robust reactions and common molecular building blocks.

    Science.gov (United States)

    Hartenfeller, Markus; Eberle, Martin; Meier, Peter; Nieto-Oberhuber, Cristina; Altmann, Karl-Heinz; Schneider, Gisbert; Jacoby, Edgar; Renner, Steffen

    2012-05-25

    In the search for new bioactive compounds, there is a trend toward increasingly complex compound libraries aiming to target the demanding targets of the future. In contrast, medicinal chemistry and traditional library design rely mainly on a small set of highly established and robust reactions. Here, we probe a set of 58 such reactions for their ability to sample the chemical space of known bioactive molecules, and the potential to create new scaffolds. Combined with ~26,000 common available building blocks, the reactions retrieve around 9% of a scaffold-diverse set of compounds active on human target proteins covering all major pharmaceutical target classes. Almost 80% of generated scaffolds from virtual one-step synthesis products are not present in a large set of known bioactive molecules for human targets, indicating potential for new discoveries. The results suggest that established synthesis resources are well suited to cover the known bioactivity-relevant chemical space and that there are plenty of unexplored regions accessible by these reactions, possibly providing valuable "low-hanging fruit" for hit discovery. PMID:22512717

  11. Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice.

    Science.gov (United States)

    Han, Mi Hwa; Yoon, Won Kee; Lee, Hyunju; Han, Sang-Bae; Lee, Kiho; Park, Song-Kyu; Yang, Kyu-Hwan; Kim, Hwan Mook; Kang, Jong Soon

    2007-12-15

    Irritant contact dermatitis (ICD) is a non-allergic local inflammatory reaction of a skin and one of the most frequent occupational health problems. Silymarin has been clinically used in Europe for a long time to treat liver diseases and also known to have anti-cancer and anti-inflammatory activities. In the present study, we report that topical application of silymarin reduces chemical-induced ICD. Topical application of 2,4-dinitrochlorobenzene (DNCB) induced an ear swelling in BALB/c mice and silymarin suppressed DNCB-induced increase in ear thickness. Prophylactic and therapeutic application of silymarin showed similar effect on DNCB-induced increase in ear thickness and skin water content. In addition, phobor ester- or croton oil-induced increase in ear thickness was also inhibited by silymarin treatment. Silymarin also blocked neutrophil accumulation into the ear induced by these irritants. Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT. Silymarin also blocked TNF-alpha- and DNCB-induced NF-kappaB activation in HaCaT. Collectively, these results demonstrate that topically applied silymarin inhibits chemical-induced ICD in mice and this might be mediated, at least in part, by blocking NF-kappaB activation and consequently inhibiting the expression of cytokines and adhesion molecules. PMID:17996674

  12. Acute and subacute chemical-induced lung injuries: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Akira, Masanori, E-mail: Akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555 (Japan); Suganuma, Narufumi [Department of Environmental Medicine, Kochi Medical School (Japan)

    2014-08-15

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals.

  13. Acute and subacute chemical-induced lung injuries: HRCT findings

    International Nuclear Information System (INIS)

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals

  14. Chemically induced compaction bands in geomaterials

    Science.gov (United States)

    Stefanou, Ioannis; Sulem, Jean

    2013-04-01

    Compaction bands play an important role in oil production and may provide useful information on various geological processes. Various mechanisms can be involved at different scales: the micro scale (e.g. the grain scale), the meso scale (e.g. the Representative Element Volume) and the macro scale (e.g. the structure). Moreover, hydro-chemo-mechanical couplings might play an important role in triggering instabilities in the form of compaction bands. Compaction bands can be seen as an instability of the underneath mathematical problem leading to localization of deformation [1,2,3]. Here we explore the conditions of compaction banding in quartz-based geomaterials by considering the effect of chemical dissolution and precipitation [4,5]. In due course of the loading process grain crushing affects the residual strength, the porosity and the permeability of the material. Moreover, at the micro-level, grain crushing results in an increase of the grain specific surface, which accelerates the dissolution [6]. Consequently, the silica is removed more rapidly from the grain skeleton and the overall mechanical properties are degraded due to chemical factors. The proposed model accounts for these phenomena. In particular, the diffusion of the diluted in the water silica is considered through the mass balance equation of the porous medium. The reduction of the mechanical strength of the material is described through a macroscopic failure criterion with chemical softening. The grain size reduction is related to the total energy input [7]. A grain size and porosity dependent permeability law is adopted. These degradation mechanisms are coupled with the dissolution/precipitation reaction kinetics. The obtained hydro-chemo-mechanical model is used to investigate the conditions, the material parameters and the chemical factors inducing compaction bands formation. References [1] J.W. Rudnicki, and J.R. Rice. "Conditions for the Localization of Deformation in Pressure

  15. THE EFFECT OF CLONIDINE ON LIDOCAINE INDUCED SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Shrinivas

    2014-08-01

    Full Text Available BACKGROUND: Brachial plexus nerve blocks (BPB are the most common nerve blocks used for upper limb surgeries. Techniques using only Local Anaesthetics (LA have limited duration of post-operative analgesia. Clonidine has been used to prolong the duration of LA s for neuraxial blocks. Hence the effect of clonidine on Lidocaine induced BPB was studied. METHODS: 60 patients of American Society of Anesthesiologists (ASA class I and II were randomly divided into 2 groups. Group L given 30 ml of Lidocaine with adrenaline 1.5% with 0.6 ml of normal saline and the Group C given 30 ml of same LA with 0.6 ml of 90mcg of Clonidine. All the patients’ supraclavicular BPB was given using Winnies’ peri-vascular approach. The primary outcome was onset, duration of sensory and motor blockade. The secondary outcomes were motor block duration, opioid supplementation, and BPB complication. RESULTS: There was no statistically significant difference in the onset of sensory and motor block, motor blockade quality and overall quality of block. Duration of sensory and motor blockade was prolonged in groups with Clonidine. No adverse events / hemodynamic instability noted in either group. Sedation scores were higher in Clonidine group. No patients required any intervention. CONCLUSIONS: 90µg Clonidine added to Lidocaine 1.5% with adrenaline produces prolongation of both the duration of sensory and motor blockade with minimal adverse effects.

  16. Phase diagram of selectively cross-linked block copolymers shows chemically microstructured gel

    Science.gov (United States)

    von der Heydt, Alice; Zippelius, Annette

    2015-02-01

    We study analytically the intricate phase behavior of cross-linked AB diblock copolymer melts, which can undergo two main phase transitions due to quenched random constraints. Gelation, i.e., spatially random localisation of polymers forming a system-spanning cluster, is driven by increasing the number parameter μ of irreversible, type-selective cross-links between random pairs of A blocks. Self-assembly into a periodic pattern of A/B-rich microdomains (microphase separation) is controlled by the AB incompatibility χ inversely proportional to temperature. Our model aims to capture the system's essential microscopic features, including an ensemble of random networks that reflects spatial correlations at the instant of cross-linking. We identify suitable order parameters and derive a free-energy functional in the spirit of Landau theory that allows us to trace a phase diagram in the plane of μ and χ. Selective cross-links promote microphase separation at higher critical temperatures than in uncross-linked diblock copolymer melts. Microphase separation in the liquid state facilitates gelation, giving rise to a novel gel state whose chemical composition density mirrors the periodic AB pattern.

  17. Phase diagram of selectively cross-linked block copolymers shows chemically microstructured gel.

    Science.gov (United States)

    von der Heydt, Alice; Zippelius, Annette

    2015-02-01

    We study analytically the intricate phase behavior of cross-linked AB diblock copolymer melts, which can undergo two main phase transitions due to quenched random constraints. Gelation, i.e., spatially random localisation of polymers forming a system-spanning cluster, is driven by increasing the number parameter μ of irreversible, type-selective cross-links between random pairs of A blocks. Self-assembly into a periodic pattern of A/B-rich microdomains (microphase separation) is controlled by the AB incompatibility χ inversely proportional to temperature. Our model aims to capture the system's essential microscopic features, including an ensemble of random networks that reflects spatial correlations at the instant of cross-linking. We identify suitable order parameters and derive a free-energy functional in the spirit of Landau theory that allows us to trace a phase diagram in the plane of μ and χ. Selective cross-links promote microphase separation at higher critical temperatures than in uncross-linked diblock copolymer melts. Microphase separation in the liquid state facilitates gelation, giving rise to a novel gel state whose chemical composition density mirrors the periodic AB pattern. PMID:25662662

  18. Progesterone-induced blocking factor activates STAT6 via binding to a novel IL-4 receptor.

    Science.gov (United States)

    Kozma, Noemi; Halasz, Melinda; Polgar, Beata; Poehlmann, Tobias G; Markert, Udo R; Palkovics, Tamas; Keszei, Marton; Par, Gabriella; Kiss, Katalin; Szeberenyi, Jozsef; Grama, Laszlo; Szekeres-Bartho, Julia

    2006-01-15

    Progesterone-induced blocking factor (PIBF) induces Th2-dominant cytokine production. Western blotting and EMSA revealed phosphorylation as well as nuclear translocation of STAT6 and inhibition of STAT4 phosphorylation in PIBF-treated cells. The silencing of STAT6 by small interfering RNA reduced the cytokine effects. Because the activation of the STAT6 pathway depends on the ligation of IL-4R, we tested the involvement of IL-4R in PIBF-induced STAT6 activation. Although PIBF does not bind to IL-4R, the blocking of the latter with an Ab abolished PIBF-induced STAT6 activation, whereas the blocking of the IL-13R had no effect. PIBF activated suppressor of cytokine signaling-3 and inhibited IL-12-induced suppressor of cytokine signaling-1 activation. The blocking of IL-4R counteracted all the described effects, suggesting that the PIBF receptor interacts with IL-4R alpha-chain, allowing PIBF to activate the STAT6 pathway. PIBF did not phosphorylate Jak3, suggesting that the gamma-chain is not needed for PIBF signaling. Confocal microscopic analysis revealed a colocalization and at 37 degrees C a cocapping of the FITC PIBF-activated PIBF receptor and PE anti-IL-4R-labeled IL-4R. After the digestion of the cells with phosphatidylinositol-specific phospholipase C, the STAT6-activating effect of PIBF was lost, whereas that of IL-4 remained unaltered. These data suggest the existence of a novel type of IL-4R composed of the IL-4R alpha-chain and the GPI-anchored PIBF receptor. PMID:16393965

  19. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  20. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

    DEFF Research Database (Denmark)

    Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo;

    2006-01-01

    Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

  1. Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to PIBF-receptor in lymphocytes.

    Science.gov (United States)

    de la Haba, Carlos; Palacio, José R; Palkovics, Tamas; Szekeres-Barthó, Júlia; Morros, Antoni; Martínez, Paz

    2014-01-01

    Receptor-ligand binding is an essential interaction for biological function. Oxidative stress can modify receptors and/or membrane lipid dynamics, thus altering cell physiological functions. The aim of this study is to analyze how oxidative stress may alter receptor-ligand binding and lipid domain distribution in the case of progesterone-induced blocking factor/progesterone-induced blocking factor-receptor. For membrane fluidity regionalization analysis of MEC-1 lymphocytes, two-photon microscopy was used in individual living cells. Lymphocytes were also double stained with AlexaFluor647/progesterone-induced blocking factor and Laurdan to evaluate -induced blocking factor/progesterone-induced blocking factor-receptor distribution in the different membrane domains, under oxidative stress. A new procedure has been developed which quantitatively analyzes the regionalization of a membrane receptor among the lipid domains of different fluidity in the plasma membrane. We have been able to establish a new tool which detects and evaluates lipid raft clustering from two-photon microscopy images of individual living cells. We show that binding of progesterone-induced blocking factor to progesterone-induced blocking factor-receptor causes a rigidification of plasma membrane which is related to an increase of lipid raft clustering. However, this clustering is inhibited under oxidative stress conditions. In conclusion, oxidative stress decreases membrane fluidity, impairs receptor-ligand binding and reduces lipid raft clustering. PMID:23954806

  2. Chemical prevention of light-induced degradation in amorphous silicon films

    Science.gov (United States)

    Kobayashi, Hikaru; Kasama, Yoshiko; Fujinaga, Tetsushi; Takahashi, Masao; Koinuma, Hideomi

    2002-07-01

    The most serious problem for hydrogenated amorphous silicon (a-Si:H) solar cells is light induced-degradation due to the formation of defect states. A simple room temperature chemical method, i.e. the immersion of a-Si:H in crown-ether-containing KCN solutions under a positive bias, has been found to prevent light-induced deterioration of a-Si:H films. The prevention is attributed to the selective reaction of cyanide ions (CN -) with defect and defect precursor states. The inclusion of crown-ether completely prevents contamination of a-Si:H by K + ions, and the applied positive bias enhances inward migration of CN - ions. The experimental results suggest that this chemical reaction is useful to block the light-induced degradation of a-Si:H solar cells and systems.

  3. Tuning of Block Copolymer Membrane Morphology through Water Induced Phase Inversion Technique

    KAUST Repository

    Madhavan, Poornima

    2016-06-01

    Isoporous membranes are attractive for the regulation and detection of transport at the molecular level. A well-defined asymmetric membranes from diblock copolymers with an ordered nanoporous membrane morphologies were fabricated by the combination of block copolymer self-assembly and non-solvent-induced phase separation (NIPS) technique. This is a straightforward and fast one step procedure to develop integrally anisotropic (“asymmetric”) membranes having isoporous top selective layer. Membranes prepared via this method exhibit an anisotropic cross section with a thin separation layer supported from underneath a macroporous support. These membrane poses cylindrical pore structure with ordered nanopores across the entire membrane surfaces with pore size in the range from 20 to 40 nm. Tuning the pore morphology of the block copolymer membranes before and after fabrication are of great interest. In this thesis, we first investigated the pore morphology tuning of asymmetric block copolymer membrane by complexing with small organic molecules. We found that the occurrence of hydrogen-bond formation between PS-b-P4VP block copolymer and –OH/ –COOH functionalized organic molecules significantly tunes the pore morphology of asymmetric nanoporous membranes. In addition, we studied the complexation behavior of ionic liquids with PS-b-P4VP block copolymer in solutions and investigated their effect on final membrane morphology during the non-solvent induced phase separation process. We found that non-protic ionic liquids facilitate the formation of hexagonal nanoporous block copolymer structure, while protic ionic liquids led to a lamella-structured membrane. Secondly, we demonstrated the catalytic activity of the gold nanoparticle-enhanced hollow fiber membranes by the reduction of nitrophenol. Also, we systematically investigated the pore morphology of isoporous PS-b-P4VP using 3D imaging technique. Thirdly, we developed well-distributed silver nanoparticles on the

  4. Mechanisms of chemical-induced porphyrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Silbergeld, E.K. Fowler, B.A.

    1987-01-01

    This book contains 45 selections. Some of the titles are: Genetic Regulation of the Heme Pathway; Porphyrins in Urine as an Indication of Exposure to Chlorinated Hydrocarbons; Mechanisms of PCB-induced Porphyria and Yusho Disease; and Lead-Induced Abnormalities of Porphyrin Metabolism: The Relationship with Iron Deficiency.

  5. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    Science.gov (United States)

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  6. Blocking p55PIK signaling inhibits proliferation and induces differentiation of leukemia cells.

    Science.gov (United States)

    Wang, G; Deng, Y; Cao, X; Lai, S; Tong, Y; Luo, X; Feng, Y; Xia, X; Gong, J; Hu, J

    2012-11-01

    p55PIK, a regulatory subunit of phosphatidylinositol 3-kinases, promotes cell cycle progression by interacting with cell cycle modulators such as retinoblastoma protein (Rb) via its unique amino-terminal 24 amino-acid residue (N24). Overexpression of N24 specifically inhibits these interactions and leads to cell cycle arrest. Herein, we describe the generation of a fusion protein (Tat transactivator protein (TAT)-N24) that contains the protein transduction domain and N24, and examined its effects on the proliferation and differentiation of leukemia cells. TAT-N24 not only blocks cell proliferation but remarkably induces differentiation of leukemia cells in vitro and in vivo. Systemically administered TAT-N24 also significantly decreases growth of leukemia cell tumors in animal models. Furthermore, overexpression of p55PIK in leukemia cells leads to increased proliferation; however, TAT-N24 blocks this effect and concomitantly induces differentiation. There is significant upregulation of p55PIK mRNA and protein expression in leukemia cells from patients. TAT-N24 inhibits cell cycle progression and induces differentiation of bone marrow cells derived from patients with several different types of leukemia. These results show that cell-permeable N24 peptide induces leukemia cell differentiation and suggest that p55PIK may be a novel drug target for the treatment of hematopoetic malignancies. PMID:22722333

  7. Radiation-induced chemical evolution of biomolecules

    International Nuclear Information System (INIS)

    Chemical evolution in glycilglycine (Gly2) films irradiated with 146 nm vacuum ultraviolet light was studied. It is found that quantum efficiency of chemical evolution from Gly2 to glycilglycilglycine (Gly3) is smaller than that to glycilglycilglycilglycine (Gly4) due to the multiple step of reaction. Furthermore, we have carried out measurement of soft X-ray natural circular dichroism spectra for serine and alanine films in the energy region of oxygen 1s transition and we report the splitting of 1s→π* transitions.

  8. Morphology-controlled growth of perylene derivative induced by double-hydrophilic block copolymers

    Directory of Open Access Journals (Sweden)

    Minghua Huang

    2016-01-01

    Full Text Available Controlled growth of technically relevant perylene derivative 3, 4, 9, 10-perylenetetracarboxylic acid potassium salt (PTCAPS, with tuneable morpologies, has been successfully realized by a recrystallization method using a double-hydrophilic block copolymer poly (ethylene glycol-block poly (ethyleneimine (PEG-b-PEI as the structure directing agent. The {001} faces of PTCAPS are most polar and adsorb the oppositively charged polymer additive PEG-b-PEI well by electrostatic attraction. By simply adjusting the PEG-b-PEI concentration, systematic morphogenesis of PTCAPS from plates to microparticles composed of various plates splaying outwards could be realized. Furthermore, the variation of pH value of the recrystallization solution could induce the change of the interaction strength between PEG-b-PEI additive and PTCAPS and thus modify the morphology of PTCAPS from microparticles composed of various plates to ultralong microbelts.

  9. Morphology-controlled growth of perylene derivative induced by double-hydrophilic block copolymers

    Science.gov (United States)

    Huang, Minghua; Antonietti, Markus; Cölfen, Helmut

    2016-01-01

    Controlled growth of technically relevant perylene derivative 3, 4, 9, 10-perylenetetracarboxylic acid potassium salt (PTCAPS), with tuneable morpologies, has been successfully realized by a recrystallization method using a double-hydrophilic block copolymer poly (ethylene glycol)-block poly (ethyleneimine) (PEG-b-PEI) as the structure directing agent. The {001} faces of PTCAPS are most polar and adsorb the oppositively charged polymer additive PEG-b-PEI well by electrostatic attraction. By simply adjusting the PEG-b-PEI concentration, systematic morphogenesis of PTCAPS from plates to microparticles composed of various plates splaying outwards could be realized. Furthermore, the variation of pH value of the recrystallization solution could induce the change of the interaction strength between PEG-b-PEI additive and PTCAPS and thus modify the morphology of PTCAPS from microparticles composed of various plates to ultralong microbelts.

  10. Chemical Incorporation of Chain-Terminating Nucleoside Analogs as 3'-Blocking DNA Damage and Their Removal by Human ERCC1-XPF Endonuclease.

    Science.gov (United States)

    Yamamoto, Junpei; Takahata, Chiaki; Kuraoka, Isao; Hirota, Kouji; Iwai, Shigenori

    2016-01-01

    Nucleoside/nucleotide analogs that lack the 3'-hydroxy group are widely utilized for HIV therapy. These chain-terminating nucleoside analogs (CTNAs) block DNA synthesis after their incorporation into growing DNA, leading to the antiviral effects. However, they are also considered to be DNA damaging agents, and tyrosyl-DNA phosphodiesterase 1, a DNA repair enzyme, is reportedly able to remove such CTNA-modifications of DNA. Here, we have synthesized phosphoramidite building blocks of representative CTNAs, such as acyclovir, abacavir, carbovir, and lamivudine, and oligonucleotides with the 3'-CTNAs were successfully synthesized on solid supports. Using the chemically synthesized oligonucleotides, we investigated the excision of the 3'-CTNAs in DNA by the human excision repair cross complementing protein 1-xeroderma pigmentosum group F (ERCC1-XPF) endonuclease, which is one of the main components of the nucleotide excision repair pathway. A biochemical analysis demonstrated that the ERCC1-XPF endonuclease cleaved 2-7 nt upstream from the 3'-blocking CTNAs, and that DNA synthesis by the Klenow fragment was resumed after the removal of the CTNAs, suggesting that ERCC1-XPF participates in the repair of the CTNA-induced DNA damage. PMID:27294910

  11. EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice.

    Science.gov (United States)

    Li, Weixin; Fang, Qilu; Zhong, Peng; Chen, Lingfeng; Wang, Lintao; Zhang, Yali; Wang, Jun; Li, Xiaokun; Wang, Yi; Wang, Jingying; Liang, Guang

    2016-01-01

    Obesity is often associated with increased risk of cardiovascular diseases. Previous studies suggest that epidermal growth factor receptor (EGFR) antagonism may be effective for the treatment of angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. This study was performed to demonstrate if EGFR plays a role in the pathogenesis of hyperlipidemia/obesity-related cardiac injuries. The in vivo studies using both wild type (WT) and apolipoprotein E (ApoE) knockout mice fed with high fat diet (HFD) showed the beneficial effects of small-molecule EGFR inhibitors, AG1478 and 542, against obesity-induced myocardial injury. Administration of AG1478 and 542 significantly reduced myocardial inflammation, fibrosis, apoptosis, and dysfunction in both two obese mouse models. In vitro, EGFR signaling was blocked by either siRNA silencing or small-molecule EGFR inhibitors in palmitic acid (PA)-stimulated cardiomyocytes. EGFR inhibition attenuated PA-induced inflammatory response and apoptosis in H9C2 cells. Furthermore, we found that PA-induced EGFR activation was mediated by the upstream TLR4 and c-Src. This study has confirmed the detrimental effect of EGFR activation in the pathogenesis of obesity-induced cardiac inflammatory injuries in experimental mice, and has demonstrated the TLR4/c-Src-mediated mechanisms for PA-induced EGFR activation. Our data suggest that EGFR may be a therapeutic target for obesity-related cardiovascular diseases. PMID:27087279

  12. Biorefineries for the production of top building block chemicals and their derivatives

    DEFF Research Database (Denmark)

    Choi, Sol; Song, Chan Woo; Shin, Jae Ho;

    2015-01-01

    Due to the growing concerns on the climate change and sustainability on petrochemical resources, DOE selected and announced the bio-based top 12 building blocks and discussed the needs for developing biorefinery technologies to replace the current petroleum based industry in 2004. Over the last 1...

  13. How the chemical structure influence the dynamics of association of amphiphilic block copolymers

    Czech Academy of Sciences Publication Activity Database

    Deniau-Lejeune, E.; Charbonneau, C.; Borisova, O.; Chassenieux, C.; Colombani, O.; Štěpánek, Petr; Borisov, O.

    Saint-Petersburg: Institute of Macromolecular Compounds RAS, 2014. s. 46. ISBN 978-5-98340-329-1. [International Symposium "Molecular Order and Mobility in Polymer Systems" /8./. 02.06.2014-06.06.2014, St. Petersburg] Institutional support: RVO:61389013 Keywords : block copolymer * nanoparticles Subject RIV: CD - Macromolecular Chemistry

  14. Tn5-induced pBS286 plasmid mutations blocking early stages of napthalene oxidation

    International Nuclear Information System (INIS)

    The authors present data on the further analysis of the structural and functional organization of the nah region of plasmid pBS286 controlling the constitutive oxidation of naphthalene by Pseudomonas putida cells. They have studied Tn5-induced mutations blocking early stages of naphthalene oxidation. They present and discuss data providing evidence that, in contrast to plasmid NAH7, the mechanism of regulation of the nahl operon of plasmid NPL-1, the parent plasmid of plasmid pBS286, with inducible synthesis of naphthalene dioxygenase can include elements of a negative control with participation of the regulatory locus R, located proximal to the structural nah genes and closely linked to or overlapped by the inverted control DNA segment (4.2 kb). They also present data on the possibility of regulation of the activity of the catechol-splitting meta-pathway genes with the participation of products of early stages of naphthalene oxidation

  15. Baclofen blocks yohimbine-induced increases in ethanol-reinforced responding in rats.

    Science.gov (United States)

    Williams, Keith L; Nickel, Melissa M; Bielak, Justin T

    2016-05-01

    Chronic or repeated stress increases alcohol consumption. The GABA-B agonist baclofen decreases alcohol consumption and may be most effective for individuals with comorbid anxiety/stress disorders. The present study sought to determine if baclofen blocks stress-induced increases in ethanol self-administration as modeled by repeated yohimbine injections in rats. Rats were trained to respond for 15% w/v ethanol in operant chambers using a method that applies neither water deprivation nor saccharin/sucrose fading. Following training, the rats received 6 injections of 1.25mg/kg yohimbine were given immediately prior to the operant sessions during a 2-week time period. Subsequently, some rats were pair-matched to receive either 1.25mg/kg yohimbine or saline in the presence of 0.3, 1, and 3mg/kg baclofen prior to sessions. Acquisition of ethanol self-administration was poor. Pretreatment with yohimbine consistently increased responding across repeated injections. Yohimbine's effect on ethanol intake unexpectedly diverged from the effect on responding as the rats failed to consume all reinforcers earned. Smaller doses of baclofen paired with saline injections had no effect on ethanol responding; only 3mg/kg baclofen reduced ethanol self-administration. The smallest baclofen dose of 0.3mg/kg failed to block the yohimbine-induced increase in self-administration. The large baclofen dose of 3mg/kg continued to suppress ethanol self-administration when given with yohimbine. Baclofen 1mg/kg blocked the effect of yohimbine even though it had no effect when given in the absence of yohimbine. Exposure to high ethanol concentrations may induce self-administration only in certain conditions. The dissociation between responding and intake suggests that repeated yohimbine injections may initiate other behavioral or physiological mechanisms that confound its effects as a pharmacological stressor. Furthermore, an optimal baclofen dose range may specifically protect against stress-induced

  16. Synthesis of bio-based building blocks from vegetable oils: a platform chemicals approach

    Directory of Open Access Journals (Sweden)

    Desroches Myriam

    2013-01-01

    Full Text Available This review reports the synthesis of various building blocks from vegetable oils in one or two-steps syntheses. Thiol-ene coupling allows to synthesize new biobased reactants with various function and functionality with reaction conditions in agreement with green chemistry principles: it does not use neither solvent nor initiator or need simple purification step, feasible at industrial scale. Esterification and amidification were also used to insert ester or amide groups in fatty chains in order to modifiy properties of thereof synthesized polymers. Building blocks synthesized have various functions and functionality: polyols, polyacids, polyamines and dicyclocarbonates from vegetable oils and from glycerine derivatives. They were used for the synthesis of biobased polyurethanes, polyhydroxyurethanes and epoxy resins.

  17. Phase diagram of selectively cross-linked block copolymers shows chemically microstructured gel

    OpenAIRE

    von der Heydt, Alice; Zippelius, Annette

    2014-01-01

    We study analytically the intricate phase behavior of cross-linked $AB$ diblock copolymer melts, which can undergo two main phase transitions due to quenched random constraints: Gelation, i.e., spatially random localization of polymers forming a system-spanning cluster, is driven by increasing the number parameter $\\mu$ of irreversible, type-selective cross-links between random pairs of $A$ blocks. Self-assembly into a periodic pattern of $A$/$B$-rich microdomains (microphase separation) is c...

  18. Approaches to the evaluation of chemical-induced immunotoxicity.

    OpenAIRE

    Krzystyniak, K; Tryphonas, H; Fournier, M

    1995-01-01

    The immune system plays a crucial role in maintaining health; however, accumulating evidence indicates that this system can be the target for immunotoxic effects caused by a variety of chemicals including the environmental pollutants of polychlorinated biphenyls, chlorinated dibenzo-p-dioxins, pesticides, and heavy metals. Adverse chemical-induced immunomodulation, which is studied within the discipline of immunotoxicology, may be expressed either as immunosuppression/immunodepression or immu...

  19. Some economic problems associated with the damping of chemical extraction of uranium in the Straz block

    International Nuclear Information System (INIS)

    Both mining and chemical extraction of uranium are practised in the Straz pod Ralskem region. The production of uranium was by 18% lower in 1992 than in the preceding years. An economic model of chemical extraction was developed. So far, the production cost did not include the cost of land reclamation after terminating the extraction. Rehabilitation scenarios have been developed for the various alternatives of termination of the chemical extraction, ranging from immediate shutdown to shutdown after complete extraction. The governmental decision was postponed to 1994, when the desalination technology should have been solved. (M.D.). 9 refs

  20. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    International Nuclear Information System (INIS)

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO2) was less cytolethal over 24 h in WT cells (LC50 = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC50 = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic

  1. Neuro-immune interactions in chemical-induced airway hyperreactivity.

    Science.gov (United States)

    Devos, Fien C; Boonen, Brett; Alpizar, Yeranddy A; Maes, Tania; Hox, Valérie; Seys, Sven; Pollaris, Lore; Liston, Adrian; Nemery, Benoit; Talavera, Karel; Hoet, Peter H M; Vanoirbeek, Jeroen A J

    2016-08-01

    Asthma may be induced by chemical sensitisers, via mechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitro intracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using an in vivo model, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, in Trpa1 and Trpv1 knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficient Kit(Wsh) (/Wsh) mice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR. PMID:27126687

  2. Chemical changes induced by ultrasound in iron

    Science.gov (United States)

    Albertini, G.; Calbucci, V.; Cardone, F.; Petrucci, A.; Ridolfi, F.

    2014-03-01

    The focus of this work is a careful chemical investigation of structural damage produced by the exposure of an iron bar to pressure waves generated using an ultrasound machine (called the R-1-S reactor). In addition to the emission of neutron bursts, the ultrasound treatment caused the appearance of zones of macroscopic damage (˜1 mm in size) on the exterior of the bar. Reflected-light optical and environmental scanning electron microscopy (ESEM) has shown that these external damage zones are characterized by microcraters and are covered by a thin layer of cracked amorphous material. Under back scattered electron (BSE) observation, this material shows a lower brightness than the intact ferrite surface. In addition, a zone with a high density of deformed cavities (˜1300 per mm2) with irregular walls and a maximum size of 10 μm was found inside the bar. These deformed microcavities are partially filled with a material composed of a chaotic assemblage of submicron-sized (most likely amorphous) particles. A careful compositional investigation of the chaotic material inside the microcavities using the semi-quantitative data obtained with the ESEM X-ray Energy Dispersive System (EDS) has shown that it is primarily composed of carbon, manganese and chromium. These elements are also found in lower amounts within the intact ferrite matrix. In contrast, the damaged surface surrounding the craters is characterized by elements not found in the ferrite at all (i.e., O, Cl, K, Cu); elements the presence of which cannot be attributed to the occurrence of non-metallic inclusions or to contamination during fabrication. These results are also difficult to explain using the generally accepted laws of physics; however, they do appear to agree with a recent theory predicting the deformation of the local spacetime and the violation of the Local Lorentz Invariance. Such a violation should occur following the collapse of micron-sized discontinuities internal to the materials

  3. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species†

    Science.gov (United States)

    Yuan, Hengjie; Houck, Katie L.; Tian, Ye; Bharadwaj, Uddalak; Hull, Ken; Zhou, Zhou; Zhou, Mingzhao; Wu, Xiaoping; Tweardy, David J.; Romo, Daniel; Fu, Xiaoyun; Zhang, Yanjun; Zhang, Jianning; Dong, Jing-fei

    2015-01-01

    Background Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. Objective We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. Results PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. Conclusions PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals. PMID:26645674

  4. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species.

    Directory of Open Access Journals (Sweden)

    Hengjie Yuan

    Full Text Available Piperlongumine (PL is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known.We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen.PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect.PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.

  5. Inhibitors of the cytochrome P-450 enzymes block the secretagogue-induced release of corticotropin in mouse pituitary tumor cells.

    OpenAIRE

    Luini, A G; Axelrod, J

    1985-01-01

    A mouse pituitary tumor cell line (AtT-20) releases corticotropin (ACTH) in response to a number of secretagogues, including corticotropin-releasing factor (CRF), beta-adrenergic agents, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2 cAMP), and potassium. The stimulation of ACTH secretion induced by the secretagogues can be blocked by inhibitors of the enzymes that generate (phospholipase A2) and metabolize (lipoxygenase and epoxygenase) arachidonic acid. The phospholipase A2 block...

  6. Sugammadex reversal of rocuronium-induced neuromuscular block in a patient with ataxia-telangiectasia

    International Nuclear Information System (INIS)

    A 17-year-old adolescent with ataxia-telangiectasia was scheduled to have laparoscopic colectomy for a resection of colon cancer. He had symptoms and signs of dyspnea, generalized dystonia, dysmetria, ataxia, and telangiectasia on the orbit. General anesthesia was performed, and rocuronium 30 mg was administered for muscle relaxation. Deep neuromuscular block (post-tetanic count: 0-8) was maintained for 95 minutes without additional rocuronium. On completion of surgery, sugammadex 80 mg was injected and train-of-four ratio was 0.93 at 210 seconds after administration. The tracheal tube was removed 5 min after the end of surgery. He recovered full spontaneous respiration and voluntary movements within 1 minute after extubation. After the surgery, he transferred to the intensive care unit and discharged 14 days after the surgery without any concrete problem. The reversal of rocuronium induced neuromuscular block by sugammadex was fast, complete, and recovered to the initial preoperative level of neuromuscular function in this patient. (author)

  7. Inhibition of tankyrases induces Axin stabilization and blocks Wnt signalling in breast cancer cells.

    Science.gov (United States)

    Bao, Renyue; Christova, Tania; Song, Siyuan; Angers, Stephane; Yan, Xiaojun; Attisano, Liliana

    2012-01-01

    Constitutive Wnt signalling is characterized by excessive levels of β-catenin protein and is a frequent occurrence in cancer. APC and Axin are key components of the β-catenin destruction complex that acts to promote β-catenin degradation. The levels of Axin are in turn controlled by tankyrases, members of the PARP-family of poly-ADP-ribosylation enzymes. In colorectal cancer cells, which typically harbor APC mutations, inhibition of tankyrase activity promotes Axin stabilization and attenuates Wnt signalling. Here, we examined the effect of inhibiting tankyrases in breast cancer cells with normal APC. We show that application of the small molecule tankyrase inhibitor, XAV939 or siRNA-mediated abrogation of tankyrase expression increases Axin1 and Axin2 protein levels and attenuates Wnt-induced transcriptional responses in several breast cancer lines. In MDA-MB-231 cells, inhibiton of tankyrase activity also attenuate Wnt3a induced cell migration. Moreover, in both MDA-MB-231 and colorectal cancer cells, XAV939 inhibits cell growth under conditions of serum-deprivation. However, the presence of serum prevents this growth inhibitory effect, although inhibition of Wnt-induced transcriptional and migratory responses was maintained. These results indicate that stabilization of Axin by inhibition of tankyrases alone, may not be an effective means to block tumor cell growth and that combinatorial therapeutic approaches should be considered. PMID:23144924

  8. Cold saline is more effective than room temperature saline in inducing paresthesia during axillary block.

    Science.gov (United States)

    Rodríguez, J; Carceller, J; Bárcena, M; Pedraza, I; Calvo, B; Alvarez, J

    1995-08-01

    Confirmation of the perivascular position of the needle by the injection of cold saline may be helpful to the perivascular technique, since the elicitation of a paresthesia indicates the correct positioning of the needle. In this prospective, randomized study of 48 patients, we found a 100% incidence of successful block with saline at 8-11 degrees C compared to 75% in a control group with saline at room temperature. The paresthesia induced by cold saline appears to be due to thermic stimulation and not to mechanical nerve compression by the saline entering the axillary space. A more frequent rate of correct positioning of the needle was found in the group with cold saline. PMID:7618724

  9. Estrogen in prefrontal cortex blocks stress-induced cognitive impairments in female rats.

    Science.gov (United States)

    Yuen, Eunice Y; Wei, Jing; Yan, Zhen

    2016-06-01

    Animal and human studies have found that males and females show distinct stress responses. Recent studies suggest the contribution of estrogen in the brain to this sexual dimorphism. Repeated stress has been found to impair cognitive behaviors via suppressing glutamatergic transmission and glutamate receptor surface expression in pyramidal neurons of prefrontal cortex (PFC) in male rats. On the contrary, female rats exposed to the same stress paradigms show normal synaptic function and PFC-mediated cognition. The level of aromatase, the enzyme for the biosynthesis of estrogen, is significantly higher in the PFC of females than males. The stress-induced glutamatergic deficits and memory impairment are unmasked by blocking estrogen receptors or aromatase in females, suggesting a protective role of estrogen against the detrimental effects of repeated stress. PMID:26321384

  10. Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development.

    Science.gov (United States)

    Rijntjes, Eddy; Swarts, Hans J M; Anand-Ivell, Ravinder; Teerds, Katja J

    2009-02-01

    Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were put on a diet consisting of an iodide-poor feed supplemented with a low dose of perchlorate and, with their offspring, were kept on this diet until death. In the pups at day 12 postpartum, plasma thyroid-stimulating hormone levels were increased by 20-fold, whereas thyroxine and free tri-iodothyronine levels were severely depressed, confirming a hypothyroid condition. Adult-type progenitor Leydig cell formation and proliferation were reduced by 40-60% on days 16 and 28 postpartum. This was followed by increased Leydig cell proliferation at later ages, suggesting a possible slower developmental onset of the adult-type Leydig cell population under hypothyroid conditions. Testosterone levels were increased 2- to 10-fold in the hypothyroid animals between days 21 and 42 postpartum compared with the age-matched controls. Combined with the decreased presence of 5alpha-reductase, this implicates a lower production capacity of 5alpha-reduced androgens. In 84-day-old rats, after correction for body weight-to-testis weight ratio, plasma insulin-like factor-3 levels were 35% lower in the hypothyroid animals, suggestive of a reduced Leydig cell population. This is confirmed by a 37% reduction in the Sertoli cell-to-Leydig cell ratio in hypothyroid rats. In conclusion, we show that dietary-induced hypothyroidism delays but, unlike propyl-2-thiouracyl, does not block the development of the adult-type Leydig cell population. PMID:19033542

  11. Acute clenbuterol induces hypotension, atrioventricular block and cardiac asystole in the rabbit.

    Science.gov (United States)

    Ke, Yan; Fu, Li-Lan; Hong, Xia-Fei; Dong, Run; Xu, Tian-Ming; Guo, Jing-Fei; Liu, Yan; Cao, Ji-Min

    2013-03-01

    Clenbuterol is a long-lasting β-adrenoceptor (β-AR) agonist and was once medicated as a bronchial dilatator, and is also used by body-building enthusiasts and athletes and in livestock breeding because of its anabolic effect on skeletal muscles and ability to promote lipolysis. Though prohibited from pharmacological uses, clenbuterol intoxication cases are frequently reported, and most of the cardiac symptoms are tachyarrhythmia. Here, we reported a different cardiovascular toxic response to clenbuterol. Using a rabbit model, we tested the dose-response pattern of the cardiovascular system to intravenous administration of clenbuterol. Routine arterial blood pressure (BP) and surface electrocardiogram (ECG) were monitored. We observed that clenbuterol at a lower dose (0.4 mg/kg, n = 3) did not significantly affect the ECG, but decreased the mean BP roughly by 15-18 mmHg. At a medial dose (3.6 mg/kg, n = 3), clenbuterol induced significant hypotension (mean BP dropped by about 30 mmHg), first-degree atrioventricular (AV) block and intermittent ectopic activities with a relatively slow rate. The hypotension and arrhythmia recovered slowly, and animals did not die. Higher-dose clenbuterol (10 mg/kg, n = 6) induced severe hypotension, second-degree AV block (Mobitz type II), 2:1 ventricular capture and progressive prolongations of P-R intervals and QRS duration, and the animals soon died of cardiac asystole. Different from other reports, we had not observed lethal tachyarrhythmia in all experiments except for the slight heart rate acceleration during the recovery stage of medial clenbuterol dosage. These results indicate that acute intravenous administration of clenbuterol has serious, dose-dependent cardiovascular toxicities and is even life threatening. PMID:22991173

  12. DNA and RNA induced enantioselectivity in chemical synthesis

    NARCIS (Netherlands)

    Roelfes, Gerard

    2007-01-01

    One of the hallmarks of DNA and RNA structures is their elegant chirality. Using these chiral structures to induce enantioselectivity in chemical synthesis is as enticing as it is challenging. In recent years, three general approaches have been developed to achieve this, including chirality transfer

  13. Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats

    Directory of Open Access Journals (Sweden)

    Marx Romy

    2008-09-01

    protein. The most potent corticosteroid tested, dexamethasone, was shown to counteract cytokine effects on membrane surface extension and capacitance. Furthermore, coapplication of dexamethasone blocked the cytokine-induced downregulation of the inwardly rectifying potassium current in 80% of the precursor cells and restored the cytokine-blocked down-regulation of the voltage activated Na+- and K+ currents during subsequent differentiation. Conclusion Our results show that treatment of oligodendrocyte precursors with the inflammatory cytokines TNF-α and IFN-γ block the differentiation of oligodendrocyte precursors at the level of the differentiation of the voltage-gated ion currents. Co-treatment with corticosteroids at the time of cytokine application restores to a considerable extent survival and differentiation of oligodendrocytes at the level of morphological, myelin protein as well as ion current maturation suggesting the option for a functional restoration of cytokine-damaged immature oligodendrocytes.

  14. Gametocytocidal screen identifies novel chemical classes with Plasmodium falciparum transmission blocking activity.

    Directory of Open Access Journals (Sweden)

    Natalie G Sanders

    Full Text Available Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds.

  15. Morphological control via chemical and shear forces in block copolymer self-assembly in the lab-on-chip.

    Science.gov (United States)

    Wang, Chih-Wei; Sinton, David; Moffitt, Matthew G

    2013-02-26

    We investigate the effects of variation in chemical conditions (solvent composition, water content, polymer concentration, and added salt) on the morphologies formed by PS-b-PAA in DMF/dioxane/water mixtures in a two-phase gas-liquid segmented microfluidic reactor. The differences in morphologies between off-chip and on-chip self-assembly and on-chip morphological trends for different chemical conditions are explained by the interplay of top-down shear effects (coalescence and breakup) and bottom-up chemical forces. Using off-chip morphology results, we construct a water content-solvent composition phase diagram showing disordered, sphere, cylinder, and vesicle regions. On-chip morphologies are found to deviate from off-chip morphologies by three identified shear-induced paths: 1) sphere-to-cylinder, and 2) sphere-to-vesicle transitions, both via shear-induced coalescence when initial micelle sizes are small, and 3) cylinder-to-sphere transitions via shear-induced breakup when initial micelle sizes are large (high capillary number conditions). These pathways contribute to the generation of large extended bilayer aggregates uniquely on-chip, at either increased polymer or salt concentrations. Collectively these results demonstrate the broad utility of top-down directed molecular self-assembly in conjunction with chemical forces to control morphology and size of polymer colloids at the nanoscale. PMID:23311400

  16. A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia▿

    Science.gov (United States)

    Sonda, Sabrina; Štefanić, Saša; Hehl, Adrian B.

    2008-01-01

    Sphingolipid biosynthesis pathways have recently emerged as a promising target for therapeutic intervention against pathogens, including parasites. A key step in the synthesis of complex sphingolipids is the glucosylation of ceramide, mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we investigated whether PPMP inhibits the proliferation and differentiation of the pathogenic parasite Giardia lamblia, the major cause of parasite-induced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 μM. The inhibition of parasite replication was irreversible at 10 μM PPMP, a concentration that did not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion of cell division at a specific stage in late cytokinesis. Microscopic analysis of cells incubated with PPMP revealed the aberrant accumulation of cellular membranes belonging to the endoplasmic reticulum network in the caudal area of the parasites. Finally, PPMP induced a 90% reduction in G. lamblia differentiation into cysts, the parasite stage responsible for the transmission of the disease. These results show that PPMP is a powerful inhibitor of G. lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic pathways are potential targets for the development of anti-G. lamblia agents. PMID:18086854

  17. A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage differentiation in Giardia lamblia.

    Science.gov (United States)

    Sonda, Sabrina; Stefanic, Sasa; Hehl, Adrian B

    2008-02-01

    Sphingolipid biosynthesis pathways have recently emerged as a promising target for therapeutic intervention against pathogens, including parasites. A key step in the synthesis of complex sphingolipids is the glucosylation of ceramide, mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we investigated whether PPMP inhibits the proliferation and differentiation of the pathogenic parasite Giardia lamblia, the major cause of parasite-induced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 muM. The inhibition of parasite replication was irreversible at 10 muM PPMP, a concentration that did not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion of cell division at a specific stage in late cytokinesis. Microscopic analysis of cells incubated with PPMP revealed the aberrant accumulation of cellular membranes belonging to the endoplasmic reticulum network in the caudal area of the parasites. Finally, PPMP induced a 90% reduction in G. lamblia differentiation into cysts, the parasite stage responsible for the transmission of the disease. These results show that PPMP is a powerful inhibitor of G. lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic pathways are potential targets for the development of anti-G. lamblia agents. PMID:18086854

  18. A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

    Directory of Open Access Journals (Sweden)

    Frédérique Végran

    Full Text Available Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.

  19. Antihistamines block radiation-induced increased intestinal blood flow in canines

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-06-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure.

  20. Antihistamines block radiation-induced increased intestinal blood flow in canines

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Gossett-Hagerman, C.J.

    1985-01-01

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H/sub 1/ and H/sub 2/ histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H sub 1 and H sub 2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systematic plasma histamine levels were determined simultaneously. Data obtained indicated that the H sub 1 and H sub 2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure. (Author)

  1. Antihistamines block radiation-induced increased intestinal blood flow in canines

    International Nuclear Information System (INIS)

    Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure

  2. Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.

    Science.gov (United States)

    Tamminen, Kirsi; Malm, Maria; Vesikari, Timo; Blazevic, Vesna

    2016-06-01

    Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface. PMID:27135874

  3. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  4. Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N. [Harvard Medical School, Boston, MA (United States)

    1995-03-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

  5. Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

    Directory of Open Access Journals (Sweden)

    Arvand Haschemi

    Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

  6. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

  7. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  8. A model for chemically-induced mechanical loading on MEMS

    DEFF Research Database (Denmark)

    Amiot, Fabien

    2007-01-01

    The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain, and...... displacements). As these phenomena usually arise from species adsorption, adsorbate modification or surface reconstruction, they are surface-related by nature and thus require some dedicated mechanical modeling. The accompanying mechanical modeling proposed herein is intended to represent the chemical part of...... drawn from the energy balance in the accompanying model, highlighting the role of surface functionalization parameters in micromechanical sensors engineering....

  9. RNA interference blocking the apoptosis in HEK293 cells induced by overexpression of alpha-synuclein

    Institute of Scientific and Technical Information of China (English)

    Tao Chen; Beisha Tang; Xiaoping Liao; Guoqiang Wen; Xinxiang Yan; Jifeng Guo; Yuhu Zhang; Feng Ouyang; Zhigang Long; Li Cao; Jing Li

    2009-01-01

    BACKGROUND: Overexpression of o-synuclein can induce cell apoptosis. RNA interference (RNAi)may block specific gene function and cause gene silencing.OBJECTIVE: To construct a specific and effective RNAi plasmid for the a-synuclein gene and investigate if RNAi can block apoptosis in HEK293 cells, induced by overexpression of wild-type α-synuclein.DESIGN, TIME AND SETTING: A contrast experiment based on genetically engineered cytobiology was performed at the State Key Lab of Medical Genetics of China, Xiangya Medical College of Central South University, between October 2004 and October 2008.MATERIALS: HEK293 cells and pBSHH1 plasmid were provided by the State Key Lab of Medical Genetics of China; OligDNA sequence by Sagon Bioengineering Company, Shanghai;Lipofectamine 2000 by Invitrogen, USA;α-synuclein monoclonal antibody, Hoechst 33258, and MTT by Sigma, USA; Horseradish peroxidase-coupled goat anti-rat luG by KPL, USA; FACSan flow cytometry by BD, USA.METHODS: Four target sites were used to construct hairpin RNA pBSHH1 vectors-pSYNi-1,pSYNi-2, pSYNi-3 and pSYNi-4-which were cloned in the pBSHH1 plasmid. HEK293 cells were transfected using Lipofectamine 2000. In addition, a non-transfect group and a negative plasmid transfect group were established. The cultured HEK293 cells were processed as follows:transfection of blank plasmid (blank control group), transfection of α-synuclein-pEGFP and RNAi negative vector (negative control group), and transfection of a-synuclein-pEGFP and pSYNi-1 (transfection group). Cells in all groups were transfected with Lipofectamine 2000 for 48 hours.MAIN OUTCOME MEASURES: Expression of α-synuclein mRNA and protein were detected by RT-PCR and Western blot. Cell morphology was observed under an inverted fluorescence microscope; cell viability was measured using MTT method; and cell apoptosis was determined with Annexin V-PE flow cytometry.RESULTS: a-synuclein mRNA and protein expressions were significantly decreased in the pSYNi-1

  10. Keratin expression in chemically induced mouse lung adenomas.

    OpenAIRE

    Gunning, W T; Goldblatt, P. J.; Stoner, G D

    1992-01-01

    Chemically induced mouse lung tumors exhibit distinctive growth patterns, characterized by an alveolar or solid appearance, a papillary appearance, or a combination of the two. Lung tumors induced in strain A/J mice by either benzo(a)pyrene (BP) or by N-nitrosoethylurea (ENU) were examined for expression of low- and high-molecular-weight cytokeratins. Simple cytokeratins (low molecular weight) were found in all epithelial cells of the normal mouse lung and in all tumor types, whereas higher-m...

  11. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species†

    OpenAIRE

    Hengjie Yuan; Houck, Katie L.; Ye Tian; Uddalak Bharadwaj; Ken Hull; Zhou Zhou; Mingzhao Zhu; Xiaoping Wu; David J Tweardy; Daniel Romo; Xiaoyun Fu; Yanjun Zhang; Jianning Zhang; Jing-fei Dong

    2015-01-01

    Background Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. Objective We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce t...

  12. Laser-Induced Chemical Vapour Deposition of Silicon Carbonitride

    OpenAIRE

    Besling, W.; van der Put, P.; Schoonman, J.

    1995-01-01

    Laser-induced Chemical Vapour Deposition of silicon carbonitride coatings and powders has been investigated using hexamethyldisilazane (HMDS) and ammonia as reactants. An industrial CW CO2-laser in parallel configuration has been used to heat up the reactant gases. HMDS dissociates in the laser beam and reactive radicals are formed which increase rapidly in molecular weight by an addition mechanism. Dense polymer-like silicon carbonitride thin films and nanosized powders are formed depending ...

  13. Methylphenidate blocks effort-induced depletion of regulatory control in healthy volunteers.

    Science.gov (United States)

    Sripada, Chandra; Kessler, Daniel; Jonides, John

    2014-06-01

    A recent wave of studies--more than 100 conducted over the last decade--has shown that exerting effort at controlling impulses or behavioral tendencies leaves a person depleted and less able to engage in subsequent rounds of regulation. Regulatory depletion is thought to play an important role in everyday problems (e.g., excessive spending, overeating) as well as psychiatric conditions, but its neurophysiological basis is poorly understood. Using a placebo-controlled, double-blind design, we demonstrated that the psychostimulant methylphenidate (commonly known as Ritalin), a catecholamine reuptake blocker that increases dopamine and norepinephrine at the synaptic cleft, fully blocks effort-induced depletion of regulatory control. Spectral analysis of trial-by-trial reaction times revealed specificity of methylphenidate effects on regulatory depletion in the slow-4 frequency band. This band is associated with the operation of resting-state brain networks that produce mind wandering, which raises potential connections between our results and recent brain-network-based models of control over attention. PMID:24756766

  14. ‘Geo’chemical research: A key building block for nuclear waste disposal safety cases

    Science.gov (United States)

    Altmann, Scott

    2008-12-01

    Disposal of high level radioactive waste in deep underground repositories has been chosen as solution by several countries. Because of the special status this type waste has in the public mind, national implementation programs typically mobilize massive R&D efforts, last decades and are subject to extremely detailed and critical social-political scrutiny. The culminating argument of each program is a 'Safety Case' for a specific disposal concept containing, among other elements, the results of performance assessment simulations whose object is to model the release of radionuclides to the biosphere. Public and political confidence in performance assessment results (which generally show that radionuclide release will always be at acceptable levels) is based on their confidence in the quality of the scientific understanding in the processes included in the performance assessment model, in particular those governing radionuclide speciation and mass transport in the geological host formation. Geochemistry constitutes a core area of research in this regard. Clay-mineral rich formations are the subjects of advanced radwaste programs in several countries (France, Belgium, Switzerland…), principally because of their very low permeabilities and demonstrated capacities to retard by sorption most radionuclides. Among the key processes which must be represented in performance assessment models are (i) radioelement speciation (redox state, speciation, reactions determining radionuclide solid-solution partitioning) and (ii) diffusion-driven transport. The safety case must therefore demonstrate a detailed understanding of the physical-chemical phenomena governing the effects of these two aspects, for each radionuclide, within the geological barrier system. A wide range of coordinated (and internationally collaborated) research has been, and is being, carried out in order to gain the detailed scientific understanding needed for constructing those parts of the Safety Case

  15. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    International Nuclear Information System (INIS)

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

  16. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  17. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-12-01

    Full Text Available Tumor-associated macrophages (TAMs promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA blocks occurrence of tumor associated macrophages (TAMs in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA, a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  18. Guided self-assembly of block-copolymer for CMOS technology: a comparative study between grapho-epitaxy and surface chemical modification

    Science.gov (United States)

    Oria, Lorea; Ruiz de Luzuriaga, Alaitz; Chevalier, Xavier; Alduncin, Juan A.; Mecerreyes, David; Tiron, Raluca; Gaugiran, Stephanie; Perez-Murano, Francesc

    2011-04-01

    Recent progress in Block Copolymer lithography has shown that guided self-assembly is a viable alternative for pushing forward the resolution limits of optical lithography. The main two self assembly methods considered so far have been the surface chemical modification, which is based on the chemical modification of a brush grafted to the silicon, and the grapho-epitaxy, which is based on creating topographic patterns on the surface. We have tested these two approaches for the 22 nm node and beyond CMOS technology, using PS-PMMA block copolymers synthesized by RAFT (Reversible Addition-Fragmentation Chain Transfer) polymerization.

  19. Radiation induced G1-block and p53 status in six human cell lines

    International Nuclear Information System (INIS)

    Considerable attention has recently been focused on the fact that the tumor suppressor protein p53 is involved in the cellular response to radiation. In its wild-type form the protein appears to control a cell cycle check point, preventing entry into S-phase following DNA damage. A number of authors observed a radiation induced G1-block in cells expressing wild-type p53, but not in p53 mutant cells. We obtained similar results with four human tumour cell lines as well as two strains of human fibroblasts, whose p53 status was ascertained at the protein as well as DNA levels. In addition to cell cycle delays in exponentially growing cell cultures, we have studied the possible role of the p53 in the transition from quiescence to active proliferation. Cells were irradiated after 6 days of serum-starvation and labelled with BrdU at different times after addition of fresh medium. Entry into S-phase was found to be delayed by several hours in the p53 wild-type cells, but no such effect was observed in the p53 mutants. Where a delay occurred, it was roughly proportional to the X-ray dose. Although it remains to be clarified, whether the cells were delayed only in G1 or also in G0, it is interesting to note that entry into S-phase can be delayed by irradiation in a quiescent state immediately before serum-stimulation, provided the cells are wild-type with respect to p53. Certain differences in the cell cycle response of transformed and untransformed cells were noted

  20. Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C.R.; Kleeberger, S.R.; Spannhake, E.W. (Johns Hopkins Medical Institutions, Baltimore, MD (USA))

    1989-01-01

    The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

  1. Neural signatures of experimentally induced flow experiences identified in a typical fMRI block design with BOLD imaging.

    Science.gov (United States)

    Ulrich, Martin; Keller, Johannes; Grön, Georg

    2016-03-01

    Previously, experimentally induced flow experiences have been demonstrated with perfusion imaging during activation blocks of 3 min length to accommodate with the putatively slowly evolving "mood" characteristics of flow. Here, we used functional magnetic resonance imaging (fMRI) in a sample of 23 healthy, male participants to investigate flow in the context of a typical fMRI block design with block lengths as short as 30 s. To induce flow, demands of arithmetic tasks were automatically and continuously adjusted to the individual skill level. Compared against conditions of boredom and overload, experience of flow was evident from individuals' reported subjective experiences and changes in electrodermal activity. Neural activation was relatively increased during flow, particularly in the anterior insula, inferior frontal gyri, basal ganglia and midbrain. Relative activation decreases during flow were observed in medial prefrontal and posterior cingulate cortex, and in the medial temporal lobe including the amygdala. Present findings suggest that even in the context of comparably short activation blocks flow can be reliably experienced and is associated with changes in neural activation of brain regions previously described. Possible mechanisms of interacting brain regions are outlined, awaiting further investigation which should now be possible given the greater temporal resolution compared with previous perfusion imaging. PMID:26508774

  2. PIXE and PIXE-induced XRF for chemical specification

    International Nuclear Information System (INIS)

    Wavelength dispersive X-ray spectra with fine structures in the PIXE and PIXE-induced XRF spectra have been proved to be very much useful for chemical specification of condensed matters. The fine structures have been reproduced theoretically by introducing molecular orbital calculations, the shake-off and resonant orbital rearrangement (ROR) processes, together with the direct Coulomb interaction between projectiles and target atoms, and the self-absorption of emitted X-rays through the targets. Comparison between observed and theoretical spectra is given here for F and S atoms

  3. Chemical modification of polyurethanes by radiation-induced grafting

    International Nuclear Information System (INIS)

    Basic methods of radiation-induced modification of polyurethanes for biomedical applications and of their characterization are briefly described. The most important works found in literature on radiation grafting of polyurethanes are discussed. The radiation grafting of polyetherurethane films and tubings by the preswelling method using various monomers and their physico-chemical characterization are discussed in detail with respect to the antithrombogenic properties of the materials. Novel applications for radiation-modified polyurethanes as drug delivery systems or antiinfectious materials are briefly mentioned. 52 references

  4. Environment-induced self-assembly in phase separated block copolymer systems: A SANS investigation

    International Nuclear Information System (INIS)

    In this research, we examine the effect of non-selective solvent on the large-scale mesoscopic ordering in asymmetric block copolymers, poly(styrene-block-ethylene/butylene-block-styrene) (SEBS) using small angle neutron scattering technique (SANS). SANS measurements were carried out over a wide range of concentrations and temperatures. Evolution of the self-assembled phase morphology in such polymer with the thermodynamic selectivity of solvent, temperature and concentration has been discussed. Correlation between morphology and thermorheological behavior of the gels has also been established

  5. Electrical Injury-Induced Complete Atrioventricular Block: Is Permanent Pacemaker Required?

    Directory of Open Access Journals (Sweden)

    Osman Beton

    2015-01-01

    Full Text Available A considerable percentage of electrical injuries occur as a result of work activities. Electrical injury can lead to various cardiovascular disorders: acute myocardial necrosis, myocardial ischemia, heart failure, arrhythmias, hemorrhagic pericarditis, acute hypertension with peripheral vasospasm, and anomalous, nonspecific ECG alterations. Ventricular fibrillation is the most common arrhythmia resulting from electrical injury and is the leading cause of death in electrical (especially low voltage alternating current injury cases. Asystole, premature ventricular contractions, ventricular tachycardia, conduction disorders (various degrees of heart blocks, bundle-brunch blocks, supraventricular tachycardia, and atrial fibrillation are the other arrhythmic complications of electrical injury. Complete atrioventricular block has rarely been reported and permanent pacemaker was required for the treatment in some of these cases. Herein, we present a case of reversible complete atrioventricular block due to low voltage electrical injury in a young electrical technician.

  6. Electrical Injury-Induced Complete Atrioventricular Block: Is Permanent Pacemaker Required?

    Science.gov (United States)

    Beton, Osman; Efe, Tolga Han; Kaya, Hakki; Bilgin, Murat; Dinc Asarcikli, Lale; Yilmaz, Mehmet Birhan

    2015-01-01

    A considerable percentage of electrical injuries occur as a result of work activities. Electrical injury can lead to various cardiovascular disorders: acute myocardial necrosis, myocardial ischemia, heart failure, arrhythmias, hemorrhagic pericarditis, acute hypertension with peripheral vasospasm, and anomalous, nonspecific ECG alterations. Ventricular fibrillation is the most common arrhythmia resulting from electrical injury and is the leading cause of death in electrical (especially low voltage alternating current) injury cases. Asystole, premature ventricular contractions, ventricular tachycardia, conduction disorders (various degrees of heart blocks, bundle-brunch blocks), supraventricular tachycardia, and atrial fibrillation are the other arrhythmic complications of electrical injury. Complete atrioventricular block has rarely been reported and permanent pacemaker was required for the treatment in some of these cases. Herein, we present a case of reversible complete atrioventricular block due to low voltage electrical injury in a young electrical technician. PMID:26839721

  7. Study of carrier blocking property of poly-linalyl acetate thin layer by electric-field-induced optical second-harmonic generation measurement

    Science.gov (United States)

    Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa; Anderson, Liam J.; Jacob, Mohan V.

    2014-02-01

    By using electric-field-induced optical second-harmonic generation (EFISHG) measurement, we studied the carrier-blocking property of poly-linalyl acetate (PLA) thin layers sandwiched in indium-zinc-oxide (IZO)/PLA/C60/Al double-layer diodes. Results showed that the PLA layer totally blocks electrons crossing the C60 layer, and also blocks holes entering from the IZO layer. The EFISHG measurement effectively substantiates the hole-blocking electron-blocking property of the PLA layer sandwiched in double layer diodes.

  8. 5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats.

    OpenAIRE

    Archer, T.; Danysz, W; Jonsson, G.; Minor, B. G.; Post, C

    1986-01-01

    The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in ...

  9. Morphology-controlled growth of perylene derivative induced by double-hydrophilic block copolymers

    OpenAIRE

    Minghua Huang; Markus Antonietti; Helmut Cölfen

    2016-01-01

    Controlled growth of technically relevant perylene derivative 3, 4, 9, 10-perylenetetracarboxylic acid potassium salt (PTCAPS), with tuneable morpologies, has been successfully realized by a recrystallization method using a double-hydrophilic block copolymer poly (ethylene glycol)-block poly (ethyleneimine) (PEG-b-PEI) as the structure directing agent. The {001} faces of PTCAPS are most polar and adsorb the oppositively charged polymer additive PEG-b-PEI well by electrostatic attraction. By s...

  10. Tea Flavanols Block Advanced Glycation of Lens Crystallins Induced by Dehydroascorbic Acid.

    Science.gov (United States)

    Zhu, Yingdong; Zhao, Yantao; Wang, Pei; Ahmedna, Mohamed; Ho, Chi-Tang; Sang, Shengmin

    2015-01-20

    Growing evidence has shown that ascorbic acid (ASA) can contribute to protein glycation and the formation of advanced glycation end products (AGEs), especially in the lens. The mechanism by which ascorbic acid can cause protein glycation probably originates from its oxidized form, dehydroascorbic acid (DASA), which is a reactive dicarbonyl species. In the present study, we demonstrated for the first time that four tea flavanols, (-)-epigallocatechin 3-O-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin 3-O-gallate (ECG), and (-)-epicatechin (EC), could significantly trap DASA and consequently form 6C- or 8C-ascorbyl conjugates. Among these four flavanols, EGCG exerted the strongest trapping efficacy by capturing approximate 80% of DASA within 60 min. We successfully purified and identified seven 6C- or 8C-ascorbyl conjugates of flavanols from the chemical reaction between tea flavanols and DASA under slightly basic conditions. Of which, five ascorbyl conjugates, EGCGDASA-2, EGCDASA-2, ECGDASA-1, ECGDASA-2 and ECDASA-1, were recognized as novel compounds. The NMR data showed that positions 6 and 8 of the ring A of flavanols were the major active sites for trapping DASA. We further demonstrated that tea flavanols could effectively inhibit the formation of DASA-induced AGEs via trapping DASA in the bovine lens crystallin-DASA assay. In this assay, 8C-ascorbyl conjugates of flavanols were detected as the major adducts using LC-MS. This study suggests that daily consumption of beverages containing tea flavanols may prevent protein glycation in the lens induced by ascorbic acid and its oxidized products. PMID:25437149

  11. Lactobacillus rhamnosus GG Reverses Insulin Resistance but Does Not Block Its Onset in Diet-Induced Obese Mice.

    Science.gov (United States)

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-05-01

    Recently, Lactobacillus rhamnosus GG (LGG) was shown to exert insulin-sensitizing and adiposity-reducing effects in high-fat (HF) diet-fed mice. In the present study, we observed that the effects were correlated with the extent of dysbiosis induced by HF diet feeding before LGG administration. LGG-treated mice were protected from HF diet-induced adiposity and/ or insulin resistance when LGG was treated after, not along with, HF diet feeding. Results indicate that, under HF dietary condition, supplemented LGG reverses insulin resistance, but does not block its onset. PMID:25433553

  12. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, A.M.; Ashmawi, H.A.; Costa, L.S.; Posso, I.P. [LIM-08 - Anestesiologia Experimental, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Slullitel, A. [Departamento de Anestesiologia, Hospital Santa Paula, São Paulo, SP (Brazil)

    2011-12-23

    Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

  13. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    Directory of Open Access Journals (Sweden)

    A.M. Sousa

    2012-02-01

    Full Text Available Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

  14. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    International Nuclear Information System (INIS)

    Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics

  15. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    SudinBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, “Toxicity testing in the 21st Century: A Vision and A Strategy”. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular “virtual tissue” model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  16. A high-throughput chemically induced inflammation assay in zebrafish

    Directory of Open Access Journals (Sweden)

    Liebel Urban

    2010-12-01

    Full Text Available Abstract Background Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. Results Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. Conclusions This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay. See Commentary article: http://www.biomedcentral.com/1741-7007/8/148.

  17. Chemically Induced and Light-Independent Cryptochrome Photoreceptor Activation

    Institute of Scientific and Technical Information of China (English)

    Gesa Rosenfeldt; Rafael Mu(n)oz Viana; Henning D.Mootz; Albrecht G.Von Arnim; Alfred Batschauer

    2008-01-01

    The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

  18. Mercaptoacetate blocks fatty acid-induced GLP-1 secretion in male rats by directly antagonizing GPR40 fatty acid receptors.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Simasko, Steve M; Ritter, Sue

    2016-04-15

    Mercaptoacetate (MA) is an orexigenic agent reported to block fatty acid (FA) oxidation. Recently, however, we reported evidence from isolated nodose ganglion neurons that MA antagonizes the G protein-coupled long- and medium-chain FA receptor GPR40. GPR40 mediates FA-induced secretion of the satietogenic incretin peptide glucagon-like peptide 1 (GLP-1), by enteroendocrine L cells, as well as FA-induced enhancement of glucose-stimulated insulin secretion. Our results in cultured nodose neurons suggest that MA would also block GPR40 in enteroendocrine cells controlling GLP-1 secretion. If so, this would suggest an alternative mechanism by which MA increases food intake. We tested the hypothesis that MA blocks FA-induced GLP-1 secretion in vitro using cultured STC-1 cells (a murine enteroendocrine cell line) and in vivo in adult male rats. In vitro, MA blocked the increase in both cytosolic Ca(2+)and GLP-1 release stimulated by FAs and also reduced (but less effectively) the response of STC-1 cells to grifolic acid, a partial agonist of the GPR120 FA receptor. In vivo, MA reduced GLP-1 secretion following olive oil gavage while also increasing glucose and decreasing insulin levels. The carnitine palmatoyltransferase 1 antagonist etomoxir did not alter these responses. Results indicate that MA's actions, including its orexigenic effect, are mediated by GPR40 (and possibly GPR120) receptor antagonism and not by blockade of fat oxidation, as previously believed. Analysis of MA's interaction with GPR40 may facilitate understanding of the multiple functions of this receptor and the manner in which FAs participate in the control of hunger and satiety. PMID:26791830

  19. Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

    2014-02-14

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  20. Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

    2014-01-01

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  1. Blocking TWEAK-Fn14 interaction inhibits hematopoietic stem cell transplantation-induced intestinal cell death and reduces GVHD.

    Science.gov (United States)

    Chopra, Martin; Brandl, Andreas; Siegmund, Daniela; Mottok, Anja; Schäfer, Viktoria; Biehl, Marlene; Kraus, Sabrina; Bäuerlein, Carina A; Ritz, Miriam; Mattenheimer, Katharina; Schwinn, Stefanie; Seher, Axel; Grabinger, Thomas; Einsele, Hermann; Rosenwald, Andreas; Brunner, Thomas; Beilhack, Andreas; Wajant, Harald

    2015-07-23

    Inhibition of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) system reduces intestinal cell death and disease development in several models of colitis. In view of the crucial role of TNF and intestinal cell death in graft-versus-host disease (GVHD) and the ability of TWEAK to enhance TNF-induced cell death, we tested here the therapeutic potential of Fn14 blockade on allogeneic hematopoietic cell transplantation (allo-HCT)-induced intestinal GVHD. An Fn14-specific blocking human immunoglobulin G1 antibody variant with compromised antibody-dependent cellular cytotoxicity (ADCC) activity strongly inhibited the severity of murine allo-HCT-induced GVHD. Treatment of the allo-HCT recipients with this monoclonal antibody reduced cell death of gastrointestinal cells but neither affected organ infiltration by donor T cells nor cytokine production. Fn14 blockade also inhibited intestinal cell death in mice challenged with TNF. This suggests that the protective effect of Fn14 blockade in allo-HCT is based on the protection of intestinal cells from TNF-induced apoptosis and not due to immune suppression. Importantly, Fn14 blockade showed no negative effect on graft-versus-leukemia/lymphoma (GVL) activity. Thus, ADCC-defective Fn14-blocking antibodies are not only possible novel GVL effect-sparing therapeutics for the treatment of GVHD but might also be useful for the treatment of other inflammatory bowel diseases where TNF-induced cell death is of relevance. PMID:26012567

  2. Light-induced chemical vapour deposition painting with titanium dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Halary-Wagner, E.; Bret, T.; Hoffmann, P

    2003-03-15

    Light-induced chemical vapour deposits of titanium dioxide are obtained from titanium tetra-isopropoxide (TTIP) in an oxygen and nitrogen atmosphere with a long pulse (250 ns) 308 nm XeCl excimer laser using a mask projection set-up. The demonstrated advantages of this technique are: (i) selective area deposition, (ii) precise control of the deposited thickness and (iii) low temperature deposition, enabling to use a wide range of substrates. A revolving mask system enables, in a single reactor load, to deposit shapes of controlled heights, which overlap to build up a complex pattern. Interferential multi-coloured deposits are achieved, and the process limitations (available colours and resolution) are discussed.

  3. Quantum measurement corrections to chemically induced dynamic nuclear polarization

    CERN Document Server

    Kominis, I K

    2013-01-01

    Chemically induced dynamic nuclear polarization has emerged as a universal signature of spin order in photosynthetic reaction centers. Such polarization, significantly enhanced above thermal equilibrium, is known to result from the nuclear spin sorting inherent in the radical pair mechanism underlying long-lived charge-separated states in photosynthetic reaction centers. We will here show that the recently understood fundamental quantum dynamics of radical-ion-pair reactions open up a new and completely unexpected venue towards obtaining CIDNP signals. The fundamental decoherence mechanism inherent in the recombination process of radical pairs is shown to produce nuclear spin polarizations on the order of $10^4$ times or more higher than thermal equilibrium values at low fields relevant to natural photosynthesis in earth's magnetic field. This opens up the possibility of a fundamentally new exploration of the biological significance of high nuclear polarizations in photosynthesis.

  4. Light-induced chemical vapour deposition painting with titanium dioxide

    Science.gov (United States)

    Halary-Wagner, E.; Bret, T.; Hoffmann, P.

    2003-03-01

    Light-induced chemical vapour deposits of titanium dioxide are obtained from titanium tetra-isopropoxide (TTIP) in an oxygen and nitrogen atmosphere with a long pulse (250 ns) 308 nm XeCl excimer laser using a mask projection set-up. The demonstrated advantages of this technique are: (i) selective area deposition, (ii) precise control of the deposited thickness and (iii) low temperature deposition, enabling to use a wide range of substrates. A revolving mask system enables, in a single reactor load, to deposit shapes of controlled heights, which overlap to build up a complex pattern. Interferential multi-coloured deposits are achieved, and the process limitations (available colours and resolution) are discussed.

  5. Ion beam induced conductivity in chemically vapor deposited diamond films

    International Nuclear Information System (INIS)

    Polycrystalline diamond films deposited by the microwave plasma chemical vapor deposition (CVD) technique onto quartz substrates have been irradiated with 100 keV C and 320 keV Xe ions at room temperature and at 200 degree C. The dose dependence of the electrical conductivity measured in situ exhibited complicated, nonmonotonic behavior. High doses were found to induce an increase of up to ten orders of magnitude in the electrical conductivity of the film. The dose dependence of the conductivity for the CVD films was found to be very similar to that measured for natural, type IIa, single-crystal diamonds irradiated under identical conditions. This result suggests that the conduction mechanism in ion beam irradiated polycrystalline CVD diamond films is not dominated by grain boundaries and graphitic impurities as one might have expected, but rather is determined by the intrinsic properties of diamond itself

  6. Electrocardiographic imaging-based recognition of possible induced bundle branch blocks during transcatheter aortic valve implantations

    NARCIS (Netherlands)

    Dam, P.M. van; Proniewska, K.; Maugenest, A.M.; Mieghem, N.M. van; Maan, A.C.; Jaegere, P.P. de; Bruining, N.

    2014-01-01

    AIMS: Conventional electrocardiogram (ECG)-based diagnosis of left bundle branch block (LBBB) in patients with left ventricular hypertrophy (LVH) is ambiguous. Left ventricular hypertrophy is often seen in patients with severe aortic stenosis in which a transcatheter aortic valve implantation (TAVI)

  7. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    International Nuclear Information System (INIS)

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  8. Melatonin Prevents Chemical-Induced Haemopoietic Cell Death

    Directory of Open Access Journals (Sweden)

    Sara Salucci

    2014-04-01

    Full Text Available Melatonin (MEL, a methoxyindole synthesized by the pineal gland, is a powerful antioxidant in tissues as well as within cells, with a fundamental role in ameliorating homeostasis in a number of specific pathologies. It acts both as a direct radical scavenger and by stimulating production/activity of intracellular antioxidant enzymes. In this work, some chemical triggers, with different mechanisms of action, have been chosen to induce cell death in U937 hematopoietic cell line. Cells were pre-treated with 100 µM MEL and then exposed to hydrogen peroxide or staurosporine. Morphological analyses, TUNEL reaction and Orange/PI double staining have been used to recognize ultrastructural apoptotic patterns and to evaluate DNA behavior. Chemical damage and potential MEL anti-apoptotic effects were quantified by means of Tali® Image-Based Cytometer, able to monitor cell viability and apoptotic events. After trigger exposure, chromatin condensation, micronuclei formation and DNA fragmentation have been observed, all suggesting apoptotic cell death. These events underwent a statistically significant decrease in samples pre-treated with MEL. After caspase inhibition and subsequent assessment of cell viability, we demonstrated that apoptosis occurs, at least in part, through the mitochondrial pathway and that MEL interacts at this level to rescue U937 cells from death.

  9. Charged impurity-induced scatterings in chemical vapor deposited graphene

    Science.gov (United States)

    Li, Ming-Yang; Tang, Chiu-Chun; Ling, D. C.; Li, L. J.; Chi, C. C.; Chen, Jeng-Chung

    2013-12-01

    We investigate the effects of defect scatterings on the electric transport properties of chemical vapor deposited (CVD) graphene by measuring the carrier density dependence of the magneto-conductivity. To clarify the dominant scattering mechanism, we perform extensive measurements on large-area samples with different mobility to exclude the edge effect. We analyze our data with the major scattering mechanisms such as short-range static scatters, short-range screened Coulomb disorders, and weak-localization (WL). We establish that the charged impurities are the predominant scatters because there is a strong correlation between the mobility and the charge impurity density. Near the charge neutral point (CNP), the electron-hole puddles that are induced by the charged impurities enhance the inter-valley scattering, which is favorable for WL observations. Away from the CNP, the charged-impurity-induced scattering is weak because of the effective screening by the charge carriers. As a result, the local static structural defects govern the charge transport. Our findings provide compelling evidence for understanding the scattering mechanisms in graphene and pave the way for the improvement of fabrication techniques to achieve high-quality CVD graphene.

  10. Computational Investigation of Block Copolymer Surfactants for Stabilizing Fluctuation-Induced Polymeric Microemulsions

    Science.gov (United States)

    Delaney, Kris; Fredrickson, Glenn

    2013-03-01

    High molecular weight diblock copolymers introduced into a blend of immiscible homopolymers can act as a surfactant to suppress macroscopic two-fluid phase separation. With variation of block copolymer composition, the crossover between low-temperature ordering into microphase or macrophase separated states is marked by a mean-field isotropic Lifshitz multi-critical point. Strong fluctuations close to the Lifshitz point are observed to suppress the low-temperature ordering; a microemulsion state emerges, with large, co-continuous domains of segregated fluid lacking any long-range order. We study this phenomenon with fully fluctuating field-theoretic simulations based on complex Langevin sampling, and we attempt to design new block polymer surfactants that can produce the microemulsion state with a wider composition tolerance.

  11. Thermally induced structural evolution and performance of mesoporous block copolymer-directed alumina perovskite solar cells.

    KAUST Repository

    Tan, Kwan Wee

    2014-04-11

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x) material evolution to be characterized by three distinct structures: a crystalline precursor structure not described previously, a 3D perovskite structure, and a mixture of compounds resulting from degradation. Finally, we demonstrate how understanding the processing parameters provides the foundation needed for optimal perovskite film morphology and coverage, leading to enhanced block copolymer-directed perovskite solar cell performance.

  12. Humidity-Induced Phase Transitions in Ion-Containing Block Copolymer Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Park, Moon Jeong; Nedoma, Alisyn J.; Geissler, Phillip L.; Balsara, Nitash P.; Jackson, Andrew; Cookson, David (UCB); (NIST); (Aust. Synch.); (LBNL)

    2008-08-21

    The phase behavior of ion-containing block copolymer membranes in equilibrium with humidified air is studied as a function of the relative humidity (RH) of the surrounding air, ion content of the copolymer, and temperature. Increasing RH at constant temperature results in both disorder-to-order and order-to-order transitions. In-situ small-angle neutron scattering experiments on the open block copolymer system, when combined with water uptake measurement, indicate that the disorder-to-order transition is driven by an increase in the partial molar entropy of the water molecules in the ordered phase relative to that in the disordered phase. This is in contrast to most systems wherein increasing entropy results in stabilization of the disordered phase.

  13. Detection of stress-induced ischemia in patients with intraventricular conduction blocks

    OpenAIRE

    Polyakova I. P.; Feofanova T. B.; Golukhova E. Z.

    2012-01-01

    Non-invasive diagnosis of ischemic heart disease (IHD) in patients with intraventricular conduction block (IVCB) is difficult. Changed morphology of complex QRS and ST segment completely masks ischemic symptoms associated with stress-test. It is known that multichannel surface ECG-mapping (SM) makes it possible to reveal the zones of post postinfarction scars in IVCB patients. Objective: To evaluate SM potentials to reveal ischemia developed in IVCB patients associated with stress-test and de...

  14. Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed

    OpenAIRE

    Rasher, Douglas B; Hay, Mark E.

    2014-01-01

    Many seaweeds and terrestrial plants induce chemical defences in response to herbivory, but whether they induce chemical defences against competitors (allelopathy) remains poorly understood. We evaluated whether two tropical seaweeds induce allelopathy in response to competition with a reef-building coral. We also assessed the effects of competition on seaweed growth and seaweed chemical defence against herbivores. Following 8 days of competition with the coral Porites cylindrica, the chemica...

  15. Ondansetron blocks LiCl-induced conditioned place avoidance but not conditioned taste/flavor avoidance in rats

    OpenAIRE

    Rinaman, Linda; Saboury, Mitra; Litvina, Elizabeth

    2009-01-01

    The ability of an experimental agent to support conditioned taste/flavor avoidance (CT/FA) in rats often is interpreted as sufficient evidence that the agent produced a state of malaise or nausea. Paradoxically, however, CT/FA also is induced by certain drugs that support conditioned preferences in rats, suggesting that CT/FA is insufficient to reveal a negative hedonic state. The present study tested the hypothesis that the anti-nausea drug ondansetron (OND) would block the ability of nauseo...

  16. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R.R.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1990-06-01

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author).

  17. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    International Nuclear Information System (INIS)

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author)

  18. κ Opioid Receptor Antagonism and Prodynorphin Gene Disruption Block Stress-Induced Behavioral Responses

    OpenAIRE

    McLaughlin, Jay P.; Marton-Popovici, Monica; Chavkin, Charles

    2003-01-01

    Previous studies have demonstrated that stress may increase prodynorphin gene expression, and κ opioid agonists suppress drug reward. Therefore, we tested the hypothesis that stress-induced release of endogenous dynorphin may mediate behavioral responses to stress and oppose the rewarding effects of cocaine. C57Bl/6 mice subjected to repeated forced swim testing (FST) using a modified Porsolt procedure at 30°C showed a characteristic stress-induced immobility response and a stress-induced ana...

  19. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Dong, E-mail: austhudong@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wu, Jing, E-mail: wujing8008@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Xiao, Jian [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Hu, Fengyu; Yang, Yabo [Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (China); Zhang, Rongbo, E-mail: lory456@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China)

    2015-05-29

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.

  20. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    International Nuclear Information System (INIS)

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy

  1. [Case of painful muscle spasm induced by thoracic vertebral fracture: successful treatment with lumbar sympathetic ganglia block].

    Science.gov (United States)

    Shimizu, Fumitaka; Kawai, Motoharu; Koga, Michiaki; Ogasawara, Jun-ichi; Negoro, Kiyoshi; Kanda, Takashi

    2008-10-01

    We report a 70-year-old man, who developed painful involuntary muscle contraction of the left leg after the lumbar discectomy, which exacerbated after a vertebral fracture of Th12. This involuntary movement was accompanied with the abnormal position of left leg simulating triple flexion response, and was induced by active or passive movement of his left knee and foot joints. Several drugs including benzodiazepines and dantrolene were ineffective, although treatment with baclofen or carbamazepine was effective. These findings suggest that hyperexcitability of the anterior horn cells following the disturbance of spinal inhibitory interneurons was involved. Electophysiological studies suggested the disturbance of left lumber nerve roots. The spinal root blocks from L3 to S1 were performed, after which the painful involuntary muscle spasm was resolved. The lumbar sympathetic ganglia block was also effective; suggesting that abnormal afferent neuronal input to spinal cord was caused by the nerve root trauma which triggered the formation of secondary abnormal network in the spine. Lumbar sympathetic ganglia block should be recommended to a therapeutic option for the refractory painful muscle spasm of the leg. PMID:19086429

  2. The influence of incompatibility and dielectric contrast on the electric field-induced orientation of lamellar block copolymers

    International Nuclear Information System (INIS)

    We investigate the influence of incompatibility and dielectric contrast on the reorientation kinetics of concentrated solutions of lamellar block copolymers in the presence of an external DC electric field. We study solutions of AC diblock copolymer and ABC triblock terpolymers. The inclusion of a short, polar middle block B is used to tailor both the degree of incompatibility and the dielectric contrast between the two majority phases. In situ synchrotron radiation small-angle X-ray scattering is used to monitor the reorientation process. For the AC diblock copolymer sample only weak electric field induced reorientation could be achieved, following a very slow kinetics, whereas for the ABC triblock terpolymer, reorientation is observed above a threshold value of 0.3 kV/mm. The orientation kinetics is well described by a single exponential with characteristic time constants varying between a few seconds and several minutes depending on the polymer concentration and the electric field strength. We identify a narrow concentration window, in which the interplay between chain mobility and gain in free energy in the electric field allows the preparation of highly anisotropic bulk polymer samples by exposure to an electric field. The results are compared to free energy calculations revealing a distinct difference in the driving force for reorientation as a consequence of an increase in dielectric contrast and chain mobility upon introduction of the B middle block.

  3. Atomic force microscopy assessment of mechanically induced scratch damage in polypropylenes and ethylene-propylene di-block copolymers

    International Nuclear Information System (INIS)

    Atomic force microscopy (AFM) in tapping mode has been used to determine the extent of surface damage induced during a scratch test in different grades of polypropylenes (PPs) and ethylene-propylene (EP) di-block copolymers. The surface damage is examined for long chain polymeric materials and their respective short chains. The extent of surface damage is evaluated in terms of average surface height of the plastically deformed region, depth of the scratch tracks, and thickness and density of the scratch tracks. The ability of the polymeric materials to resist scratch deformation under identical conditions of scratch test follows the sequence (from maximum resistance to minimum resistance): high crystallinity PPs>low crystallinity PPs>EP di-block copolymers. Also, short chain polymeric materials have greater resistance to scratch deformation than their respective long chain polymers. The scratch tracks are zigzag in PPs and parabolic in EP di-block copolymers with localized plastic flow involving voids. It is interpreted that modulus and yield strength are the determining factors that dictate the scratch resistance of polymeric materials

  4. Effect of non-symmetric waveform on conduction block induced by high-frequency (kHz) biphasic stimulation in unmyelinated axon.

    Science.gov (United States)

    Zhao, Shouguo; Yang, Guangning; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-10-01

    The effect of a non-symmetric waveform on nerve conduction block induced by high-frequency biphasic stimulation is investigated using a lumped circuit model of the unmyelinated axon based on Hodgkin-Huxley equations. The simulation results reveal that the block threshold monotonically increases with the stimulation frequency for the symmetric stimulation waveform. However, a non-monotonic relationship between block threshold and stimulation frequency is observed when the stimulation waveform is non-symmetric. Constant activation of potassium channels by the high-frequency stimulation results in the increase of block threshold with increasing frequency. The non-symmetric waveform with a positive pulse 0.4-0.8 μs longer than the negative pulse blocks axonal conduction by hyperpolarizing the membrane and causes a decrease in block threshold as the frequency increases above 12-16 kHz. On the other hand, the non-symmetric waveform with a negative pulse 0.4-0.8 μs longer than the positive pulse blocks axonal conduction by depolarizing the membrane and causes a decrease in block threshold as the frequency increases above 40-53 kHz. This simulation study is important for understanding the potential mechanisms underlying the nerve block observed in animal studies, and may also help to design new animal experiments to further improve the nerve block method for clinical applications. PMID:24928360

  5. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats

    Science.gov (United States)

    Akella, Aparna; Tiwari, Anil K.; Rai, Om P.; Deshpande, Shripad B.

    2016-01-01

    Objective: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Materials and Methods: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. Results: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema. PMID:26997727

  6. Characterizing Block Graphs in Terms of their Vertex-Induced Partitions

    OpenAIRE

    Dress, A.; Huber, K.T.; Koolen, J.; Moulton, V.; Spillner, A.

    2014-01-01

    Given a finite connected simple graph $G=(V,E)$ with vertex set $V$ and edge set $E\\subseteq \\binom{V}{2}$, we will show that $1.$ the (necessarily unique) smallest block graph with vertex set $V$ whose edge set contains $E$ is uniquely determined by the $V$-indexed family ${\\bf P}_G:=\\big(\\pi_0(G^{(v)})\\big)_{v \\in V}$ of the various partitions $\\pi_0(G^{(v)})$ of the set $V$ into the set of connected components of the graph $G^{(v)}:=(V,\\{e\\in E: v\

  7. Thermally Induced Structural Evolution and Performance of Mesoporous Block Copolymer-Directed Alumina Perovskite Solar Cells

    OpenAIRE

    Tan, Kwan Wee; Moore, David T.; Saliba, Michael; Sai, Hiroaki; Estroff, Lara A.; Hanrath, Tobias; Snaith, Henry J.; Wiesner, Ulrich

    2014-01-01

    Structure control in solution-processed hybrid perovskites is crucial to design and fabricate highly efficient solar cells. Here, we utilize in situ grazing incidence wide-angle X-ray scattering and scanning electron microscopy to investigate the structural evolution and film morphologies of methylammonium lead tri-iodide/chloride (CH3NH3PbI3–x Cl x ) in mesoporous block copolymer derived alumina superstructures during thermal annealing. We show the CH3NH3PbI3–x Cl x material evolution to be ...

  8. Mechanical Induction of PGE2 in Osteocytes Blocks Glucocorticoid-Induced Apoptosis Through Both the β-Catenin and PKA Pathways

    OpenAIRE

    Kitase, Yukiko; Barragan, Leonardo; Qing, Hai; Kondoh, Shino; Jiang, Jean X.; Johnson, Mark L.; Bonewald, Lynda F.

    2010-01-01

    Glucocorticoids are known to induce osteocyte apoptosis, whereas mechanical loading has been shown to sustain osteocyte viability. Here we show that mechanical loading in the form of fluid-flow shear stress blocks dexamethasone-induced apoptosis of osteocyte-like cells (MLO-Y4). Prostaglandin E2 (PGE2), a rapidly induced signaling molecule produced by osteocytes, was shown to be protective against dexamethasone-induced apoptosis, whereas indomethacin reversed the antiapoptotic effects of shea...

  9. Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced Apoptosis.

    Directory of Open Access Journals (Sweden)

    Sudhakar S Agnihothram

    Full Text Available Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV. We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP, caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together.

  10. Dealing naturally with stumbling blocks on highways and byways of TRAIL induced signaling.

    Science.gov (United States)

    Rana, Aamir; Attar, Rukset; Qureshi, Muhammad Zahid; Gasparri, Maria Luisa; Donato, Violante Di; Ali, Ghulam Muhammad; Farooqi, Ammad Ahmad

    2014-01-01

    In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside. PMID:25338981

  11. Chemically induced skin carcinogenesis: Updates in experimental models (Review)

    Science.gov (United States)

    NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  12. Chemically induced skin carcinogenesis: Updates in experimental models (Review).

    Science.gov (United States)

    Neagu, Monica; Caruntu, Constantin; Constantin, Carolina; Boda, Daniel; Zurac, Sabina; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  13. Radiation induced chemical reaction of carbon monoxide and hydrogen mixture

    International Nuclear Information System (INIS)

    Previous studies of radiation induced chemical reactions of CO-H2 mixture have revealed that the yields of oxygen containing products were larger than those of hydrocarbons. In the present study, methane was added to CO-H2 mixture in order to increase further the yields of the oxygen containing products. The yields of most products except a few products such as formaldehyde increased with the addition of small amount of methane. Especially, the yields of trioxane and tetraoxane gave the maximum values when CO-H2 mixture containing 1 mol% methane was irradiated. When large amounts of methane were added to the mixture, the yields of aldehydes and carboxylic acids having more than two carbon atoms increased, whereas those of trioxane and tetraoxane decreased. From the study at reaction temperature over the range of 200 to 473 K, it was found that the yields of aldehydes and carboxylic acids showed maxima at 323 K. The studies on the effects of addition of cationic scavenger (NH3) and radical scavenger (O2) on the products yields were also carried out on the CO-H2-CH4 mixture. (author)

  14. Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats.

    Science.gov (United States)

    Kim, Jeong-Hwan; Jin, Soojung; Kwon, Hyun Ju; Kim, Byung Woo

    2016-08-28

    Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations. PMID:27197667

  15. Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR

    Directory of Open Access Journals (Sweden)

    Zhongxia Wang

    2016-01-01

    Full Text Available The inflammatory response after polymer-based drug-eluting stent (DES placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ activators thiazolidinedione (TZD remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO on circulating peripheral blood mononuclear cells (MNCs in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO or placebo (control; Con treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and matrix metalloproteinase-9 (MMP-9 were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.. DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.. In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.

  16. Raloxifene and Desmethylarzoxifene Block Estrogen-Induced Malignant Transformation of Human Breast Epithelial Cells

    OpenAIRE

    Kastrati, Irida; Edirisinghe, Praneeth D.; Hemachandra, L-P-Madhubani P.; Chandrasena, Esala R.; Choi, Jaewoo; Wang, Yue-Ting; Bolton, Judy L.; Thatcher, Gregory R.J.

    2011-01-01

    There is association between exposure to estrogens and the development and progression of hormone-dependent gynecological cancers. Chemical carcinogenesis by catechol estrogens derived from oxidative metabolism is thought to contribute to breast cancer, yet exact mechanisms remain elusive. Malignant transformation was studied in MCF-10A human mammary epithelial cells, since estrogens are not proliferative in this cell line. The human and equine estrogen components of estrogen replacement ther...

  17. Inducing an Order-Order Morphological Transition via Chemical Degradation of Amphiphilic Diblock Copolymer Nano-Objects.

    Science.gov (United States)

    Ratcliffe, Liam P D; Couchon, Claudie; Armes, Steven P; Paulusse, Jos M J

    2016-06-13

    The disulfide-based cyclic monomer, 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MTC), is statistically copolymerized with 2-hydroxypropyl methacrylate to form a range of diblock copolymer nano-objects via reversible addition-fragmentation chain transfer (RAFT) polymerization. Poly(glycerol monomethacrylate) (PGMA) is employed as the hydrophilic stabilizer block in this aqueous polymerization-induced self-assembly (PISA) formulation, which affords pure spheres, worms or vesicles depending on the target degree of polymerization for the core-forming block. When relatively low levels (99%) are achieved and high blocking efficiencies are observed, as judged by (1)H NMR spectroscopy and gel permeation chromatography (GPC), respectively. However, the side reactions that are known to occur when cyclic allylic sulfides such as MTC are statistically copolymerized with methacrylic comonomers lead to relatively broad molecular weight distributions. Nevertheless, the worm-like nanoparticles obtained via PISA can be successfully transformed into spherical nanoparticles by addition of excess tris(2-carboxyethyl)phosphine (TCEP) at pH 8-9. Surprisingly, DLS and TEM studies indicate that the time scale needed for this order-order transition is significantly longer than that required for cleavage of the disulfide bonds located in the worm cores indicated by GPC analysis. This reductive degradation pathway may enable the use of these chemically degradable nanoparticles in biomedical applications, such as drug delivery systems and responsive biomaterials. PMID:27228898

  18. Inducing an Order–Order Morphological Transition via Chemical Degradation of Amphiphilic Diblock Copolymer Nano-Objects

    Science.gov (United States)

    2016-01-01

    The disulfide-based cyclic monomer, 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MTC), is statistically copolymerized with 2-hydroxypropyl methacrylate to form a range of diblock copolymer nano-objects via reversible addition–fragmentation chain transfer (RAFT) polymerization. Poly(glycerol monomethacrylate) (PGMA) is employed as the hydrophilic stabilizer block in this aqueous polymerization-induced self-assembly (PISA) formulation, which affords pure spheres, worms or vesicles depending on the target degree of polymerization for the core-forming block. When relatively low levels (99%) are achieved and high blocking efficiencies are observed, as judged by 1H NMR spectroscopy and gel permeation chromatography (GPC), respectively. However, the side reactions that are known to occur when cyclic allylic sulfides such as MTC are statistically copolymerized with methacrylic comonomers lead to relatively broad molecular weight distributions. Nevertheless, the worm-like nanoparticles obtained via PISA can be successfully transformed into spherical nanoparticles by addition of excess tris(2-carboxyethyl)phosphine (TCEP) at pH 8–9. Surprisingly, DLS and TEM studies indicate that the time scale needed for this order–order transition is significantly longer than that required for cleavage of the disulfide bonds located in the worm cores indicated by GPC analysis. This reductive degradation pathway may enable the use of these chemically degradable nanoparticles in biomedical applications, such as drug delivery systems and responsive biomaterials. PMID:27228898

  19. A Robust Cross-Linking Strategy for Block Copolymer Worms Prepared via Polymerization-Induced Self-Assembly

    Science.gov (United States)

    2016-01-01

    A poly(glycerol monomethacrylate) (PGMA) chain transfer agent is chain-extended by reversible addition–fragmentation chain transfer (RAFT) statistical copolymerization of 2-hydroxypropyl methacrylate (HPMA) with glycidyl methacrylate (GlyMA) in concentrated aqueous solution via polymerization-induced self-assembly (PISA). A series of five free-standing worm gels is prepared by fixing the overall degree of polymerization of the core-forming block at 144 while varying its GlyMA content from 0 to 20 mol %. 1H NMR kinetics indicated that GlyMA is consumed much faster than HPMA, producing a GlyMA-rich sequence close to the PGMA stabilizer block. Temperature-dependent oscillatory rheological studies indicate that increasing the GlyMA content leads to progressively less thermoresponsive worm gels, with no degelation on cooling being observed for worms containing 20 mol % GlyMA. The epoxy groups in the GlyMA residues can be ring-opened using 3-aminopropyltriethoxysilane (APTES) in order to prepare core cross-linked worms via hydrolysis-condensation with the siloxane groups and/or hydroxyl groups on the HPMA residues. Perhaps surprisingly, 1H NMR analysis indicates that the epoxy–amine reaction and the intermolecular cross-linking occur on similar time scales. Cross-linking leads to stiffer worm gels that do not undergo degelation upon cooling. Dynamic light scattering studies and TEM analyses conducted on linear worms exposed to either methanol (a good solvent for both blocks) or anionic surfactant result in immediate worm dissociation. In contrast, cross-linked worms remain intact under such conditions, provided that the worm cores comprise at least 10 mol % GlyMA. PMID:27134311

  20. Comparison of bilateral pulse arrival time before and after induced vasodilation by axillary block

    International Nuclear Information System (INIS)

    The propagation time of arterial pulse waves provides information about arterial stiffness. Pulse arrival time (PAT) is calculated as the time between the R-wave (ECG) and three reference points on photoplethysmographic (PPG) pulse waves: foot, first derivative and peak. Because large variation in PAT-values between patients exists, measurements of the contra-lateral arm as reference could be a solution. However, anatomical differences between arteries of the arms could introduce an offset of PAT. Furthermore, when arterial stiffness decreases (e.g. after axillary blockade (AxB)) and pulse wave amplitude increases (vasodilation), the pulse waveform can change. The aim of this study was to investigate whether there is a difference between the PAT of both arms and to evaluate the effect of vasodilation after AxB on PAT. ECG and PPG was measured on both hands in 34 patients, starting 2 min before the injection of local anaesthetic of an AxB and continuing for a period of 30 min after block placement. PAT of the baseline and after AxB were calculated and compared. The mean-PAT of both arms were not significantly different for the three reference points. After AxB, PAT significantly increased for all reference points. PAT can be used for intra-subject comparison. (paper)

  1. Radiation-induced crosslinking of poly(styrene-butadiene-styrene) block copolymers and their sulfonation

    Science.gov (United States)

    Lee, Sun-Young; Song, Ju-Myung; Sohn, Joon-Yong; Shul, Yong-Gun; Shin, Junhwa

    2013-12-01

    Several crosslinked poly(styrene-butadiene-styrene) (c-SBS) block copolymer films were prepared using a gamma ray or electron beam with various irradiation doses and the prepared c-SBS film was then subjected to sulfonation using a chlorosulfonic acid (CSA) solution to introduce a sulfonic acid group. To estimate the degree of crosslinking, the gel fractions and FT-IR spectra of the c-SBS films were used and the results indicate that the degree of crosslinking is increased with an increase in the radiation dose. The surface morphology and mechanical property of the c-SBS films were observed using SEM and UTM instruments, respectively. The sulfonated c-SBS films were investigated by measuring the ion exchange capacity (IEC) and by observing the cross-sectional distribution patterns of sulfonic acid group using an SEM-EDX instrument. The IEC and SEM-EDX studies indicate that the sulfonated c-SBS membranes can be successfully prepared through the radiation crosslinking of the SBS film and the subsequent sulfonation with a diluted CSA solution.

  2. Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity

    Science.gov (United States)

    Stasiak, Marta; Boncela, Joanna; Perreau, Corinne; Karamanou, Konstantina; Chatron-Colliet, Aurore; Proult, Isabelle; Przygodzka, Patrycja; Chakravarti, Shukti; Maquart, François-Xavier; Kowalska, M. Anna; Wegrowski, Yanusz; Brézillon, Stéphane

    2016-01-01

    Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment. PMID:26930497

  3. Gadolinium blocks membrane permeabilization induced by nanosecond electric pulses and reduces cell death

    OpenAIRE

    André, Franck M; Rassokhin, Mikhail A.; Bowman, Angela M.; Pakhomov, Andrei G.

    2009-01-01

    It has been widely accepted that nanosecond electric pulses (nsEP) are distinguished from micro-and millisecond duration pulses by their ability to cause intracellular effects and cell death with reduced effects on the cell plasma membrane. However, we found that nsEP-induced cell death is most likely mediated by the plasma membrane disruption. We showed that nsEP can cause long-lasting (minutes) increase in plasma membrane electrical conductance and disrupt electrolyte balance, followed by w...

  4. Contrast variation SANS experiments to the study of detergent-induced micellization of block copolymers

    Indian Academy of Sciences (India)

    V K Aswal; J Kohlbrecher

    2004-08-01

    PEO-PPO-PEO triblock copolymer P85 [(EO)26 (PO)39 (EO)26] dissolves as unimers and detergent sodium dodecyl sulfate (SDS) forms micelles in aqueous solution at 20°C. The mixing of detergent with triblock copolymer induces the micellization of triblock copolymers. Contrast variation small-angle neutron scattering measurements show that triblock copolymer forms mixed micelles with detergent and the mixing of two components in the mixed micelles is uniform.

  5. AMPK inhibition blocks ROS-NFκB signaling and attenuates endotoxemia-induced liver injury.

    Directory of Open Access Journals (Sweden)

    Yuan Guo

    Full Text Available BACKGROUND: AMP-activated protein kinase (AMPK is an important enzyme in regulation of cellular energy homeostasis. We have previously shown that AMPK activation by 5-aminoimidazole-4-carboxamide (AICAR results in suppression of immune responses, indicating the pivotal role of AMPK in immune regulation. However, the cellular mechanism underpinning AMPK inhibition on immune response remains largely to be elucidated. The study aimed to investigate the effects of AMPK inhibition on reactive oxygen species (ROS-nuclear factor κB (NFκB signaling and endotoxemia-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: RAW 264.7 cells were pretreated with AMPK activator or inhibitor, followed by LPS challenge. In addition, LPS was injected intraperitoneally into mice to induce systemic inflammation. The parameters of liver injury and immune responses were determined, and survival of mice was monitored respectively. LPS challenge in RAW 264.7 cells resulted in AMPK activation which was then inhibited by compound C treatment. Both AMPK activation by AICAR or inhibition by compound C diminished LPS-induced ROS generation, inhibited phosphorylation of IKK, IκB, and NFκB p65, and consequently, decreased TNF production of RAW 264.7 cells. AICAR or compound C treatment decreased ALT, AST, and TNF levels in serum, reduced CD68 expression and MPO activity in liver tissue of mice with endotoxemia. Moreover, AICAR or compound C treatment improved survival of endotoxemic mice. CONCLUSIONS: AICAR or compound C treatment attenuates LPS-induced ROS-NFκB signaling, immune responses and liver injury. Strategies to activate or inhibit AMPK signaling may provide alternatives to the current clinical approaches to inhibit immune responses of endotoxemia.

  6. Slug inhibits pancreatic cancer initiation by blocking Kras-induced acinar-ductal metaplasia

    OpenAIRE

    Kazumi Ebine; Chow, Christina R.; DeCant, Brian T.; Hattaway, Holly Z.; Grippo, Paul J.; Krishan Kumar; Munshi, Hidayatullah G.

    2016-01-01

    Cells in the pancreas that have undergone acinar-ductal metaplasia (ADM) can transform into premalignant cells that can eventually become cancerous. Although the epithelial-mesenchymal transition regulator Snail (Snai1) can cooperate with Kras in acinar cells to enhance ADM development, the contribution of Snail-related protein Slug (Snai2) to ADM development is not known. Thus, transgenic mice expressing Slug and Kras in acinar cells were generated. Surprisingly, Slug attenuated Kras-induced...

  7. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection

  8. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazuyo [Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States); Adhikari, Rewati [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2015-08-14

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.

  9. Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

    International Nuclear Information System (INIS)

    CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells

  10. Chemical -induced apoptotic cell death in tomato cells : involvement of caspase-like proteases

    NARCIS (Netherlands)

    Jong, de A.J.; Hoeberichts, F.A.; Yakimova, E.T.; Maximova, E.; Woltering, E.J.

    2000-01-01

    A new system to study programmed cell death in plants is described. Tomato (Lycopersicon esculentum Mill.) suspension cells were induced to undergo programmed cell death by treatment with known inducers of apoptosis in mammalian cells. This chemical-induced cell death was accompanied by the characte

  11. Deletion of GPR40 fatty acid receptor gene in mice blocks mercaptoacetate-induced feeding.

    Science.gov (United States)

    Li, Ai-Jun; Wiater, Michael F; Wang, Qing; Wank, Stephen; Ritter, Sue

    2016-05-15

    Both increased and decreased fatty acid (FA) availability contribute to control of food intake. For example, it is well documented that intestinal FA reduces feeding by triggering enterondocrine secretion of satietogenic peptides, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). In contrast, mechanisms by which decreased FA availability increase feeding are not well understood. Over the past three decades substantial research related to FA availability and increased feeding has involved use of the orexigenic compound mercaptoacetate (MA). Because MA reportedly inhibits FA oxidation, it has been assumed that reduced FA oxidation accounts for the orexigenic action of MA. Recently, however, we demonstrated that MA antagonizes G protein-coupled receptor 40 (GPR40), a membrane receptor for long and medium chain FA. We also demonstrated that, by antagonizing GPR40, MA inhibits GLP-1 secretion and attenuates vagal afferent activation by FA. Because both vagal afferent activation and GLP-1 inhibit food intake, we postulated that inhibition of GPR40 by MA might underlie the orexigenic action of MA. We tested this hypothesis using male and female GPR40 knockout (KO) and wild-type (WT) mice. Using several testing protocols, we found that MA increased feeding in WT, but not GPR40 KO mice, and that GPR40 KO mice gained more weight than WT on a high-fat diet. Metabolic monitoring after MA or saline injection in the absence of food did not reveal significant differences in respiratory quotient or energy expenditure between treatment groups or genotypes. These results support the hypothesis that MA stimulates food intake by blocking FA effects on GPR40. PMID:26984894

  12. Radiation-induced crosslinking of poly(styrene–butadiene–styrene) block copolymers and their sulfonation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun-Young [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Song, Ju-Myung; Sohn, Joon-Yong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Shul, Yong-Gun [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shin, Junhwa, E-mail: shinj@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of)

    2013-12-01

    Highlights: • The c-SBS films were prepared using a gamma ray or electron beam. • The crosslinking degree of the c-SBS films were increased with the irradiation dose. • The prepared c-SBS films were sulfonated with various concentration of CSA. • The sulfonation of the c-SBS film is largely dependent on the concentration of CSA. • The sulfonation process is progressed from the surface to the inner part of c-SBS film. -- Abstract: Several crosslinked poly(styrene–butadiene–styrene) (c-SBS) block copolymer films were prepared using a gamma ray or electron beam with various irradiation doses and the prepared c-SBS film was then subjected to sulfonation using a chlorosulfonic acid (CSA) solution to introduce a sulfonic acid group. To estimate the degree of crosslinking, the gel fractions and FT-IR spectra of the c-SBS films were used and the results indicate that the degree of crosslinking is increased with an increase in the radiation dose. The surface morphology and mechanical property of the c-SBS films were observed using SEM and UTM instruments, respectively. The sulfonated c-SBS films were investigated by measuring the ion exchange capacity (IEC) and by observing the cross-sectional distribution patterns of sulfonic acid group using an SEM-EDX instrument. The IEC and SEM-EDX studies indicate that the sulfonated c-SBS membranes can be successfully prepared through the radiation crosslinking of the SBS film and the subsequent sulfonation with a diluted CSA solution.

  13. Chemically and temperature-induced phase transformations of metal vanadates

    Science.gov (United States)

    Patridge, Christopher James

    Metal vanadates contain a diverse family of compounds due to the facile accessibility of different vanadium oxidation states and local coordination environments. Though these systems present a number of applications in catalysis and electronics, there may exist untapped physical phenomena that only reveal themselves when scaling these materials to nanoscale dimensions. Finite-size effects result from a number of factors including surface energy structural instabilities, nanostructure "self-purification," and physical constraints on mechanistic or conductive pathways. The MxV2O 5 bronze materials possess non-stoichiometry and this interesting property has hindered synthetic techniques to procure perfect crystalline material which is needed to expose the true physical properties. Through hydrothermal synthesis methods, pseudo one---dimensional nanostructures of Mx V2O5 display fascinating new properties and may be model systems for studying fundamentals associated with correlated electron dynamics in solid-state physics. Electron microscopy and powder X-ray diffraction reveal the near-perfect crystalline nanostructures. X-ray absorption spectroscopy studies show strong evidence for the localization of electron density and long-range crystal structure alignment of the nanowires. Single-nanowire electron transport measurements for the beta'-CuxV2O5 and the delta-KxV2O5 data shows novel temperature-induced reversible metal---insulator transition (MIT) near room temperature. The unprecedented magnitude (˜105) and discontinuous nature of the MIT suggests a mechanism closely associated with correlated electron motion. Additionally, the MIT can be induced by voltage ramping. The simultaneous temperature/voltage studies of single-nanowire transport support the existence of a critical threshold to overcome in order to facilitate instability in the insulating phase and transition to a metallic phase for the delta-KxV2O5 bronze. The MIT transition magnitudes of several

  14. Surface chemical reactions induced by molecules electronically-excited in the gas

    DEFF Research Database (Denmark)

    Petrunin, Victor V.

    2011-01-01

    alignment are taking place, guiding all the molecules towards the intersections with the ground state PES, where transitions to the ground state PES will occur with minimum energy dissipation. The accumulated kinetic energy may be used to overcome the chemical reaction barrier. While recombination chemical...... be readily produced. Products of chemical adsorption and/or chemical reactions induced within adsorbates are aggregated on the surface and observed by light scattering. We will demonstrate how pressure and spectral dependencies of the chemical outcomes, polarization of the light and interference of...... two laser beams inducing the reaction can be used to distinguish the new process we try to investigate from chemical reactions induced by photoexcitation within adsorbed molecules and/or gas phase photolysis....

  15. ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone

    International Nuclear Information System (INIS)

    The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide names from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and 86Rb+ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of APT-sensitive K+ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamine. Glibenclamide blocks the galanin-activated ATP-sensitive K+ channel. 86Rb+ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced 86Rb+ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K+ channel reported earlier. 86Rb+ efflux studies confirm the electrophysiological demonstration that galanin activates and ATP-dependent K+ channel

  16. Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion-Induced Kidney Growth.

    Science.gov (United States)

    Wu, Huijuan; Chen, Jianchun; Xu, Jinxian; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang

    2016-04-01

    The molecular mechanisms underlying renal growth and renal growth-induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in theseTsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast,Tsc1single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules ofTsc1andrpS6double-mutant mice. Furthermore, pharmacologic treatment ofTsc1single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis inTsc1-deleted kidneys. PMID:26296742

  17. 5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats.

    Science.gov (United States)

    Archer, T; Danysz, W; Jonsson, G; Minor, B G; Post, C

    1986-10-01

    The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats. PMID:2877697

  18. PAN-811 Blocks Chemotherapy Drug-Induced In Vitro Neurotoxicity, While Not Affecting Suppression of Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Jiang

    2016-01-01

    Full Text Available Chemotherapy often results in cognitive impairment, and no neuroprotective drug is now available. This study aimed to understand underlying neurotoxicological mechanisms of anticancer drugs and to evaluate neuroprotective effects of PAN-811. Primary neurons in different concentrations of antioxidants (AOs were insulted for 3 days with methotrexate (MTX, 5-fluorouracil (5-FU, or cisplatin (CDDP in the absence or presence of PAN-811·Cl·H2O. The effect of PAN-811 on the anticancer activity of tested drugs was also examined using mouse and human cancer cells (BNLT3 and H460 to assess any negative interference. Cell membrane integrity, survival, and death and intramitochondrial reactive oxygen species (ROS were measured. All tested anticancer drugs elicited neurotoxicity only under low levels of AO and elicited a ROS increase. These results suggested that ROS mediates neurotoxicity of tested anticancer drugs. PAN-811 dose-dependently suppressed increased ROS and blocked the neurotoxicity when neurons were insulted with a tested anticancer drug. PAN-811 did not interfere with anticancer activity of anticancer drugs against BNLT3 cells. PAN-811 did not inhibit MTX-induced death of H460 cells but, interestingly, demonstrated a synergistic effect with 5-FU or CDDP in reducing cancer cell viability. Thus, PAN-811 can be a potent drug candidate for chemotherapy-induced cognitive impairment.

  19. CD-REST: a system for extracting chemical-induced disease relation in literature.

    Science.gov (United States)

    Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

    2016-01-01

    Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug-disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed fromhttp://clinicalnlptool.com/cdr The online CD-REST demonstration system is available athttp://clinicalnlptool.com/cdr/cdr.html. Database URL:http://clinicalnlptool.com/cdr;http://clinicalnlptool.com/cdr/cdr.html. PMID:27016700

  20. Drugs to block cytokine signaling for the prevention and treatment of inflammation induced preterm birth

    Directory of Open Access Journals (Sweden)

    Pearl Y Ng

    2015-04-01

    Full Text Available Preterm birth (PTB at less than 37 weeks of gestation is the leading cause of neonatal morbidity and mortality. Intrauterine infection (IUI due to microbial invasion of the amniotic cavity is the leading cause of early PTB (<32 weeks. Commensal genital tract Ureaplasma and Mycoplasma species, as well as Gram-positive and Gram-negative bacteria, have been associated with IUI-induced PTB. Bacterial activation of toll-like receptors (TLRs and other pattern recognition receptors initiates a cascade of inflammatory signaling via the NF-κB and p38 MAPK signaling pathways, prematurely activating parturition. Antenatal antibiotic treatment has had limited success in preventing PTB or fetal inflammation. Administration of anti-inflammatory drugs with antibiotics could be a viable therapeutic option to prevent PTB and fetal complications in women at risk of IUI and inflammation. In this mini-review we will discuss the potential for anti-inflammatory drugs in obstetric care, focusing on the class of drugs termed ‘cytokine suppressive anti-inflammatory drugs’ or CSAIDs. These inhibitors work by specifically targeting the NF-κB and p38 MAPK inflammatory signaling pathways. Several CSAIDs are discussed, together with clinical and toxicological considerations associated with the administration of anti-inflammatory agents in pregnancy.

  1. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Directory of Open Access Journals (Sweden)

    Mini Balakrishnan

    Full Text Available HIV-1 integrase (IN is the target for two classes of antiretrovirals: i the integrase strand-transfer inhibitors (INSTIs and ii the non-catalytic site integrase inhibitors (NCINIs. NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly.

  2. Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce a reverse transcription block in target cells.

    Science.gov (United States)

    Balakrishnan, Mini; Yant, Stephen R; Tsai, Luong; O'Sullivan, Christopher; Bam, Rujuta A; Tsai, Angela; Niedziela-Majka, Anita; Stray, Kirsten M; Sakowicz, Roman; Cihlar, Tomas

    2013-01-01

    HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA) integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we show that treatment of virus-producing cells, but not of mature virions or target cells, drives NCINI antiviral potency. NCINIs target an essential late-stage event in HIV replication that is insensitive to LEDGF levels in the producer cells. Virus particles produced in the presence of NCINIs displayed normal Gag-Pol processing and endogenous reverse transcriptase activity, but were defective at initiating vDNA synthesis following entry into the target cell. NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was less sensitive to the compound-induced late-stage effects, including the reverse transcription block. Wild-type, but not T174I virus, produced in the presence of NCINIs exhibited striking defects in core morphology and an increased level of IN oligomers that was not observed upon treatment of mature cell-free particles. Collectively, these results reveal that NCINIs act through a novel mechanism that is unrelated to the previously observed inhibition of IN activity or IN-LEDGF interaction, and instead involves the disruption of an IN function during HIV-1 core maturation and assembly. PMID:24040198

  3. Spectroscopic Observation of Chemical Interaction Between Impact-induced Vapor Clouds and the Ambient Atmosphere

    Science.gov (United States)

    Sugita, S.; Heineck, J. T.; Schultz, P. H.

    2000-01-01

    Chemical reactions within impact-induced vapor clouds were observed in laboratory experiments using a spectroscopic method. The results indicate that projectile-derived carbon-rich vapor reacts intensively with atmospheric nitrogen.

  4. Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ-Induced IL-27 and Airway Hyperresponsiveness in Mice.

    Science.gov (United States)

    Liao, Wupeng; Tan, W S Daniel; Wong, W S Fred

    2016-06-01

    LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-γ, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-γ-induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-γ-induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-γ markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-γ also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-γ, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2-related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders

  5. Preconditioning with associated blocking of Ca2+ inflow alleviates hypoxia-induced damage to pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Zuheng Ma

    Full Text Available OBJECTIVE: Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia. METHODS AND DESIGN: Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to the hypoxic period and/or following a 22 h re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during a 22 h period prior to hypoxia. RESULTS: Insulin contents decreased by 23% after 5.5 h of hypoxia and by 61% after a re-oxygenation period. Preconditioning with diazoxide time-dependently alleviated these hypoxia effects in rat and human islets. Hypoxia reduced proinsulin biosynthesis ((3H-leucine incorporation into proinsulin by 35%. Preconditioning counteracted this decrease by 91%. Preconditioning reduced hypoxia-induced necrosis by 40%, attenuated lowering of proteins of mitochondrial complexes I-IV and enhanced stimulation of HIF-1-alpha and phosphorylated AMPK proteins. Preconditioning by diazoxide was abolished by co-exposure to tolbutamide or elevated potassium (i.e. conditions which increase Ca(2+ inflow. Preconditioning with nifedipine, a calcium channel blocker, partly reproduced effects of diazoxide. Both diazoxide and nifedipine moderately reduced basal glucose oxidation whereas glucose-induced oxygen consumption (tested with diazoxide was unaffected. Preconditioning with diaxoxide enhanced insulin contents in transplants of rat islets to non-diabetic rats and lowered hyperglycemia vs. non-preconditioned islets in streptozotocin-diabetic rats. Preconditioning of human islet transplants lowered hyperglycemia in streptozotocin-diabetic nude mice. CONCLUSIONS: 1 Prior blocking of Ca(2+ inflow associates with lesser hypoxia-induced damage, 2 preconditioning affects basal mitochondrial metabolism and accelerates

  6. Comparison of Skeletal Effects of Ovariectomy Versus Chemically Induced Ovarian Failure in Mice

    OpenAIRE

    Wright, Laura E; Christian, Patricia J.; Rivera, Zelieann; Van Alstine, William G.; L Funk, Janet; L Bouxsein, Mary; Hoyer, Patricia B.

    2008-01-01

    Bone loss associated with menopause leads to an increase in skeletal fragility and fracture risk. Relevant animal models can be useful for evaluating the impact of ovarian failure on bone loss. A chemically induced model of menopause in which mice gradually undergo ovarian failure yet retain residual ovarian tissue has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). This study was designed to compare skeletal effects of VCD-induced ovarian failure to those associated wit...

  7. AT2R autoantibodies block angiotensin II and AT1R autoantibody-induced vasoconstriction.

    Science.gov (United States)

    Liles, Campbell; Li, Hongliang; Veitla, Vineet; Liles, Jonathan T; Murphy, Taylor A; Cunningham, Madeleine W; Yu, Xichun; Kem, David C

    2015-10-01

    Activating autoantibodies to the angiotensin type 1 receptor (AT1R) are associated with hypertensive disorders. The angiotensin type 2 receptor (AT2R) is known to counter-regulate the actions of AT1R. We investigated whether AT2R autoantibodies produced in immunized rabbits will activate AT2R and suppress the vasopressor responses to angiotensin II and AT1R-activating autoantibodies. Five rabbits immunized with a peptide corresponding to the second extracellular loop of AT2R developed high AT2R antibody titers. Rabbit anti-AT2R sera failed to directly dilate isolated rat cremaster arterioles; however, when co-perfused with angiotensin II or AT1R-activating autoantibodies, the anti-AT2R sera significantly inhibited their contractile effects. Rabbit anti-AT2R sera recognized a predominant sequence near the N-terminus of the AT2R second extracellular loop. A decoy peptide based on this sequence effectively reversed the opposing effect of the anti-AT2R sera on angiotensin II-induced contraction of rat cremaster arterioles. A similar blockade of the anti-AT2R sera effect was observed with the AT2R antagonist PD 123319 and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Rabbit anti-AT2R sera reacted specifically with AT2R. No cross-reactivity with AT1R was observed. Blood pressure did not change in immunized animals. However, the pressor responses to incremental angiotensin II infusions were blunted in immunized animals. Thirteen subjects with primary aldosteronism demonstrated increased AT2R autoantibody levels compared with normal controls. In conclusion, AT2R autoantibodies produced in immunized rabbits have the ability to activate AT2R and counteract the AT1R-mediated vasoconstriction. These autoantibodies provide useful and selective tools for the study of their roles in blood pressure regulation and possible therapeutic intervention. PMID:26259590

  8. Chemically-induced Mouse Lung Tumors: Applications to Human Health Assessments

    Science.gov (United States)

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbe...

  9. Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research

    OpenAIRE

    Liu, Yewei; YIN Ting; Feng, Yuanbo; Cona, Marlein Miranda; Huang, Gang; Liu, Jianjun; Song, Shaoli; Jiang, Yansheng; Xia, Qian; Swinnen, Johannes V; Bormans, Guy; Himmelreich, Uwe; Oyen, Raymond; Ni, Yicheng

    2015-01-01

    Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-spe...

  10. Chlorine Dioxide Induced Multiple Chemical Sensitivity: MMPI Validity Problems.

    Science.gov (United States)

    Tentoni, Stuart C.

    This paper discusses Minnesota Multiphasic Personality Inventory (MMPI) data obtained from individuals exposed to chlorine dioxide in the workplace who developed Multiple Chemical Sensitivity Syndrome. The paper explores current research on chlorine dioxide exposed persons who were misdiagnosed on the basis of MMPI interpretations. Difficulties…

  11. IR Laser-induced Chemical Vapour Deposition of Polyselenocarbosilane Films

    Czech Academy of Sciences Publication Activity Database

    Santos, M.; Díaz, L.; Pola, Josef

    - : -, 2006, s. 1-2. [Reunión Nacional de Espectroscopia (RNE) y IV Congresso Ibérico de Espectroscopia (CIE) /20./. Ciúdad Real (ES), 10.09.2006-14.09.2006] Institutional research plan: CEZ:AV0Z40720504 Keywords : chemical vapour deposition Subject RIV: CH - Nuclear ; Quantum Chemistry

  12. Chemically Induced Phase Transformation in Austenite by Focused Ion Beam

    Science.gov (United States)

    Basa, Adina; Thaulow, Christian; Barnoush, Afrooz

    2013-11-01

    A highly stable austenite phase in a super duplex stainless steel was subjected to a combination of different gallium ion doses at different acceleration voltages. It was shown that contrary to what is expected, an austenite to ferrite phase transformation occurred within the focused ion beam (FIB) milled regions. Chemical analysis of the FIB milled region proved that the gallium implantation preceded the FIB milling. High resolution electron backscatter diffraction analysis also showed that the phase transformation was not followed by the typical shear and plastic deformation expected from the martensitic transformation. On the basis of these observations, it was concluded that the change in the chemical composition of the austenite and the local increase in gallium, which is a ferrite stabilizer, results in the local selective transformation of austenite to ferrite.

  13. Chemical products induce resistance to Xanthomonas perforans in tomato

    Directory of Open Access Journals (Sweden)

    Adriana Terumi Itako

    2015-09-01

    Full Text Available The bacterial spot of tomato, caused by Xanthomonas spp., is a very important disease, especially in the hot and humid periods of the year. The chemical control of the disease has not been very effective for a number of reasons. This study aimed to evaluate, under greenhouse conditions, the efficacy of leaf-spraying chemicals (acibenzolar-S-methyl (ASM (0.025 g.L−1, fluazinam (0.25 g.L−1, pyraclostrobin (0.08 g.L−1, pyraclostrobin + methiran (0.02 g.L−1 + 2.2 g.L−1, copper oxychloride (1.50 g.L−1, mancozeb + copper oxychloride (0.88 g.L−1 + 0.60 g.L−1, and oxytetracycline (0.40 g.L−1 on control of bacterial spot. Tomatoes Santa Clara and Gisele cultivars were pulverized 3 days before inoculation with Xanthomonas perforans. The production of enzymes associated with resistance induction (peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and protease was quantified from leaf samples collected 24 hours before and 24 hours after chemical spraying and at 1, 2, 4, 6, and 8 days after bacterial inoculation. All products tested controlled bacterial spot, but only ASM, pyraclostrobin, and pyraclostrobin + metiram increased the production of peroxidase in the leaves of the two tomato cultivars, and increased the production of polyphenol oxidase and β-1,3-glucanase in the Santa Clara cultivar.

  14. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement.

    Science.gov (United States)

    Hearing, Matthew C; Jedynak, Jakub; Ebner, Stephanie R; Ingebretson, Anna; Asp, Anders J; Fischer, Rachel A; Schmidt, Clare; Larson, Erin B; Thomas, Mark John

    2016-01-19

    Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies. PMID:26739562

  15. Improving the chemical compatibility of sealing glass for solid oxide fuel cells: Blocking the reactive species by controlled crystallization

    Science.gov (United States)

    Zhang, Teng; Zou, Qi; Zeng, Fanrong; Wang, Shaorong; Tang, Dian; Yang, Hiswen

    2012-10-01

    The chemical compatibility of sealing glass is of great importance for Solid oxide fuel cell (SOFC). In this work, the interfacial reaction between sealing glass and Cr-containing interconnect alloy is characterized by reacting Cr2O3 powders with a representative SrO-containing glass crystallized by different heat-treatment schedules. The crystalline structure and crystalline content of sealing glass are determined by X-ray diffraction. The results show that the fraction of Cr6+ decreases from 39.8 ± 1.9% for quenched glass to 8.2 ± 0.4% for glass crystallized at 900 °C for 2 h. In addition, the interfacial reaction can be further reduced with increasing crystallization temperature and time as well as the addition of nucleation agent (TiO2). The formation of some Sr-containing crystalline phases, Sr2SiO4 and Sr(TiO3), contributes to the improvement of chemical compatibility of sealing glass, in agreement with the results of thermodynamic calculations.

  16. Noise-induced multistability in chemical systems: Discrete versus continuum modeling.

    Science.gov (United States)

    Duncan, Andrew; Liao, Shuohao; Vejchodský, Tomáš; Erban, Radek; Grima, Ramon

    2015-04-01

    The noisy dynamics of chemical systems is commonly studied using either the chemical master equation (CME) or the chemical Fokker-Planck equation (CFPE). The latter is a continuum approximation of the discrete CME approach. It has recently been shown that for a particular system, the CFPE captures noise-induced multistability predicted by the CME. This phenomenon involves the CME's marginal probability distribution changing from unimodal to multimodal as the system size decreases below a critical value. We here show that the CFPE does not always capture noise-induced multistability. In particular we find simple chemical systems for which the CME predicts noise-induced multistability, whereas the CFPE predicts monostability for all system sizes. PMID:25974443

  17. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons

    Science.gov (United States)

    2014-01-01

    Background Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. Methods CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). Results The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia

  18. Chemical consequences of laser-induced breakdown in molecular gases

    Czech Academy of Sciences Publication Activity Database

    Babánková, Dagmar; Civiš, Svatopluk; Juha, Libor

    2006-01-01

    Roč. 30, č. 2-3 (2006), s. 75-88. ISSN 0079-6727 R&D Projects: GA ČR GA203/06/1278; GA MŠk LC510; GA MŠk LC528; GA MŠk 1P04LA235 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z10100523 Keywords : laser spark * laser-induced dielectric breakdown * laser-plasma chemistry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.500, year: 2006

  19. Electron beam-induced nanoparticle formation in Au and Pt salt-loaded polystyrene-block-poly(4-vinylpyridine) micelles

    International Nuclear Information System (INIS)

    Using diblock copolymer micelles as nanoreactors for the generation of metal colloids has proven to be a universal route to regular arrays of uniformly sized nanoparticles (NPs) for a variety of metals. When PS-b-P4VP micelles in toluene are loaded with metal salts, the formation of a single NP in each P4VP core can be achieved in a subsequent reduction step induced either chemically, by plasma or by UV or electron irradiation. We present a detailed TEM study of metal colloid formation during this reduction step in Au and Pt salt-loaded PS-b-P4VP micelles at variable temperature in the range 95-300 K. Electron irradiation-induced coagulation of metal and initial formation of particulates with subnanometer diameters within the P4VP cores is observed in the entire temperature range for Au as well as for Pt. Particle coarsening and ripening, however, strongly depend on the metal, the electron dose and, in particular, on temperature. Counter-intuitively, the dynamics of metal aggregation into a single NP within each micelle core is faster at low temperature whereas at 300 K even high densities of subnanometer particulates remain stable. Stability of the P4VP is probably essential for metal mobility within the core.

  20. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-03-22

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  1. Spin Manipulation in Graphene by Chemically Induced Pseudospin Polarization

    Science.gov (United States)

    Van Tuan, Dinh; Roche, Stephan

    2016-03-01

    Spin manipulation is one of the most critical challenges to realize spin-based logic devices and spintronic circuits. Graphene has been heralded as an ideal material to achieve spin manipulation, but so far new paradigms and demonstrators are limited. Here we show that certain impurities such as fluorine adatoms, which locally break sublattice symmetry without the formation of strong magnetic moment, could result in a remarkable variability of spin transport characteristics. The impurity resonance level is found to be associated with a long-range sublattice pseudospin polarization, which by locally decoupling spin and pseudospin dynamics provokes a huge spin lifetime electron-hole asymmetry. In the dilute impurity limit, spin lifetimes could be tuned electrostatically from 100 ps to several nanoseconds, providing a protocol to chemically engineer an unprecedented spin device functionality.

  2. Methyl chloride via oxyhydrochlorination of methane: A building block for chemicals and fuels from natural gas. Environmental assessment

    International Nuclear Information System (INIS)

    DOE's natural gas mission, in partnership with its stakeholders, is to undertake and promote activities to maximize the Nation's ability to supply, transport, and use natural gas to encourage economic growth, enhance energy interests security, and improve the environment. In implementing this mission, DOE has been involved in promoting domestic natural gas as a clean, abundant, and reliable source of energy. In particular, DOE is interested in technologies capable of converting natural gas to other valuable resources, such as transportation fuels, hydrogen, and premium chemicals. The purpose of the proposed action is to further examine the potential of one such technology for natural gas conversion. Over the past five years, DOE's Pittsburgh Energy Technology Center has supported a research program to determine the feasibility of producing methyl chloride (CH3Cl), a key ingredient used in the silicone industry, directly from methane (the primary component of natural gas) via an oxyhydrochlorination (OHC) process. As a result of this research program the OHC process is now ready for further development. The proposed action would advance the OHC natural gas conversion technology to an integrated engineering-scale process at the Dow Corning plant in Carrollton, Kentucky

  3. Altered Acer Rubrum Fecundity Induced By Chemical Climate Change

    Science.gov (United States)

    Deforest, J. L.; Peters, A.

    2014-12-01

    Red maple (Acer rubrum L.) is becoming the most dominating tree in North American eastern deciduous forests. Concurrently, human activities have altered the chemical climate of terrestrial ecosystems via acidic deposition, which increases the available of nitrogen (N), while decreasing phosphorus (P) availability. Once a minor forest component prior to European settlement, the abundance of red maple may be a symptom of the modern age. The current paradigm explaining red maple's rise to prominence concerns fire suppression that excludes competitors. However, this still does not explain why red maple is unique compared to other functionally similar trees. The objective of this study was to investigate the interactive influence of acid rain mitigation on the fecundity of red maple. Objectives were achieved by measuring flowering, seed production, germination, and growth from red maple on plots that have been experimentally manipulated to increase soil pH, P, or both in three unglaciated eastern deciduous hardwood forests. At least 50% of the red maple population is seed bearing in our control soils, however the median percent of seed-bearing trees declined to zero when mitigating soils from acidic deposition. This can be explained by the curious fact that red maple is polygamodioecious, or has labile sex-expression, in which an individual tree can change its sex-expression in response to the environment. Furthermore, seed-bearing trees in the mitigated plots grew less, produced less seeds, and germinated at lower rates than their counterparts in control soils. Our results provide evidence that chemical climate change could be the primary contributing factor accelerating the dominance of red maple in eastern North American forests. Our observations can provide a boarder conceptual framework for understanding how nutrient limitations can be applied beyond plant productivity towards explaining distribution changes in vegetation.

  4. Xiaokeping mixture inhibits diabetic nephropathy in streptozotocin-induced rats through blocking TGF-β1/Smad7 signaling

    Directory of Open Access Journals (Sweden)

    Xin C

    2015-11-01

    Full Text Available Chuanwei Xin, Zhongni Xia, Cheng Jiang, Mengmeng Lin, Gonghua Li Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China Background: Diabetic nephropathy (DN is a major cause of chronic kidney failure and characterized by excessive deposition of extracellular matrix. Evidence have shown that transforming growth factor-β1 (TGF-β1 is a key mediator in the development of DN. However, treatment of DN by blocking the TGF-β1/Smad7 pathway remains limited. Xiaokeping mixture (XKP, a traditional Chinese herbal compound, has been used for treatment in patients with DN for many years.Methods: In the present study, TGF-β1/Smad7 pathway analysis was used to evaluate the therapeutic effect of XKP on DN rats induced by streptozotocin and to address the underlying molecular mechanism. Male rats were divided into four groups: normal control, untreated control group (fed with high fat, irbesartan-treated DN, and XKP-treated DN, respectively. Levels of serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol were detected. Pathological changes of renal tissues were observed by hematoxylin–eosin staining. Immunohistochemical and Western blot analysis were used to detect the expressions of TGF-β1 and Smad7.Results: The results demonstrated that XKP can effectively reduce the levels of glucose, serum creatinine, blood urea nitrogen, urine protein of 24 hours, and triacylglycerol. Further studies indicated that inhibition of DN in XKP-treated DN rats was associated with inhibition of TGF-β1/Smad7 signaling as demonstrated by downregulation of TGF-β1 but upregulation of Smad7.Conclusion: The data obtained from the present study indicate that XKP may be a therapeutic agent for DN. Keywords: Xiaokeping mixture, diabetic nephropathy, transforming growth factor-beta, Smad7

  5. Hygienic grooming is induced by contact chemicals in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Aya Yanagawa

    2014-07-01

    Full Text Available In social insects, grooming is considered as a behavioral defense against pathogen and parasite infections since it contributes to remove microbes from their cuticle. However, stimuli which trigger this behavior are not well characterized yet. We examined if activating contact chemoreceptive sensilla could trigger grooming activities in Drosophila melanogaster. We monitored the grooming responses of decapitated flies to compounds known to activate the immune system e.g. dead Escherichia coli (Ec and lipopolysaccharides (LPS, and to tastants such as quinine, sucrose, and salt. LPS, quinine and Ec were quite effective in triggering grooming movements when touching the distal border of the wings and the legs, while sucrose had no effect. Contact chemoreceptors are necessary and sufficient to elicit such responses, as grooming could not be elicited by LPS in poxn mutants deprived of external taste sensilla, and as grooming was elicited by light when a channel rhodopsin receptor was expressed in bitter-sensitive cells expressing Gr33a. Contact chemoreceptors distributed along the distal border of the wings respond to these tastants by an increased spiking activity, in response to quinine, Ec, LPS, sucrose and KCl. These results demonstrate for the first time that bacterial compounds trigger grooming activities in D. melanogaster, and indicate that contact chemoreceptors located on the wings participate to the detection of such chemicals.

  6. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    Science.gov (United States)

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. PMID:25407640

  7. Chemical Changes Induced by Irradiation in Meats and Meat Components

    International Nuclear Information System (INIS)

    The acceptability of meats preserved by irradiation has been hampered by the formation of an irradiation flavour and odour. This flavour and odour is believed to be due to the volatile chemical compounds produced by radiation impact on the protein and lipid molecules. The analysis of the volatile compounds has been accomplished, employing programmed cryogenic temperature gas chromatography for separation of the complex mixtures obtained, and rapid scanning mass spectrometry for identification of the individually separated components. Comprehensive analyses of the volatiles from irradiated ground beef, pork, mutton, lamb, and veal, as well as the volatile irradiation degradation products of several amino acids and proteins, animal fats, methyl esters of fatty acids, and triglycerides have been made. The results of the analysis of the irradiated component meat substances are compared with those obtained from the irradiation of meat itself, and of separate meat fractions, thus establishing the contribution of each fraction to the total. Mechanisms are postulated for the formation of the volatile components from each fraction and for interactions among intermediates from different fractions. (author)

  8. Additive Driven Self Assembly and Photo-induced Ordering in Poly(ethylene glycol)monomethyl ether monomethacrylate-block-Poly(ethyl methacrylate) Copolymers

    Science.gov (United States)

    Li, Cheng; Watkins, James

    2013-03-01

    Recent work in our labs has shown that blending of hydrogen-bond donating polymers, small molecules or nanoparticles with a block copolymer that contains poly(ethylene oxide) (PEO) can enhance microphase segregation strength and yield well ordered morphologies. While PEO crystallization in these polymers is suppressed by strong interactions between the additive and the PEO segments at high additive loadings, crystallization of the PEO block in the absence of these interactions or at low additive loadings is highly undesirable for many applications. To remedy this issue, poly[poly(ethylene glycol) monomethyl ether monomethacrylate]-block-poly(ethyl methacrylate) was prepared using reversible addition-fragmentation chain transfer polymerization(RAFT). This block copolymer is a phase mixed, non-crystallizable system at room temperature. We find that incorporation of organic additives with multiple carboxylic acid groups such as mellitic acid induces phase segregation in this system. Furthermore, the use of additives in which the hydrogen bond donating group is protected with an acid labile group in combination with a photo acid generator enables photo-induced microphase segregation of the composite to yield well ordered films.

  9. Heart Block

    Science.gov (United States)

    ... the signal causes the heart to contract and pump blood. Heart block occurs if the electrical signal is ... degree heart block limits the heart's ability to pump blood to the rest of the body. This type ...

  10. Chemical and radiation-induced mutagenesis of the rat liver chromosomes

    International Nuclear Information System (INIS)

    It was shown that radiation and chemical mutagenesis in rat liver cells is determined chiefly by long-lived premutational potential changes. The intensification of intrachromosomal processes under the action of an inducer of gene activity - phenobarbital - does not modify the yield of chromosome aberrations, both under the action of radiation and under the action of an alkylating agent -dipin. The facts obtained support the hypothesis that the chemical nature of the premutational changes differs from the primary molecular damages to DNA. (author)

  11. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger;

    2011-01-01

    the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used in...... experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare)....

  12. Chemically-induced Jahn-Teller ordering on manganite surfaces

    Science.gov (United States)

    Gai, Zheng; Lin, Wenzhi; Burton, J. D.; Tsymbal, Evgeny Y.; Fuchigami, K.; Shen, Jian; Snijders, P. C.; Ward, T. Z.; Jesse, Stephen; Kalinin, Sergei V.; Baddorf, A. P.

    2014-03-01

    Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields, and establish their coupling to electronic properties. Here we demonstrate that measuring the sub 30 pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunneling microscopy (STM) allows the physical order parameter fields to be visualized in real space on the single atom level. Here, this local crystallographic analysis is applied to the in-situ grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level. Research was supported by MSED and CNMS, which are sponsored at Oak Ridge National Laboratory by the Office of Basic Energy Sciences, U.S. Department of Energy.

  13. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  14. Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

    International Nuclear Information System (INIS)

    SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

  15. Preparation Of Polystyrene Nanoparticles Using Both GAMMA Radiation And Chemical Induced Emulsion Polymerization

    International Nuclear Information System (INIS)

    Polystyrene nanoparticles were synthesized by radiation-induced polymerization and chemical emulsion polymerization. Compared with the chemical emulsion polymerization, the radiation process easily prepared the polystyrene (PS) nanoparticles at room temperature and without the pollutant of chemical initiator. The effects of various polymerization parameters in both systems such as total dose for radiation polymerization, monomer concentration, sodium dodecyl sulfate (SDS) stabilizer content on the particle size and size distribution were systematically investigated. The diameter of a polymer particle and its distribution were measured on a Marvern Zetasizer. Monomer conversion was studied gravimetric ally and the structure of PS was analyzed by Differential Scanning Calorimeter (DSC) and Fourier Transform Infrared (FT-IR) Spectrophotometer

  16. Mutagenic efficiency of radiations and chemical mutagens in inducing viable mutations in rice

    International Nuclear Information System (INIS)

    Studies were undertaken to compare the effectiveness and efficiency of radiations (gamma rays and fast neutrons) and chemical mutagens (EMS and NMU) in inducing viable mutations in rice. Radiations were more effective than chemical mutagens, the most effective being fast neutrons. Mutagenic efficiency when estimated on the basis of lethality was higher for radiations but when based on sterility was higher for chemical mutagens. Fast neutrons, more effective than gamma rays, were less efficient. NMU was more effective but less efficient than EMS. (author)

  17. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Yukihiro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Nakamura, Yuji [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kitahara, Ken [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Harada, Takuma [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kato, Kazuhiko; Ninomiya, Tomohisa [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Cao, Xin [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Ohara, Hiroshi [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Izumi-Nakaseko, Hiroko [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Suzuki, Kokichi [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Ando, Kentaro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); and others

    2014-11-15

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not

  18. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    International Nuclear Information System (INIS)

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct IKr inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P1,3,4,5 and S1P1,5 receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P1 in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by siponimod.

  19. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    International Nuclear Information System (INIS)

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  20. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  1. Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin

    OpenAIRE

    Jiang, Haibo; Xiong, Siqi; Xia, Xiaobo

    2014-01-01

    Background Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M. Results ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chas...

  2. Physico-chemical study of the focused electron beam induced deposition process

    OpenAIRE

    Bret, Tristan; Hoffmann, Patrik

    2007-01-01

    The focused electron beam induced deposition process is a promising technique for nano and micro patterning. Electrons can be focused in sub-angström dimensions, which allows atomic-scale resolution imaging, analysis, and processing techniques. Before the process can be used in controlled applications, the precise nature of the deposition mechanism must be described and modelled. The aim of this research work is to present a physical and chemical description of the focused electron beam induc...

  3. Controlling Solution Self-assembly and Non-Solvent Induced Microphase Separation of Triblock Terpolymers to Generate Nanofiltration Membranes with Chemically-Tailored Pore Walls

    Science.gov (United States)

    Boudouris, Bryan; Mulvenna, Ryan; Weidman, Jacob; Phillip, William

    2014-03-01

    Block polymer-based templates have been utilized in a number of membrane applications; however, there has yet to be a demonstration of a nanoporous block polymer thin film that can achieve high flux and high selectivity simultaneously while also allowing for the facile tuning of the pore wall chemistry. Here, we demonstrate that by synthesizing and controlling the solution self-assembly of a triblock terpolymer, polyisoprene- b-polystyrene- b-poly(N, N-dimethylacrylamide) (PI-PS-PDMA), and precisely inducing non-solvent induced phase separation during the self-assembly process allows for the creation of an asymmetric nanoporous membrane with PDMA-lined pore walls. This PDMA functionality is then converted to any number of side chain functionalities through simple chemistry in the solid state. In this way, we are able to show a highly selectivity membrane that can separate analytes of interest based both on size and chemical composition at a high solution flux. In fact, this high fidelity structure has a very narrow distribution of pore sizes (500 cm2) . This has allowed for the separation of particles with hydrodynamic radii as low as 0.8 nm, which is the smallest separation achieved using a block polymer-based membrane to date.

  4. Gentamicin Blocks the ACh-Induced BK Current in Guinea Pig Type II Vestibular Hair Cells by Competing with Ca2+ at the l-Type Calcium Channel

    Directory of Open Access Journals (Sweden)

    Hong Yu

    2014-04-01

    Full Text Available Type II vestibular hair cells (VHCs II contain big-conductance Ca2+-dependent K+ channels (BK and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh evoked the BK current by triggering the influx of Ca2+ ions through l-type Ca2+ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs. Aminoglycoside antibiotics, such as gentamicin (GM, are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC50 value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca2+ concentration ([Ca2+]o could antagonize it. Moreover, 50 µM GM potently blocked Ca2+ currents activated by (--Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca2+ at the l-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  5. Chemically-induced mouse lung tumors: applications to human health assessments [Poster 2014

    Science.gov (United States)

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to discuss issues related to the use of mouse lung tumor data in human health assessments. Naphthalene, styrene, and ethylbenzene were chosen for the anal...

  6. Supramolecular chemical shift reagents inducing conformational transitions: NMR analysis of carbohydrate homooligomer mixtures

    DEFF Research Database (Denmark)

    Beeren, Sophie; Meier, Sebastian

    2015-01-01

    We introduce the concept of supramolecular chemical shift reagents as a tool to improve signal resolution for the NMR analysis of homooligomers. Non-covalent interactions with the shift reagent can constrain otherwise flexible analytes inducing a conformational transition that results in signal...

  7. A review on chemical effects in aqueous solution induced by plasma with glow discharge

    International Nuclear Information System (INIS)

    Chemical effects in different aqueous solutions induced by plasma with glow discharge electrolysis (GDE) and contact glow discharge electrolysis (CGDE) are described. The experimental and discharge characteristics are also reviewed. These are followed by a discussion of their mechanisms of both anodic and cathodic CGDE

  8. Cleavage enhancement of specific chemical bonds in DNA-Cisplatin complexes induced by X-rays

    International Nuclear Information System (INIS)

    The chemical bond transformation of cisplatin-DNA complexes can be probed efficiently by XPS which provides a concomitant X-ray irradiation source as well. The presence to Pt could considerably increase formation of the SE induced by X-ray and that the further interaction of these LEE with DNA leads to the enhancement of bond cleavages.

  9. Biomarkers of DNA and cytogenetic damages induced by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    This paper presents and discusses results from the studies on various biomarkers of the DNA and cytogenetic damages induced by environmental chemicals or radiation. Results of the biomonitoring studies have shown that particularly in the condition of Poland, health hazard from radiation exposure is overestimated in contradistinction to the environmental hazard

  10. Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex.

    Science.gov (United States)

    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Borland, Michael S; Salgado-Delgado, Roberto; Salgado, Humberto; D'Mello, Santosh; Kilgard, Michael P; Rose-John, Stefan; Atzori, Marco

    2015-01-01

    The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10mg/kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic α7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar results were obtained by activating the "anti-inflammatory reflex" - a neural circuit regulating peripheral immune response - by stimulation of the vagal nerve or through peripheral administration of the α7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression. PMID:25128387

  11. Imprint Control of BaTiO3 Thin Films via Chemically Induced Surface Polarization Pinning.

    Science.gov (United States)

    Lee, Hyungwoo; Kim, Tae Heon; Patzner, Jacob J; Lu, Haidong; Lee, Jung-Woo; Zhou, Hua; Chang, Wansoo; Mahanthappa, Mahesh K; Tsymbal, Evgeny Y; Gruverman, Alexei; Eom, Chang-Beom

    2016-04-13

    Surface-adsorbed polar molecules can significantly alter the ferroelectric properties of oxide thin films. Thus, fundamental understanding and controlling the effect of surface adsorbates are crucial for the implementation of ferroelectric thin film devices, such as ferroelectric tunnel junctions. Herein, we report an imprint control of BaTiO3 (BTO) thin films by chemically induced surface polarization pinning in the top few atomic layers of the water-exposed BTO films. Our studies based on synchrotron X-ray scattering and coherent Bragg rod analysis demonstrate that the chemically induced surface polarization is not switchable but reduces the polarization imprint and improves the bistability of ferroelectric phase in BTO tunnel junctions. We conclude that the chemical treatment of ferroelectric thin films with polar molecules may serve as a simple yet powerful strategy to enhance functional properties of ferroelectric tunnel junctions for their practical applications. PMID:26901570

  12. Using chemically patterned substrates to suppress thermal placement errors in the directed self-assembly of block copolymer multi-cylinder linear arrays

    Science.gov (United States)

    Carpenter, Corinne; Delaney, Kris; Fredrickson, Glenn

    Directed self assembly (DSA) of block copolymers is a promising alternative approach for ~10nm microelectronics patterning, both for feature-size reduction and rectification. One prototypical application of DSA is the use of vertical interconnect access (VIA) cylinders for fabricating conducting channels between circuit layers. Typically a compromise exists between the fidelity and low defect density obtained by using a small number of cylinders per pre-pattern guide and the objective to further increase feature density. In particular for 1D linear arrays of multiple VIAs in a single prepattern, prior experimental and theoretical work has demonstrated that thermal fluctuations in larger arrays cause cylinder placement to vary widely around the equilibrium positions in a manner analogous to the collective excitations in a simple 1D coupled oscillator model (Landau-Peierls instability). In the present work, we assess the efficacy of using chemically patterned substrates to suppress the thermal placement errors using both a phenomenological oscillator model and full field theoretic simulations.

  13. Emergent pacemaker placement in a patient with Lyme carditis-induced complete heart block and ventricular asystole.

    Science.gov (United States)

    Brownstein, Adam J; Gautam, Samir; Bhatt, Paras; Nanna, Michael

    2016-01-01

    We report a case of a 31-year-old man who presented to the emergency department after four episodes of syncope within a 24 h time span. He was found to have symptomatic complete heart block associated with episodes of ventricular asystole lasting 5-6 s. He underwent emergent permanent pacemaker insertion during which he was found to have no underlying rhythm. He was later found to have positive serologies for Lyme disease despite no known exposure to ticks and neither signs nor symptoms of the disease. The pacemaker was ultimately removed due to resolution of his heart block with antibiotic therapy. PMID:27207985

  14. Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Sachin Diwadkar

    2016-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

  15. Capsaicin-induced neurogenic inflammation in the skin in patients with symptoms induced by odorous chemicals

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger; Serup, Jørgen; Elberling, Jesper

    2011-01-01

    Intradermal injection of capsaicin induces the axonal release of neuropeptides, vasodilatation and flare, e.g. neurogenic inflammation. The spatial profile of neurogenic inflammation in the skin has been studied in various experimental models. Polarization spectroscopy imaging introduced recently...

  16. Plume-induced dynamic instabilities near cratonic blocks: Implications for P-T-t paths and metallogeny

    Science.gov (United States)

    Guillou-Frottier, L.; Burov, E.; Cloetingh, S.; Le Goff, E.; Deschamps, Y.; Huet, B.; Bouchot, V.

    2012-06-01

    Plume head-lithosphere interactions around cratonic blocks result in thermo-mechanical disturbances that lead to heating and burial phases of crustal rocks. We present results from numerical models of plume head-cratonic blocks interactions where a free upper surface condition and realistic rheologies are accounted for. These models include distinct cratonic blocks embedded within a continental lithosphere and separated by several hundreds of kilometers. Surface topography, thermal field and effective viscosity values are tracked for 20 Myr of interactions. The modeled dynamic interaction of a plume head around cratonic blocks results in two main types of instabilities, each of them resulting in a distinct P-T-t path. The "slab-like" instability, focused on cratonic edges when plume head is away from the craton center, shows a near-isothermal burial phase, while the "drip-like" instability occurring above plume head material results in a near-isobaric heating phase. Consequently, both clockwise and counterclockwise P-T-t paths can be expected around cratons, as actually observed around the Tanzanian craton and other cratonic areas. Metallogenic data from gemstone-bearing rocks in south-east Africa and data from ultrahigh temperature and ultrahigh pressure metamorphism are compatible with our model. It appears that vertical mantle dynamics around cratons may also explain thermobarometric signatures that are often attributed to horizontal tectonics.

  17. Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

    NARCIS (Netherlands)

    Staals, L.M.; Boer, H.D. de; Egmond, J. van; Hope, F.; Pol, F.M. van de; Bom, A.H.; Driessen, J.J.; Booij, L.H.D.J.

    2011-01-01

    PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugam

  18. Electrochemically induced chemical sensor properties in graphite screen-printed electrodes: The case of a chemical sensor for uranium

    Energy Technology Data Exchange (ETDEWEB)

    Kostaki, Vasiliki T.; Florou, Ageliki B. [Laboratory of Analytical Chemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina (Greece); Prodromidis, Mamas I., E-mail: mprodrom@cc.uoi.gr [Laboratory of Analytical Chemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina (Greece)

    2011-10-01

    Highlights: > Electrochemical treatment endows analytical characteristics to SPEs. > A sensitive chemical sensor for uranium is described. > Performance is due to a synergy between electrochemical treatment and ink's solvents. > The amount of the solvent controls the achievable sensitivity. - Abstract: We report for the first time on the possibility to develop chemical sensors based on electrochemically treated, non-modified, graphite screen-printed electrodes (SPEs). The applied galvanostatic treatment (5 {mu}A for 6 min in 0.1 M H{sub 2}SO{sub 4}) is demonstrated to be effective for the development of chemical sensors for the determination of uranium in aqueous solutions. A detailed study of the effect of various parameters related to the fabrication of SPEs on the performance of the resulting sensors along with some diagnostic experiments on conventional graphite electrodes showed that the inducible analytical characteristics are due to a synergy between electrochemical treatment and ink's solvents. Indeed, the amount of the latter onto the printed working layer controls the achievable sensitivity. The preconcentration of the analyte was performed in an electroless mode in an aqueous solutions of U(VI), pH 4.6, and then, the accumulated species was reduced by means of a differential pulse voltammetry scan in 0.1 M H{sub 3}BO{sub 3}, pH 3. Under selected experimental conditions, a linear calibration curve over the range 5 x 10{sup -9} to 10{sup -7} M U(VI) was constructed. The 3{sigma} limit of detection at a preconcentration time of 30 min, and the relative standard deviation of the method were 4.5 x 10{sup -9} M U(VI) and >12% (n = 5, 5 x 10{sup -8} M U(VI)), respectively. The effect of potential interferences was also examined.

  19. Physical and chemical effects of red cells in the shear-induced aggregation of human platelets.

    OpenAIRE

    Goldsmith, H L; Bell, D N; Braovac, S; Steinberg, A.; McIntosh, F

    1995-01-01

    Both chemical and physical effects of red cells have been implicated in the spontaneous aggregation of platelets in sheared whole blood (WB). To determine whether the chemical effect is due to ADP leaking from the red cells, a previously described technique for measuring the concentration and size of single platelets and aggregates was used to study the shear-induced aggregation of platelets in WB flowing through 1.19-mm-diameter polyethylene tubing in the presence and absence of the ADP scav...

  20. A chemical pollen suppressant inhibits auxin-induced growth in maize coleoptile sections

    Energy Technology Data Exchange (ETDEWEB)

    Vesper, M.J. (Univ. of Dayton, OH (USA)); Cross, J.W. (Sogetal, Inc., Hayward, CA (USA))

    1990-05-01

    Chemical inhibitors of pollen development having a phenylcinnoline carboxylate structure were found to inhibit IAA- and 1-NAA-induced growth in maize coleoptile sections. The inhibitor (100 {mu}M) used in these experiments caused approx. 35% reduction in auxin-induced growth over the auxin concentration range of 0.3 to 100 {mu}M. Growth inhibition was noted as a lengthening of the latent period and a decrease in the rate of an auxin-induced growth response. An acid growth response to pH 5 buffer in abraded sections was not impaired. The velocity of basipetal transport of ({sup 3}H)IAA through the coleoptile sections also was not inhibited by the compound, nor was uptake of ({sup 3}H)IAA. Similarly, the inhibitor does not appear to alter auxin-induced H{sup +} secretion. We suggest that the agent targets some other process necessary for auxin-dependent growth.

  1. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  2. Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation

    Science.gov (United States)

    Ye, Wei; Wu, Hongqing; He, Xin; Wang, Lei; Zhang, Weimin; Li, Haohua; Fan, Yunfei; Tan, Guohui; Liu, Taomei; Gao, Xiaoxia

    2016-01-01

    Background Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. Methodology/Principal Findings A five-year-old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant–pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. Conclusions/Significance The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of

  3. Perpendicular Orientation of Nanodomains on Versatile Substrates through Self-Neutralization Induced by Star-Shaped Block Copolymers

    Science.gov (United States)

    Kim, Mooseong; Jang, Sangshin; Lee, Kyu Seong; Moon, Hong Chul; Kwak, Jongheon; Park, Jicheol; Jeon, Gumhye; Kim, Jin Kon

    A novel self-neutralization concept is introduced by designing molecular architecture of a block copolymer. Star-shaped 18 arm poly(methyl methacrylate)-block-polystyrene copolymers ((PMMA-b-PS)18) exhibiting lamellar and PMMA cylindrical nanodomains are synthesized. When a thin film of (PMMA-b-PS)18 is spin-coated on a substrate, vertically aligned lamellar and cylindrical nanodomains are obtained without any pre- or post-treatment, although thermal annealing for a short time (less than 30 min) is required to improve the spatial array of vertically aligned nanodomains. This result is attributed to the star-shaped molecular architecture that overcomes the difference in the surface affinity between PS and PMMA chains. Moreover, vertical orientations are observed on versatile substrates, for instance, semiconductor (Si, SiOx), metal (Au), PS or PMMA-brushed substrate, and a flexible polymer sheet of polyethylene naphthalate.

  4. Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

    Directory of Open Access Journals (Sweden)

    Kristine von Maltzan

    2016-02-01

    Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

  5. A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity

    OpenAIRE

    Goodman, Anna L.; Blagborough, Andrew M.; Sumi Biswas; Yimin Wu; Hill, Adrian V.; Sinden, Robert E.; Draper, Simon J

    2011-01-01

    The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a ...

  6. Fabrication of highly ultramicroporous carbon nanofoams by SF6-catalyzed laser-induced chemical vapor deposition

    Science.gov (United States)

    Hattori, Yoshiyuki; Shuhara, Ai; Kondo, Atsushi; Utsumi, Shigenori; Tanaka, Hideki; Ohba, Tomonori; Kanoh, Hirofumi; Takahashi, Kunimitsu; Vallejos-Burgos, Fernando; Kaneko, Katsumi

    2016-05-01

    We have developed a laser-induced chemical vapor deposition (LCVD) method for preparing nanocarbons with the aid of SF6. This method would offer advantages for the production of aggregates of nanoscale foams (nanofoams) at high rates. Pyrolysis of the as-grown nanofoams induced the high surface area (1120 m2 g-1) and significantly enhanced the adsorption of supercritical H2 (16.6 mg g-1 at 77 K and 0.1 MPa). We also showed that the pyrolized nanofoams have highly ultramicroporous structures. The pyrolized nanofoams would be superior to highly microporous nanocarbons for the adsorption of supercritical gases.

  7. Chemical leucoderma induced by ear-ring stoppers made of polyvinyl chloride

    Directory of Open Access Journals (Sweden)

    Reena Sharma

    2012-01-01

    Full Text Available We report a case of chemical leucoderma (CL in a 15-year-old girl, who developed patterned depigmentation at the back of both ear lobules after contact with plastic ear-ring stoppers made of polyvinyl chloride (PVC after continuous use for 6-7 months. Patch test with Indian standard series and cosmetic series was negative after 48 h, but she refused patch testing for extended duration as the possibility of induced depigmentation at the test site was unacceptable to her. To the best of our knowledge, this is the first report of plastic ear-ring stopper induced CL.

  8. Anti mutagenesis of chemical modulators against damage induced by reactor thermal neutrons

    International Nuclear Information System (INIS)

    The mutations are changes in the genetic information whether for spontaneous form or induced by the exposure of the genetic material to certain agents, called mutagens: chemical or physical (diverse types of radiations). As well as exist a great variety of mutagens and pro mutagens (these last are agents which transform themselves in mutagens after the metabolic activation). Also several chemical compounds exist which are called antimutagens because they reduce the mutagens effect. The C vitamin or ascorbic acid (A A) presents antimutagenic and anti carcinogenic properties. On the other hand a sodium/copper salt derived from chlorophyll belonging to the porphyrin group (C L) contains a chelated metal ion in the center of molecule. It is also an antioxidant, antimutagenic and anti carcinogenic compound, it is called chlorophyllin. The objective of this work is to establish if the A A or the C L will reduce the damages induced by thermal and fast reactor neutrons. (Author)

  9. Ion transport through chemically induced pores in protein-free phospholipid membranes.

    Science.gov (United States)

    Gurtovenko, Andrey A; Anwar, Jamshed

    2007-11-29

    We address the possibility of being able to induce the trafficking of salt ions and other solutes across cell membranes without the use of specific protein-based transporters or pumps. On the basis of realistic atomic-scale molecular dynamics simulations, we demonstrate that transmembrane ionic leakage can be initiated by chemical means, in this instance through addition of dimethyl sulfoxide (DMSO), a solvent widely used in cell biology. Our results provide compelling evidence that the small amphiphilic solute DMSO is able to induce transient defects (water pores) in membranes and to promote a subsequent diffusive pore-mediated transport of salt ions. The findings are consistent with available experimental data and offer a molecular-level explanation for the experimentally observed activities of DMSO solvent as an efficient penetration enhancer and a cryoprotectant, as well as an analgesic. Our findings suggest that transient pore formation by chemical means could emerge as an important general principle for therapeutics. PMID:17983219

  10. Chemical changes induced on a TiO2 surface by electron bombardment

    International Nuclear Information System (INIS)

    We study the TiO2 (Ti4+) chemical reduction induced by electron bombardment using Auger electron spectroscopy and factor analysis. We show that the electron irradiation of a TiO2 sample is characterized by the appearance of a lower Ti oxidation state, Ti2O3 (Ti3+), followed by a further deposition of carbon, which is present inevitably in the environment even under ultra-high vacuum conditions. The appearance of C over the surface is found to be a complex mechanism which affects the reduction process through passivation of the electron-induced oxygen desorption and formation of titanium carbide. For very high irradiation doses, we also found that the chemical changes on the surface are stopped due to the deposition of carbon in a graphitic form

  11. Chemical changes induced on a TiO{sub 2} surface by electron bombardment

    Energy Technology Data Exchange (ETDEWEB)

    Vergara, L.I. [Laboratorio de Superficies e Interfaces, Instituto de Desarrollo Tecnologico para la Industria Quimica, INTEC (CONICET-UNL), Gueemes 3450, (S3000GLN) Santa Fe (Argentina); Passeggi, M.C.G. [Laboratorio de Superficies e Interfaces, Instituto de Desarrollo Tecnologico para la Industria Quimica, INTEC (CONICET-UNL), Gueemes 3450, (S3000GLN) Santa Fe (Argentina)], E-mail: mpggih@intec.unl.edu.ar; Ferron, J. [Laboratorio de Superficies e Interfaces, Instituto de Desarrollo Tecnologico para la Industria Quimica, INTEC (CONICET-UNL), Gueemes 3450, (S3000GLN) Santa Fe (Argentina); Departamento de Materiales, Facultad de Ingenieria Quimica, Universidad Nacional del Litoral, Santiago del Estero 2829, (S3000AOM) Santa Fe (Argentina)

    2007-09-14

    We study the TiO{sub 2} (Ti{sup 4+}) chemical reduction induced by electron bombardment using Auger electron spectroscopy and factor analysis. We show that the electron irradiation of a TiO{sub 2} sample is characterized by the appearance of a lower Ti oxidation state, Ti{sub 2}O{sub 3} (Ti{sup 3+}), followed by a further deposition of carbon, which is present inevitably in the environment even under ultra-high vacuum conditions. The appearance of C over the surface is found to be a complex mechanism which affects the reduction process through passivation of the electron-induced oxygen desorption and formation of titanium carbide. For very high irradiation doses, we also found that the chemical changes on the surface are stopped due to the deposition of carbon in a graphitic form.

  12. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2.

    Science.gov (United States)

    El Ali, Zeina; Gerbeix, Cédric; Hemon, Patrice; Esser, Philipp R; Martin, Stefan F; Pallardy, Marc; Kerdine-Römer, Saadia

    2013-07-01

    Allergic contact dermatitis (ACD) is induced by low-molecular weight electrophilic chemicals and metal ions. Chemical contact sensitizers trigger reactive oxygen species production and provoke electrophilic stress, leading to the accumulation of the transcription factor nuclear-related factor 2 (Nrf2) in innate immune cell types. The objective of this work was to identify the role of Nrf2 in the regulation of ACD. We used the local lymph node assay (LLNA) and the mouse ear swelling test (MEST) to study the role of Nrf2 in both the sensitization and elicitation phase in nrf2 knockout (nrf2(-/-)) and wild-type (nrf2(+/+)) mice. Five chemicals were used: two compounds known to react with cysteine residues, 2,4-dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA); one sensitizer known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate; and one reacting specifically with lysine residues, trimellitic anhydride and croton oil, a well-known irritant. In the MEST assay, DNCB (1 and 2%) induced a significant increase in ear thickness in nrf2(-/-) compared with nrf2(+/+) mice, suggesting a role for Nrf2 in the control of the inflammatory process. When DNCB was used at 0.25 and 0.5% or when mice were treated with CinA, inflammation was found only in nrf2(-/-) mice. In the LLNA, all chemical sensitizers induced an increase of lymphocyte proliferation in nrf2(-/-) compared with nrf2(+/+) mice for the same chemical concentration. These results reveal an important role for Nrf2 in controlling ACD and lymphocyte proliferation in response to sensitizers. PMID:23564646

  13. Influence of duration of exposition in the Chernobyl zone on spontaneous and chemically induced mutagenesis

    International Nuclear Information System (INIS)

    The cycle of researches according to influence of an exposition of laboratory mice of line Af in a zone of Chernobyl disaster on spontaneous and chemically induced mutagenesis has been performed. The frequency of micronucleated erythrocytes in the mouse bone marrow was increase in term of an exposition in a zone of Chernobyl disaster with 1 till 4 months in comparison with the control. (authors)

  14. Selective light induced chemical vapour deposition of titanium dioxide thin films

    OpenAIRE

    Wagner, Estelle; Hoffmann, Patrik

    2005-01-01

    Light Induced Chemical Vapour Deposition (LICVD) of titanium dioxide thin films is studied in this work. It is shown that this technique enables to deposit locally and selectively a chosen crystalline phase with a precise controlled thickness at low substrate temperature, allowing even the use of polymer substrates. A home made LICVD reactor was set up, consisting of a main chamber in which the substrate was placed on a temperature controlled plate and could be irradiated perpendicularly thro...

  15. Selective light induced chemical vapour deposition of titanium dioxide thin films

    OpenAIRE

    Wagner, Estelle

    2003-01-01

    Light Induced Chemical Vapour Deposition (LICVD) of titanium dioxide thin films is studied in this work. It is shown that this technique enables to deposit locally and selectively a chosen crystalline phase with a precise controlled thickness at low substrate temperature, allowing even the use of polymer substrates. A home made LICVD reactor was set up, consisting of a main chamber in which the substrate was placed on a temperature controlled plate and could be irradiated perpendicularly thro...

  16. Laser induced chemical vapour deposition of TiN coatings at atmospheric pressure

    OpenAIRE

    Croonen, Y.; Verspui, G.

    1993-01-01

    Laser induced Chemical Vapour Deposition of a wide variety of materials has been studied extensively at reduced pressures. However, for this technique to be economically and industrially applicable, processes at atmospheric pressure are preferred. A model study was made on the substrate-coating system molybdenum-titaniumnitride focussing on the feasibility to deposit TiN films locally at atmospheric pressure. The results of this study turned out to be very promising. A Nd-YAG laser beam ([MAT...

  17. Improving analytical methods for protein-protein interaction through implementation of chemically inducible dimerization

    OpenAIRE

    Tonni Grube Andersen; Nintemann, Sebastian J.; Magdalena Marek; Halkier, Barbara A.; Alexander Schulz; Meike Burow

    2016-01-01

    When investigating interactions between two proteins with complementary reporter tags in yeast two-hybrid or split GFP assays, it remains troublesome to discriminate true- from false-negative results and challenging to compare the level of interaction across experiments. This leads to decreased sensitivity and renders analysis of weak or transient interactions difficult to perform. In this work, we describe the development of reporters that can be chemically induced to dimerize independently ...

  18. The understanding of the R7T7 glass blocks long term behavior: chemical and transport coupling in fractured media; Comprehension de l'alteration a long terme des colis de verre R7T7: etude du couplage chimie transport dans un milieu fissure

    Energy Technology Data Exchange (ETDEWEB)

    Chomat, L

    2008-04-15

    The long term behavior of nuclear waste glass blocks depends highly on chemical reactions which occur at the surface in contact with water. Studies carried out on inactive fractured glass blocks show that fracture networks play a significant part in reactive surface area. Nevertheless, the complexity of results interpretation, due to a weak knowledge of fracture networks and local lixiviation conditions, does not allow us to comprehend the physical and chemical mechanisms involved. Model cracks are a key step to study chemical and transport coupling in fractured media. Crack lixiviation in aggressive conditions (pH{>=}11) show that the crack's position (horizontal or vertical) determines the dominant transport mechanism (respectively diffusion or convection induced by gravity). This gravity driven flow seems to be negligible in lower pH conditions. The convective velocity is estimated by a 1D model of reactive transport. Two other parameters are studied: the influence of thermal gradient and the influence of interconnected cracks on alteration. A strong retroactive effect of convection, due to thermal gradient, on the alteration kinetic is observed inside the crack. These works lead to a complete alteration experiment of a 163 crack network subject to a thermal gradient. The use of the geochemical software, HYTEC, within the framework of this study shows the potential of the software which is however limited by the kinetics law used. (author)

  19. Shock-induced solid-state chemical reactivity studies using time-resolved radiation pyrometry

    International Nuclear Information System (INIS)

    Time-resolved radiation pyrometry has been used to study materials which undergo solid-state chemical reactions due to shock loading. Shock-induced chemical reactivity in solids is fundamentally different than that in high explosives and other energetic materials because, if no volatiles are present, the reaction products end up in the condensed, rather than the vapor, state. Bulk property changes accompanying the solid-state reactions may therefore be too small to be observable with wave profile or shock-velocity measurements. However, some solid-state reactions, such as that between metallic nickel and aluminum, are exothermic enough to give rise to a measurable increase in temperature, so pyrometry can be used to detect the reactions. Unfortunately, these measurements are complicated by the large temperature increases generated by other sources. Possible mechanisms for generation of these high temperatures, and their effect on the chemical reaction, are suggested

  20. Blood chemical changes and renal histological alterations induced by gentamicin in rats

    Science.gov (United States)

    Alarifi, Saud; Al-Doaiss, Amin; Alkahtani, Saad; Al-Farraj, S.A.; Al-Eissa, Mohammed Saad; Al-Dahmash, B.; Al-Yahya, Hamad; Mubarak, Mohammed

    2011-01-01

    Gentamicin is an effective widely used antibiotic, but the risk of nephrotoxicity and oxidative damage limit its long-term use. Hence, the current study aims to elucidate such hazardous effects. To achieve the study aim male Wistar albino rats (Rattus norvegicus) were exposed to gentamicin to investigate the resultant blood chemical changes and renal histological alterations. In comparison with control rats, gentamicin produced outstanding tubular, glomerular and interstitial alterations that included degeneration, necrosis, cytolysis and cortical tubular desquamation together with mesangial hypercellularity, endothelial cell proliferation and blood capillary congestion. Compared with control animals significant blood chemical changes (P < 0.05) including free radicals, ALT, AST, ALP, serum creatinine and serum urea were recorded in gentamicin-injected animals. The findings revealed that exposure to gentamicin can induce significant histological alterations in the kidney as well as remarkable blood chemical changes that might indicate marked renal failure. PMID:23961168

  1. Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

    International Nuclear Information System (INIS)

    Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

  2. A crowdsourcing workflow for extracting chemical-induced disease relations from free text.

    Science.gov (United States)

    Li, Tong Shu; Bravo, Àlex; Furlong, Laura I; Good, Benjamin M; Su, Andrew I

    2016-01-01

    Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available athttps://github.com/SuLab/crowd_cid_relexDatabase URL:https://github.com/SuLab/crowd_cid_relex. PMID:27087308

  3. CHEMICALS

    CERN Multimedia

    Medical Service

    2002-01-01

    It is reminded that all persons who use chemicals must inform CERN's Chemistry Service (TIS-GS-GC) and the CERN Medical Service (TIS-ME). Information concerning their toxicity or other hazards as well as the necessary individual and collective protection measures will be provided by these two services. Users must be in possession of a material safety data sheet (MSDS) for each chemical used. These can be obtained by one of several means : the manufacturer of the chemical (legally obliged to supply an MSDS for each chemical delivered) ; CERN's Chemistry Service of the General Safety Group of TIS ; for chemicals and gases available in the CERN Stores the MSDS has been made available via EDH either in pdf format or else via a link to the supplier's web site. Training courses in chemical safety are available for registration via HR-TD. CERN Medical Service : TIS-ME :73186 or service.medical@cern.ch Chemistry Service : TIS-GS-GC : 78546

  4. The role of blocking life-time measurements in the study of heavy-ion-induced fission

    International Nuclear Information System (INIS)

    The crystal-blocking technique has been used to study the time development of fission of highly excited Hg nuclei produced by bombarding a thin W crystal with 12C ions in the energy range of 80-87 MeV. Life-times are extracted by comparing the fission-blocking patterns with those for backscattering of low-energy 12C ions. The large differences are attributed to fission components with intermediate life-time (tau approximately 10-17s) and with long life-time (tau approximately >10-16s). These results have been supplemented with measurements of fission cross-sections and fission angular distributions for 12C bombardment of the four W isotopes (182, 3, 4, 6W) for the energies used in the blocking measurements. The results are analysed with the aid of statistical model calculations, which follow the spin and energy distribution of compound nuclei through the neutron evaporation cascade. The three sets of measurements supplement each other and together determine a set of model parameters, with which all the experimental data are reproduced by the calculations. The role of the life-time measurements is to provide the information on the average number of neutrons evaporated before fission, which is needed in particular for the interpretation of fission angular distributions. With barrier deformations from the liquid-drop model and rigid-body moments of inertia, cross-sections for complete fusion are obtained which agree with the semi-empirical estimates from the Bass model. (author)

  5. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  6. Failure of interpolated tests in inducing memory impairment with final modified tests: evidence unfavorable to the blocking hypothesis.

    Science.gov (United States)

    Belli, R F

    1993-01-01

    Whether interpolated recall or recognition tests will enhance the impairing influence of postevent misinformation on a final modified recognition test of original event information was examined in two experiments. Both used short retention intervals. Postevent information led to differences between control and misled conditions on interpolated tests, but no differences were found on modified tests. Arguments are presented that discredit the blocking hypothesis as a potential mechanism responsible for impairment found with postevent misinformation experiments that use short retention intervals. Instead, various rejection mechanisms are favorably assessed. PMID:8238667

  7. Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant.

    Science.gov (United States)

    Tjiurutue, Muvari Connie; Sandler, Hilary A; Kersch-Becker, Monica F; Theis, Nina; Adler, Lynn A

    2016-02-01

    Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics. PMID:26905738

  8. Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression

    Directory of Open Access Journals (Sweden)

    Braithwaite Antony W

    2011-06-01

    Full Text Available Abstract Background The aim of both classical (e.g. taxol and targeted anti-mitotic agents (e.g. Aurora kinase inhibitors is to disrupt the mitotic spindle. Such compounds are currently used in the clinic and/or are being tested in clinical trials for cancer treatment. We recently reported a new class of targeted anti-mitotic compounds that do not disrupt the mitotic spindle, but exclusively block completion of cytokinesis. This new class includes MiTMAB and OcTMAB (MiTMABs, which are potent inhibitors of the endocytic protein, dynamin. Like other anti-mitotics, MiTMABs are highly cytotoxic and possess anti-proliferative properties, which appear to be selective for cancer cells. The cellular response following cytokinesis failure and the mechanistic pathway involved is unknown. Results We show that MiTMABs induce cell death specifically following cytokinesis failure via the intrinsic apoptotic pathway. This involves cleavage of caspase-8, -9, -3 and PARP, DNA fragmentation and membrane blebbing. Apoptosis was blocked by the pan-caspase inhibitor, ZVAD, and in HeLa cells stably expressing the anti-apoptotic protein, Bcl-2. This resulted in an accumulation of polyploid cells. Caspases were not cleaved in MiTMAB-treated cells that did not enter mitosis. This is consistent with the model that apoptosis induced by MiTMABs occurs exclusively following cytokinesis failure. Cytokinesis failure induced by cytochalasin B also resulted in apoptosis, suggesting that disruption of this process is generally toxic to cells. Conclusion Collectively, these data indicate that MiTMAB-induced apoptosis is dependent on both polyploidization and specific intracellular signalling components. This suggests that dynamin and potentially other cytokinesis factors are novel targets for development of cancer therapeutics.

  9. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    Science.gov (United States)

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-01-01

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis. PMID:26393541

  10. Photo-induced isomerization and chemical reaction dynamics in superfluid helium droplets

    Science.gov (United States)

    Merritt, Jeremy; Douberly, Gary; Miller, Roger

    2008-03-01

    Near threshold photo-induced isomerization and photo-induced chemical reactions have long been sough after as sensitive probes of the underlying potential energy surface. One of the most important questions asked is how the initially bright quantum state couples to the reaction coordinate, and thus relates to energy transfer in general. Helium droplets have now allowed us to stabilize entrance channel clusters behind very small reaction barriers such that vibrational excitation may result in reaction. Through two examples, namely the isomerization of the 2 binary complexes of HF-HCN Douberly et al. PCCP 2005, 7,463, and the induced reaction of the gallium-HCN complex Merritt et al. JPCA 2007, DOI:10.1021/jp074981e we will show how the branching ratios for reaction and predissociation can determined and the influence of the superfluid He solvent.

  11. Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation

    Directory of Open Access Journals (Sweden)

    Solá Ricardo J

    2010-08-01

    Full Text Available Abstract Background Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state. Results First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH. Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution. To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa. The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size. Conclusion Water sorption leads to

  12. Multi-block analysis coupled to laser-induced breakdown spectroscopy for sorting geological materials from caves.

    Science.gov (United States)

    Ammari, Faten; Bassel, Léna; Ferrier, Catherine; Lacanette, Delphine; Chapoulie, Rémy; Bousquet, Bruno

    2016-10-01

    In this study, multi-block analysis was applied for the first time to LIBS spectra provided by a portable LIBS system (IVEA Solution, France) equipped with three compact Czerny-Turner spectrometers covering the spectral ranges 200-397nm, 398-571nm and 572-1000nm. 41 geological samples taken from a laboratory-cave situated in the "Vézère valley", an area rich with prehistoric sites and decorated caves listed as a UNESCO world heritage in the south west of France, were analyzed. They were composed of limestone and clay considered as underlying supports and of two types of alterations referred as moonmilk and coralloid. Common Components and Specific Weights Analysis (CCSWA) allowed sorting moonmilk and coralloid samples. The loadings revealed higher amounts of magnesium, silicon, aluminum and strontium in coralloids and the saliences emphasized that among the three spectrometers installed in the LIBS instrument used in this work; that covering the range 572-1000nm was less contributive. This new approach for processing LIBS data not only provides good results for sorting geological materials but also clearly reveals which spectral range contains most of the information. This specific advantage of multi-block analysis could lead for some applications to simplify the design and to reduce the size of LIBS instruments. PMID:27474310

  13. Connexin 43 remodeling induced by LMNA gene mutation Glu82Lys in familial dilated cardiomyopathy with atrial ventricular block

    Institute of Scientific and Technical Information of China (English)

    SUN Li-ping; WANG Lin; WANG Hui; ZHANG Yin-hui; PU Jie-lin

    2010-01-01

    Background Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases. Methods We studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C) using confocal imaging and Western blotting analysis.Results Cx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all.Conclusions Our findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.

  14. Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Aparna Akella

    2016-01-01

    Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema.

  15. Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission

    OpenAIRE

    Park, Hye Jin; Lee, Seungheon; Jung, Ji Wook; Lee, Young Choon; Choi, Seong-Min; Kim, Dong hyun

    2016-01-01

    Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. ...

  16. Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission.

    Science.gov (United States)

    Park, Hye Jin; Lee, Seungheon; Jung, Ji Wook; Lee, Young Choon; Choi, Seong-Min; Kim, Dong Hyun

    2016-07-01

    Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 μg/ml) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol. PMID:27257009

  17. Self-organized subwavelength ripple by nanosecond laser induced chemical vapor deposition

    International Nuclear Information System (INIS)

    Polymeric hydrogenated amorphous carbon (α-C:H) thin films were prepared by laser induced chemical vapor deposited method using a KrF excimer laser (λ = 248 nm, Ofwhm = 25 ns) with different laser intensities. Field emission scanning electron microscopy and atomic force microscopy were used to investigate the surface morphology of the films. It was found that the surface morphologies were affected by the laser intensity significantly. Self-organized subwavelength fine ripples perpendicular to the laser beam polarization with periodicities of about 200 nm were observed and a reasonable explanation was proposed for the formation of the ripples. Raman spectroscopy and Fourier transform infrared spectroscopy were used to study the structure of the α-C:H films. The results suggested that there was oxygen in the films, which came from the ambient contamination and the incomposited impurities during and after deposition. The relationships between the composition and chemical bond types were discussed in detail. - Highlights: • Polymeric α-C:H thin films prepared by laser induced CVD with the laser wavelength of 248 nm • Fine ripples with periodicities of about 200 nm observed on the surface of the films • Composition and chemical bonds studied by Raman and Fourier transform infrared spectroscopy

  18. Effect of Thermal and Chemical Treatment on the Microstructural, Mechanical and Machining Performance of W319 Al-Si-Cu Cast Alloy Engine Blocks and Directionally Solidified Machinability Test Blocks

    Science.gov (United States)

    Szablewski, Daniel

    The research presented in this work is focused on making a link between casting microstructural, mechanical and machining properties for 319 Al-Si sand cast components. In order to achieve this, a unique Machinability Test Block (MTB) is designed to simulate the Nemak V6 Al-Si engine block solidification behavior. This MTB is then utilized to cast structures with in-situ nano-alumina particle master alloy additions that are Mg based, as well as independent in-situ Mg additions, and Sr additions to the MTB. The Universal Metallurgical Simulator and Analyzer (UMSA) Technology Platform is utilized for characterization of each cast structure at different Secondary Dendrite Arm Spacing (SDAS) levels. The rapid quench method and Jominy testing is used to assess the capability of the nano-alumina master alloy to modify the microstructure at different SDAS levels. Mechanical property assessment of the MTB is done at different SDAS levels on cast structures with master alloy additions described above. Weibull and Quality Index statistical analysis tools are then utilized to assess the mechanical properties. The MTB is also used to study single pass high speed face milling and bi-metallic cutting operations where the Al-Si hypoeutectic structure is combined with hypereutectoid Al-Si liners and cast iron cylinder liners. These studies are utilized to aid the implementation of Al-Si liners into the Nemak V6 engine block and bi-metallic cutting of the head decks. Machining behavior is also quantified for the investigated microstructures, and the Silicon Modification Level (SiML) is utilized for microstructural analysis as it relates to the machining behavior.

  19. Ultrastructure of cells after reversible dark-induced blocking of mitotic divisions in antheridial filaments of Chara vulgaris L.

    Directory of Open Access Journals (Sweden)

    Maria Kwiatkowska

    2014-02-01

    Full Text Available As compared with the control plants cultured under photoperiodic L : D = =14 : 10 conditions (K w i a t k o w s k a, M a s z e w s k i, 1978, the ultrastructure of nuclei -in cells blocked by a 5 day exposure to continuous darkness is characterized by homogenous arrangement. This homogeneity is maintained in all generations of antheridial filaments irrespective of cell length, which in the controls, being directly correlated with particular type of nuclear structure, may serve as a precise indicator of a given stage of interphase. From similarities in both the spatial distribution and content of condensed chromatin in is concluded that the block of the cell cycle is imposed at the beginning of the G2 phase. On comparing these cells with the early G2 period (stage VII in the control plants, marked changes in the structure of nucleoli were found. They decrease in size by half owing to the complete decline of granular component. The area occupied by endoplasmic reticulum undergoes a 50% reduction. The decrease in the activity of Golgi apparatus expressed by a drop in number of smooth vesicles surrounding a single dictyosome is found to parallel the limited rate of cell growth. The number of coated vesicles and cisterns of dictyosome slightly increases. Mitochondria show typical condensed configuration with dense matrices and swollen cristae, while in the control orthodox forms are prevailing. The mean size of mitochondria is smaller, but their number exceeds that of the control plants. The surface area of mitochondrial profiles is found to remain constant proportion of the cytoplasm section, e.g., about 3%. Dark-cultured antheridial filaments show absolute decline of lipid droplets. No differences were found in structure of plastids and vacuols, as well as in number of ribosomes in cytoplasm surface unit.

  20. Berberine Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Apoptosis by Blocking JNK-Mediated Signaling

    Science.gov (United States)

    Guo, Junping; Wang, Lijun; Wang, Linyao; Qian, Senmi; Fang, Jie

    2016-01-01

    Endothelial dysfunction is a critical factor during the initiation of atherosclerosis. Berberine has a beneficial effect on endothelial function; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of berberine on lipopolysaccharide- (LPS-) induced apoptosis in human umbilical vein endothelial cells (HUVECs) and the molecular mechanisms mediating the effect. The effects of berberine on LPS-induced cell apoptosis and viability were measured with 5-ethynyl-2′-deoxyuridine staining, flow cytometry, and Cell Counting Kit-8 assays. The expression and/or activation of proapoptotic and antiapoptotic proteins or signaling pathways, including caspase-3, poly(ADP-ribose) polymerase, myeloid cell leukemia-1 (MCL-1), p38 mitogen-activated protein kinase, C-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase, were determined with western blotting. The malondialdehyde levels, superoxide dismutase (SOD) activity, and production of proinflammatory cytokines were measured with enzyme-linked immunosorbent assays. The results demonstrated that berberine pretreatment protected HUVECs from LPS-induced apoptosis, attenuated LPS-induced injury, inhibited LPS-induced JNK phosphorylation, increased MCL-1 expression and SOD activity, and decreased proinflammatory cytokine production. The effects of berberine on LPS-treated HUVECs were prevented by SP600125, a JNK-specific inhibitor. Thus, berberine might be a potential candidate in the treatment of endothelial cell injury-related vascular diseases. PMID:27478481

  1. Histopathological image analysis of chemical-induced hepatocellular hypertrophy in mice.

    Science.gov (United States)

    Asaoka, Yoshiji; Togashi, Yuko; Mutsuga, Mayu; Imura, Naoko; Miyoshi, Tomoya; Miyamoto, Yohei

    2016-04-01

    Chemical-induced hepatocellular hypertrophy is frequently observed in rodents, and is mostly caused by the induction of phase I and phase II drug metabolic enzymes and peroxisomal lipid metabolic enzymes. Liver weight is a sensitive and commonly used marker for detecting hepatocellular hypertrophy, but is also increased by a number of other factors. Histopathological observations subjectively detect changes such as hepatocellular hypertrophy based on the size of a hepatocyte. Therefore, quantitative microscopic observations are required to evaluate histopathological alterations objectively. In the present study, we developed a novel quantitative method for an image analysis of hepatocellular hypertrophy using liver sections stained with hematoxylin and eosin, and demonstrated its usefulness for evaluating hepatocellular hypertrophy induced by phenobarbital (a phase I and phase II enzyme inducer) and clofibrate (a peroxisomal enzyme inducer) in mice. The algorithm of this imaging analysis was designed to recognize an individual hepatocyte through a combination of pixel-based and object-based analyses. Hepatocellular nuclei and the surrounding non-hepatocellular cells were recognized by the pixel-based analysis, while the areas of the recognized hepatocellular nuclei were then expanded until they ran against their expanding neighboring hepatocytes and surrounding non-hepatocellular cells by the object-based analysis. The expanded area of each hepatocellular nucleus was regarded as the size of an individual hepatocyte. The results of this imaging analysis showed that changes in the sizes of hepatocytes corresponded with histopathological observations in phenobarbital and clofibrate-treated mice, and revealed a correlation between hepatocyte size and liver weight. In conclusion, our novel image analysis method is very useful for quantitative evaluations of chemical-induced hepatocellular hypertrophy. PMID:26776450

  2. Chemical cues from kingsnakes do not cause inducible defenses in house mice

    Institute of Scientific and Technical Information of China (English)

    W.Wallace STARKE III; Michael H.FERKIN

    2012-01-01

    Many rodents exhibit inducible defenses when exposed to chemical cues from mammalian predators.These responses may include delays in sexual maturation,smaller adult body size and decreases in litter size and pup weight.We exposed the hybrid juvenile offspring of field-caught and lab-descended house mice Mus musculus to the chemical cues of mouse-fed or chick-fed kingsnakes,Lampropeltis getula,for 20 days after weaning,to examine the effects of ophidian predator cues on prey development.We hypothesized that these cues would elicit inducible defenses such as alteration of growth rates,and/or the timing of reproductive development in mice.Once mature,the reproductive effort of the mice might also be impacted by producing smaller litter sizes or lighter pups or not reproducing at all.We found no effect of kingsnake cues on any of the measures.These findings support the hypothesis that inducible defenses may have evolved as a strategy to deal with specific predators.

  3. Ghost Block

    OpenAIRE

    Webb, Neil

    2011-01-01

    Filmed on the English south coast 'Ghost Block' depicts the uncanny and eerie atmosphere at the site of a WW2 coastal defence line. The concrete cubes were used as an anti-invasion blockade against potential landing forces. This protection line now slowly decaying and becoming enmeshed into the environment still acts as a defence to repel unwanted visitors. The area is a natural reserve to nesting birds that often lay eggs directly onto the beach surface. The blocks act as a final barrier ...

  4. Chemical ordering in magnetic FePd/Pd(001) epitaxial thin films induced by annealing

    International Nuclear Information System (INIS)

    Chemically disordered FePd epitaxial layers are grown at room temperature by molecular beam epitaxy on a Pd(001) buffer layer and then annealed in order to induce the chemically ordered L10 (AuCu I) structure. Contrary to what is observed in the case of ordering during growth above room temperature, the ordered structure appears here with the three possible variants of the L10 phase. The ratio of the three different variant volumes is set by the residual epitaxial strain in the layer before annealing. It thus explains that for long annealing times, the long-range order parameter associated with the L10 variant with c along the (100) growth direction saturates at a value close to 0.65, and never reaches unity. Magnetic consequences of the ordering are studied

  5. Chemical effects induced by low-energy particle beams in fluorozirconate glasses

    International Nuclear Information System (INIS)

    The modification of the chemical structure of fluorozirconate glasses (ZBLAN) with Ar ion and atom beams of low energy (2-10keV) has been studied in comparison with the damage produced in the starting polycrystalline ZrF4 and BaF2. A variety of reduced chemical states of Zr is produced in ZrF4 as well as in ZBLAN glasses, including metallic Zr0State. A strong enhancement of the amount of the metallic Zr formed under irradiation is observed in ZBLAN, while it is present only as trace in the irradiated pure ZrF4 samples. The reported effect is tentatively attributed to the presence of Ba ions in the glass network which could prompt the self-trapping of radiation-induced defects at the Zr sites, involving their progressive reduction

  6. Fluctuation Induced Structure in Chemical Reaction with Small Number of Molecules

    Science.gov (United States)

    Suzuki, Yasuhiro

    We investigate the behaviors of chemical reactions of the Lotka-Volterra model with small number of molecules; hence the occurrence of random fluctuations modifies the deterministic behavior and the law of mass action is replaced by a stochastic model. We model it by using Abstract Rewriting System on Multisets, ARMS; ARMS is a stochastic method of simulating chemical reactions and it is based on the reaction rate equation. We confirmed that the magnitude of fluctuations on periodicity of oscillations becomes large, as the number of involved molecules is getting smaller; and these fluctuations induce another structure, which have not observed in the reactions with large number of molecules. We show that the underling mechanism through investigating the coarse grained phase space of ARMS.

  7. An interleukin-1 receptor antagonist blocks lipopolysaccharide-induced colony-stimulating factor production and early endotoxin tolerance.

    OpenAIRE

    Henricson, B E; Neta, R; Vogel, S N

    1991-01-01

    In this report, administration of a recombinant interleukin-1 receptor antagonist protein to mice was found to inhibit induction of colony-stimulating factor as well as induction of early endotoxin tolerance by lipopolysaccharide. These findings provide direct evidence that interleukin-1 is an intermediate in these two lipopolysaccharide-induced phenomena.

  8. Depletion of STAT5 blocks TEL–SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice

    International Nuclear Information System (INIS)

    The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYKwt, TEL–SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYKwt enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK–SYK caused lethal T-cell lymphomas and the cytoplasmic TEL–SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL–SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL–SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL–SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases

  9. Block copolymer/DNA vaccination induces a strong allergen-specific local response in a mouse model of house dust mite asthma.

    Directory of Open Access Journals (Sweden)

    Camille Rolland-Debord

    Full Text Available BACKGROUND: Allergic asthma is caused by abnormal immunoreactivity against allergens such as house dust mites among which Dermatophagoides farinae (Der f is a common species. Currently, immunotherapy is based on allergen administration, which has variable effect from patient to patient and may cause serious side effects, principally the sustained risk of anaphylaxis. DNA vaccination is a promising approach by triggering a specific immune response with reduced allergenicity. OBJECTIVE: The aim of the study is to evaluate the effects of DNA immunization with Der f1 allergen specific DNA on allergic sensitization, inflammation and respiratory function in mice. METHODS: Mice were vaccinated 28 and 7 days before allergen exposure with a Der f1-encoding plasmid formulated with a block copolymer. Asthma was induced by skin sensitization followed by intra-nasal challenges with Der f extract. Total lung, broncho-alveolar lavage (BAL and spleen cells were analyzed by flow cytometry for their surface antigen and cytokine expression. Splenocytes and lung cell IFN-γ production by CD8+ cells in response to Der f CMH1-restricted peptides was assessed by ELISPOT. IgE, IgG1 and IgG2a were measured in serum by ELISA. Specific bronchial hyperresponsiveness was assessed by direct resistance measurements. RESULTS: Compared to animals vaccinated with an irrelevant plasmid, pVAX-Der f1 vaccination induced an increase of B cells in BAL, and an elevation of IL-10 and IFN-γ but also of IL-4, IL-13 and IL-17 producing CD4+ lymphocytes in lungs and of IL-4 and IL-5 in spleen. In response to CD8-restricted peptides an increase of IFN-γ was observed among lung cells. IgG2a levels non-specifically increased following block copolymer/DNA vaccination although IgE, IgG1 levels and airways resistances were not impacted. CONCLUSIONS & CLINICAL RELEVANCE: DNA vaccination using a plasmid coding for Der f1 formulated with the block copolymer 704 induces a specific immune response

  10. Epidural block

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools Español You Are Here: Home ... It numbs or causes a loss of feeling in the lower half your body. This lessens the pain of contractions during childbirth. An epidural block may also be used to ...

  11. Changes in ultraweak luminescence from living fish induced by three chemicals

    International Nuclear Information System (INIS)

    Ultraweak luminescence is a ubiquitous phenomenon in biological systems, which differs from bioluminescence of luciferin-luciferase. This low-intensity emission is inherently associated with the following important process such as oxidative metabolism, cell division, carcinogenesis, photosynthesis, and cell death. In general, ultraweak luminescence may be classified as two kinds, namely spontaneous and induced. Zebra fish is a recommended specimen for toxicity and toxicological test. The purpose of this, the changes before and after the treatment with three chemicals: uranium oxides, sodium azide or cyclophosphamide and their correlations between the dose and effect

  12. Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

    OpenAIRE

    Steven Haenen; Jeroen A.J. Vanoirbeek; Vanessa De Vooght; Liliane Schoofs; Benoit Nemery; Elke Clynen; Hoet, Peter H. M.

    2015-01-01

    Introduction and Aim The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mi...

  13. LASER-INDUCED DECOMPOSITION OF METAL CARBONYLS FOR CHEMICAL VAPOR DEPOSITION OF MICROSTRUCTURES

    OpenAIRE

    Tonneau, D.; Auvert, G.; Pauleau, Y.

    1989-01-01

    Tungsten and nickel carbonyls were used to produce metal microstructures by laser-induced chemical vapor deposition (CVD) on various substrates. The deposition rate of microstructures produced by thermodecomposition of W(CO)6 on Si substrates heated with a cw Ar+ laser beam was relatively low (10 to 30 nm/s) even at high temperatures (above 900°C). Ni microstructures were deposited on quartz substrates irradiated with a CO2 laser beam. Relatively high laser powers were needed to heat the Ni s...

  14. Nuclear magnetic resonance in pulse radiolysis. Chemically induced dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Nuclear magnetic resonance and chemically induced dynamic nuclear polarization (CIDNP) were applied to the study of pulse radiolysis. Samples were irradiated with a 3-MeV electron beam from the Argonne Van de Graaff accelerator in an EPR magnet (approximately 4000 G) which had axial holes for beam access. A fast flow system transferred the irradiated solution to the rotating 5-mm NMR sample tube. The NMR spectra of mixtures of sodium acetate and methanol were presented to demonstrate the features of the CIDNP in pulse radiolysis

  15. Shock-induced hotspot formation and chemical reaction initiation in PETN containing a spherical void

    International Nuclear Information System (INIS)

    We present results of reactive molecular dynamics simulations of hotspot formation and chemical reaction initiation in shock-induced compression of pentaerythritol tetranitrate (PETN) with the ReaxFF reactive force field. A supported shockwave is driven through a PETN crystal containing a 20 nm spherical void at a sub-threshold impact velocity of 2 km/s. Formation of a hotspot due to shock-induced void collapse is observed. During void collapse, NO2 is the dominant species ejected from the upstream void surface. Once the ejecta collide with the downstream void surface and the hotspot develops, formation of final products such as N2 and H2O is observed. The simulation provides a detailed picture of how void collapse and hotspot formation leads to initiation at sub-threshold impact velocities.

  16. Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective

    DEFF Research Database (Denmark)

    Muller, A.; Jacobsen, Helene; Healy, E.;

    2006-01-01

    such effects is then performed and correlated with the general classification criteria used for this endpoint. This review intends to give guidance when carrying out an assessment for classification for this endpoint and to allow for better transparency in the decision-making process on when to......Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure......! Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia and...

  17. Phytohemagglutinin-induced change in the distribution of acidic sugars in surface membrane of lymphoid cells and blocking of the radiation effect. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sato, C.; Kojima, K.

    1976-01-01

    Cell electrophoretic mobilities (EPM) of cultured lymphoblastoid cells were measured after removal of acidic sugars to investigate whether the localization of these acidic sugars was altered by the action of phytohaemagglutinin (PHA). After treatment with neuraminidase or hyaluronidase, the EPM of control cells decreased 50.1 and 0.3 percent, while that of PHA-treated cells decreased 25.2 and 39.0 percent, respectively. These results suggest that hyaluronic acid appeared at the periphery of the cell surface in place of some sialic acid after incubation with PHA. The change became evident after 10 min incubation with PHA and reached its maximum after 20 min at 37/sup 0/C, but no change was observed at 4/sup 0/C. The EPM decreased with time after x-irradiation, and reached a minimum value after 4 h. The addition of PHA to culture before irradiation completely blocked the x-ray mediated reduction in EPM. PHA administration after irradiation stopped further EPM reduction. These results seem to suggest a rapid rearrangement of membrane molecules linking with the receptors and acidic sugars induced by PHA, and blocking of further conformation change by x-irradiation.

  18. Phytohemagglutinin-induced change in the distribution of acidic sugars in surface membrane of lymphoid cells and blocking of the radiation effect

    International Nuclear Information System (INIS)

    Cell electrophoretic mobilities (EPM) of cultured lymphoblastoid cells were measured after removal of acidic sugars to investigate whether the localization of these acidic sugars was altered by the action of phytohaemagglutinin (PHA). After treatment with neuraminidase or hyaluronidase, the EPM of control cells decreased 50.1 and 0.3 percent, while that of PHA-treated cells decreased 25.2 and 39.0 percent, respectively. These results suggest that hyaluronic acid appeared at the periphery of the cell surface in place of some sialic acid after incubation with PHA. The change became evident after 10 min incubation with PHA and reached its maximum after 20 min at 370C, but no change was observed at 40C. The EPM decreased with time after x-irradiation, and reached a minimum value after 4 h. The addition of PHA to culture before irradiation completely blocked the x-ray mediated reduction in EPM. PHA administration after irradiation stopped further EPM reduction. These results seem to suggest a rapid rearrangement of membrane molecules linking with the receptors and acidic sugars induced by PHA, and blocking of further conformation change by x-irradiation

  19. A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.

    Science.gov (United States)

    Jones, R Mark; Chichester, Jessica A; Mett, Vadim; Jaje, Jennifer; Tottey, Stephen; Manceva, Slobodanka; Casta, Louis J; Gibbs, Sandra K; Musiychuk, Konstantin; Shamloul, Moneim; Norikane, Joey; Mett, Valentina; Streatfield, Stephen J; van de Vegte-Bolmer, Marga; Roeffen, Will; Sauerwein, Robert W; Yusibov, Vidadi

    2013-01-01

    Malaria transmission blocking vaccines (TBVs) are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs). We engineered VLPs (Pfs25-CP VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP) and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter) with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases. PMID:24260245

  20. A plant-produced Pfs25 VLP malaria vaccine candidate induces persistent transmission blocking antibodies against Plasmodium falciparum in immunized mice.

    Directory of Open Access Journals (Sweden)

    R Mark Jones

    Full Text Available Malaria transmission blocking vaccines (TBVs are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs. We engineered VLPs (Pfs25-CP VLP comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.

  1. Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents.

    Science.gov (United States)

    Dong, Jie; Yu, Xiaoqing; Porter, Dale W; Battelli, Lori A; Kashon, Michael L; Ma, Qiang

    2016-02-01

    Pulmonary fibrosis results from the excessive deposition of collagen fibers and scarring in the lungs with or without an identifiable cause. The mechanism(s) underlying lung fibrosis development is poorly understood, and effective treatment is lacking. Here we compared mouse lung fibrosis induced by pulmonary exposure to prototypical particulate (crystalline silica) or soluble chemical (bleomycin or paraquat) fibrogenic agents to identify the underlying mechanisms. Young male C57BL/6J mice were given silica (2 mg), bleomycin (0.07 mg), or paraquat (0.02 mg) by pharyngeal aspiration. All treatments induced significant inflammatory infiltration and collagen deposition, manifesting fibrotic foci in silica-exposed lungs or diffuse fibrosis in bleomycin or paraquat-exposed lungs on day 7 post-exposure, at which time the lesions reached their peaks and represented a junction of transition from an acute response to chronic fibrosis. Lung genome-wide gene expression was analyzed, and differential gene expression was confirmed by quantitative RT-PCR, immunohistochemistry, and immunoblotting for representative genes to demonstrate their induced expression and localization in fibrotic lungs. Canonical signaling pathways, gene ontology, and upstream transcription networks modified by each agent were identified. In particular, these inducers elicited marked proliferative responses; at the same time, silica preferentially activated innate immune functions and the defense against foreign bodies, whereas bleomycin and paraquat boosted responses related to cell adhesion, platelet activation, extracellular matrix remodeling, and wound healing. This study identified, for the first time, the shared and unique genes, signaling pathways, and biological functions regulated by particulate and soluble chemical fibrogenic agents during lung fibrosis, providing insights into the mechanisms underlying human lung fibrotic diseases. PMID:26345256

  2. Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents

    Science.gov (United States)

    Dong, Jie; Yu, Xiaoqing; Porter, Dale W.; Battelli, Lori A.; Kashon, Michael L.

    2016-01-01

    Pulmonary fibrosis results from the excessive deposition of collagen fibers and scarring in the lungs with or without an identifiable cause. The mechanism(s) underlying lung fibrosis development is poorly understood, and effective treatment is lacking. Here we compared mouse lung fibrosis induced by pulmonary exposure to prototypical particulate (crystalline silica) or soluble chemical (bleomycin or paraquat) fibrogenic agents to identify the underlying mechanisms. Young male C57BL/6J mice were given silica (2 mg), bleomycin (0.07 mg), or paraquat (0.02 mg) by pharyngeal aspiration. All treatments induced significant inflammatory infiltration and collagen deposition, manifesting fibrotic foci in silica-exposed lungs or diffuse fibrosis in bleomycin or paraquat-exposed lungs on day 7 post-exposure, at which time the lesions reached their peaks and represented a junction of transition from an acute response to chronic fibrosis. Lung genomewide gene expression was analyzed, and differential gene expression was confirmed by quantitative RT-PCR, immunohistochemistry, and immunoblotting for representative genes to demonstrate their induced expression and localization in fibrotic lungs. Canonical signaling pathways, gene ontology, and upstream transcription networks modified by each agent were identified. In particular, these inducers elicited marked proliferative responses; at the same time, silica preferentially activated innate immune functions and the defense against foreign bodies, whereas bleomycin and paraquat boosted responses related to cell adhesion, platelet activation, extracellular matrix remodeling, and wound healing. This study identified, for the first time, the shared and unique genes, signaling pathways, and biological functions regulated by particulate and soluble chemical fibrogenic agents during lung fibrosis, providing insights into the mechanisms underlying human lung fibrotic diseases. PMID:26345256

  3. Influence of melt processing induced orientation on the morphology and mechanical properties of poly(styrene-b-ethylene/butylene-b-styrene) block copolymers and their composites with graphite

    International Nuclear Information System (INIS)

    Highlights: • Orientation was induced during processing of SEBS, SEBS-MA and their composites. • Static and dynamic mechanical tests in perpendicular directions were performed. • 400–1600% difference in Young’s or storage modulus in function of orientation. • Micro/nanoscale morphology and orientation investigated by POM, SEM and AFM. • A method to improve the mechanical behavior by morphology control was proposed. - Abstract: The effect of orientation induced during the manufacturing process on the self-assembled morphology and mechanical properties of poly(styrene-b-ethylene/butylene-b-styrene) block copolymer (SEBS), maleated SEBS (SEBS-MA) and their composites with graphite was examined in this paper. The roll milling process induced higher stiffness along the rolling direction, emphasized by the increase of Young’s modulus with 645% in this direction relative to the perpendicular one and the increase of storage modulus at room temperature with one order of magnitude. The addition of graphite particles diminished the anisotropy of static and dynamic mechanical properties but contributed to the increase of the total energy absorbed till break. The different self-assembled morphologies and degree of order observed by polarized optical microscopy (POM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) in SEBS and SEBS-MA explained some of the differences in their static and dynamic mechanical behavior. For the first time the anisotropy was emphasized by the different glass transition values obtained on the two stretching directions

  4. Inhibition of protein synthesis or mTOR in the basolateral amygdala blocks retrieval-induced memory strengthening.

    Science.gov (United States)

    Pedroso, Thiago R; Jobim, Paulo F C; Carvalho, Leonardo M; Christoff, Raissa R; Maurmann, Natasha; Reolon, Gustavo K; Werenicz, Aline; Roesler, Rafael

    2013-11-01

    Fear memory retrieval can lead to either reconsolidation (accompanied or not by strengthening of the memory trace) or extinction. Here, we show that non-reinforced retrieval of inhibitory avoidance (IA) conditioning can induce memory strengthening assessed in a subsequent retention test trial. Infusion of the protein synthesis inhibitor cycloheximide or the mTOR inhibitor rapamycin into the rat basolateral complex of the amygdala (BLA) after a reactivation (retrieval) session impaired retrieval-induced strengthening. Intra-BLA infusion of the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) after retrieval had no effect. These findings provide the first evidence suggesting that non-reinforced IA retrieval can lead to memory strengthening through a mechanism dependent on protein synthesis and mTOR activity in the BLA. PMID:23649124

  5. Aqueous suspension of anise "Pimpinella anisum" protects rats against chemically induced gastric ulcers

    Institute of Scientific and Technical Information of China (English)

    Ibrahim A Al Mofleh; Abdulqader A Alhaider; Jaber S Mossa; Mohammed O Al-Soohaibani; Syed Rafatullah

    2007-01-01

    AIM:To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise,"Pimpinella anisum L." on experimentally-induced gastric ulceration and secretion in rats.METHODS:Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol,0.2 mol/L NaOH,25% NaCl and indomethacin.Anti-secretory studies were undertaken using pylorusligated Shay rat technique.Levels of gastric non-protein sulfhydryls(NP-SH)and wall mucus were estimated and gastric tissue was also examined histologically.Anise aqueous suspension was used in two doses(250 and 500 mg/kg body weight)in all experiments.RESULTS:Anise significantly inhibited gastric mucosal damage induced by necrotizing agents and indomethacin.The anti-ulcer effect was further confirmed histologically.In pylorus-ligated Shay rats,anise suspension significantly reduced the basal gastric acid secretion,acidity and completely inhibited the rumenal ulceration.On the other hand,the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration.CONCLUSION:Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions.The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties.

  6. Reversal by Dithiothreitol Treatment of the Block in Murine Leukemia Virus Maturation Induced by Disulfide Cross-Linking

    OpenAIRE

    Campbell, Stephen; Oshima, Masamichi; Mirro, Jane; Nagashima, Kunio; Rein, Alan

    2002-01-01

    We previously reported that if murine leukemia virus particles are produced in the presence of the mild oxidizing agent disulfide-substituted benzamide-2, they fail to undergo the normal process of virus maturation. We now show that treatment of these immature particles with a reducing agent (dithiothreitol) induces their maturation in vitro, as evidenced by proteolytic cleavage of Gag, Gag-Pol, and Env proteins and by their morphology. The identification of partial cleavage products in these...

  7. Fenofibrate, a peroxisome proliferator-activated receptor α-agonist, blocks lipopolysaccharide-induced inflammatory pathways in mouse liver

    OpenAIRE

    Won, Tae Wan

    2013-01-01

    Backgrounds/Aims During the acute phase response, cytokines induce marked alterations in lipid metabolism including an increase in serum triglyceride levels and a decrease in hepatic fatty acid oxidation, in bile acid synthesis, and in high-density lipoprotein levels. Methods Peroxisome proliferator-activated receptors (PPARs: PPARα, β/δ, and γ) regulate fatty acid metabolism, glucose homeostasis, cell proliferation, differentiation and inflammation. Proinflammatory profiles including tumor n...

  8. Heterologous desensitization of bombesin-induced mitogenesis by prolonged exposure to vasopressin: a post-receptor signal transduction block.

    OpenAIRE

    Millar, J B; Rozengurt, E

    1989-01-01

    Prolonged exposure of quiescent Swiss 3T3 cells to vasopressin prevents mitogenic stimulation on subsequent addition of bombesin. This heterologous desensitization is selective and can be mimicked by vasopressin agonists, including [Lys8]vasopressin and oxytocin but not by the V1-type-specific vasopressin receptor antagonist [Pmp1,O-Me-Tyr2,Arg8]vasopressin [where Pmp is 1-(beta-mercapto-beta,beta-cyclopenthamethylene propionic acid)]. Furthermore, vasopressin-induced loss of responsiveness t...

  9. Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

    OpenAIRE

    McGee, Halvor S; Yagita, Hideo; Shao, Zhifei; Devendra K Agrawal

    2009-01-01

    We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein–transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challen...

  10. Ginkgetin Blocks Constitutive STAT3 Activation and Induces Apoptosis through Induction of SHP-1 and PTEN Tyrosine Phosphatases.

    Science.gov (United States)

    Baek, Seung Ho; Lee, Jae Hwi; Ko, Jeong-Hyeon; Lee, Hanwool; Nam, Dongwoo; Lee, Seok Geun; Yang, Woong Mo; Um, Jae-Young; Lee, Junhee; Kim, Sung-Hoon; Shim, Bum Sang; Ahn, Kwang Seok

    2016-04-01

    Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c-Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin-induced down-modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP-1 and PTEN proteins and its mRNAs. Further, deletion of SHP-1 and PTEN genes by siRNA suppressed the induction of SHP-1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down-regulation of STAT3-regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP-1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27059688

  11. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    cultures were more sensitive to neurite outgrowth inhibitors, they also had a lower dynamic range for detecting chemical-induced neurite outgrowth inhibition and greater variability from culture-to-culture as compared to rat primary cortical cultures.

  12. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    cultures were more sensitive to neurite outgrowth inhibitors, they also had a lower dynamic range for detecting chemical-induced neurite outgrowth inhibition and greater variability from culture-to-culture as compared to rat primary cortical cultures.

  13. Using poly(3-aminophenylboronic acid) thin film with binding-induced ion flux blocking for amperometric detection of hemoglobin A1c.

    Science.gov (United States)

    Wang, Jen-Yuan; Chou, Tse-Chuan; Chen, Lin-Chi; Ho, Kuo-Chuan

    2015-01-15

    This study reports a novel enzyme-free, label-free amperometric method for direct detection of hemoglobin A1c (Hb(A1c)), a potent biomarker for diabetes diagnosis and prognosis. The method relies on an electrode modified with poly(3-aminophenylboronic acid) (PAPBA) nanoparticles (20-50 nm) and a sensing scheme named "binding-induced ion flux blocking." The PAPBA nanoparticles were characterized by FT-IR, XPS, TEM, and SEM. Being a polyaniline derivative, PAPBA showed an ion-dependent redox behavior, in which insertion or extraction of ions into or out of PABPA occurred for charge balance during the electron transfer process. The polymer allowed Hb(A1c) selectively bound to its surface via forming the cis-diol linkage between the boronic acid and sugar moieties. Voltammetric analyses showed that Hb(A1c) binding decreased the redox current of PAPBA; however, the binding did not alter the redox potentials and the apparent diffusivities of ions. This suggests that the redox current of PAPBA decreased due to an Hb(A1c) binding-induced ion flux blocking mechanism, which was then verified and characterized through an in situ electrochemical quartz crystal microbalance (EQCM) study. Assay with Hb(A1c) by differential pulse voltammetry (DPV) indicates that the peak current of a PAPBA electrode has a linear dependence on the logarithm of Hb(A1c) concentration ranging from 0.975 to 156 μM. The Hb(A1c) assay also showed high selectivity against ascorbic acid, dopamine, uric acid, glucose and bovine serum albumin. This study has demonstrated a new method for developing an electrochemical Hb(A1c) biosensor and can be extended to other label-free, indicator-free protein biosensors based on a similar redox polymer electrode. PMID:25113050

  14. Uniaxial backfill block compaction

    International Nuclear Information System (INIS)

    The main parts of the project were: to make a literature survey of the previous uniaxial compaction experiments; do uniaxial compaction tests in laboratory scale; and do industrial scale production tests. Object of the project was to sort out the different factors affecting the quality assurance chain of the backfill block uniaxial production and solve a material sticking to mould problem which appeared during manufacturing the blocks of bentonite and cruched rock mixture. The effect of mineralogical and chemical composition on the long term functionality of the backfill was excluded from the project. However, the used smectite-rich clays have been tested for mineralogical consistency. These tests were done in B and Tech OY according their SOPs. The objective of the Laboratory scale tests was to find right material- and compaction parameters for the industrial scale tests. Direct comparison between the laboratory scale tests and industrial scale tests is not possible because the mould geometry and compaction speed has a big influence for the compaction process. For this reason the selected material parameters were also affected by the previous compaction experiments. The industrial scale tests were done in summer of 2010 in southern Sweden. Blocks were done with uniaxial compaction. A 40 tons of the mixture of bentonite and crushed rock blocks and almost 50 tons of Friedland-clay blocks were compacted. (orig.)

  15. Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation.

    Science.gov (United States)

    Chakraborti, Dipankar; Rahman, Mohammad Mahmudur; Ahamed, Sad; Dutta, Rathindra Nath; Pati, Shyamapada; Mukherjee, Subhash Chandra

    2016-05-01

    The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 μg/l, respectively, with maximum concentration of 1805 μg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 μg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur. PMID:26838039

  16. The relationship between chemically-induced meiotic delay and aneuploidy in mouse oocytes and zygotes

    Energy Technology Data Exchange (ETDEWEB)

    Mailhes, J.B.; Marchetti, F. [Louisiana State Univ. Medical Center, Shreveport, LA (United States)

    1993-12-31

    Aneuploidy is a relatively common genetic disorder that results in human morbidity and mortality. Approximately 30% of embryonic and fetal deaths and 3.45 per thousand livebirths are associated with an abnormal number of chromosomes. Unfortunately, very little is known about the etiology and mechanism of chromosome missegregation. This situation dictates that considerable research be directed toward understanding the causes of aneuploidy. Although several hypotheses have been advanced for the etiology of aneuploidy, there still exists a paucity of information about the direct cuases and mechanisms of aneuploidy production. Without such specific knowledge, there is little hope of reducing the incidence of aneuploidy in humans. Some progress has been made. We now know that various chemicals can induce aneuploidy by interacting with certain cellular organelles, especially components of the spindle apparatus. These results have been demonstrated in various organisms and cell types both in vivo and in vitro. Since the ultimate objective of aneuploidy research is to obtain information that can be used to reduce the aneuploidy burden in humans, we have concentrated our research efforts on studying chemically-induced aneuploidy in mammalian germ cells and zygotes.

  17. Improving analytical methods for protein-protein interaction through implementation of chemically inducible dimerization.

    Science.gov (United States)

    Andersen, Tonni Grube; Nintemann, Sebastian J; Marek, Magdalena; Halkier, Barbara A; Schulz, Alexander; Burow, Meike

    2016-01-01

    When investigating interactions between two proteins with complementary reporter tags in yeast two-hybrid or split GFP assays, it remains troublesome to discriminate true- from false-negative results and challenging to compare the level of interaction across experiments. This leads to decreased sensitivity and renders analysis of weak or transient interactions difficult to perform. In this work, we describe the development of reporters that can be chemically induced to dimerize independently of the investigated interactions and thus alleviate these issues. We incorporated our reporters into the widely used split ubiquitin-, bimolecular fluorescence complementation (BiFC)- and Förster resonance energy transfer (FRET)- based methods and investigated different protein-protein interactions in yeast and plants. We demonstrate the functionality of this concept by the analysis of weakly interacting proteins from specialized metabolism in the model plant Arabidopsis thaliana. Our results illustrate that chemically induced dimerization can function as a built-in control for split-based systems that is easily implemented and allows for direct evaluation of functionality. PMID:27282591

  18. Pressure-induced phase and chemical transformations of lithium peroxide (Li2O2).

    Science.gov (United States)

    Dunuwille, Mihindra; Kim, Minseob; Yoo, Choong-Shik

    2016-08-28

    We present the pressure-induced phase/chemical changes of lithium peroxide (Li2O2) to 63 GPa using diamond anvil cells, confocal micro-Raman spectroscopy, and synchrotron x-ray diffraction. The Raman data show the emergence of the major vibrational peaks associated with O2 above 30 GPa, indicating the subsequent pressure-induced reversible chemical decomposition (disassociation) in dense Li2O2. The x-ray diffraction data of Li2O2, on the other hand, show no dramatic structural change but remain well within a P63/mmc structure to 63 GPa. Nevertheless, the Rietveld refinement indicates a subtle change in the structural order parameter z of the oxygen position O (13, 23, z) at around 35 GPa, which can be considered as a second-order, isostructural phase transition. The nearest oxygen-oxygen distance collapses from 1.56 Å at ambient condition to 1.48 Å at 63 GPa, resulting in a more ionic character of this layered crystal lattice, 3Li(+)+(LiO2)3 (3-). This structural change in turn advocates that Li2O2 decomposes to 2Li and O2, further augmented by the densification in specific molar volumes. PMID:27586935

  19. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor.

    Science.gov (United States)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. PMID:25582704

  20. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    International Nuclear Information System (INIS)

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  1. Steady-State Methadone Blocks Cocaine Seeking and Cocaine-Induced Gene Expression Alterations in the Rat Brain

    OpenAIRE

    Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Levy, AnneMarie; Jacklin, Derek; Kreek, Mary Jeanne

    2008-01-01

    To elucidate the effects of steady-state methadone exposure on responding to cocaine conditioned stimuli and on cocaine-induced alterations in central opioid, hypocretin/orexin, and D2 receptor systems, male Sprague-Dawley rats received intravenous infusions of 1 mg/kg/inf cocaine paired with an audiovisual stimulus over three days of conditioning. Then, mini pumps releasing vehicle or 30 mg/kg/day methadone were implanted (SC), and lever pressing for the stimulus was assessed in the absence ...

  2. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  3. Melt and Solid-State Structures of Polydisperse Polyolefin Block Copolymers

    Science.gov (United States)

    Register, Richard; Li, Sheng

    2013-03-01

    Recent developments in coordinative chain transfer polymerization have enabled the synthesis of ethylene-co-octene block copolymers, where the blocks are either crystallizable (an ethylene-co-octene random copolymer block with low octene content) or amorphous (analogous block with high octene content). With a suitable choice of catalyst type(s) and reactor train configuration, accessible chain architectures include diblock, where each block ideally has the most-probable distribution of chain lengths, and multiblock, where both the individual blocks and the number of blocks per chain follow the most-probable distribution. With a sufficiently large interblock octene differential, block copolymers of both architectures, containing roughly equal masses of the two types of block, self-assemble in the melt into well-ordered lamellar structures, despite the large polydispersity. Interblock mixing, induced by the modest Flory interaction parameter and the broad distribution of block lengths, yields an enormous domain spacing (> 100 nm) despite the relatively low average block molecular weights (< 50 kg/mol). Extensive interblock mixing also allows the polyethylene crystals to grow freely and nearly isotropically across the domain interfaces, while preserving the domain structure present in the melt; in the solid state, the optical and x-ray contrasts between dissimilar domains are greatly enhanced due to their different levels of crystallinity. (Work conducted in collaboration with Jeffrey Weinhold, Philip Hustad, and Brian Landes of Dow Chemical Core R&D.) Support from the NSF Polymers Program (DMR-1003942).

  4. Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in μ-opioid receptor knockout mice

    OpenAIRE

    Ide, Soichiro; Minami, Masabumi; Ishihara, Kumatoshi; Uhl, George R; Satoh, Masamichi; Sora, Ichiro; Ikeda, Kazutaka

    2008-01-01

    Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the μ-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice com...

  5. Extraction of chemical-induced diseases using prior knowledge and textual information.

    Science.gov (United States)

    Pons, Ewoud; Becker, Benedikt F H; Akhondi, Saber A; Afzal, Zubair; van Mulligen, Erik M; Kors, Jan A

    2016-01-01

    We describe our approach to the chemical-disease relation (CDR) task in the BioCreative V challenge. The CDR task consists of two subtasks: automatic disease-named entity recognition and normalization (DNER), and extraction of chemical-induced diseases (CIDs) from Medline abstracts. For the DNER subtask, we used our concept recognition tool Peregrine, in combination with several optimization steps. For the CID subtask, our system, which we named RELigator, was trained on a rich feature set, comprising features derived from a graph database containing prior knowledge about chemicals and diseases, and linguistic and statistical features derived from the abstracts in the CDR training corpus. We describe the systems that were developed and present evaluation results for both subtasks on the CDR test set. For DNER, our Peregrine system reached anF-score of 0.757. For CID, the system achieved anF-score of 0.526, which ranked second among 18 participating teams. Several post-challenge modifications of the systems resulted in substantially improvedF-scores (0.828 for DNER and 0.602 for CID). RELigator is available as a web service athttp://biosemantics.org/index.php/software/religator. PMID:27081155

  6. Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan Peter Boettcher

    Full Text Available Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp-producing Neisseria gonorrhoeae (P(+GC induces an immediate recruitment of caveolin-1 (Cav1 in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.

  7. Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2011-07-25

    Abstract Introduction To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO2) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. Results 4-HNE levels pre\\/post anti TNF-α therapy were inversely correlated with in vivo tpO2 (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO2 levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. Conclusions High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF

  8. Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms

    International Nuclear Information System (INIS)

    Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. The authors examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 μM Na2SeO3 (selenium) or with 7 μM α-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by and alternate complementary mechanism

  9. Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Borek, C.; Ong, A.; Mason, H.; Donahue, L.; Biaglow, J.E.

    1986-03-01

    Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. The authors examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo(a)pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 ..mu..M Na/sup 2/SeO/sup 3/ (selenium) or with 7 ..mu..M ..cap alpha..-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by and alternate complementary mechanism.

  10. Large Block Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W

    2001-12-01

    This report documents the Large-Block Test (LBT) conducted at Fran Ridge near Yucca Mountain, Nevada. The LBT was a thermal test conducted on an exposed block of middle non-lithophysal Topopah Spring tuff (Tptpmn) and was designed to assist in understanding the thermal-hydrological-mechanical-chemical (THMC) processes associated with heating and then cooling a partially saturated fractured rock mass. The LBT was unique in that it was a large (3 x 3 x 4.5 m) block with top and sides exposed. Because the block was exposed at the surface, boundary conditions on five of the six sides of the block were relatively well known and controlled, making this test both easier to model and easier to monitor. This report presents a detailed description of the test as well as analyses of the data and conclusions drawn from the test. The rock block that was tested during the LBT was exposed by excavation and removal of the surrounding rock. The block was characterized and instrumented, and the sides were sealed and insulated to inhibit moisture and heat loss. Temperature on the top of the block was also controlled. The block was heated for 13 months, during which time temperature, moisture distribution, and deformation were monitored. After the test was completed and the block cooled down, a series of boreholes were drilled, and one of the heater holes was over-cored to collect samples for post-test characterization of mineralogy and mechanical properties. Section 2 provides background on the test. Section 3 lists the test objectives and describes the block site, the site configuration, and measurements made during the test. Section 3 also presents a chronology of events associated with the LBT, characterization of the block, and the pre-heat analyses of the test. Section 4 describes the fracture network contained in the block. Section 5 describes the heating/cooling system used to control the temperature in the block and presents the thermal history of the block during the test

  11. Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice.

    Science.gov (United States)

    Karadayian, A G; Mac Laughlin, M A; Cutrera, R A

    2012-09-10

    Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as 'anti-estrogenic' effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E(2)). Mice received melatonin (25 μg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8 g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (phangover (phangover led to a better motor performance in OVX compared with intact females (phangover. PMID:22819771

  12. Characterization of chemically induced liver injuries using gene co-expression modules.

    Directory of Open Access Journals (Sweden)

    Gregory J Tawa

    Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

  13. Exposure to Gulf War Illness chemicals induces functional muscarinic receptor maladaptations in muscle nociceptors.

    Science.gov (United States)

    Cooper, B Y; Johnson, R D; Nutter, T J

    2016-05-01

    Chronic pain is a component of the multisymptom disease known as Gulf War Illness (GWI). There is evidence that pain symptoms could have been a consequence of prolonged and/or excessive exposure to anticholinesterases and other GW chemicals. We previously reported that rats exposed, for 8 weeks, to a mixture of anticholinesterases (pyridostigmine bromide, chlorpyrifos) and a Nav (voltage activated Na(+) channel) deactivation-inhibiting pyrethroid, permethrin, exhibited a behavior pattern that was consistent with a delayed myalgia. This myalgia-like behavior was accompanied by persistent changes to Kv (voltage activated K(+)) channel physiology in muscle nociceptors (Kv7, KDR). In the present study, we examined how exposure to the above agents altered the reactivity of Kv channels to a muscarinic receptor (mAChR) agonist (oxotremorine-M). Comparisons between muscle nociceptors harvested from vehicle and GW chemical-exposed rats revealed that mAChR suppression of Kv7 activity was enhanced in exposed rats. Yet in these same muscle nociceptors, a Stromatoxin-insensitive component of the KDR (voltage activated delayed rectifier K(+) channel) exhibited decreased sensitivity to activation of mAChR. We have previously shown that a unique mAChR-induced depolarization and burst discharge (MDBD) was exaggerated in muscle nociceptors of rats exposed to GW chemicals. We now provide evidence that both muscle and vascular nociceptors of naïve rats exhibit MDBD. Examination of the molecular basis of the MDBD in naïve animals revealed that while the mAChR depolarization was independent of Kv7, the action potential burst was modulated by Kv7 status. mAChR depolarizations were shown to be dependent, in part, on TRPA1. We argue that dysfunction of the MDBD could be a functional convergence point for maladapted ion channels and receptors consequent to exposure to GW chemicals. PMID:27058124

  14. Perturbing microtubule integrity blocks AMP-activated protein kinase-induced meiotic resumption in cultured mouse oocytes.

    Science.gov (United States)

    Ya, Ru; Downs, Stephen M

    2014-02-01

    The oocyte meiotic spindle is comprised of microtubules (MT) that bind chromatin and regulate both metaphase plate formation and karyokinesis during meiotic maturation; however, little information is known about their role in meiosis reinitiation. This study was conducted to determine if microtubule integrity is required for meiotic induction and to ascertain how it affects activation of AMP-activated protein kinase (AMPK), an important participant in the meiotic induction process. Treatment with microtubule-disrupting agents nocodazole and vinblastine suppressed meiotic resumption in a dose-dependent manner in both arrested cumulus cell-enclosed oocytes (CEO) stimulated with follicle-stimulating hormone (FSH) and arrested denuded oocytes (DO) stimulated with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR). This effect coincided with suppression of AMPK activation as determined by western blotting and germinal vesicle immunostaining. Treatment with the MT stabilizer paclitaxel also suppressed meiotic induction. Targeting actin filament polymerization had only a marginal effect on meiotic induction. Immunolocalization experiments revealed that active AMPK colocalized with γ-tubulin during metaphase I and II stages, while it localized at the spindle midzone during anaphase. This discrete localization pattern was dependent on MT integrity. Treatment with nocodazole led to disruption of proper spindle pole localization of active AMPK, while paclitaxel induced excessive polymerization of spindle MT and formation of ectopic asters with accentuated AMPK colocalization. Although stimulation of AMPK increased the rate of germinal vesicle breakdown (GVB), spindle formation and polar body (PB) extrusion, the kinase had no effect on peripheral movement of the spindle. These data suggest that the meiosis-inducing action and localization of AMPK are regulated by MT spindle integrity during mouse oocyte maturation. PMID:23199370

  15. Inducing an Order-Order Morphological Transition via Chemical Degradation of Amphiphilic Diblock Copolymer Nano-Objects

    OpenAIRE

    Ratcliffe, L.P.; Couchon, C.; Armes, S. P.; Paulusse, J.M.

    2016-01-01

    The disulfide-based cyclic monomer, 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MTC), is statistically copolymerized with 2-hydroxypropyl methacrylate to form a range of diblock copolymer nano-objects via reversible addition-fragmentation chain transfer (RAFT) polymerization. Poly(glycerol monomethacrylate) (PGMA) is employed as the hydrophilic stabilizer block in this aqueous polymerization-induced self-assembly (PISA) formulation, which affords pure spheres, worms or ...

  16. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    International Nuclear Information System (INIS)

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury

  17. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Jeong, Jae-Hoon [Division of Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kang, Seongman [Division of Life Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Lim, Young-Bin, E-mail: yblim@kirams.re.kr [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-07-25

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  18. Antagonism of NMDA receptors but not AMPA/kainate receptors blocks bursting in dopaminergic neurons induced by electrical stimulation of the prefrontal cortex.

    Science.gov (United States)

    Tong, Z Y; Overton, P G; Clark, D

    1996-01-01

    Evidence suggests that the prefrontal cortex (PFC) plays an important role in the burst activity of midbrain dopaminergic (DA) neurons. In particular, electrical stimulation of the PFC elicits patterns of activity in DA neurons, closely time-locked to the stimulation, which resemble natural bursts. Given that natural bursts are produced by the activity of excitatory amino acid (EAA)-ergic afferents, if PFC-induced time-locked bursts are homologues of natural bursts, EAA antagonists should attenuate them. Hence, the NMDA (N-methyl-D-aspartate) antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) and the AMPA (D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid)/kainate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were applied by iontophoresis to DA neurons exhibiting time-locked bursts during PFC stimulation. CPP produced a significant reduction in time-locked bursting. In contrast, CNQX (at currents which antagonised AMPA responses) did not. These effects of CPP and CNQX on time-locked bursting mirror the effects previously reported for these drugs on natural bursting. Since natural bursting and bursting induced by PFC stimulation are both blocked selectively by CPP, the present results increase the degree of analogy between the two burst phenomena, thereby adding extra support to the contention that the cortex is involved in producing the natural bursting in DA neurons. PMID:9013383

  19. Nitric Oxide Blocks Blue Light-Induced K+ Influx by Elevating the Cytosolic Ca2+ Concentration in Vicia faba L.Guard Cells

    Institute of Scientific and Technical Information of China (English)

    Xiang Zhao; Yuan-Yuan Li; Hui-Li Xiao; Chang-Shui Xu; Xiao Zhang

    2013-01-01

    Ca2+ plays a pivotal role in nitric oxide (NO)-promoted stomatal closure.However,the function of Ca2+ in NO inhibition of blue light (BL)-induced stomatal opening remains largely unknown.Here,we analyzed the role of Ca2+ in the crosstalk between BL and NO signaling in Vicia faba L.guard cells.Extracellular Ca2+ modulated the BL-induced stomatal opening in a dose-dependent manner,and an application of 5 μM Ca2+ in the pipette solution significantly inhibited BL-activated K+ influx.Sodium nitroprusside (SNP),a NO donor,showed little effect on BL-induced K+ influx and stomatal opening response in the absence of extracellular Ca2+,but K+ influx and stomatal opening were inhibited by SNP when Ca2+ was added to the bath solution.Interestingly,although both SNP and BL could activate the plasma membrane Ca2+ channels and induce the rise of cytosolic Ca2+,the change in levels of Ca2+ channel activity and cytosolic Ca2+ concentration were different between SNP and BL treatments.SNP at 100 μM obviously activated the plasma membrane Ca2+ channels and induced cytosolic Ca2+ rise by 102.4%.In contrast,a BL pulse (100 μmol/m2 per s for 30 s) slightly activated the Ca2+ channels and resulted in a Ca2+ rise of only 20.8%.Consistently,cytosolic Ca2+ promoted K+ influx at 0.5 μM or below,and significantly inhibited K+ influx at 5 μM or above.Taken together,our findings indicate that Ca2+ plays dual and distinctive roles in the crosstalk between BL and NO signaling in guard cells,mediating both the BL-induced K+ influx as an activator at a lower concentration and the NO-blocked K+ influx as an inhibitor at a higher concentration.

  20. Effects of chemically induced contraction of a coordination polyhedron on the dynamical magnetism of bis(phthalocyaninato)disprosium, a single-4f-ionic single-molecule magnet with a Kramers ground state.

    Science.gov (United States)

    Ishikawa, Naoto; Mizuno, Yoshifumi; Takamatsu, Satoshi; Ishikawa, Tadahiko; Koshihara, Shin-ya

    2008-11-17

    Chemically induced longitudinal contraction of the square-antiprism coordination polyhedron of a peripherically substituted bis(phthalocyaninato)dysprosiumate(III), a dysprosium-based single-4f-ionic single-molecule magnet having a J z = +/- (13)/ 2 Kramers doublet ground state, resulted in drastic changes in dynamical magnetism including a doubling of the energy barrier, a 2-order-of-magnitude decrease of the spin reversal rate, a significant rise of the blocking temperature, and the first observation of the emergence of a large remanent magnetization. PMID:18855382

  1. Influence of substrate interaction and confinement on electric-field-induced transition in symmetric block-copolymer thin films

    Science.gov (United States)

    Mukherjee, Arnab; Mukherjee, Rajdip; Ankit, Kumar; Bhattacharya, Avisor; Nestler, Britta

    2016-03-01

    In the present work, we study morphologies arising due to competing substrate interaction, electric field, and confinement effects on a symmetric diblock copolymer. We employ a coarse-grained nonlocal Cahn-Hilliard phenomenological model taking into account the appropriate contributions of substrate interaction and electrostatic field. The proposed model couples the Ohta-Kawasaki functional with Maxwell equation of electrostatics, thus alleviating the need for any approximate solution used in previous studies. We calculate the phase diagram in electric-field-substrate strength space for different film thicknesses. In addition to identifying the presence of parallel, perpendicular, and mixed lamellae phases similar to analytical calculations, we also find a region in the phase diagram where hybrid morphologies (combination of two phases) coexist. These hybrid morphologies arise either solely due to substrate affinity and confinement or are induced due to the applied electric field. The dependence of the critical fields for transition between the various phases on substrate strength, film thickness, and dielectric contrast is discussed. Some preliminary 3D results are also presented to corroborate the presence of hybrid morphologies.

  2. Critical role of surface chemical modifications induced by length shortening on multi-walled carbon nanotubes-induced toxicity

    Directory of Open Access Journals (Sweden)

    Bussy Cyrill

    2012-11-01

    Full Text Available Abstract Given the increasing use of carbon nanotubes (CNT in composite materials and their possible expansion to new areas such as nanomedicine which will both lead to higher human exposure, a better understanding of their potential to cause adverse effects on human health is needed. Like other nanomaterials, the biological reactivity and toxicity of CNT were shown to depend on various physicochemical characteristics, and length has been suggested to play a critical role. We therefore designed a comprehensive study that aimed at comparing the effects on murine macrophages of two samples of multi-walled CNT (MWCNT specifically synthesized following a similar production process (aerosol-assisted CVD, and used a soft ultrasonic treatment in water to modify the length of one of them. We showed that modification of the length of MWCNT leads, unavoidably, to accompanying structural (i.e. defects and chemical (i.e. oxidation modifications that affect both surface and residual catalyst iron nanoparticle content of CNT. The biological response of murine macrophages to the two different MWCNT samples was evaluated in terms of cell viability, pro-inflammatory cytokines secretion and oxidative stress. We showed that structural defects and oxidation both induced by the length reduction process are at least as responsible as the length reduction itself for the enhanced pro-inflammatory and pro-oxidative response observed with short (oxidized compared to long (pristine MWCNT. In conclusion, our results stress that surface properties should be considered, alongside the length, as essential parameters in CNT-induced inflammation, especially when dealing with a safe design of CNT, for application in nanomedicine for example.

  3. Populations having different GalA blocks characteristics are present in commercial pectins which are chemically similar but have different functionalities

    NARCIS (Netherlands)

    Guillotin, S.E.; Bakx, E.J.; Boulenguer, P.; Mazoyer, J.; Schols, H.A.; Voragen, A.G.J.

    2005-01-01

    Two commercially extracted pectins having different physical properties but similar chemical characteristics were fractionated into sub-populations using ion exchange chromatography. Individual sub-populations were characterised using established strategies (galacturonic acid and neutral sugar conte

  4. Blocked strainers

    International Nuclear Information System (INIS)

    Thermal insulation was the cause of the blockages that shut down five BWRs in Sweden. The main culprit was mineral wool installed when the plants started up. Physical degradation of the wool over the lifetime of the plant meant it could easily be washed out of place during a loss of coolant accident and could quickly block strainers in the emergency core cooling systems. The five BWRs are almost all back on line, equipped with larger strainers and faster backwashing capability. But the incident prompted more detailed investigation into how materials in the containment would behave during an accident. One material that caused particular concern is Caposil, a material often used to insulate the reactor vessel. Composed of natural calcium, aluminium silicates and cellulose fibres, in the event of a LOCA Caposil becomes particularly hazardous. Under high pressure, or when brought into contact with high pressure water and steam, Caposil fragments into 1 cm clumps, free fibres, and ''fines''. It is these fines which cause major problems and can block a strainer extremely quickly. The successful testing of a high performance water filter which can handle Caposil is described. (4 figures) (Author)

  5. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

    International Nuclear Information System (INIS)

    Accumulating evidence indicates that elevated levels of prostaglandin E2 (PGE2) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE2 exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE2-induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer

  6. Lead (Pb+2) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity

    International Nuclear Information System (INIS)

    The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca2+) and cyclic adenosine monophosphate as second messengers. In particular, Ca+2/phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb+2) has been associated to its interference with normal Ca+2 signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na+ or Pb+2 acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb+2 did not affect learning of the task, but significantly impaired retention. The effects of Pb+2 selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb+2 on the induction of hippocampal Ca+2/phospholipid-dependent PKC activity during acquisition training. The results showed that Pb+2 interfered with the learning-induced activation of Ca+2/phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb+2 causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca+2-related signaling mechanisms required for normal LTM

  7. Pressure-Induced Changes in Inter-Diffusivity and Compressive Stress in Chemically Strengthened Glass

    DEFF Research Database (Denmark)

    Svenson, Mouritz Nolsøe; Thirion, Lynn M.; Youngman, Randall E.;

    Glass exhibits a significant change in microstructure and properties when subjected to high pressure, since the short- and intermediate-range structures of a glass are tunable through compression. Understanding the link between the microscopic structure and macroscopic properties of glasses under...... high pressure is important, since the glass structures frozen-in under elevated pressure may give rise to properties unattainable under ambient pressure. Chemical strengthening of glass through K+-for-Na+ ion exchange is currently receiving significant interest due to the increasing demand for stronger...... and more damage resistant glasses. However, the interplay among isostatic compression, pressure-induced changes in alkali diffusivity, compressive stress generated through ion exchange, and the resulting mechanical properties are poorly understood. In this work, we employ a specially designed gas...

  8. High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation

    Science.gov (United States)

    Sim, Kyoseung; Chen, Song; Li, Yuhang; Kammoun, Mejdi; Peng, Yun; Xu, Minwei; Gao, Yang; Song, Jizhou; Zhang, Yingchun; Ardebili, Haleh; Yu, Cunjiang

    2015-11-01

    Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated.

  9. Molecular Dynamics Study of Thermally Augmented Nanodroplet Motion on Chemical Energy Induced Wettability Gradient Surfaces.

    Science.gov (United States)

    Chakraborty, Monojit; Chowdhury, Anamika; Bhusan, Richa; DasGupta, Sunando

    2015-10-20

    Droplet motion on a surface with chemical energy induced wettability gradient has been simulated using molecular dynamics (MD) simulation to highlight the underlying physics of molecular movement near the solid-liquid interface including the contact line friction. The simulations mimic experiments in a comprehensive manner wherein microsized droplets are propelled by the surface wettability gradient against forces opposed to motion. The liquid-wall Lennard-Jones interaction parameter and the substrate temperature are varied to explore their effects on the three-phase contact line friction coefficient. The contact line friction is observed to be a strong function of temperature at atomistic scales, confirming their experimentally observed inverse functionality. Additionally, the MD simulation results are successfully compared with those from an analytical model for self-propelled droplet motion on gradient surfaces. PMID:26381847

  10. Chemical modifications induced in bisphenol A polycarbonate by swift heavy ions

    International Nuclear Information System (INIS)

    The chemical modifications in bisphenol A polycarbonate induced by swift heavy ion irradiation are analyzed in situ by means of Fourier transform infrared (FTIR) spectroscopy. Four beams (13C, 20Ne, 48Ca, 129Xe) with energy of a few MeV/amu have been used. Irradiations were performed under vacuum with electronic stopping power in the range from 1.6 to 86 MeV mg-1 cm2. Deposited doses are less than or equal to 1 MGy. The FTIR spectra obtained after the irradiation exhibit an overall reduction of the intensities of the virgin PC typical vibration bands and the appearance of new bands. The analysis of the destruction and the new vibration bands points out that the energy deposition mechanisms are quite different depending on electronic stopping power

  11. In situ chemical imaging of lithiated tungsten using laser-induced breakdown spectroscopy

    Science.gov (United States)

    Li, Cong; Wu, Xingwei; Zhang, Chenfei; Ding, Hongbin; Hu, Jiansheng; Luo, Guang-Nan

    2014-09-01

    Lithium conditioning can significantly improve the plasma confinement of EAST tokamak by reducing the amount of hydrogen and impurities recycled from the wall, but the details of this mechanism and approaches that reduce the concentrations of hydrogen and impurities recycle still remain unclear. In this paper, we studied lithiated tungsten via a cascaded-arc plasma simulator. An in situ laser-induced breakdown spectroscopy (LIBS) diagnostic system has been developed to chemically image the three-dimensional distribution of lithium and impurities on the surface of lithiated tungsten co-deposition layer for the first time. The results indicate that lithium has a strong ability to draw hydrogen and oxygen. The impurity components from the co-deposition processes present more intensity on the surface of co-deposition layer. This work improves the understanding of lithiated tungsten mechanism and is useful for using LIBS as a wall-diagnostic technique for EAST.

  12. In situ chemical imaging of lithiated tungsten using laser-induced breakdown spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Cong; Wu, Xingwei; Zhang, Chenfei [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams, Chinese Ministry of Education, School of Physics and Optical Electronic Technology, Dalian University of Technology, Dalian 116024 (China); Ding, Hongbin, E-mail: hding@dlut.edu.cn [Key Laboratory of Materials Modification by Laser, Ion and Electron Beams, Chinese Ministry of Education, School of Physics and Optical Electronic Technology, Dalian University of Technology, Dalian 116024 (China); Hu, Jiansheng; Luo, Guang-Nan [Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031 (China)

    2014-09-15

    Lithium conditioning can significantly improve the plasma confinement of EAST tokamak by reducing the amount of hydrogen and impurities recycled from the wall, but the details of this mechanism and approaches that reduce the concentrations of hydrogen and impurities recycle still remain unclear. In this paper, we studied lithiated tungsten via a cascaded-arc plasma simulator. An in situ laser-induced breakdown spectroscopy (LIBS) diagnostic system has been developed to chemically image the three-dimensional distribution of lithium and impurities on the surface of lithiated tungsten co-deposition layer for the first time. The results indicate that lithium has a strong ability to draw hydrogen and oxygen. The impurity components from the co-deposition processes present more intensity on the surface of co-deposition layer. This work improves the understanding of lithiated tungsten mechanism and is useful for using LIBS as a wall-diagnostic technique for EAST.

  13. Al-Induced Crystallization Growth of Si Films by Inductively Coupled Plasma Chemical Vapour Deposition

    Institute of Scientific and Technical Information of China (English)

    LI Jun-Shuai; WANG Jin-Xiao; YIN Min; GAO Ping-Qi; HE De-Yan

    2006-01-01

    Polycrystalline Si (poly-Si) films are in situ grown on Al-coated glass substrates by inductively coupled plasma chemical vapour deposition at a temperature as low as 350 C. Compared to the traditional annealing crystallization of amorphous Si/Al-layer structures, no layer exchange is observed and the resultant poly-Si film is much thicker than Al layer. By analysing the depth profiles of the elemental composition, no remains of Al atoms are detected in Si layer within the limit (< 0.01 at. %) of the used evaluations. It is indicated that the poly-Si material obtained by Al-induced crystallization growth has more potential applications than that prepared by annealing the amorphous Si/Al-layer structures.

  14. Isolation, chemical and functional characterization of several new K(+)-channel blocking peptides from the venom of the scorpion Centruroides tecomanus.

    Science.gov (United States)

    Olamendi-Portugal, Timoteo; Bartok, Adam; Zamudio-Zuñiga, Fernando; Balajthy, Andras; Becerril, Baltazar; Panyi, Gyorgy; Possani, Lourival D

    2016-06-01

    Six new peptides were isolated from the venom of the Mexican scorpion Centruroides tecomanus; their primary structures were determined and the effects on ion channels were verified by patch-clamp experiments. Four are K(+)-channel blockers of the α-KTx family, containing 32 to 39 amino acid residues, cross-linked by three disulfide bonds. They all block Kv1.2 in nanomolar concentrations and show various degree of selectivity over Kv1.1, Kv1.3, Shaker and KCa3.1 channels. One peptide has 42 amino acids cross-linked by four disulfides; it blocks ERG-channels and belongs to the γ-KTx family. The sixth peptide has only 32 amino acid residues, three disulfide bonds and has no effect on the ion-channels assayed. It also does not have antimicrobial activity. Systematic numbers were assigned (time of elution on HPLC): α-KTx 10.4 (time 24.1); α-KTx 2.15 (time 26.2); α-KTx 2.16 (time 23.8); α-KTx 2.17 (time 26.7) and γ-KTx 1.9 (elution time 29.6). A partial proteomic analysis of the short chain basic peptides of this venom, which elutes on carboxy-methyl-cellulose column fractionation, is included. The pharmacological properties of the peptides described in this study may provide valuable tools for understanding the structure-function relationship of K(+) channel blocking scorpion toxins. PMID:26921461

  15. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  16. Choice of mouse strain influences the outcome in a mouse model of chemical-induced asthma.

    Directory of Open Access Journals (Sweden)

    Vanessa De Vooght

    Full Text Available BACKGROUND: The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains. METHODOLOGY/PRINCIPAL FINDINGS: On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR were dermally treated with toluene-2,4-diisocyanate (TDI (0.3% or vehicle (acetone/olive oil, AOO, 2:3 on each ear (20 microl. On day 15, they received an oropharyngeal instillation of TDI (0.01% or AOO (1:4. Airway reactivity to methacholine, total and differential cell counts in bronchoalveolar lavage (BAL and total serum IgE and IgG(2a levels were measured. Lymphocyte subpopulations in auricular lymph nodes and in vitro release of cytokines by ConA stimulated lymphocytes were assessed. In TDI-sensitized and challenged mice, airway hyper-reactivity was only observed in BALB/c, BP/2, A/J and AKR mice; airway inflammation was most pronounced in BALB/c mice; numbers of T-helper (CD4(+, T-activated (CD4(+CD25(+, T-cytotoxic (CD8(+ and B- lymphocytes (CD19(+ were increased in the auricular lymph nodes of BALB/c, BP/2, A/J and CBA mice; elevated concentrations of IL-4, IL-10, IL-13 and IFN-gamma were detected in supernatant of lymphocytes from BALB/c, BP/2, A/J, C57Bl/6 and CBA mice cultured with concanavaline A, along with an increase in total serum IgE. CONCLUSION: The used mouse strain has considerable and variable impacts on different aspects of the asthma phenotype. The human phenotypical characteristics of chemically-induced occupational asthma were best reproduced in Th2-biased mice and in particular in BALB/c mice.

  17. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    Directory of Open Access Journals (Sweden)

    Thiago C Genaro-Mattos

    Full Text Available Caffeic acid (CA is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its

  18. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  19. Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

    Directory of Open Access Journals (Sweden)

    Lucie Mondoulet

    Full Text Available BACKGROUND: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes. METHODS: Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. RESULTS: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa. CONCLUSIONS: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

  20. Chemical and explosive detection with long-wave infrared laser induced breakdown spectroscopy

    Science.gov (United States)

    Jin, Feng; Trivedi, Sudhir B.; Yang, Clayton S.; Brown, Ei E.; Kumi-Barimah, Eric; Hommerich, Uwe H.; Samuels, Alan C.

    2016-05-01

    Conventional laser induced breakdown spectroscopy (LIBS) mostly uses silicon-based detectors and measures the atomic emission in the UV-Vis-NIR (UVN) region of the spectrum. It can be used to detect the elements in the sample under test, such as the presence of lead in the solder for electronics during RoHS compliance verification. This wavelength region, however, does not provide sufficient information on the bonding between the elements, because the molecular vibration modes emit at longer wavelength region. Measuring long-wave infrared spectrum (LWIR) in a LIBS setup can instead reveal molecular composition of the sample, which is the information sought in applications including chemical and explosive detection and identification. This paper will present the work and results from the collaboration of several institutions to develop the methods of LWIR LIBS for chemical/explosive/pharmaceutical material detection/identification, such as DMMP and RDX, as fast as using a single excitation laser pulse. In our latest LIBS setup, both UVN and LWIR spectra can be collected at the same time, allowing more accurate detection and identification of materials.

  1. Secondary Metabolome Variability and Inducible Chemical Defenses in the Mediterranean Sponge Aplysina cavernicola.

    Science.gov (United States)

    Reverter, M; Perez, T; Ereskovsky, A V; Banaigs, B

    2016-01-01

    Secondary metabolites play a crucial role in marine invertebrate chemical ecology. Thus, it is of great importance to understand factors regulating their production and sources of variability. This work aimed to study the variability of the bromotyrosine derivatives in the Mediterranean sponge Aplysina cavernicola, and also to better understand how biotic (reproductive state) and abiotic factors (seawater temperature) could partly explain this variability. Results showed that the A. cavernicola reproductive cycle has little effect on the variability of the sponges' secondary metabolism, whereas water temperature has a significant influence on the production level of secondary metabolites. Temporal variability analysis of the sponge methanolic extracts showed that bioactivity variability was related to the presence of the minor secondary metabolite dienone, which accounted for 50 % of the bioactivity observed. Further bioassays coupled to HPLC extract fractionation confirmed that dienone was the only compound from Aplysina alkaloids to display a strong bioactivity. Both dienone production and bioactivity showed a notable increase in October 2008, after a late-summer warming episode, indicating that A. cavernicola might be able to induce chemical changes to cope with environmental stressors. PMID:26757731

  2. Influence of physical, chemical and inducer treatments on menaquinone-7 biosynthesis by Bacillus subtilis MTCC 2756

    Directory of Open Access Journals (Sweden)

    Alka Puri

    2015-06-01

    Full Text Available Effects of physical and chemical treatment on nutrient mobility, their utilization for menaquinone-7 (MK-7 biosynthesis; growth of microbial cells has been investigated in the present research. Bacillus subtilis MTCC 2756 fermented medium was supplied with 1-naphthol and hypoxanthine resulted in a significant increase in MK-7 production. Ultrasonication, electric shock, heat shock, and tween 80 were used for inducer uptake by Bacillus subtilis and menaquinone-7 production. Induction of Bacillus subtilis (at 16 hours of fermentation using 1-naphthol (2 mg/ml, along with tween 80 (0.1% was found to increase the MK-7 production by 3 fold i.e. 14.4 µg/ml as compared to the untreated fermentation medium. The ultrasonicated (ultrasonic power 33 W, treatment time 4 min and frequency 36 KHz microbial cells yielded higher biomass and 2.5 fold increase in the MK-7 production i.e.10.3 µg/ml than control. 1-naphthol along with physical or chemical treatment is required for maximum MK-7 production by Bacillus subtilis.

  3. Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple Contaminated Aquatic Systems.

    Science.gov (United States)

    Rotter, Stefanie; Gunold, Roman; Mothes, Sibylle; Paschke, Albrecht; Brack, Werner; Altenburger, Rolf; Schmitt-Jansen, Mechthild

    2015-08-18

    Aquatic ecosystems are often contaminated with large numbers of chemicals, which cannot be sufficiently addressed by chemical target analyses. Effect-directed analysis (EDA) enables the identification of toxicants in complex contaminated environmental samples. This study suggests pollution-induced community tolerance (PICT) as a confirmation tool for EDA to identify contaminants which actually impact on local communities. The effects of three phytotoxic compounds local periphyton communities, cultivated at a reference (R-site) and a polluted site (P-site), were assessed to confirm the findings of a former EDA study on sediments. The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N-phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and exposure concentrations were determined. Prometryn and PNA concentrations were significantly higher at the P-site, whereas TBT concentrations were in the same range at both sites. Periphyton communities differed in biomass, but algal class composition and diatom diversity were similar. Community tolerance of P-communities was significantly enhanced for prometryn, but not for PNA and TBT, confirming site-specific effects on local periphyton for prometryn only. Thus, PICT enables in situ effect confirmation of phytotoxic compounds at the community level and seems to be suitable to support confirmation and enhance ecological realism of EDA. PMID:26196040

  4. ATP-sensitive K/sup +/ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone

    Energy Technology Data Exchange (ETDEWEB)

    de Weille, J.; Schmid-Antomarchi, H.; Fosset, M.; Lazdunski, M.

    1988-02-01

    The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide names from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and /sup 86/Rb/sup +/ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of APT-sensitive K/sup +/ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamine. Glibenclamide blocks the galanin-activated ATP-sensitive K/sup +/ channel. /sup 86/Rb/sup +/ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced /sup 86/Rb/sup +/ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K/sup +/ channel reported earlier. /sup 86/Rb/sup +/ efflux studies confirm the electrophysiological demonstration that galanin activates and ATP-dependent K/sup +/ channel.

  5. Chemical modification of polycarbonate induced by 1.4 GeV Ar ions

    International Nuclear Information System (INIS)

    Polycarbonate foil stacks were irradiated with 1.4 GeV Ar ions at room temperature. The induced modifications in chemical structure were studied by Fourier transform infrared (FTIR) and ultraviolet/visible absorption (UV/VIS) spectroscopies. FTIR measurements reveal that material degradation through bond breaking are the main effects. Significant reduction in absorbance of the typical infrared bands is observed at energy densities higher than 8x1022 eV/cm3. Alkyne end groups are produced by the irradiations and the electronic energy loss threshold for production of the alkyne end group is found to be below 0.61 keV/nm. UV/VIS measurements indicate a shifting of the absorption edge from ultraviolet towards visible and a strong increase of absorbance in the ultraviolet and visible regions. The irradiation induced changes in absorbance at wavelengths of 380, 450 and 500 nm follow roughly linear relationship with fluence and scale rather good with the square of electronic energy loss. The results are briefly discussed

  6. Modulatory influence of Phyllanthus niruri on oxidative stress, antioxidant defense and chemically induced skin tumors.

    Science.gov (United States)

    Sharma, Priyanka; Parmar, Jyoti; Verma, Preeti; Goyal, Pradeep Kumar

    2011-01-01

    The present study evaluates the modulatory potential of Phyllanthus niruri on chemically induced skin carcinogenesis, and its influence on oxidative stress and the antioxidant defense system. Oral administration of P. niruri extract (PNE), during peri- (Gr. III), post- (Gr. IV), or peri- and post- (Gr. V) initiational stages of 7,12-dimethylbenz(a) anthracene (DMBA)-croton oil–induced papillomagenesis considerably reduced tumor burden to 4.20, 4.00, and 3.33(positive control value 6.20); cumulative number of papillomas to 21, 16, and 10, respectively, (positive control value 62); and incidence of mice bearing papillomas to 50, 40, and 30%, respectively (positive control value 100%), but significantly increased the average latent period to 10.14, 10.62, and 11.60, and inhibition of tumor multiplicity to 66, 74,and 83%, respectively. Enzyme analysis of skin and liver showed a significant (p ≤ 0.05, ≤ 0.01, ≤ 0.001) elevation in antioxidant parameters such as superoxide dismutase, catalase, glutathione, and vitamin C in PNE-treated groups (Gr. III–V) when compared with the carcinogen-treated control (Gr. II). The elevated level of lipid peroxidation in the carcinogen-treated positive control group was significantly (p ≤ 0.05, ≤ 0.01, ≤ 0.001) inhibited by PNE administration. These results indicate that P. niruri extract has potentiality to reduce skin papillomas by enhancing antioxidant defense system. PMID:21609315

  7. Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g. dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD.

  8. Identification of Differently Expressed Genes in Chemical Carcinogen-induced Rat Bladder Cancers

    Institute of Scientific and Technical Information of China (English)

    Guangfu CHEN; Franky L. CHAN; Xu ZHANG; Peter S.F. CHAN

    2009-01-01

    Possible altered gene expression patterns in bladder turnout carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles.Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28-weeks.Equal numbers of control rats were given tap water without BBN.After treatment,the rat bladders were excised for RNA extraction and histopathological examinations.Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia.The atlas glass rat microarray was used,which included oligonucleotides of 1081 rat genes.Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting.Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs,and these included fly proto-oncogene,Lipocortin 2,COX Ⅳ,COX Ⅴ a,and cathepsin D.Also,15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1,TNFrl,APOAI and VHL.The resuits of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles.The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.

  9. Ion-beam-induced epitaxial crystallization of implanted and chemical vapor deposited amorphous silicon

    Science.gov (United States)

    La Ferla, A.; Priolo, F.; Spinella, C.; Rimini, E.; Baroetto, F.; Ferla, G.

    1989-03-01

    The dependence of ion-beam enhanced epitaxial growth of amorphous Si layers on impurities either dissolved in the film or present at the film-substrate interface is considered. In the case of ion implanted layers, electrically active dopants, like B, P, As at concentrations above 1 × 10 20/cm 3, enhance the rate by a factor of 2 with respect to the undoped layer. The enhancement shows also a weak dependence on the dopant concentration. Inert impurities, like Ar, which prevent pure thermal regrowth, do not show any appreciable influence on the ion-beam-induced growth rate. Chemical vapor deposited Si layers with a thin native interfacial oxide layer can also be epitaxially regrown under ion irradiation. A critical fluence is needed before the interfacial oxide breaks down and broadens, allowing the epitaxial crystallization to take place. This process is characterized by an activation energy of 0.44 eV. The complex phenomenon of ion-beam-induced crystallization involves a dynamical interaction between production and annealing of point defects. The presence of electrically active dopants probably influences the lifetime of point defects. Impurities which prevent thermal regrowth are instead dissolved by ballistic effects and/or radiation-enhanced mixing.

  10. Combination of high performance refractometry and infrared spectroscopy as a probe for chemically induced gelation and vitrification of epoxies

    OpenAIRE

    Müller, Ulrich; Philipp, Martine; Gervais, P. C.; Possart, Prof Dr Wulff; Wehlack, C.; Kieffer, J.; Sanctuary, Roland; Krüger, Jan-Kristian

    2010-01-01

    A combination of infrared spectroscopy and high performance refractometry was used to investigate the chemically induced sol-gel and glass transition during the polymerization of epoxies. Representations of the refractive index versus chemical conversion reveal an interesting insight in the optical properties accompanying gelation and vitrification. Whereas the electronic polarizability of the liquid state of small average molecular mass and the glassy state is dominated by the mass density, ...

  11. Near-field photochemical and radiation-induced chemical fabrication of nanopatterns of a self-assembled silane monolayer

    Directory of Open Access Journals (Sweden)

    Ulrich C. Fischer

    2014-09-01

    Full Text Available A general concept for parallel near-field photochemical and radiation-induced chemical processes for the fabrication of nanopatterns of a self-assembled monolayer (SAM of (3-aminopropyltriethoxysilane (APTES is explored with three different processes: 1 a near-field photochemical process by photochemical bleaching of a monomolecular layer of dye molecules chemically bound to an APTES SAM, 2 a chemical process induced by oxygen plasma etching as well as 3 a combined near-field UV-photochemical and ozone-induced chemical process, which is applied directly to an APTES SAM. All approaches employ a sandwich configuration of the surface-supported SAM, and a lithographic mask in form of gold nanostructures fabricated through colloidal sphere lithography (CL, which is either exposed to visible light, oxygen plasma or an UV–ozone atmosphere. The gold mask has the function to inhibit the photochemical reactions by highly localized near-field interactions between metal mask and SAM and to inhibit the radiation-induced chemical reactions by casting a highly localized shadow. The removal of the gold mask reveals the SAM nanopattern.

  12. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F1 hybrid bone marrow. The F1 → C3H chimera but not the F1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F1 → C57BL/6 chimera but not the F1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  13. Chemical-based risk assessment and in vitro models of human health effects induced by organic pollutants in soils from the Olona valley

    Energy Technology Data Exchange (ETDEWEB)

    Baderna, Diego, E-mail: diego.baderna@marionegri.it; Colombo, Andrea; Amodei, Giorgia; Cantù, Stefano; Teoldi, Federico; Cambria, Felice; Rotella, Giuseppe; Natolino, Fabrizio; Lodi, Marco; Benfenati, Emilio

    2013-10-01

    Risk assessment of soils is usually based on chemical measurements and assuming accidental soil ingestion and evaluating induced toxic and carcinogenic effects. Recently biological tools have been coupled to chemical-based risk assessment since they integrate the biological effects of all xenobiotics in soils. We employed integrated monitoring of soils based on chemical analyses, risk assessment and in vitro models in the highly urbanized semirural area of the Olona Valley in northern Italy. Chemical characterization of the soils indicated low levels of toxic and carcinogenic pollutants such as PAHs, PCDD/Fs, PCBs and HCB and human risk assessment did not give any significant alerts. HepG2 and BALB/c 3T3 cells were used as a model for the human liver and as a tool for the evaluation of carcinogenic potential. Cells were treated with soil extractable organic matters (EOMs) and the MTS assay, LDH release and morphological transformation were selected as endpoints for toxicity and carcinogenicity. Soil EOMs induced dose-dependent inhibition of cell growth at low doses and cytotoxicity after exposure to higher doses. This might be the result of block of cell cycle progression to repair DNA damage caused by oxidative stress; if this DNA damage cannot be repaired, cells die. No significant inductions of foci were recorded after exposure to EOMs. These results indicate that, although the extracts contain compounds with proven carcinogenic potential, the levels of these pollutants in the analyzed soils were too low to induce carcinogenesis in our experimental conditions. In this proposed case study, HepG2 cells were found an appropriate tool to assess the potential harm caused by the ingestion of contaminated soil as they were able to detect differences in the toxicity of soil EOMs. Moreover, the cell transformation assay strengthened the combined approach giving useful information on carcinogenic potential of mixtures. Highlights: • A combined approach for risk

  14. De Novo Assembly and Transcriptome Analysis of Wheat with Male Sterility Induced by the Chemical Hybridizing Agent SQ-1

    OpenAIRE

    Qidi Zhu; Yulong Song; Gaisheng Zhang; Lan Ju; Jiao Zhang; Yongang Yu; Na Niu; Junwei Wang; Shoucai Ma

    2015-01-01

    Wheat (Triticum aestivum L.), one of the world's most important food crops, is a strictly autogamous (self-pollinating) species with exclusively perfect flowers. Male sterility induced by chemical hybridizing agents has increasingly attracted attention as a tool for hybrid seed production in wheat; however, the molecular mechanisms of male sterility induced by the agent SQ-1 remain poorly understood due to limited whole transcriptome data. Therefore, a comparative analysis of wheat anther tra...

  15. Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat.

    Science.gov (United States)

    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Cuevas-Olguin, Roberto; Saderi, Nadia; Salgado Delgado, Roberto; Galindo Charles, Luis; Salgado Burgos, Humberto; Rose-John, Stefan; Flores, Gonzalo; Kilgard, Michael P; Atzori, Marco

    2015-06-01

    Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia-Oscos et al., 2012), as well as in the prefrontal cortex (Garcia-Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the "anti-inflammatory reflex" would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti-inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α7 receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch-clamp recording was used to monitor synaptic function. Recordings from LPS-injected Sprague Dawley rats show that activation of the anti-inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS-induced decrease of the synaptic inhibitory-to-excitatory ratio and the saturation level of inhibitory current input-output curves. Given the ample variety of pharmacologically available α7 nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress-induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex. PMID:25626997

  16. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-09-01

    Full Text Available Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing β-catenin (Lv-shβ-catenin. In vitro, Lv-shβ-catenin significantly decreased the expression of β-catenin, MMP2 and MMP9, and secretion of TGF-β1. In vivo, intratracheal treatment with Lv-shβ-catenin significantly reduced expression of β-catenin in the lung and levels of TGF-β1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/β-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/β-catenin pathway may be a target in prevention and treatment of silicosis.

  17. Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells

    International Nuclear Information System (INIS)

    Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar in vitro and in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Endostar blocked microvessel sprouting from rat aortic rings in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar

  18. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice.

    Science.gov (United States)

    Wang, Xin; Dai, Wujing; Wang, Yanrang; Gu, Qing; Yang, Deyi; Zhang, Ming

    2015-09-01

    Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing β-catenin (Lv-shβ-catenin). In vitro, Lv-shβ-catenin significantly decreased the expression of β-catenin, MMP2 and MMP9, and secretion of TGF-β1. In vivo, intratracheal treatment with Lv-shβ-catenin significantly reduced expression of β-catenin in the lung and levels of TGF-β1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/β-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/β-catenin pathway may be a target in prevention and treatment of silicosis. PMID:26340635

  19. Lateral structuring and stability phenomena induced by block copolymers and core-shell nanogel particles at immiscible polymer/polymer interfaces

    Science.gov (United States)

    Gozen, Arif Omer

    We have investigated the parameters such as copolymer/nanoparticle concentration, architecture and molecular weight combined with film thickness, time and temperature in order to develop a molecular-level insight on how lateral interfacial structuring occurs at immiscible polymer/polymer interfaces. I order to develop a molecular-level understanding of how these 'smart' self-assembling materials and core-shell nanogel particles interact both intra- and inter-molecularly and form ordered structures in bulk, as well as at immiscible interfaces, we first focused on the response of core-shell polymer nanoparticles, designated CSNGs, composed of a cross-linked divinylbenzene core and poly(methyl methacrylate) (PMMA) arms as they segregate from PMMA homopolymer. We have demonstrated that these nanogel particles exhibit autophobic character when dispersed in high molecular weight homopolymer matrices and segregate to the interface with another fluid. We have further explored the migration of these new-generation nanogel particles (CSNG-Rs) segregating from PS homopolymer to PS/PMMA interfaces. Unlike the instability patterns observed with the CSNGs, which exhibit classical nucleation and growth mechanism with circular hole formation, we have observed an intriguing dewetting pattern and CSNG-Rs forming lateral aggregates and tentacle-like structures at the interface. In parallel with our core-shell particle studies, we have also explored the structuring of copolymer molecules that are far from equilibrium in bulk and complex laminate of polymer thin films. Our early triblock copolymer studies have proven that molecular asymmetry has a profound effect on order-disorder transition temperature. We focused primarily on the effect of the copolymer chemical composition (i.e., block sizes) on the dewetting behavior of PS/SM thin films on PMMA. We elucidate the interfacial segregation and concurrent micellization of diblock copolymers in a dynamically evolving environment with

  20. Chemically induced renormalization phenomena in Pb-based relaxor ferroelectrics under high pressure

    International Nuclear Information System (INIS)

    The pressure-induced phase transition sequence in PbSc0.5Ta0.5O3 (PST) and PbSc0.5Nb0.5O3 (PSN) heavily doped with homo- and heterovalent cations on the A- or B-site of the perovskite-type structure (ABO3) was analysed by in situ synchrotron x-ray diffraction and Raman spectroscopy up to pressures of 25 GPa. We focused on the structural phenomena occurring above the first pressure-induced phase transition at pc1 from a relaxor state to a non-polar rhombohedral phase with antiphase tilting of the BO6 octahedra. The samples studied were PST doped with Nb5+ and Sn4+ on the B-site, PST doped with Ba2+ and La3+ on the A-site and PSN doped with Sr2+ and La3+ on the A-site. All of them exhibit a second pressure-induced phase transition at pc2, similar to pure PST and PSN. The second transition involves the development of either order of antiparallel Pb2+ displacements and complementary a+b−b− octahedral tilts, or a−b−b− (0 ≤ a 5+ for Ta5+ as well as the coupled substitution of Sn4+ for Sc3+ + Ta5+ on the octahedral B sites increases the second critical pressure. The doping by Nb5+ also reduces the length of coherence of antipolar Pb2+ order developed at pc2. The isovalent substitution of the larger Ba2+ for Pb2+ on the A-site suppresses the antipolar Pb2+ order due to the induced local elastic stresses and thus significantly increases pc2. The substitution of smaller cations for Pb2+ on the A-site generally favours the development of long-range order of antiparallel Pb2+ displacements because of the chemically enhanced a−a−a− octahedral tilts. However, this ordering is less when the dopant is aliovalent, due to the charge imbalance on the A-site. For all of the relaxors studied here, the dynamic compressibility estimated from the pressure derivative of the wavenumber of the soft mode associated with the first phase transition is larger in the pressure interval between pc1 and pc2 than above pc2. The dynamic compressibility of the phase above pc2

  1. Evaluation of sensitivity for positive tone non-chemically and chemically amplified resists using ionized radiation: EUV, x-ray, electron and ion induced reactions

    Science.gov (United States)

    Oshima, Akihiro; Oyama, Tomoko Gowa; Washio, Masakazu; Tagawa, Seiichi

    2013-03-01

    The different exposure sources induce a different energy deposition in resist materials. Linear energy transfer (LET) effect for resist sensitivity is very important issue from the viewpoint of radiation induced chemical reactions for high-volume nanofabrication. The sensitivities of positive tone non-chemically (non-CA, ZEP) and chemically amplified (CA, UV-3) resist materials are evaluated using various ionized radiation such as EUV, soft X-rays, EB and various ion beams. Since the notations of sensitivity of resist vary with exposure sources, in order to evaluate systematically, the resist sensitivity were estimated in terms of absorbed dose in resist materials. Highly-monochromated EUV and soft X-rays (6.7 nm - 3.1 nm) from the BL27SU of the SPring-8, high energy ion beams (C6+, Ne10+, Mg12+, Si14+ , Ar18+, Kr36+ and Xe54+) with 6 MeV/u from MEXP of HIMAC, EB from low energy EB accelerator (Hamamatsu Photonics, EB-engine®, 100 kV) and EB lithography system (30 keV and 75keV) were used for the exposure. For non-CA and CA resist materials, it was found that LET effects for sensitivity would be hardly observed except for heavier ion beams. Especially, in the case of the high energy ion beam less than Si14+ with 6 MeV/u, it is suggested that the radiation induced chemical reaction would be equivalent to EUV, soft X-ray and EB exposure. Hence, it indicates that the resist sensitivity could be systematically evaluated by absorbed dose in resist materials.

  2. Radiation-induced chemical evolution of glycine to (Gly)2, (Gly)3, and (Gly)4

    International Nuclear Information System (INIS)

    Recently amino acids were detected from some meteorites. Since these amino acids were found after hydrolysis, some oligopeptides were possibly formed in space. A simulation experiment of chemical evolution from Glycine (Gly) to Glycylglycine ((Gly)2) was reported by Kaneko et al. In this work, we irradiated (Gly)2 with 8 eV vacuum ultraviolet photons or with 530 eV soft X-ray photons and examined absolute values of quantum yield of radiation-induced chemical evolution from Gly2 to Glycylglycylglycine ((Gly)3) and Glycylglycylglycylglycine ((Gly)4). Thin films of (Gly)2 were prepared on quartz plate or CuBe plate with a vacuum evaporation technique. These samples were irradiated by 8 eV photons from a Xe2* excimer lamp or by 530 eV soft X-ray photons at SPring-8 Synchrotron Radiation Facility. Irradiated samples were analyzed with a high performance liquid chromatography HPLC. Decomposition of (Gly)2 and production of Gly, (Gly)3 and (Gly)4 were observed. Quantum yield Y was defined to be N = Y N0, where N is the number of produced or decomposed molecule, and N0 is the number of (Gly)2 molecules excited by photons. Obtained results by 8 eV irradiation were summarized in Table 1. The similar magnitude of decomposition of (Gly)2 may show that yield of the primary breaking reaction upon photo-excitation is of similar magnitude. It should be noted that (Gly)3 and (Gly)4 was produced by irradiation with the yield of 10-4 without any catalysis. For soft X-ray irradiation, yield of Gly was tentatively determined to be about 40. This largervalue than that for 8 eV irradiation may originate from large energy of incident soft X-ray photons just like a result reported by Simakov et al. We will discuss in detail at the conference. (authors)

  3. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    Science.gov (United States)

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes. PMID:18814656

  4. Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the IκB/NF-κB cascade by facilitating IκB kinase renaturation and blocking its further denaturation

    International Nuclear Information System (INIS)

    Heat shock (HS) treatment has been previously shown to suppress the IκB/nuclear factor-κB (NF-κB) cascade by denaturing, and thus inactivating IκB kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the IκB/NF-κB cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-α-induced activation of the IκB/NF-κB pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-α-induced activation of the IκB/NF-κB pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayed TNF-α-induced IκBα degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the IκBα stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the IκB/NF-κB cascade by facilitating the renaturation of IKK and blocking its further denaturation

  5. Evaluation of Yield and Chemical Characteristics of some Peanut Mutants Induced by Gamma Irradiation

    International Nuclear Information System (INIS)

    This study was conducted to evaluate some promising mutants in peanut for yielding ability over three generation (M5, M6 and M7) and to evaluate yield attributes as will as chemical characteristics of these mutants in M7 generation induced by 100 Gy gamma radiation. The obtained results showed that the increase of yield / plot over three generation as a percentage of control was 5% for mutant 7, 10.2 % for mutant 10; 22% for mutant 9 and 22.9% for mutant 8. This increase in yield may be due to increase of one or more of yield attributes for most mutant lines. The significant increase for. No .of pods and seeds/ plant, weight of pods and seeds/ plant and 100- seed weight in M7 as compared to the control. For saturated fatty acid composition, results revealed that total saturated fatty acids ranged from 17.79% for mutant 8 to 21.75 for mutant 2 compared to 24.21% for control. Reduction of total saturated fatty acid was noticed for different mutants compared to that of the original variety. However, for total unsaturated fatty acids, results indicated that total unsaturated fatty acid composition ranged from 77.95% for mutant 9 to 82.09% for mutant 8 compared to 75.49% for control. Higher total unsaturated fatty acids for all mutant lines were obtained than that of the control, however, total saturated (TS)/ total unsaturated (TU) ratio was decreased for all mutants compared to control. The physical and chemical contents of Peanut oils showed that the refractive indices were ranged from 1.4620 to 1.4718 specific gravity were in range of 0.9146 to 0.9177. Acid value was range from 0.54 to 0.89% lodine value was ranged from 94.56 to 101.85. Saponification value was ranged from 185.2 to 190.7 and unsaponifiable matter was ranged from 0.98 to 1.33. The peroxide values ranged from 1.15 to 2.33 meq/kg oil. Also, fortified yoghurt made with replaced mutant peanut oil by 50% as milk fat substitute. Data showed that chemical composition and organolyptic properties had the

  6. Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vignaux, G. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Chabbert, C.; Gaboyard-Niay, S.; Travo, C. [INSERM U1051, Institut des Neurosciences de Montpellier, Montpellier, F-34090,France (France); Machado, M.L. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Denise, P. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Comoz, F. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Hitier, M. [CHRU Caen, Service d' Otorhinolaryngologie, Caen, F-14000,France (France); Landemore, G. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Philoxène, B. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Besnard, S., E-mail: besnard-s@phycog.org [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France)

    2012-01-01

    Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3 months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

  7. Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea

    Directory of Open Access Journals (Sweden)

    S.M.G. Massironi

    2006-09-01

    Full Text Available When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s. Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s. Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives. Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc. This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning.

  8. Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells.

    Science.gov (United States)

    Chen, Honglin; Gigli, Matteo; Gualandi, Chiara; Truckenmüller, Roman; van Blitterswijk, Clemens; Lotti, Nadia; Munari, Andrea; Focarete, Maria Letizia; Moroni, Lorenzo

    2016-01-01

    Bioactive scaffolds for tissue engineering call for demands on new materials which can enhance traditional biocompatibility requirements previously considered for clinical implantation. The current commercially available thermoplastic materials, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε-caprolactone) (PCL) and their copolymers, have been used to fabricate scaffolds for regenerative medicine. However, these polymers have limitations including lacking of broadly tuning mechanical and degradable properties, and activation of specific cell-scaffold interactions, which limit their further application in tissue engineering. In the present study, electrospun scaffolds were successfully fabricated from a new class of block poly(butylene succinate)-based (PBS-based) copolyesters containing either butylene thiodiglycolate (BTDG) or butylene diglycolate (BDG) sequences. The polyesters displayed tunable mechanical properties and hydrolysis rate depending on the molecular architecture and on the kind of heteroatom introduced along the polymer backbone. To investigate their potential for skeletal regeneration, human mesenchymal stromal cells (hMSCs) were cultured on the scaffolds in basic, osteogenic and chondrogenic media. Our results demonstrated that PBS-based copolyesters containing thio-ether linkages (i.e. BTDG segments) were more favorable for chondrogenesis of hMSCs than those containing ether linkages (i.e. BDG sequences). In contrast, PBS-based copolyesters containing ether linkages showed enhanced mineralization. Therefore, these new functional scaffolds might hold potential for osteochondral tissue engineering applications. PMID:26546918

  9. Overexpression and amplification of the c-myc gene in mouse tumors induced by chemical and radiations

    International Nuclear Information System (INIS)

    We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 α-tocopherol-induced sacromas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification. (author)

  10. Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening

    International Nuclear Information System (INIS)

    High-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may be used in a battery of tests for detecting chemicals that could result in developmental neurotoxicity. Apoptosis contributes to nervous system development by regulating the size of the neuroprogenitor cell pool, and the balance between cellular proliferation and apoptosis during neuroprogenitor cell proliferation helps to determine the size and shape of the nervous system. Therefore, chemicals that affect apoptosis during neuronal development can have deleterious effects on the developing brain. The present study examined the utility of a high-throughput assay to detect chemical-induced apoptosis in mouse or human neuroprogenitor cells, as well as differentiated human neurons derived from induced pluripotent stem cells. Apoptosis was assessed using an assay that measures enzymatic activity of caspase-3/7 in a rapid and cost efficient manner. The results show that all three commercially available models generated a robust source of proliferating neuroprogenitor cells, and that the assay was sensitive and reproducible when used in a multi-well plate format. There were differences in the response of rodent and human neuroprogenitor cells to a set of chemicals previously shown to induce apoptosis in vitro. Neuroprogenitor cells were more sensitive to chemical-induced apoptosis than differentiated neurons, suggesting that neuroprogenitor cells are one of the cell models that should be considered for use in a developmental neurotoxicity screening battery

  11. Innovative methods with low energy consumption for efficient CO2 capture and its re-use as a building block for the synthesis of useful chemicals

    OpenAIRE

    Barzagli, Francesco

    2016-01-01

    The purpose of this research activity has been the development of new and efficient systems for the capture of CO2 from a gas stream in a sustainable way from an energetic, economic and environmental point of view. The chemical absorption by aqueous alkanolamines is considered the most efficient and mature technique for the CO2 capture and separation. Alkanolamines are widely used due to the fast reaction with CO2 and to their solubility in water. In particular aqueous 2-amine ethanol (M...

  12. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice.

    Science.gov (United States)

    Ye, Jian-Hong; Liu, Meng-Hua; Zhang, Xu-Lin; He, Jing-Yu

    2015-01-01

    Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography-diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones. PMID:26580602

  13. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice

    Directory of Open Access Journals (Sweden)

    Jian-Hong Ye

    2015-11-01

    Full Text Available Protective effect of Hedyotis diffusa (H. diffusa Willd against lipopolysaccharide (LPS-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography -diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and monocyte chemoattractant protein (MCP-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones.

  14. Combining machine learning, crowdsourcing and expert knowledge to detect chemical-induced diseases in text

    Science.gov (United States)

    Bravo, Àlex; Li, Tong Shu; Su, Andrew I.; Good, Benjamin M.; Furlong, Laura I.

    2016-01-01

    Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects. Database URL: https://zenodo.org/record/29887?ln¼en#.VsL3yDLWR_V PMID:27307137

  15. Combining machine learning, crowdsourcing and expert knowledge to detect chemical-induced diseases in text.

    Science.gov (United States)

    Bravo, Àlex; Li, Tong Shu; Su, Andrew I; Good, Benjamin M; Furlong, Laura I

    2016-01-01

    Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects.Database URL: https://zenodo.org/record/29887?ln¼en#.VsL3yDLWR_V. PMID:27307137

  16. A study on the improving efficiency for laser-induced chemical reaction process

    International Nuclear Information System (INIS)

    The laser-induced photoreaction process is a very useful technology in environmental aspects as well as atomic energy industry. In this study various factors which affect to the reaction process has been investigated for the increment of efficiency of reaction process. Palladium and silver have been chosen as samples for the reaction and the reaction processes have been monitored very carefully. For palladium nitric acid was identified as the best solvent for the reaction, while oxalic acid was the best reducing agent. As the concentration of the reducing agent increases, the reactivity of the samples were increased. When more laser energy was illuminated to the samples, reactivity increased, too. The wavelength of the laser beam used for the reaction was 3rd harmonic of Nd:YAG laser(355 nm). For silver case perchloric acid and ethanol were the best combination for the optimal reaction condition. As a result of the analysis of the reaction products, pure palladium and silver were the products, not any other forms of chemicals. (author). 12 refs., 3 tabs., 26 figs

  17. Mapping the chemical potential dependence of current-induced spin polarization in a topological insulator

    Science.gov (United States)

    Lee, Joon Sue; Richardella, Anthony; Hickey, Danielle Reifsnyder; Mkhoyan, K. Andre; Samarth, Nitin

    2015-10-01

    We report electrical measurements of the current-induced spin polarization of the surface current in topological insulator devices where contributions from bulk and surface conduction can be disentangled by electrical gating. The devices use a ferromagnetic tunnel junction (permalloy/Al 2O3 ) as a spin detector on a back-gated (Bi,Sb ) 2Te3 channel. We observe hysteretic voltage signals as the magnetization of the detector ferromagnet is switched parallel or antiparallel to the spin polarization of the surface current. The amplitude of the detected voltage change is linearly proportional to the applied dc bias current in the (Bi,Sb ) 2Te3 channel. As the chemical potential is tuned from the bulk bands into the surface state band, we observe an enhancement of the spin-dependent voltages up to 300% within the range of the electrostatic gating. Using a simple model, we extract the spin polarization near charge neutrality (i.e., the Dirac point).

  18. Heuristic model of chemically induced electron spin polarization in two dimensions

    International Nuclear Information System (INIS)

    Graphical abstract: Like its three-dimensional predecessor, and unlike previous 2D models, this model handles all singlet-triplet mixing rates (Q) and, as illustrated below, gives the time evolution of the polarization. - Abstract: A heuristic model of chemically induced electron spin polarization (CIDEP) that breaks the polarization mechanism into its component steps, with each step governed by an appropriate solution of the diffusion equation, is extended from a three to a two-dimensional system. The required solution of the 2D diffusion equation is provided by a relatively simple analytic approximation to the usual infinite series solution. The model yields the polarization and its time development for weak to strong singlet-triplet mixing in the radical pairs, whereas previous models are limited to very weak or very strong mixing. Its results agree with a variational solution of an integral equation of Monchick and are encouraging for observation of CIDEP in dimensionally restricted systems. The method also may be applicable to other diffusion-controlled, spin-dependent chemistry in spatially restricted environments.

  19. Acidification-induced chemical changes in coniferous forest soils in southern Sweden 1988-1999

    International Nuclear Information System (INIS)

    Acidification of south-Swedish coniferous forest soils continues and soil nutrient status is no longer sustainable in a long-term perspective. - Thirty-two Norway spruce [Picea abies (L.) Karst.] and Scots pine (Pinus sylvestris L.) stands in southern Sweden were studied for a period of 12 years to evaluate acidification-induced chemical changes in the soil. Soil, at 20-30 cm depth in the mineral layer, was sampled three times during this period (1988, 1993 and 1999). The results show that pH(BaCl2) in mineral soil decreased by, on average, 0.17 units between 1988 and 1999, accompanied by an increase in aluminium (Al) concentration and a decrease in base saturation in the soil. In 1999, the base saturation was below 5% in 58% of the 32 sites compared with 16% in 1988 and 7% in 1993. Concentrations of calcium (Ca), potassium (K) and magnesium (Mg) are low and decreasing. Based on C/N ratios in humus, 45% of the sites may be subjected to leaching of considerable amounts of nitrate. The results show that the acidification of coniferous forest soils in southern Sweden is continuing, and that the negative effects on the nutrient status in soil are extensive. The results are compared with reference values for productive, long-term sustainably managed boreal coniferous or mixed forest soils and implications for long-term sustainability are discussed

  20. Modification of tolerance of oats to crown rust induced by chemical mutagens

    International Nuclear Information System (INIS)

    Seeds of crown rust (Puccinia coronata) susceptible cultivated oats (Avena sativa) were treated with the mutagenic chemical ethyl methanesulphonate (EMS), and pure lines derived from these treated seeds were tested in later generations for the relative amount of reduction in yield and seed weight caused by crown rust infection. In the absence of crown rust, the yield of most of the treated lines was greatly reduced. The overall means of the treated lines for both yield and seed weight response to infection were significantly lower than the control, but 10 lines significantly exceeded the control for yield response and 15 exceeded it for seed weight response. Recurrent EMS treatment of once-treated lines rated as tolerant resulted in groups of lines that were more tolerant, on the average, than groups of lines from recurrently treated lines rated as susceptible. A few of the recurrently treated individual lines derived from tolerant parents had a higher degree of tolerance than their parental lines. EMS treatment of diploid (A. strigosa) and tetraploid (A. abyssinica) oats resulted in groups of lines showing significant genetic variance for response to crown rust, indicating that treatment had induced real genetic change. A few diploid lines were a little more tolerant than their control, but none of the tetraploid lines showed any consistent improvement. (author)

  1. Chemical reactions induced by oscillating external fields in weak thermal environments

    CERN Document Server

    Craven, Galen T; Hernandez, Rigoberto

    2015-01-01

    Chemical reaction rates must increasingly be determined in systems that evolve under the control of external stimuli. In these systems, when a reactant population is induced to cross an energy barrier through forcing from a temporally varying external field, the transition state that the reaction must pass through during the transformation from reactant to product is no longer a fixed geometric structure, but is instead time-dependent. For a periodically forced model reaction, we develop a recrossing-free dividing surface that is attached to a transition state trajectory [T. Bartsch, R. Hernandez, and T. Uzer, Phys. Rev. Lett. 95, 058301 (2005)]. We have previously shown that for single-mode sinusoidal driving, the stability of the time-varying transition state directly determines the reaction rate [G. T. Craven, T. Bartsch, and R. Hernandez, J. Chem. Phys. 141, 041106 (2014)]. Here, we extend our previous work to the case of multi-mode driving waveforms. Excellent agreement is observed between the rates pred...

  2. [Revision of th distribution of chromosome aberrations induced by chemical mutagens using the BUDR label].

    Science.gov (United States)

    Chebotarev, A N; Chernyshova, N A

    1990-08-01

    Cell distribution was analysed with the help of the BrDU label for the number of chromosome aberrations and breaks induced by one-center (thiophosphamide and phosphamide) and two-center (dipine and fotrine) mutagens at the stage G0 in the Ist mitosis of human lymphocytes harvested at different times of culturing (from 56 to 96 h). The comparison was made between the type of aberration distribution in cells and the dependence of their frequency on the harvesting point for various mutagens. Poisson aberration distribution in cells for two-center mutagens was found to correspond to their constant frequency observed at different times of harvesting. On the other hand, for one-center mutagens, a geometrical distribution of chromosome breaks corresponded to an exponential decrease in their frequency in time. It is suggested that two-center chemical mutagens and ionizing radiation cause largely short-live damages which are realized into chromosome aberrations rather quickly (during one cell cycle). One-center mutagens, however, cause such damages that the probability of their transformation into chromosome aberrations is decreasing rather slowly in time, under the exponential law, and their realization into chromosome aberrations can occur in subsequent cell cycle. PMID:2258036

  3. Preparation of intact chloroplasts by chemically induced lysis of the green alga Dunaliella marina.

    Science.gov (United States)

    Kombrink, E; Wöber, G

    1980-07-01

    A method for the isolation in high yield of intact chloroplasts from the unicellular green alga Dunaliella marina (Volvocales) is described. This procedure uses chemically induced lysis of cells with the polycationic macromolecules, DEAE-dextran (M=500,000) or poly-D,L-lysine (M=30,000-70,000). Reaction conditions were optimized with respect to obtaining a high yield of intact chloroplasts, after isopycnic centrifugation in a linear sucrose density gradient, by varying the concentration of polycation and the temperature and pH of incubation. Broken chloroplasts devoid of the stromal marker enzymes fructosebisphosphate phosphatase and ribulosebisphosphate carboxylase, but containing mitochondrial (fumarase) and microbody (catalase) contamination, were banded at a bouyant density of 1.18 g cm(-3). Intact chloroplasts, as indicated by their retention of alkaline fructosebisphosphate phosphatase and ribulosebisphosphate carboxylase, were found in 30% yield (chlorophyll in intact cells, 100%) at an equilibrium density of 1.24 g cm(-3). Contamination by cytoplasmic material (pyruvate kinase), mitochondria, and microbodies was less than 8% each. PMID:24306242

  4. Growth of titanium silicate thin films by photo-induced chemical vapor deposition

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.M.; Fang, Q.; Zhang, J.-Y.; Wu, J.X.; Di, Y.; Chen, W.; Chen, M.L.; Boyd, Ian W

    2004-04-01

    Titanium silicate thin films have been grown on Si substrates by photo-induced chemical vapor deposition using 222-nm ultraviolet excimer lamps. Titanium tetraisopropoxide (TTIP) and tetraethoxysilane (TEOS) were used as precursors. TTIP and TEOS were dissolved together in cyclohexane and introduced into the photochemical reaction chamber through a droplet injector vaporizer. The composition of the film was controlled by changing the ratio of TTIP to TEOS in the precursor solution. High quality titanium silicate films with various Ti/Si ratios and low carbon content have been achieved as revealed by X-ray photoelectron spectroscopy measurements. The atomic percentage of Ti content in the grown silicate films is significantly larger than that in the precursor solution. The films were measured to be 30-80 nm in thickness and 1.91-2.31 in refractive index by ellipsometry. Both the growth rate and refractive index increase with increasing Ti percentage in the silicate films. The evolution of Fourier transform infrared spectra of the silicate films with solution composition shows that the Ti-O-Si absorption at approximately 920 cm{sup -1} becomes stronger, while the Ti-O absorption at approximately 430 cm{sup -1} becomes weaker with decreasing Ti percentage in the solution. A small feature at {approx}1035 cm{sup -1} related to Si-O-Si bonds is also observed in the SiO{sub 2}-rich Ti silicate film.

  5. Changes in chemical interactions and protein conformation during heat-induced wheat gluten gel formation.

    Science.gov (United States)

    Wang, Kai-Qiang; Luo, Shui-Zhong; Zhong, Xi-Yang; Cai, Jing; Jiang, Shao-Tong; Zheng, Zhi

    2017-01-01

    In order to elucidate the heat-induced wheat gluten gel formation mechanism, changes in chemical interactions and protein conformation were investigated during gelation. The contribution of ionic and hydrogen bonds were found to decrease from 0.746 and 4.133g/L to 0.397 and 2.733g/L, respectively, as the temperature increased from 25 to 90°C. Moreover, the free SH content remarkably decreased from 37.91 to 19.79μmol/g during gelation. Ultraviolet absorption spectra and intrinsic fluorescence spectra suggested that wheat gluten unfolded during the heating process. In addition, wheat gluten gels treated at 80 and 90°C exhibited a "steric hindrance" effect, which can be attributed to the formation of aggregates. Fourier transform infrared spectra suggested that the random coil content increased at low temperatures (40 and 50°C), whereas the content of intermolecular β-sheets due to protein aggregation increased from 38.10% to 44.28% when the gelation temperature was 90°C. PMID:27507490

  6. Chemical protection against life shortening and radio-induced leukemias and cancers

    International Nuclear Information System (INIS)

    The advantage gained on the long term survival and the induction of leukemias and cancers in mice exposed to a single dose of ionizing radiation by a combination of radiochemical protectors, are examined. The results show clearly that chemical protective compounds protect mice against radiation-induced life-shortening, They demonstrate also that the obtained protection was improved by combination of various protectors acting in a supplementary manner. The optimum dose reduction factor obtained was 1.5 for AET and about 2 for a mixture of 5 radioprotectors. These dose reduction factors are lower than those offered with these two treatments against the acute effects of ionizing radiation. In addition, the dose effect curve for the long term survival obtained for irradiated untreated mice and for mice treated with a mixture of radioprotectors are not parallel. Thus, the dose reduction factors vary with the X-ray dose administered. The best protection was achieved for X-ray doses from 500 to 1000 R. After an exposure to 100 R (BALB/c+ mice) and 350 R (C5781 mice) of X-rays, the total incidence of leukemias and cancers was significantly lower in treated irradiated mice than in non treated mice

  7. Characterisation of TiO 2 deposited by photo-induced chemical vapour deposition

    Science.gov (United States)

    Kaliwoh, Never; Zhang, Jun-Ying; Boyd, Ian W.

    2002-01-01

    We report the deposition of thin TiO 2 films on crystalline Si and quartz by photo-induced chemical vapour deposition (CVD) using UV excimer lamps employing a dielectric barrier discharge in krypton chloride (KrCl ∗) to provide intense narrow band radiation at λ=222 nm. The precursor used was titanium isopropoxide (TTIP). Films from around 20-510 nm in thickness with refractive indices from 2.20 to 2.54 were grown at temperatures between 50 and 350 °C. The higher refractive index values compare favourably with the value of 2.58 recorded for the bulk material. The measured deposition rate was around 50 nm/min at 350 °C. Fourier transform infrared spectroscopy (FTIR) revealed the presence of TiO 2 through the observation of a Ti-O absorption peak and the absence of OH in films deposited at 250-350 °C indicated relatively good quality films. The phase of films deposited at 200-350 °C was anatase as determined by X-ray diffraction.

  8. Ab Initio Studies of Shock-Induced Chemical Reactions of Inter-Metallics

    Science.gov (United States)

    Zaharieva, Roussislava; Hanagud, Sathya

    2009-06-01

    Shock-induced and shock assisted chemical reactions of intermetallic mixtures are studied by many researchers, using both experimental and theoretical techniques. The theoretical studies are primarily at continuum scales. The model frameworks include mixture theories and meso-scale models of grains of porous mixtures. The reaction models vary from equilibrium thermodynamic model to several non-equilibrium thermodynamic models. The shock-effects are primarily studied using appropriate conservation equations and numerical techniques to integrate the equations. All these models require material constants from experiments and estimates of transition states. Thus, the objective of this paper is to present studies based on ab initio techniques. The ab inito studies, to date, use ab inito molecular dynamics. This paper presents a study that uses shock pressures, and associated temperatures as starting variables. Then intermetallic mixtures are modeled as slabs. The required shock stresses are created by straining the lattice. Then, ab initio binding energy calculations are used to examine the stability of the reactions. Binding energies are obtained for different strain components super imposed on uniform compression and finite temperatures. Then, vibrational frequencies and nudge elastic band techniques are used to study reactivity and transition states. Examples include Ni and Al.

  9. From building blocks of proteins to drugs: A quantum chemical study on structure-property relationships of phenylalanine, tyrosine and dopa

    CERN Document Server

    Ganesan, Aravindhan; Wang, Feng

    2014-01-01

    Density functional theory and ab initio methods have been employed to address the impacts of hydroxyl (OH) group substitutions on the physico-chemical properties of levodopa (or L-dopa) against the natural amino acids, phenylalanine and tyrosine. L-dopa, which is an important therapeutic drug for Parkinson's disease, shares structural homology with the amino acids, whose structures differ only by OH substitutions in their phenyl side chains. It is revealed that the backbone geometries of the aromatic molecules do not show apparent OH-dependent differences; however, their other molecular-level properties, such as molecular dipole moment, electronic properties and aromaticity, change significantly. The core binding energy spectra indicate that the atom sites that undergo modifications exhibit large energy shifts, so as to accommodate the changes in the intra-molecular chemical environment of the molecules. The binding energies of the modified C 1s sites in the molecules shift as much as 1.8 eV, whereas the elec...

  10. Chemical speciation of chlorine in atmospheric aerosol samples by high-resolution proton induced X-ray emission spectroscopy

    International Nuclear Information System (INIS)

    Chlorine is a main elemental component of atmospheric particulate matter (APM). The knowledge of the chemical form of chlorine is of primary importance for source apportionment and for estimation of health effects of APM. In this work the applicability of high-resolution wavelength dispersive proton induced X-ray emission (PIXE) spectroscopy for chemical speciation of chlorine in fine fraction atmospheric aerosols is studied. A Johansson-type crystal spectrometer with energy resolution below the natural linewidth of Cl K lines was used to record the high-resolution Kα and Kβ proton induced spectra of several reference Cl compounds and two atmospheric aerosol samples, which were collected for conventional PIXE analysis. The Kα spectra which refers to the oxidation state, showed very minor differences due to the high electronegativity of Cl. However, the Kβ spectra exhibited pronounced chemical effects which were significant enough to perform chemical speciation. The major chlorine component in two fine fraction aerosol samples collected during a 2010 winter campaign in Budapest was clearly identified as NaCl by comparing the high-resolution Cl Kβ spectra from the aerosol samples with the corresponding reference spectra. This work demonstrates the feasibility of high-resolution PIXE method for chemical speciation of Cl in aerosols. - Highlights: ► Chemical specation of Cl in aerosol samples by high resolution PIXE spectroscopy. ► Fine structure of Kα and Kβ lines of reference compounds and APM samples was given. ► Kα spectra were well aligned with each other confirming the same Cl oxidation state. ► Pronounced chemical effects were observed in the Kβ spectra. ► We showed that chemical speciation of Cl was possible on thin aerosol samples

  11. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  12. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  13. A novel room temperature-induced chemical etching (RTCE) technique for the enlargement of fission tracks in Lexan polycarbonate SSNTD

    Science.gov (United States)

    Chavan, Vivek; Kalsi, P. C.; Manchanda, V. K.

    2011-02-01

    The chemical or electrochemical etching is an essential step to enlarge the ion-induced latent tracks in solid state nuclear track detectors (SSNTDs). In these methods, above ambient temperatures (˜60 °C) and moderately high concentrations of alkali are required for about 1-2 h to enlarge the latent tracks. Microwave induced chemical etching method is reported to reduce the etching time for alpha tracks from 3 to 4 h to 25 min for CR-39 detector. In the present work, a room temperature-induced chemical etching employing ethanolamine as a new etchant has been investigated for the first time to enlarge the fission tracks in Lexan polycarbonate SSNTD. The tracks developed in the Lexan detectors etched at room temperature using ethanolamine are compared with those etched with routinely used chemical etching (CE) technique in 6 N NaOH at 60 °C. The bulk etch and track etch rates are also reported. The detection efficiency of RTCE method is determined and compared with that of CE method. The RTCE technique is found to be simple, fast and convenient.

  14. A novel room temperature-induced chemical etching (RTCE) technique for the enlargement of fission tracks in Lexan polycarbonate SSNTD

    Energy Technology Data Exchange (ETDEWEB)

    Chavan, Vivek [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kalsi, P.C., E-mail: pckalsi@barc.gov.i [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Manchanda, V.K. [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2011-02-11

    The chemical or electrochemical etching is an essential step to enlarge the ion-induced latent tracks in solid state nuclear track detectors (SSNTDs). In these methods, above ambient temperatures ({approx}60 {sup o}C) and moderately high concentrations of alkali are required for about 1-2 h to enlarge the latent tracks. Microwave induced chemical etching method is reported to reduce the etching time for alpha tracks from 3 to 4 h to 25 min for CR-39 detector. In the present work, a room temperature-induced chemical etching employing ethanolamine as a new etchant has been investigated for the first time to enlarge the fission tracks in Lexan polycarbonate SSNTD. The tracks developed in the Lexan detectors etched at room temperature using ethanolamine are compared with those etched with routinely used chemical etching (CE) technique in 6 N NaOH at 60 {sup o}C. The bulk etch and track etch rates are also reported. The detection efficiency of RTCE method is determined and compared with that of CE method. The RTCE technique is found to be simple, fast and convenient.

  15. Cytogenetic damages induced in vivo in human lymphocytes by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    The importance of various environmental exposures has been evident in variation in cancer incidence and mortality. Benzene is considered to be a human carcinogen, is clastogenic to rodents and humans, and it affects the immune response. Workers in various industrial plants, are exposed to benzene and benzene related compounds as a result of various activities in which benzene is processed, generated or used. Major sources of environmental exposure to benzene related compounds, continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. Benzene is of a particular interest, not only because of its known toxicity, but also because this was to be the parent compound and a model for extensive programs of metabolism of a variety of aromatic chemicals. Ionizing radiation is an unavoidable physical agent that is presented in environment, and public opinion is well aware against radiation risk and strongly against it. The aim of the presentation was comparison between cytogenetic damages induced in vivo by environmental chemicals with those of radiation. Results from biomonitoring survey on genotoxicity in human blood cells of benzene and benzene related compounds were compared to damages detected in lymphocytes of persons who had been accidentally exposed to gamma radiation. In the groups, that had been occupationally or environmentally exposed to benzene related compound, total aberration frequencies, or percent of aberrant cells ranged between 0 - 0.16 aberrations/cell or 16% of aberrant cells respectively. A multivariate regression analysis confirmed: (i) a significant association between cytogenetic damage and exposure to benzene related compound, (ii) a possible association between cytogenetic damage and cancer, (iii) a significant influence of smoking habit. In 1996 few persons were suspected of accidental exposure to gamma radiation. To estimate the absorbed doses, lymphocytes from their blood have been analyzed for the presence of

  16. Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

    Directory of Open Access Journals (Sweden)

    Melemedjian Ohannes K

    2008-03-01

    Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

  17. Combination of high-performance refractometry and infrared spectroscopy as a probe for chemically induced gelation and vitrification of epoxies

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, U; Philipp, M; Gervais, P-C; Sanctuary, R; Krueger, J K [Laboratoire de Physique des Materiaux, Universite du Luxembourg, 162A avenue de la faiencerie, L-1511 Luxembourg (Luxembourg); Possart, W; Wehlack, C [Fachbereich Werkstoffwissenschaften, Universitaet des Saarlandes, D-66123 Saarbruecken (Germany); Kieffer, J, E-mail: ulrich.mueller@uni.l [Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI (United States)

    2010-08-15

    A combination of infrared spectroscopy and high-performance refractometry was used to investigate the chemically induced sol-gel and glass transition during the polymerization of epoxies. Representations of the refractive index versus chemical conversion reveal an interesting insight into the optical properties accompanying gelation and vitrification. Whereas the electronic polarizability of the liquid state of small average molecular mass and the glassy state is dominated by the mass density, an unexpected excess polarizability observed during the gelation is attributed to cooperative dipole-dipole interactions.

  18. Stress-induced chemical detection using flexible metal-organic frameworks.

    Energy Technology Data Exchange (ETDEWEB)

    Allendorf, Mark D.; Hesketh, Peter J. (Georgia Institute of Technology, Atlanta, GA); Gall, Kenneth A. (Georgia Institute of Technology, Atlanta, GA); Choudhury, A. (Georgia Institute of Technology, Atlanta, GA); Pikarsky, J. (Georgia Institute of Technology, Atlanta, GA); Andruszkiewicz, Leanne (Georgia Institute of Technology, Atlanta, GA); Houk, Ronald J. T.; Talin, Albert Alec (National Institute of Standards & Technology, Gaithersburg, MD)

    2009-09-01

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be efficiently converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N{sub 2} or O{sub 2}. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO{sub 2}. We also report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes. A force field model is described that successfully predicts changes in MOF properties and the uptake of gases. This model is used to predict adsorption isotherms for a number of representative compounds, including explosives, nerve agents, volatile organic compounds, and polyaromatic hydrocarbons. The results show that, as a result of relatively large heats of adsorption (> 20 kcal mol{sup -1}) in most cases, we expect an onset of adsorption by MOF as low as 10{sup -6} kPa, suggesting the potential to detect compounds such as RDX at levels as low as 10 ppb at atmospheric pressure.

  19. Direct spatiotemporal analysis of femtosecond laser-induced plasma-mediated chemical reactions

    International Nuclear Information System (INIS)

    Localized, micron to millimetre-scale plasmas resulting from the fleeting interaction between ultrashort laser pulses and matter have been studied extensively in inert atmospheres. In spite of recent interest in reactive plasmas as a nanofabrication tool, ultrashort pulsed laser ablation in reactive gas atmospheres has undergone little study. In this study, we develop a methodology combining time-resolved optical emission spectroscopy and spectrally filtered time-gated fast photography to directly observe and analyse plasma-mediated chemical reactions that occur when laser ablation is performed in reactive gases. Specifically, we compare the ablation of silicon dioxide in an atmosphere of xenon difluoride gas to its ablation in nitrogen and xenon atmospheres. We show that when xenon difluoride molecules are collisionally driven into an excited state by the silicon plasma produced during laser-induced decomposition of the solid substrate, the gas undergoes dissociation. The resulting fluorine radicals react spontaneously with the silicon plasma to produce volatile fluorinated silicon compounds. In particular, mass spectroscopy shows that the primary reaction byproduct is SiF2 with small amounts of SiF and SiF4. The high spatial and temporal resolution of our methodology reveals a slowly expanding plume having an atomic silicon core with a XeF∗ shell that persists for less than 300 ns. As the silicon is fluorinated, the optical emission due to excited silicon is quenched. The absence of a silicon signal after 300 ns establishes this as the upper limit of the reaction lifetime given the conditions of the experiment. (letter)

  20. Sister chromatid exchanges in the bone marrow cells of in vivo rats induced by gamma radiation and chemical mutagens

    International Nuclear Information System (INIS)

    Sister chromatid exchanges (SCE) in the bone marrow of in vivo rats induced by gamma radiation doses and by the chemical mutagens, mitomycin C (MMC), cyclophosphamide (CP), and sulphonate-methylmethane (SMM), were studied. The purpose was to evaluate the sensitivity and reproducibility of a simplified SCE in vivo detecting system developed in our laboratory and to compare the results obtained with those reported elsewhere. Simplification consisted in administering the amounts of 5-bromo-2'-deoxyuridine (BrdU) necessary to observe the SCE, after first adsorbing the BrdU in activated carbon and then injecting it interperitoneally, into the rats. The results were a longer time in vivo ADN incorporation without convulsions in the rats, and a reduction in the time course as compared to other methods. We observed a basal rate of 3.6+-0.37 SCE/cell and that: 0.44 Gy of gamma radiation induced 7.7+-0.73 SCE/cell; 1.6 μg/g of MMC induced 8.1+-1.20 SCE/cell; 5 μg/g of CP induced 8.25+-1.5 SCE/cell, 40 μg/g of SMM induced 22.0+-5 SCE/cell and 380 μg/g of sulphonate-ethylmethane induced 8.6+-1.2 SCE/cell. This showed that all the agents were capable of inducing SCE in the bone marrow cells of rats in vivo under our conditions. We noted a greater induced efficiency for gamma radiation than the obtained by other investigators and a relatively similar efficiency in the case of chemical mutagens as reported in other studies. (author)

  1. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  2. Ingested plastic transfers hazardous chemicals to fish and induces hepatic stress

    Science.gov (United States)

    Rochman, Chelsea M.; Hoh, Eunha; Kurobe, Tomofumi; Teh, Swee J.

    2013-01-01

    Plastic debris litters aquatic habitats globally, the majority of which is microscopic (Hazards associated with the complex mixture of plastic and accumulated pollutants are largely unknown. Here, we show that fish, exposed to a mixture of polyethylene with chemical pollutants sorbed from the marine environment, bioaccumulate these chemical pollutants and suffer liver toxicity and pathology. Fish fed virgin polyethylene fragments also show signs of stress, although less severe than fish fed marine polyethylene fragments. We provide baseline information regarding the bioaccumulation of chemicals and associated health effects from plastic ingestion in fish and demonstrate that future assessments should consider the complex mixture of the plastic material and their associated chemical pollutants. PMID:24263561

  3. Exact Solution to the Extended Zwanzig Model for Quasi-Sigmoidal Chemically Induced Denaturation Profiles: Specific Heat and Configurational Entropy

    OpenAIRE

    Aguilar-Pineda, G. E.; Olivares-Quiroz, L.

    2014-01-01

    Temperature and chemically induced denaturation comprise two of the most characteristic mechanisms to achieve the passage from the native state N to any of the unstructured states Dj in the denatured ensemble in proteins and peptides. In this work we present a full analytical solution for the configurational partition function qs of a homopolymer chain poly-X in the extended Zwanzig model (EZM) for a quasisigmoidal denaturation profile. This solution is built up from an EZM exact solution in...

  4. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    Science.gov (United States)

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  5. Synthetic chemical inducers and genetic decoupling enable orthogonal control of the rhaBAD promoter

    DEFF Research Database (Denmark)

    Kelly, Ciarán L; Liu, Zilei; Yoshihara, Akihide;

    2016-01-01

    External control of gene expression is crucial in synthetic biology and biotechnology research and applications, and is commonly achieved using inducible promoter systems. The E. coli rhamnose-inducible rhaBAD promoter has properties superior to more commonly-used inducible expression systems, but......BAD expression system revealed several promising inducers. These were characterised further to determine the strength, kinetics and concentration-dependence of induction; whether the inducer was used as a carbon source by E. coli; and the modality (distribution) of induction among populations of cells. L...

  6. A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells.

    Science.gov (United States)

    Nhung, Truong Hai; Nam, Nguyen Hai; Nguyen, Nguyen Thi Kim; Nghia, Huynh; Van Thanh, Nguyen; Ngoc, Phan Kim; Van Pham, Phuc

    2015-11-01

    Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 μg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte-like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment. PMID:26275888

  7. Protein Synthesis Inhibitors Did Not Interfere with Long-Term Depression Induced either Electrically in Juvenile Rats or Chemically in Middle-Aged Rats.

    Science.gov (United States)

    Abbas, Abdul-Karim

    2016-01-01

    In testing the hypothesis that long-term potentiation (LTP) maintenance depends on triggered protein synthesis, we found no effect of protein synthesis inhibitors (PSIs) on LTP stabilization. Similarly, some studies reported a lack of effect of PSIs on long-term depression (LTD); the lack of effect on LTD has been suggested to be resulting from the short time recordings. If this proposal were true, LTD might exhibit sensitivity to PSIs when the recording intervals were enough long. We firstly induced LTD by a standard protocol involving low frequency stimulation, which is suitable for eliciting NMDAR-LTD in CA1 area of hippocampal slices obtained from juvenile Sprague-Dawley rats. This LTD was persistent for intervals in range of 8-10 h. Treating slices with anisomycin, however, did not interfere with the magnitude and persistence of this form of LTD. The failure of anisomycin to block synaptic-LTD might be relied on the age of animal, the type of protein synthesis inhibitors and/or the inducing protocol. To verify whether those variables altogether were determinant, NMDA or DHPG was used to chemically elicit LTD recorded up to 10 h on hippocampal slices obtained from middle-aged rats. In either form of LTD, cycloheximide did not interfere with LTD stabilization. Furthermore, DHPG application did show an increase in the global protein synthesis as assayed by radiolabeled methodology indicating that though triggered protein synthesis can occur but not necessarily required for LTD expression. The findings confirm that stabilized LTD in either juvenile, or middle-aged rats can be independent of triggered protein synthesis. Although the processes responsible for the independence of LTD stabilization on the triggered protein synthesis are not yet defined, these findings raise the possibility that de novo protein synthesis is not universally necessary. PMID:27517693

  8. Noise-induced multistability in chemical systems: Discrete versus continuum modeling

    Czech Academy of Sciences Publication Activity Database

    Duncan, A.; Liao, S.; Vejchodský, Tomáš; Erban, R.; Grima, R.

    2015-01-01

    Roč. 91, č. 4 (2015), s. 042111. ISSN 1539-3755 EU Projects: European Commission(XE) 328008 - STOCHDETBIOMODEL Institutional support: RVO:67985840 Keywords : chemical master equation * chemical Fokker-Planck equation * multimodality Subject RIV: BA - General Mathematics Impact factor: 2.288, year: 2014 http://journals.aps.org/pre/abstract/10.1103/PhysRevE.91.042111

  9. B-lymphocytes as key players in chemical-induced asthma.

    Directory of Open Access Journals (Sweden)

    Vanessa De Vooght

    Full Text Available T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE. We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO mice or severe combined immunodeficiency (SCID mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI (20 µl/ear. On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+ were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl or vehicle (acetone/olive oil (AOO (controls. Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40 and consisted of B effector (Be2- (IL-4 and Be1-lymphocytes (IFN-γ. The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.

  10. Permeability Enhancement in Fine-Grained Sediments by Chemically Induced Clay Fabric Shrinkage

    Energy Technology Data Exchange (ETDEWEB)

    Wijesinghe, A M; Kansa, E J; Viani, B E; Blake, R G; Roberts, J J; Huber, R D

    2004-02-26

    The National Research Council [1] identified the entrapment of contaminants in fine-grained clay-bearing soils as a major impediment to the timely and cost-effective remediation of groundwater to regulatory standards. Contaminants trapped in low-permeability, low-diffusivity, high-sorptivity clays are not accessible to advective flushing by treatment fluids from permeable zones, and slowly diffuse out to recontaminate previously cleaned permeable strata. We propose to overcome this barrier to effective remediation by exploiting the ability of certain nontoxic EPA-approved chemicals (e.g., ethanol) to shrink and alter the fabric of clays, and thereby create macro-porosity and crack networks in fine-grained sediments. This would significantly reduce the distance and time scales of diffusive mass transport to advectively flushed boundaries, to yield orders of magnitude reduction in the time required to complete remediation. Given that effective solutions to this central problem of subsurface remediation do not yet exist, the cost and time benefits of successful deployment of this novel concept, both as a stand-alone technology and as an enabling pre-treatment for other remedial technologies that rely on advective delivery, is likely to be very large. This project, funded as a 1-year feasibility study by LLNL's LDRD Program, is a multi-directorate, multi-disciplinary effort that leverages expertise from the Energy & Environment Directorate, the Environmental Restoration Division, and the Manufacturing & Materials Evaluation Division of Mechanical Engineering. In this feasibility study, a ''proof-of-principle'' experiment was performed to answer the central question: ''Can clay shrinkage induced by ethanol in clay-bearing sediments overcome realistic confining stresses, crack clay, and increase its effective permeability by orders of magnitude within a time that is much smaller than the time required for diffusive mass transport of

  11. Effects of sevoflurane on neuromuscular block induced by vecuronium%七氟烷对维库溴铵肌松效应的影响

    Institute of Scientific and Technical Information of China (English)

    吴慧; 张丽

    2011-01-01

    目的 观察七氟烷对维库溴铵肌松效应的影响.方法 择期全麻下行乳腺癌根治术患者60例,ASA Ⅰ~Ⅱ级,40~55岁,体质量45~80kg.随机分为七氟烷组(S组)和异丙酚组(P组),每组30例.S组吸入8%的七氟烷,氧气流量为6L/min,采用肺活量吸入法诱导,P组静脉推注异丙酚2mg/kg诱导.两组患者入睡后,均给予维库溴铵0.1mg/kg、芬太尼4μg/kg,行气管插管.S组吸入2%~3%七氟烷维持麻醉,P组微量泵泵注异丙酚4~8mg/(kg·h)维持麻醉,间断静注芬太尼.用TOF-WarchSX进行全程肌松监测.记录心率、平均动脉压变化,患者入睡时间、清醒时间、维库溴铵起效时间、作用时间、维库溴铵的平均用量、诱导期和苏醒期不良反应.结果 P组入睡时间、维库溴铵作用时间明显短于S组(P<0.01).S组清醒时间、维库溴铵起效时间明显快于P组(P<0.01),维库溴铵平均用量少于P组(P<0.01).插管前即刻S组心率下降明显(P<0.05),P组平均动脉压下降更明显(P<0.05),两组术中、术毕心率、平均动脉压均维持稳定.两组诱导时均无呛咳、屏气、喉痉挛、呼吸抑制,拔管时均无恶心、呕吐、躁动,均能正确回答问题,无任何不适.结论 七氟烷能增强维库溴铵的肌松效应,减少维库溴铵用量.%Objective To observe the effects of sevoflurane on neuromuscular block induced by vecuronium.Methods This study included 60 ASA Ⅰ or Ⅱ patients ( aged 40-60 yr, weighing 45-80 kg) who underwent radial breast cancer surgery under general anesthesia.They were randomly divided into the sevoflurane group and the propofol group( n=30 in each).Anesthesia was induced by 8% sevoflurane with vital capacity and oxygen flow at 6L/min in the sevoflurane group or 2 mg/kg of propofol in the propofol group.When the patients' eyelash reflex disappeared in the two groups, 0.1 mg/kg of vecuronium and 4 μg/kg of fentanyl were given before tracheal intubation.Anesthesia was

  12. Effect of chronic administration of green tea extract on chemically induced electrocardiographic and biochemical changes in rat heart

    Directory of Open Access Journals (Sweden)

    Patil Leena

    2010-01-01

    Full Text Available Many chemicals induce cell-specific cytotoxicity. Chemicals like doxorubicin induce oxidative stress leading to cardiotoxicity causing abnormalities in ECG and increase in the biomarkers indicating toxicity. Green tea extract (GTE, Camellia sinensis (Theaceae, is reported to exert antioxidant activity mainly by means of its polyphenolic constituent, catechins. Our study was aimed to find out the effect of GTE (25, 50, 100 mg/kg/day p.o. for 30 days on doxorubicin-induced (3 mg/kg/week, i.p. for 5 weeks electrocardiographic and biochemical changes in rat heart. It is observed that GTE administered rats were less susceptible to doxorubicin-induced electrocardiographic changes and changes in biochemical markers like lactate dehydrogenase (LDH, creatine kinase (CK, and glutamic oxaloacetate transaminase (GOT in serum, and superoxide dismutase (SOD, catalase (CAT and reduced glutathione (GSH, membrane bound enzymes like Na + K + ATPase, Ca 2+ ATPase, Mg 2+ ATPase and decreased lipid peroxidation (LP in heart tissue, indicating the protection afforded by GTE administration.

  13. Small-Angle X-ray and Neutron Scattering Study on Microphase Separation Induced by Non-Solvent in a Semi-Dilute Solution of an Ultra-High-Molecular-Weight Block Copolymer

    International Nuclear Information System (INIS)

    Full text: A block copolymer consists of immiscible different polymers covalently connected to each other and form micro domain structures such as lamellae, cylinders, spheres, gyroids, etc of the size of their own molecular size. Utilization of an ultra-high-molecular-weight block copolymer enables us to create micro domains on the order of several hundred nanometers. However, such large molecules have high viscosity due to the large number of entanglements per chain. Therefore the structures usually contain a lot of defects or distortion and are far from the equilibrated state. Here, We found a very interesting phenomenon that a microphase separation is induced by addition of a non-solvent into a semi dilute solution of an ultra-high-molecular-weight block copolymer. The solvent mixture of the common solvent and the non-solvent act as a highly selective solvent and are selectively introduced into one phase of the phase-separated state. We investigated the structures by the small-angle x-ray scattering (SAXS) technique using synchrotron radiation and the small-angle neutron scattering (SANS) technique. The results showed that micro domain structures were highly ordered and the grain size was gigantic because block copolymers in a semi dilute solution has high mobility due to the dilution effect by solvents. The SANS results showed there was not the composition fluctuation of constituent different solvent molecules in both phases. In other words, the results means the common good solvent was also selectively introduced into one phase. (author)

  14. Bacterial Cell Wall-Induced Arthritis: Chemical Composition and Tissue Distribution of Four Lactobacillus Strains

    OpenAIRE

    Šimelyte, Egle; Rimpiläinen, Marja; Lehtonen, Leena; Zhang, Xiang; Toivanen, Paavo

    2000-01-01

    To study what determines the arthritogenicity of bacterial cell walls, cell wall-induced arthritis in the rat was applied, using four strains of Lactobacillus. Three of the strains used proved to induce chronic arthritis in the rat; all were Lactobacillus casei. The cell wall of Lactobacillus fermentum did not induce chronic arthritis. All arthritogenic bacterial cell walls had the same peptidoglycan structure, whereas that of L. fermentum was different. Likewise, all arthritogenic cell walls...

  15. Docosahexaenoic acid inhibits UVB-induced activation of NF-κB and expression of COX-2 and NOX-4 in HR-1 hairless mouse skin by blocking MSK1 signaling.

    Directory of Open Access Journals (Sweden)

    Mostafizur Rahman

    Full Text Available Exposure to ultraviolet-B (UVB radiation induces inflammation and photocarcinogenesis in mammalian skin. Docosahexaenoic acid (DHA, a representative ω-3 polyunsaturated fatty acid, has been reported to possess anti-inflammatory and chemopreventive properties. In the present study, we investigated the molecular mechanisms underlying the inhibitory effects of DHA on UVB-induced inflammation in mouse skin. Our study revealed that topical application of DHA prior to UVB irradiation attenuated the expression of cyclooxygenase-2 (COX-2 and NAD(PH:oxidase-4 (NOX-4 in hairless mouse skin. DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB (NF-κB through the inhibition of phosphorylation of IκB kinase-α/β, phosphorylation and degradation of IκBα and nuclear translocation of p50 and p65. In addition, UVB-induced phosphorylation of p65 at the serine 276 residue was significantly inhibited by topical application of DHA. Irradiation with UVB induced phosphorylation of mitogen and stress-activated kinase-1 (MSK1, extracellular signal-regulated kinase (ERK and p38 mitogen-activated protein (MAP kinase, and all these events were attenuated by pretreatment with DHA. Blocking ERK and p38 MAP kinase signaling by U0126 and SB203580, respectively, diminished MSK1 phosphorylation in UVB-irradiated mouse skin. Pretreatment with H-89, a pharmacological inhibitor of MSK1, abrogated UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 in mouse skin. In conclusion, topically applied DHA inhibits the UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 by blocking the phosphorylation of MSK1, a kinase downstream of ERK and p38 MAP kinase, in hairless mouse skin.

  16. Induced mutations in chickpea (Cicer arietinum L.) I. comparative mutagenic effectiveness and efficiency of physical & chemical mutagens

    International Nuclear Information System (INIS)

    Mutagenic effectiveness usually means the rate of mutation as related to dose. Mutagenic efficiency refers to the mutation rate in relation to damage. Studies on comparative mutagenic effectiveness and efficiency of two physical (gamma rays and fast neutrons) and two chemical mutagens (NMU and EMS) on two desi (G 130 & H 214), one kabuli (C 104) and one green seeded (L 345) chickpea (Cicer arietinum L.) have been reported. The treatments included three doses each of gamma rays (400, 500 and 600 Gy) and fast neutrons (5, 10 and 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU 0.01% 20h and 0.02% 8h) and EMS (0.1% 20h and 0.2% 8h). Results indicated that chemical mutagens, particularly NMU are not only more effective but also efficient than physical mutagens in inducing mutations in chickpea. Mutagenic effectiveness and efficiency showed differential behaviour depending upon mutagen and varietal type. Chemical mutagens were more efficient than physical in inducing cholorophyll as well as viable and total number of mutations. Among the mutagens NMU was the most potent, while in the physical, gamma rays were more effective. Out of four mutagens, NMU was the most effective and efficient in inducing a high frequency and wide spectrum of chlorophyll mutations in the M2 followed by fast neutrons. While gamma rays showed least effectiveness, EMS was least efficient mutagens. Major differences in the mutagenic response of the four cultivars were observed. The varieties of desi type were more resistant towards mutagenic treatment than kabuli and green seeded type

  17. Block clustering with collapsed latent block models

    OpenAIRE

    Wyse, Jason; Friel, Nial

    2010-01-01

    We introduce a Bayesian extension of the latent block model for model-based block clustering of data matrices. Our approach considers a block model where block parameters may be integrated out. The result is a posterior defined over the number of clusters in rows and columns and cluster memberships. The number of row and column clusters need not be known in advance as these are sampled along with cluster memberhips using Markov chain Monte Carlo. This differs from existing work on latent bloc...

  18. Literature survey of chemical analysis by thermal neutron induced capture gamma ray spectrometry

    International Nuclear Information System (INIS)

    A brief discussion of the principles and techniques of chemical analysis by neutron capture gamma radiation is presented, and the widely scattered literature is collected into a single table arranged by element measured

  19. Characterization of nonpolar lipids and steroids by using laser-induced acoustic desorption/chemical ionization, atmospheric pressure chemical ionization, and electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Z; Daiya, S; Kenttämaa, Hilkka I

    Laser-induced acoustic desorption (LIAD) combined with ClMn(H{sub 2}O){sup +} chemical ionization (CI) was tested for the analysis of nonpolar lipids and selected steroids in a Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR). The nonpolar lipids studied, cholesterol, 5α-cholestane, cholesta-3,5-diene, squalene, and β-carotene, were found to solely form the desired water replacement product (adduct-H{sub 2}O) upon reaction with the ClMn(H{sub 2}O){sup +} ions. The steroids, androsterone, dehydroepiandrosterone (DHEA), estrone, estradiol, and estriol, also form abundant adduct-H{sub 2}O ions, but less abundant adduct-2H{sub 2}O ions were also observed. Neither (+)APCI nor (+)ESI can ionize the saturated hydrocarbon lipid, cholestane. APCI successfully ionizes the unsaturated hydrocarbon lipids to form exclusively the intact protonated analytes. However, it causes extensive fragmentation for cholesterol and the steroids. The worst case is cholesterol that does not produce any stable protonated molecules. On the other hand, ESI cannot ionize any of the hydrocarbon analytes, saturated or unsaturated. However, ESI can be used to protonate the oxygen-containing analytes with substantially less fragmentation than for APCI in all cases except for cholesterol and estrone. In conclusion, LIAD/ClMn(H{sub 2}O){sup +} chemical ionization is superior over APCI and ESI for the mass spectrometric characterization of underivatized nonpolar lipids and steroids.

  20. The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulin β1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Takamiya, Rina, E-mail: rinataka0429@gmail.com; Takahashi, Motoko; Uehara, Yasuaki; Ariki, Shigeru; Hashimoto, Jiro; Hasegawa, Yoshihiro; Kuroki, Yoshio

    2014-11-21

    Highlights: • The sErbB3 N418Q mutant blocks heregulin β1 induced nuclear accumulation of HIF-1α. • The sErbB3 N418Q mutant attenuates cancer cell migration induced by heregulin β1. • The sErbB3 N418Q mutant blocks heregulin β1 induced nuclear accumulation of Nrf2. • The sErbB3 N418Q mutant may be a potential therapeutic application for tumor. - Abstract: It has been well documented that activation of the ErbB3–PI3K–Akt pathway is implicated in tumor survival and progression. We previously demonstrated that the single N-glycan deletion mutant of soluble ErbB3 protein (sErbB3 N418Q) attenuates heregulin β1-induced ErbB3 signaling. The active PI3K–Akt pathway augments the nuclear accumulation of hypoxia inducible factor (HIF)-1α, which activates the transcription of many target genes and drives cancer progression. In this study, we focused on the effects of sErbB3 N418Q mutant on nuclear accumulation of HIF-1α. Pretreatment with the sErbB3 N418Q mutant suppressed heregulin β1-induced HIF-1α activation in MCF7 cells. Similar results were also obtained in other breast cancer cell lines, T47D and BT474. Interestingly, these suppressive effects were not observed with the sErbB3 wild type. In addition, pretreatment with the sErbB3 N418Q mutant suppressed the cell migration of MCF7 cells induced by heregulin β1. Furthermore, incubation with heregulin β1 also induced the nuclear accumulation of Nrf2, and this effect was also reduced by the sErbB3 N418Q mutant, but not the sErbB3 wild type. These findings indicated that the sErbB3 N418Q mutant suppressed malignant formation of cancer cells by blocking of the HIF-1α and Nrf2 pathways.

  1. Chemical gastritis induced by naproxen in the absence of Helicobacter pylori infection.

    OpenAIRE

    McCarthy, C J; McDermott, M.; Hourihane, D; O'MORAIN, C

    1995-01-01

    AIM--To evaluate the histological changes that occur in the antral mucosa of healthy male subjects before and after one week of naproxen administration, using a chemical gastritis score according to the Helicobacter pylori status. METHODS--Nineteen male subjects (mean age 31 years) underwent two endoscopies: one before and the other after one week of naproxen treatment (1 g daily). Antral biopsy specimens were assessed for the presence of H pylori infection and for chemical gastritis, defined...

  2. Ingested plastic transfers hazardous chemicals to fish and induces hepatic stress

    OpenAIRE

    Rochman, Chelsea M; Eunha Hoh; Tomofumi Kurobe; Teh, Swee J

    2013-01-01

    Plastic debris litters aquatic habitats globally, the majority of which is microscopic (< 1 mm), and is ingested by a large range of species. Risks associated with such small fragments come from the material itself and from chemical pollutants that sorb to it from surrounding water. Hazards associated with the complex mixture of plastic and accumulated pollutants are largely unknown. Here, we show that fish, exposed to a mixture of polyethylene with chemical pollutants sorbed from the marine ...

  3. Effect of Two Different Doses ofDexmedetomidine as Adjuvant in BupivacaineInduced Subarachnoid Block for ElectiveAbdominal Hysterectomy Operations: A Prospective, Double-blind, RandomizedControlled Study

    Directory of Open Access Journals (Sweden)

    Anjan Das

    2015-07-01

    Full Text Available Objectives: Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients’ long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia.  Methods: A total of 100 patients, aged 35–60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10 in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS scores, hemodynamics, and side effects were recorded.  Results: Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p0.050 without any appreciable side effects.  Conclusion: Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner.

  4. AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID:26859676

  5. Rat epidermal keratinocyte organotypic culture (ROC) as a model for chemically induced skin irritation testing

    International Nuclear Information System (INIS)

    The potential of rat epidermal keratinocyte (REK) organotypic culture (ROC) with proper stratum corneum barrier as a model for screening skin irritants was evaluated. The test chemicals were selected from ECETOC database (1995) and the observed in vitro irritation potential was compared to ECETOC in vivo primary irritation index (PII), to EU risk phrases, and to the harmonized OECD criteria. Chemicals were applied onto the stratum corneum surface of ROC for 30 min and samples were taken from the underlying medium at 4 and 8 h after exposure. Cell membrane integrity (determined by LDH assay) and pro-inflammatory effect (determined by IL-1α release) were verified at both time points and correlated to PII values. The best correlation (R 2 = 0.831) was seen with LDH leakage test. Based on obtained data, chemicals were classified according to criteria defined by EU and OECD. From 12 chemicals, only two were incorrectly classified according to OECD criteria when using LDH leakage and IL-1α release as irritation markers. At the end of experiment, chemical-treated ROC cultures were fixed and histological changes were assessed. Typical signs for irritation were lightly stained cytoplasm, condensed nuclei, cellular vacuolization, eosinophilic cytoplasms, and blebbing. These irritation effects of chemicals were graded visually into four classes (A-D). The extent of morphological perturbations of the cultures mostly correlated with PII. The present results indicate the validity of the ROC model in predicting skin irritation potential of chemicals and show that the use of set of irritation markers with different mechanistic responses gives more information on irritation than if only one marker was used

  6. Protein assay for heme oxygenase-1 (HO-1) induced by chemicals in HepG2 cells.

    Science.gov (United States)

    Miyamoto, Yohei; Ohshida, Keiyu; Sasago, Kaori

    2009-12-01

    Levels of heme oxygenase-1 (HO-1), a stress response protein, were measured to examine oxidative stress induced by several chemicals in HepG2 cells with and without S9mix using an ELISA. CdCl(2), heme, and diclofenac sodium salt (diclofenac) were used as inducers of HO-1. Acetaminophen (AAP) and cyclophosphamide (CP) were used as oxidative stress inducers. Stannic mesoporphyrin (SnMP) was used as an inhibitor of HO activity. Cytotoxicity was determined, and HO-1 levels were measured in HepG2 cells exposed to chemicals other than CP with non-metabolic activation without S9mix, and to diclofenac, AAP and CP with metabolic activation with S9mix. HO-1 levels were increased by CdCl(2) (7.5 microM), heme (10, 100 microM), and stannic mesoporphyrin (SnMP) (10 microM), but were not changed by AAP, and were decreased by diclofenac. HO-1 levels were increased by diclofenac (300 microM), and CP (36 microM), but were unaffected by AAP because of low sensitivity in HepG2 cells. The induction of HO-1 expression was first observed in cultured HepG2 cells treated with CP under conditions involving metabolic activation. These results showed the measurement of HO-1 protein levels in this system is useful when assessing oxidative stress as a tool for detecting drug toxicity. PMID:19952508

  7. Photo-induced isomerization of three nitrotoluene isomers: A matrix-isolation infrared spectroscopic and quantum-chemical study

    International Nuclear Information System (INIS)

    Graphical abstract: The photo-induced isomerization reactions of ortho-, meta- and para-nitrotoluene molecules were investigated by matrix isolation infrared spectroscopy. Besides the previously reported hydrogen atom transfer isomer of ortho-nitrotoluene, the nitrite isomers as well as the dissociation product tolyloxy radicals were formed upon UV excitation of the three nitrotoluene molecules. Infrared spectra and vibrational frequency assignments are reported. Highlights: ► Photo-induced isomerization reactions of three nitrotoluene isomers are studied. ► The nitrite isomers as well as the dissociation product tolyloxy radicals are formed. ► Infrared spectra and vibrational frequency assignments are reported. - Abstract: The photo-induced isomerization reactions of ortho-, meta- and para-nitrotoluene molecules were investigated by matrix isolation infrared spectroscopy and quantum chemical calculations. Under UV irradiation of ortho-nitrotoluene in solid argon, the hydrogen atom transfer isomer was formed, as reported previously. It was found that the hydrogen atom transfer isomer is unstable and rearranged to its nitro isomer upon annealing. In addition, the nitrite isomer as well as its dissociation product tolyloxy radical was also formed. Only the nitrite isomers and the tolyloxy radicals were formed upon UV excitation of the meta- and para-nitrotoluene molecules. Infrared spectra and vibrational frequency assignments of the newly observed nitrite isomers and tolyloxy radicals are reported, which are supported by quantum chemical calculations.

  8. Investigation of chemical vapour deposition diamond detectors by X- ray micro-beam induced current and X-ray micro-beam induced luminescence techniques

    CERN Document Server

    Olivero, P; Vittone, E; Fizzotti, F; Paolini, C; Lo Giudice, A; Barrett, R; Tucoulou, R

    2004-01-01

    Tracking detectors have become an important ingredient in high-energy physics experiments. In order to survive the harsh detection environment of the Large Hadron Collider (LHC), trackers need to have special properties. They must be radiation hard, provide fast collection of charge, be as thin as possible and remove heat from readout electronics. The unique properties of diamond allow it to fulfill these requirements. In this work we present an investigation of the charge transport and luminescence properties of "detector grade" artificial chemical vapour deposition (CVD) diamond devices developed within the CERN RD42 collaboration, performed by means of X-ray micro-beam induced current collection (XBICC) and X-ray micro- beam induced luminescence (XBIL) techniques. XBICC technique allows quantitative estimates of the transport parameters of the material to be evaluated and mapped with micrometric spatial resolution. In particular, the high resolution and sensitivity of the technique has allowed a quantitati...

  9. Tharsis block tectonics on Mars

    Science.gov (United States)

    Raitala, Jouko T.

    1988-01-01

    The concept of block tectonics provides a framework for understanding many aspects of Tharsis and adjoining structures. This Tharsis block tectonics on Mars is manifested partly by mantle-related doming and partly by response to loading by subsequent volcanic construction. Although the origin of the volcanism from beneath Tharsis is a subject of controversy explanations have to include inhomogeneities in Martian internal structure, energy distribution, magma accumulation and motion below the lithosphere. Thermal convection can be seen as a necessary consequence for transient initial phase of Martian cooling. This produced part of the elevated topography with tensional stresses and graben systems radial to the main bulge. The linear grabens, radial to the Tharsis center, can be interpreted to indicate rift zones that define the crustal block boundaries. The load-induced stresses may then have contributed on further graben and ridge formation over an extended period of time.

  10. Chemopreventive effect of Quercus infectoria against chemically induced renal toxicity and carcinogenesis

    OpenAIRE

    Rehman, Muneeb U.; Mir Tahir, Farrah Ali; Wajhul Qamar; Rehan Khan; Abdul Quaiyoom Khan; Abdul Lateef; Oday-O-Hamiza; Sarwat Sultana

    2012-01-01

    In this study we have shown that Quercus infectoria attenuates Fe- NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA promoted DEN (N-diethyl nitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC) level and PCNA expression. Fe- NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal Malondialdehyde, xanthine oxidase and hydrogen ...

  11. Characterization of root agravitropism induced by genetic, chemical, and developmental constraints

    International Nuclear Information System (INIS)

    The patterns and rates of organelle redistribution in columella (i.e., putative statocyte) cells of agravitropic agt mutants of Zea mays are not significantly different from those of columella cells in graviresponsive roots. Graviresponsive roots of Z. mays are characterized by a strongly polar movement of 45Ca2+ across the root tip from the upper to the lower side. Horizontally-oriented roots of agt mutants exhibit only a minimal polar transport of 45Ca2+. Exogenously-induced asymmetries of Ca result in curvature of agt roots toward the Ca source. A similar curvature can be induced by a Ca asymmetry in normally nongraviresponsive (i.e., lateral) roots of Phaseolus vulgaris. Similarly, root curvature can be induced by placing the roots perpendicular to an electric field. This electrotropism increase with (1) currents between 8-35 mA, and (2) time between 1-9 hr when the current is constant. Electrotropism is reduced significantly by treating roots with triiodobenzoic acid (TIBA), an inhibitor of auxin transport. These results suggest that (1) if graviperception occurs via the sedimentation of amyloplasts in columella cells, then nongraviresponsive roots apparently sense gravity as do graviresponsive roots, (2) exogenously induced asymmetries of a gravitropic effector (i.e., Ca) can induce curvature of normally nongraviresponsive roots, (3) the gravity-induced downward movement of exogenously-applied 45Ca2+ across tips of graviresponsive roots does not occur in nongraviresponsive roots, (4) placing roots in an electrical field (i.e., one favoring the movement of ions such as Ca2+) induces root curvature and (5) electrically-induced curvature is apparently dependent on auxin transport. These result are discussed relative to a model to account for the lack of graviresponsiveness by these roots

  12. Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Myung-Hoon; Kim, Do-Hee [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Na, Hye-Kyung [Department of Food and Nutrition, Sungshin Women' s University, Seoul (Korea, Republic of); Kim, Jung-Hwan; Kim, Ha-Na [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Haegeman, Guy [LEGEST, University of Gent (Belgium); Surh, Young-Joon, E-mail: surh@snu.ac.kr [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2014-10-15

    Genistein, an isoflavone present in soy products, has chemopreventive effects on mammary carcinogenesis. In the present study, we have investigated the effects of genistein on phorbol ester-induced expression of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of inflammation-associated carcinogenesis. Pretreatment of cultured human breast epithelial (MCF10A) cells with genistein reduced COX-2 expression induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). There are multiple lines of evidence supporting that the induction of COX-2 is regulated by the eukaryotic transcription factor NF-κB. Genistein failed to inhibit TPA-induced nuclear translocation and DNA binding of NF-κB as well as degradation of IκB. However, genistein abrogated the TPA-induced transcriptional activity of NF-κB as determined by the luciferase reporter gene assay. Genistein inhibited phosphorylation of the p65 subunit of NF-κB and its interaction with cAMP regulatory element-binding protein-binding protein (CBP)/p300 and TATA-binding protein (TBP). TPA-induced NF-κB phosphorylation was abolished by pharmacological inhibition of extracellular signal-regulated kinase (ERK). Likewise, pharmacologic inhibition or dominant negative mutation of ERK suppressed phosphorylation of p65. The above findings, taken together, suggest that genistein inhibits TPA-induced COX-2 expression in MCF10A cells by blocking ERK-mediated phosphorylation of p65 and its subsequent interaction with CBP and TBP.

  13. Incomplete block designs

    CERN Document Server

    Dey, Aloke

    2010-01-01

    This book presents a systematic, rigorous and comprehensive account of the theory and applications of incomplete block designs. All major aspects of incomplete block designs are considered by consolidating vast amounts of material from the literature - the classical incomplete block designs, like the balanced incomplete block (BIB) and partially balanced incomplete block (PBIB) designs. Other developments like efficiency-balanced designs, nested designs, robust designs, C-designs and alpha designs are also discussed, along with more recent developments in incomplete block designs for special t

  14. Telemetry degradation due to a CW RFI induced carrier tracking error for the block IV receiving system with maximum likelihood convolution decoding

    Science.gov (United States)

    Sue, M. K.

    1981-01-01

    Models to characterize the behavior of the Deep Space Network (DSN) Receiving System in the presence of a radio frequency interference (RFI) are considered. A simple method to evaluate the telemetry degradation due to the presence of a CW RFI near the carrier frequency for the DSN Block 4 Receiving System using the maximum likelihood convolutional decoding assembly is presented. Analytical and experimental results are given.

  15. Chemically induced dynamic electron polarization investigation of the triplet-radical system in the solution of the triplet quencher

    Institute of Scientific and Technical Information of China (English)

    LU, Tong-Xing; CUI, Zhi-Feng; XU, Xin-Sheng; ZHANG, Xian-Yi

    2000-01-01

    The chemically induced dynamic electron polariztiion (CIDEP) of the triplet molecule/triplet quencher/2,2,6,6-te tranethyl-1-piperidinyioxyl (TEMPO) systems were measured using the high time-resolved FESR spectrometer. The competi tion between the radical-triplet pair mechanism (RTPM) and triplet mechanism (TM) or radical pair mechanism (RPM) polarization in the solution of the triplet quencher was investi gated, and the relationship between reaction rate of the radi cal-triplet pair and quenching rate of triplet was deduced.

  16. Direct writing of carbon nanotube patterns by laser-induced chemical vapor deposition on a transparent substrate

    International Nuclear Information System (INIS)

    Dot array and line patterns of multi-walled carbon nanotubes (MWCNTs) were successfully grown by laser-induced chemical vapor deposition (LCVD) on a transparent substrate at room temperature. In the proposed technique, a Nd:YVO4 laser with a wavelength of 532 nm irradiates the backside of multiple catalyst layers (Ni/Al/Cr) through a transparent substrate to induce a local temperature rise, thereby allowing the direct writing of dense dot and line patterns of MWCNTs below 10 μm in size to be produced with uniform density on the controlled positions. In this LCVD method, a multiple-catalyst-layer with a Cr thermal layer is the central component for enabling the growth of dense MWCNTs with good spatial resolution.

  17. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    OpenAIRE

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Carolina H. Andrade; Tropsha, Alexander

    2015-01-01

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop ...

  18. Solar and chemical reaction-induced heating in the terrestrial mesosphere and lower thermosphere

    Science.gov (United States)

    Mlynczak, Martin G.

    1992-01-01

    Airglow and chemical processes in the terrestrial mesosphere and lower thermosphere are reviewed, and initial parameterizations of the processes applicable to multidimensional models are presented. The basic processes by which absorbed solar energy participates in middle atmosphere energetics for absorption events in which photolysis occurs are illustrated. An approach that permits the heating processes to be incorporated in numerical models is presented.

  19. Aggregate formation in a freshwater bacterial strain induced by growth state and conspecific chemical cues

    Czech Academy of Sciences Publication Activity Database

    Blom, J. F.; Horňák, Karel; Šimek, Karel; Pernthaler, J.

    2010-01-01

    Roč. 12, č. 9 (2010), s. 2486-2495. ISSN 1462-2912 R&D Projects: GA ČR(CZ) GA206/08/0015 Institutional research plan: CEZ:AV0Z60170517 Keywords : aggregate formation * Sphingobium sp. * chemical cues * growth state Subject RIV: EE - Microbiology, Virology Impact factor: 5.537, year: 2010

  20. Inducing fertility restoration in the genic male sterile line of rice with chemical regulators

    Institute of Scientific and Technical Information of China (English)

    WANGKaizhi

    1994-01-01

    For the first time, the fertility of rice genic male sterile line was partially restored with the application of chemical regulators at Hainan Rice Breeding Nursery on Mar 1993. A single panicle of the rice plant couldbear as many as 27 grains.

  1. Optimizing chemically induced resistance in tomato against Botrytis cinerea

    DEFF Research Database (Denmark)

    Luna, Estrella; Beardon, Emily G; Ravnskov, Sabine;

    2016-01-01

    repressed plant growth at higher concentrations of the chemicals, which was particularly pronounced in hydroponically grown plants after BABA treatment. Both seed coating with BABA, and seedling treatments with BABA or JA, did not affect AMF root colonization in soil-grown tomato. Our study has identified...

  2. DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-α-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-κB pathways in human gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Suck-Chei Choi; Kang-Min Lee; Won-Jung Lee; Jae-Sik Park; Chang-Yell Shin; Tae-Young Oh; Chang-Duk Jun; Eun-Ju Choi; Hyun-Mee Oh; SungGa Lee; Jeong-Kun Lee; Meung-Su Lee; Yong-Il Shin; Suck-Jun Choi; Jeong-Ryong Chae

    2006-01-01

    AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-α-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferease reporter gene assay. NF-κB-dependent transcriptional activity was determined by I-κBα degradation, NF-κB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzymelinked immunosorbent assay (ELISA). Total and phosphorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-α-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-α also induced NF-κB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-α-induced NF-κB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-α, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF κB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-κB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-α.CONCLUSION: DA-9601 blocked TNF-α-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-κB dependent pathways in gastric epithelial cells.

  3. Influence of caffeine on chromosome lesions induced by chemical mutagens and radiation. 2

    International Nuclear Information System (INIS)

    The modifying influence of caffeine on γ-ray induced chromosome lesions was studied by chromosome aberration anaysis. Caffeine was applied as a pre- and post-treatment agent following seed (G1) and root meristem (G2 and S) irradiation of C.capillaris. The frequency of chromosome aberrations induced in G1 was changed neither by post- nor by pre-treatment with caffeine. This fact proves the lack of caffeine modifying effect. Applied as a post-treatment agent caffeine enhances considerably the frequency of chromosome aberrations induced in root meristem cells. This is especially valid for G2 irradiated cells, while in S cells no synergistic effect was established between induced chromosome lesions and caffeine. The enhancement of chromosome aberration frequency produced in G2 shows a clearly manifested dependence on the time (moment) of caffeine application post irradiation. Most considerable enhancement was obtained following post-treatment with caffeine immediately after irradiation. In the following intervals - 15 and 30 min - it decreases progressively, while after 60, 180 and 300 min no enhancing effect is observed. The probable causes for the manifestation and the lack of synergistic effect between chromosome lesions induced in the various mitotic cycle phases and caffeine are discussed. (author)

  4. Dormancy in potato tuber meristems: chemically induced cessation in dormancy matches the natural process based on transcript profiles.

    Science.gov (United States)

    Campbell, Michael; Segear, Erika; Beers, Lee; Knauber, Donna; Suttle, Jeffrey

    2008-11-01

    Meristem dormancy in perennial plants is a developmental process that results in repression of metabolism and growth. The cessation of dormancy results in rapid growth and should be associated with the production of nascent transcripts that encode for gene products controlling for cell division and growth. Dormancy cessation was allowed to progress normally or was chemically induced using bromoethane (BE), and microarray analysis was used to demonstrate changes in specific transcripts in response to dormancy cessation before a significant increase in cell division. Comparison of normal dormancy cessation to BE-induced dormancy cessation revealed a commonality in both up and downregulated transcripts. Many transcripts that decrease as dormancy terminates are inducible by abscisic acid particularly in the conserved BURP domain proteins, which include the RD22 class of proteins and in the storage protein patatin. Transcripts that are associated with an increase in expression encoded for proteins in the oxoglutarate-dependent oxygenase family. We conclude that BE-induced cessation of dormancy initiates transcript profiles similar to the natural processes that control dormancy. PMID:18317824

  5. Chemical profiling with HPLC-FTMS of exogenous and endogenous chemicals susceptible to the administration of chotosan in an animal model of type 2 diabetes-induced dementia.

    Science.gov (United States)

    Niu, Yimin; Li, Feng; Inada, Chikako; Tanaka, Ken; Watanabe, Shiro; Fujiwara, Hironori; Sasaki-Hamada, Sachie; Oka, Jun-Ichiro; Matsumoto, Kinzo

    2015-02-01

    In our previous study, the daily administration of chotosan (CTS), a Kampo formula consisting of Uncaria and other 10 different crude drugs, ameliorated cognitive deficits in several animal models of dementia including type 2 diabetic db/db mice in a similar manner to tacrine, an acetylcholinesterase inhibitor. The present study investigated the metabonomics of CTS in db/db mice, a type 2 diabetes model, and m/m mice, a non-diabetes control strain, to identify the exogenous and endogenous chemicals susceptible to the administration of CTS using high performance liquid chromatography equipped with an orbitrap hybrid Fourier transform mass spectrometer. The results obtained revealed that the systemic administration of CTS for 20 days led to the distribution of Uncalia plant-derived alkaloids such as rhynchophylline, hirsuteine, and corynoxeine in the plasma and brains of db/db and m/m mice and induced alterations in four major metabolic pathways; i.e., (1) purine, (2) tryptophan, (3) cysteine and methionine, (4) glycerophospholipids in db/db mice. Moreover, glycerophosphocholine (GPC) levels in the plasma and brain were significantly higher in CTS-treated db/db mice than in vehicle-treated control animals. The results of the in vitro experiment using organotypic hippocampal slice cultures demonstrated that GPC (10-30 μM), as well as tacrine, protected hippocampal cells from N-methyl-d-aspartate-induced excitotoxicity in a manner that was reversible with the muscarinic receptor antagonist scopolamine, whereas GPC had no effect on the activity of acetylcholinesterase in vitro. Our results demonstrated that some CTS constituents with neuropharmacological activity were distributed in the plasma and brain tissue following the systemic administration of CTS and may subsequently have affected some metabolic pathways including glycerophospholipid metabolism and cognitive function in db/db mice. Moreover, the present metabonomic analysis suggested that GPC is a putative

  6. Bio-molecular alterations induced by a chemical or radiating stress in isolated human cells

    International Nuclear Information System (INIS)

    After having recalled some aspects of radiobiology (effects of ionizing radiations, molecular targets of radiations, cellular responses with respect to the radiation), the author discusses various aspects of radio-sensitivity: intrinsic radio-sensitivity of tumoral and normal cells, DNA injuries and in vitro radio-sensitivity, genes of susceptibility to ionizing radiations, clustered injuries. Then she reports investigations performed by infrared micro-spectroscopy: characterization of pathological lines, of biological processes, of oxidative injuries induced by xenobiotics, of injuries induced by ionizing radiations

  7. Postural heart block.

    OpenAIRE

    Seda, P E; McAnulty, J H; Anderson, C J

    1980-01-01

    A patient presented with orthostatic dizziness and syncope caused by postural heart block. When the patient was supine, atrioventricular conduction was normal and he was asymptomatic; when he was standing he developed second degree type II block and symptoms. The left bundle-branch block on his electrocardiogram and intracardiac electrophysiological study findings suggest that this heart block occurred distal to the His bundle. Orthostatic symptoms are usually presumed to be secondary to an i...

  8. Graphene-Semiconductor Catalytic Nanodiodes for Quantitative Detection of Hot Electrons Induced by a Chemical Reaction.

    Science.gov (United States)

    Lee, Hyosun; Nedrygailov, Ievgen I; Lee, Young Keun; Lee, Changhwan; Choi, Hongkyw; Choi, Jin Sik; Choi, Choon-Gi; Park, Jeong Young

    2016-03-01

    Direct detection of hot electrons generated by exothermic surface reactions on nanocatalysts is an effective strategy to obtain insight into electronic excitation during chemical reactions. For this purpose, we fabricated a novel catalytic nanodiode based on a Schottky junction between a single layer of graphene and an n-type TiO2 layer that enables the detection of hot electron flows produced by hydrogen oxidation on Pt nanoparticles. By making a comparative analysis of data obtained from measuring the hot electron current (chemicurrent) and turnover frequency, we demonstrate that graphene's unique electronic structure and extraordinary material properties, including its atomically thin nature and ballistic electron transport, allow improved conductivity at the interface between the catalytic Pt nanoparticles and the support. Thereby, graphene-based nanodiodes offer an effective and facile way to approach the study of chemical energy conversion mechanisms in composite catalysts with carbon-based supports. PMID:26910271

  9. Size-Induced Enhancement of Chemical Exchange Saturation Transfer (CEST) Contrast in Liposomes

    OpenAIRE

    Zhao, Jason M.; Har-el, Yah-el; McMahon, Michael T.; Zhou, Jinyuan; Sherry, A. Dean; Sgouros, George; Bulte, Jeff W. M.; van Zijl, Peter C.M.

    2008-01-01

    Liposome-based chemical exchange saturation transfer (lipoCEST) agents have shown great sensitivity and potential for molecular magnetic resonance imaging (MRI). Here we demonstrate that the size of liposomes can be exploited to enhance the lipoCEST contrast. A concise analytical model is developed to describe the contrast dependence on size for an ensemble of liposomes. The model attributes the increased lipoCEST contrast in smaller liposomes to their larger surface-to-volume ratio, causing ...

  10. Conformational Changes in Azurin from Pseudomona aeruginosa Induced through Chemical and Physical Protocols

    OpenAIRE

    Fuentes, Lymari; Oyola, Jessica; Fernández, Mónica; Quiñones, Edwin

    2004-01-01

    Azurin from Pseudomona aeruginosa is a small copper protein with a single tryptophan (Trp) buried in the structure. The Gibbs free energies associated with the folding of holo azurin, calculated monitoring Trp fluorescence and changes in absorbance on the ligand-to-metal band, are different because these techniques probe their local environments, thereby being able to probe different conformational changes. The presence of an intermediate state was observed during the chemical denaturation of...

  11. Laser-induced chemical liquid deposition of discontinuous and continuous copper films

    Czech Academy of Sciences Publication Activity Database

    Ouchi, A.; Bastl, Zdeněk; Boháček, Jaroslav; Šubrt, Jan; Pola, Josef

    2007-01-01

    Roč. 201, č. 8 (2007), s. 4728-4733. ISSN 0257-8972 R&D Projects: GA AV ČR 1ET400400413 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502; CEZ:AV0Z40720504 Keywords : copper films * laser photolysis * Cu(II) acetylacetonate * chemical liquid deposition Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.678, year: 2007

  12. Synthesis of High-Purity Chemical Library Reveals a Potent Inducer of Oxidative Stress

    OpenAIRE

    Cui, Jiayue; Matsumoto, Kenji; Wang, Cindy Y.; Peter, Marcus E.; Kozmin, Sergey A.

    2010-01-01

    Synthesis of high-purity biogenic heterocyclic library enabled identification of a small molecule, which potently inhibited proliferation of several cancer cell lines and induces rapid oxidative stress. This agent elicited unusual mechanism of cell death induction, which entailed activation of both caspase-dependent and independent pathways.

  13. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Science.gov (United States)

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-01-01

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID:27271106

  14. Room temperature chemically oxidized La2CuO4+y: Phase separation induced by thermal treatment

    DEFF Research Database (Denmark)

    Rial,C.; Moran, E.; Alario-Franco, M.A.;

    1997-01-01

    The structure of roam temperature chemically oxidized La2CuO4+y [y = 0.103(4)] has been refined from powder neutron diffraction data using the space group Bmab. The modifications induced in the CuO2 and the LaO planes by the insertion of oxygen are consistent with the high T-c measured for this m......The structure of roam temperature chemically oxidized La2CuO4+y [y = 0.103(4)] has been refined from powder neutron diffraction data using the space group Bmab. The modifications induced in the CuO2 and the LaO planes by the insertion of oxygen are consistent with the high T-c measured...... for this material. The thermogravimetric analysis(TGA) of La2CuO4.103(4) evidences an unexplained two-step mass loss process. Based on this observation, three samples obtained by different thermal treatments of the fully oxidized material were studied by TGA, X-ray diffraction and AC magnetic susceptibility, After......, it seems likely that the plateau observed in the TGA curve of La2CuO4.103(4) might be due to the formation on heating of a stable phase with a fixed oxygen stoichiometry, i.e. La2CuO4.086(4). The stability of this phase could be related-to the presence of one-dimensional interstitial oxygen ordering along...

  15. Protective Effect of Zanthoxylum nitidum Bark in Chemical and Stress Induced Gastric Mucosal Lesions in Male Albino Rats

    Directory of Open Access Journals (Sweden)

    K. Zaman

    2012-01-01

    Full Text Available Zanthoxylum nitidum (Roxb. DC (Rutaceae, called Tez-mui or Tejamool in Assamese, is a large prickly shrub occurring in North-Eastern India and its roots are used traditionally for several medicinal purposes. In the present study, the aqueous extract from the stem bark of Zanthoxylum nitidum (ZNA was evaluated for its protective effects on gastric mucosal lesions in male Wistar albino rats against acetylsalicylic acid (ASA, ethanol and water immersion restraint stress induced gastric mucosal damage. In each model, ZNA was administered orally to rats at the doses of 100 and 200 mg kg-1 body weight, prior to chemical or stress challenge, followed by determination of ulcer index. Ranitidine hydrochloride at the dose of 35 mg kg-1, p.o. served as the reference drug. The test extract exhibited dose dependent and significant amelioration of gastric mucosal lesions in chemical (ASA and ethanol as well as in stress-induced ulcers in male Wistar albino rats, thus confirming its antiulcer potential.

  16. Chemical characterization of nuclear technology materials by in situ current normalized particle induced gamma-ray emission method

    International Nuclear Information System (INIS)

    Chemical characterization of materials is the most important step in chemical quality control (CQC) exercise, which provides a means to ensure the quality of the fabricated/prepared/procured material as per the required chemical specifications. In the case of nuclear technology materials, the finished products should meet the stringent chemical specifications at major to trace concentration levels. Routine chemical characterization methods include mainly wet chemical (classical), chromatographic (IC and HPLC) and, atomic and mass spectroscopic techniques (AAS, ICP-AES and ICP-MS) and in some cases radio/nuclear analytical techniques like alpha and gamma-ray spectrometry, XRF, neutron activation analysis (NAA) and ion beam analysis (IBA) are used. If the samples are of glass, ceramic, carbide and alloy matrices, nuclear analytical techniques (NATs) namely NAA, prompt gamma-ray NAA (PGNAA) and particle induced gamma-ray emission (PIGE) have edge over wet-chemical methods due to many advantageous properties including nondestructive in nature. PIGE, an on-line technique of ion beam analysis (IBA), is capable of determining low to medium Z elements like Li, Be, B, C, N, O, F, Na, Mg, Si, Al, P and S or still higher depending on the energy of proton beam from tandem accelerators. It involves measurement of prompt gamma-rays from nuclear reactions like (p, p'γ), (p, γ), (p, nγ) and (p, αγ) for concentration of an isotope thus element in a sample. Radiochemistry Division (RCD), BARC set-up and utilized PIGE facilities at FOTIA, BARC, IOP, Bhubaneswar and BARC-TIFR using 4 and 8 MeV proton beam. An in situ current normalized PIGE method has been developed, wherein an element namely F, Li or Al is externally added to the target pellet or a thin aluminium foil is kept in front of the target. The variation of beam current, if any, is obtained by measuring simultaneously the count rate of element of interest and the in situ current normalizer

  17. The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity

    Directory of Open Access Journals (Sweden)

    Andersson David A

    2010-01-01

    Full Text Available Abstract Background The cooling agents menthol and icilin act as agonists at TRPM8 and TRPA1. In vitro, activation of TRPM8 by icilin and cold, but not menthol, is dependent on the activity of a sub-type of phospholipase A2, iPLA2. Lysophospholipids (e.g. LPC produced by PLA2 activity can also activate TRPM8. The role of TRPA1 as a primary cold sensor in vitro is controversial, although there is evidence that TRPA1 plays a role in behavioural responses to noxious cold stimuli. In this study, we have investigated the roles of TRPM8 and TRPA1 and the influence of iPLA2 on noxious cold sensitivities in naïve animals and after local administration of menthol, icilin and LPC. The roles of the channels in cold sensitivity were investigated in mice lacking either TRPM8 (Trpm8-/- or TRPA1 (Trpa1-/-. Results Intraplantar administration of icilin evoked a dose-dependent increase in sensitivity to a 10°C stimulus that was inhibited by iPLA2 inhibition with BEL. In contrast the cold hypersensitivities elicited by intraplantar menthol and LPC were not inhibited by BEL treatment. BEL had no effect on basal cold sensitivity and mechanical hypersensitivities induced by the TRPV1 agonist, capsaicin, and the P2X3 agonist α,β-methylene ATP. Both Trpm8-/- and Trpa1-/- mice showed longer latencies for paw withdrawal from a 10°C stimulus than wild-type littermates. Cold hypersensitivities induced by either icilin or LPC were absent in Trpm8-/- mice but were retained in Trpa1-/- mice. In contrast, cold hypersensitivity evoked by menthol was present in Trpm8-/- mice but was lost in Trpa1-/- mice. Conclusions The findings that iPLA2 inhibition blocked the development of cold hypersensitivity after administration of icilin but failed to affect menthol-induced hypersensitivity agree well with our earlier in vitro data showing a differential effect of iPLA2 inhibition on the agonist activities of these agents. The ability of LPC to induce cold hypersensitivity

  18. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  19. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

    OpenAIRE

    Xin Wang; Wujing Dai; Yanrang Wang; Qing Gu; Deyi Yang; Ming Zhang

    2015-01-01

    Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short ha...

  20. Modeling early physical and chemical events for DNA damage induced by photons and tritium beta particles

    International Nuclear Information System (INIS)

    A method has been developed to model production of single-strand breaks (SSB) and double-strand breaks (DSB) in Deoxyribo Nucleic Acid (DNA) by ionizing radiations. Modeling is carried out by Monte Carlo means and includes consideration of direct energy depositions in DNA molecules, production of chemical species following water radiolysis, diffusion of chemical species, and their interactions with each other and DNA. Computer-generated electron tracks in liquid water are used to model energy deposition and to derive the initial localization of chemical species. Atomistic representation of the DNA with a first hydration shell is used to derive direct energy depositions in DNA molecules and the resulting consequences, and to derive coordinates of reactive sites for modeling of the chemical stage of radiation damage. Diffusion of chemical species is followed in time, and the reactions of species with each other and DNA are considered to occur in an encounter-controlled manner. Time of diffusion follow-up is restricted to 10-12- 10-9 s, which yields a diffusion length of hydroxyl radicals comparable to that in the cellular environment. DNA SSB are assumed to result from any direct energy depositions in the sugar/phosphate moiety, ionizations in water molecules bound to sugar/phosphate and hydroxyl attacks on deoxyribose. DSB are assumed to result from two SSB on opposite strands separated by 10 or fewer base pairs. Photon radiations in the energy range 70 keV-1 MeV and tritium beta particles are considered. It is shown that for naked DNA in B-form (the configuration thought to be most biologically relevant) the effectiveness of tritium for SSB and DSB production is, within statistical uncertainties, comparable to photon radiation with energies in the range 70 keV-1 MeV, although a tendency for increased DSB production has been observed for 70 keV photons that represent orthovoltage X-rays and for tritium beta particles. It is predicted that hydroxyl radicals react

  1. Modeling early physical and chemical events for DNA damage induced by photons and tritium beta particles

    Energy Technology Data Exchange (ETDEWEB)

    Moiseenko, V. [McMaster Univ., Dept. of Physics and Astronomy, Hamilton, Ontario (Canada); Waker, A.J. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Prestwich, W.V. [McMaster Univ., Dept. of Physics and Astronomy, Hamilton, Ontario (Canada)

    1998-02-01

    A method has been developed to model production of single-strand breaks (SSB) and double-strand breaks (DSB) in Deoxyribo Nucleic Acid (DNA) by ionizing radiations. Modeling is carried out by Monte Carlo means and includes consideration of direct energy depositions in DNA molecules, production of chemical species following water radiolysis, diffusion of chemical species, and their interactions with each other and DNA. Computer-generated electron tracks in liquid water are used to model energy deposition and to derive the initial localization of chemical species. Atomistic representation of the DNA with a first hydration shell is used to derive direct energy depositions in DNA molecules and the resulting consequences, and to derive coordinates of reactive sites for modeling of the chemical stage of radiation damage. Diffusion of chemical species is followed in time, and the reactions of species with each other and DNA are considered to occur in an encounter-controlled manner. Time of diffusion follow-up is restricted to 10{sup -12}- 10{sup -9} s, which yields a diffusion length of hydroxyl radicals comparable to that in the cellular environment. DNA SSB are assumed to result from any direct energy depositions in the sugar/phosphate moiety, ionizations in water molecules bound to sugar/phosphate and hydroxyl attacks on deoxyribose. DSB are assumed to result from two SSB on opposite strands separated by 10 or fewer base pairs. Photon radiations in the energy range 70 keV-1 MeV and tritium beta particles are considered. It is shown that for naked DNA in B-form (the configuration thought to be most biologically relevant) the effectiveness of tritium for SSB and DSB production is, within statistical uncertainties, comparable to photon radiation with energies in the range 70 keV-1 MeV, although a tendency for increased DSB production has been observed for 70 keV photons that represent orthovoltage X-rays and for tritium beta particles. It is predicted that hydroxyl

  2. Depth-resolved chemical mapping of rock coatings using Laser-Induced Breakdown Spectroscopy: Implications for geochemical investigations on Mars

    Science.gov (United States)

    Lefebvre, C.; Catalá-Espí, A.; Sobron, P.; Koujelev, A.; Léveillé, R.

    2016-07-01

    We demonstrate that Laser-Induced Breakdown Spectroscopy (LIBS) is capable of identifying the presence of natural rock coatings, and we define LIBS signatures of complex multi-layered coatings. This is illustrated by detailed LIBS analysis, in Mars-simulated conditions, of a rock collected in the Svalbard Islands, and which is analogous to some altered Martian rocks. The sample is a basaltic rock with sub-mm Ca-Mg-Fe-Si rich mineral coatings. LIBS elemental analysis of several distinct regions on the surface of the rock demonstrates the variability of chemical compositions of the various coatings, which is confirmed by complementary scanning electron microscope (SEM) analysis. Furthermore, the LIBS analysis as a function of the depth at different locations shows chemical variability, indicative of penetration through thin coatings of varying composition. Fine-scale, three-dimensional LIBS analysis is of interest for identifying and characterizing coatings on martian rocks, likely originating from aqueous processes, providing a rapid chemical composition as a function of the layers and further understanding of the formation of the deposits and on planetary evolution.

  3. 2-Methoxy-4-vinylphenol can induce cell cycle arrest by blocking the hyper-phosphorylation of retinoblastoma protein in benzo[a]pyrene-treated NIH3T3 cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Bioresource Sciences, Andong National University, Andong 760749 (Korea, Republic of); Jeong, Hyung Jin, E-mail: jhj@andong.ac.kr [Bioresource Sciences, Andong National University, Andong 760749 (Korea, Republic of)

    2010-10-01

    Research highlights: {yields} 2M4VP activated the expression of p21 and p15 protein, and down-regulated the expression of cyclin D1 and cyclin E. {yields} 2M4VP inhibited hyper-phosphorylation of Rb protein. {yields} 2M4VP induced cell cycle arrest from G1 to S. {yields} 2M4VP inhibited hyper-proliferation of the cells in BaP-treated cells. {yields} 2M4VP induces growth arrest of BaP-treated cells by blocking hyper-phosphorylation of Rb via regulating the expression of cell cycle-related proteins. -- Abstract: Benzo[a]pyrene (BaP) is an environment carcinogen that can enhance cell proliferation by disturbing the signal transduction pathways in cell cycle regulation. In this study, the effects of 2M4VP on cell proliferation, cell cycle and cell cycle regulatory proteins were studied in BaP-treated NIH 3T3 cells to establish the molecular mechanisms of 2M4VP as anti-proliferative agents. 2M4VP exerted a dose-dependent inhibitory effect on cell growth correlated with a G1 arrest. Analysis of G1 cell cycle regulators expression revealed 2M4VP increased expression of CDK inhibitor, p21Waf1/Cip1 and p15 INK4b, decreased expression of cyclin D1 and cyclin E, and inhibited kinase activities of CDK4 and CDK2. However, 2M4VP did not affect the expression of CDK4 and CDK2. Also, 2M4VP inhibited the hyper-phosphorylation of Rb induced by BaP. Our results suggest that 2M4VP induce growth arrest of BaP-treated NIH 3T3 cells by blocking the hyper-phosphorylation of Rb via regulating the expression of cell cycle-related proteins.

  4. Rapid self-assembly of block copolymers to photonic crystals

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Yan; Sveinbjornsson, Benjamin R; Grubbs, Robert H; Weitekamp, Raymond; Miyake, Garret M; Atwater, Harry A; Piunova, Victoria; Daeffler, Christopher Scot; Hong, Sung Woo; Gu, Weiyin; Russell, Thomas P.

    2016-07-05

    The invention provides a class of copolymers having useful properties, including brush block copolymers, wedge-type block copolymers and hybrid wedge and polymer block copolymers. In an embodiment, for example, block copolymers of the invention incorporate chemically different blocks comprising polymer size chain groups and/or wedge groups that significantly inhibit chain entanglement, thereby enhancing molecular self-assembly processes for generating a range of supramolecular structures, such as periodic nanostructures and microstructures. The present invention also provides useful methods of making and using copolymers, including block copolymers.

  5. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    International Nuclear Information System (INIS)

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  6. Rheosmin, a naturally occurring phenolic compound inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-kappaB activation pathway.

    Science.gov (United States)

    Jeong, Jin Boo; Jeong, Hyung Jin

    2010-01-01

    Inflammation is part of the host defense mechanism against harmful matters and injury; however, aberrant inflammation is associated to the development of chronic disease such as cancer. Raspberry ketone is a natural phenolic compound. It is used in perfumery, in cosmetics, and as a food additive to impart a fruity odor. In this study, we evaluated whether rheosmin, a phenolic compound isolated from pine needles regulates the expression of iNOS and COX-2 protein in LPS-stimulated RAW264.7 cells. Rheosmin dose-dependently inhibited NO and PGE(2) production and also blocked LPS-induced iNOS and COX-2 expression. Rheosmin potently inhibited the translocation of NF-kappaB p65 into the nucleus by IkappaB degradation following IkappaB-alpha phosphorylation. This result shows that rheosmin inhibits NF-kappaB activation. In conclusion, our results suggest that rheosmin inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-kappaB activation pathway. PMID:20478352

  7. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along......Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes....

  8. De Novo Assembly and Transcriptome Analysis of Wheat with Male Sterility Induced by the Chemical Hybridizing Agent SQ-1.

    Directory of Open Access Journals (Sweden)

    Qidi Zhu

    Full Text Available Wheat (Triticum aestivum L., one of the world's most important food crops, is a strictly autogamous (self-pollinating species with exclusively perfect flowers. Male sterility induced by chemical hybridizing agents has increasingly attracted attention as a tool for hybrid seed production in wheat; however, the molecular mechanisms of male sterility induced by the agent SQ-1 remain poorly understood due to limited whole transcriptome data. Therefore, a comparative analysis of wheat anther transcriptomes for male fertile wheat and SQ-1-induced male sterile wheat was carried out using next-generation sequencing technology. In all, 42,634,123 sequence reads were generated and were assembled into 82,356 high-quality unigenes with an average length of 724 bp. Of these, 1,088 unigenes were significantly differentially expressed in the fertile and sterile wheat anthers, including 643 up-regulated unigenes and 445 down-regulated unigenes. The differentially expressed unigenes with functional annotations were mapped onto 60 pathways using the Kyoto Encyclopedia of Genes and Genomes database. They were mainly involved in coding for the components of ribosomes, photosynthesis, respiration, purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, RNA transport and signal transduction, reactive oxygen species metabolism, mRNA surveillance pathways, protein processing in the endoplasmic reticulum, protein export, and ubiquitin-mediated proteolysis. This study is the first to provide a systematic overview comparing wheat anther transcriptomes of male fertile wheat with those of SQ-1-induced male sterile wheat and is a valuable source of data for future research in SQ-1-induced wheat male sterility.

  9. De Novo Assembly and Transcriptome Analysis of Wheat with Male Sterility Induced by the Chemical Hybridizing Agent SQ-1.

    Science.gov (United States)

    Zhu, Qidi; Song, Yulong; Zhang, Gaisheng; Ju, Lan; Zhang, Jiao; Yu, Yongang; Niu, Na; Wang, Junwei; Ma, Shoucai

    2015-01-01

    Wheat (Triticum aestivum L.), one of the world's most important food crops, is a strictly autogamous (self-pollinating) species with exclusively perfect flowers. Male sterility induced by chemical hybridizing agents has increasingly attracted attention as a tool for hybrid seed production in wheat; however, the molecular mechanisms of male sterility induced by the agent SQ-1 remain poorly understood due to limited whole transcriptome data. Therefore, a comparative analysis of wheat anther transcriptomes for male fertile wheat and SQ-1-induced male sterile wheat was carried out using next-generation sequencing technology. In all, 42,634,123 sequence reads were generated and were assembled into 82,356 high-quality unigenes with an average length of 724 bp. Of these, 1,088 unigenes were significantly differentially expressed in the fertile and sterile wheat anthers, including 643 up-regulated unigenes and 445 down-regulated unigenes. The differentially expressed unigenes with functional annotations were mapped onto 60 pathways using the Kyoto Encyclopedia of Genes and Genomes database. They were mainly involved in coding for the components of ribosomes, photosynthesis, respiration, purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, RNA transport and signal transduction, reactive oxygen species metabolism, mRNA surveillance pathways, protein processing in the endoplasmic reticulum, protein export, and ubiquitin-mediated proteolysis. This study is the first to provide a systematic overview comparing wheat anther transcriptomes of male fertile wheat with those of SQ-1-induced male sterile wheat and is a valuable source of data for future research in SQ-1-induced wheat male sterility. PMID:25898130

  10. Ability of structurally diverse natural products and synthetic chemicals to induce gene expression mediated by estrogen receptors from various species.

    Science.gov (United States)

    Matthews, J B; Fertuck, K C; Celius, T; Huang, Y-W; Fong, C J; Zacharewski, T R

    2002-10-01

    The ability of 14 structurally diverse estrogenic compounds to induce reporter gene expression mediated by estrogen receptors (ERs) from different species was examined. MCF-7 cells were transiently transfected with a Gal4-regulated luciferase reporter gene (17m5-G-Luc) and Gal4-ER chimeric receptors containing the D, E and F domains of the human alpha (Gal4-hERalphadef), mouse alpha (Gal4-mERalphadef), mouse beta (Gal4-mERbetadef), chicken (Gal4-cERalphadef), green anole (Gal4-aERalphadef), Xenopus (Gal4-xERdef) or rainbow trout alpha ERs (Gal4-rtERalphadef). The efficacy of 17beta-estradiol (E2) in inducing reporter gene expression was similar among the different constructs overall, with EC(50) values ranging from 0.05 to 0.7nM. However, Gal4-rtERalphadef had an EC(50) value at 37 degrees C of 28nM, though at 20 degrees C an EC(50) value of 1nM was observed. Despite a similar response to E2 treatment among the ERs, many differences were observed in the magnitude of the response to other structurally diverse chemicals. For example, coumestrol induced Gal4-mERbetadef- and Gal4-aERdef-mediated reporter gene expression 164- and 8-fold greater, respectively, than mediated with the other Gal4-ERs. As well, in contrast to results with other Gal4-ERs, alpha-zearalenol consistently induced Gal4-rtERalphadef-mediated reporter gene activity at lower concentrations than did E2. Overall, the results demonstrate that selected estrogenic compounds exhibit a differential ability to induce reporter gene activity mediated by ERs from different vertebrate species. These data also highlight the importance of incubation temperature when examining rtERalpha-mediated activity. PMID:12477484

  11. Synthesis and Characterization of Novel Magnetite Nanoparticle Block Copolymer Complexes

    OpenAIRE

    Zhang, Qian

    2007-01-01

    Superparamagnetic Magnetite (Fe3O4) nanoparticles were synthesized and complexed with carboxylate-functionalized block copolymers, and aqueous dispersions of the complexes were investigated as functions of their chemical and morphological structures. The block copolymer dispersants possessed either poly(ethylene oxide), poly(ethylene oxide-co-propylene oxide), or poly(ethylene oxide-b-propylene oxide) outer blocks, and all contained a polyurethane center block with pendant carboxylate functi...

  12. Chronic desipramine prevents acute stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Liebenberg, Nico;

    2014-01-01

    acute foot-shock (FS)-stress. By means of serial section electron microscopy, the structural remodeling of medial prefrontal cortex (mPFC) glutamate synapses was assessed soon after acute stressor cessation and stress hormone levels were measured. FS-stress induced a remarkable increase in the number of...... docked vesicles and small excitatory synapses, partially and strongly prevented by DMI pretreatment, respectively. Acute stress-induced corticosterone elevation was not affected by drug treatment. Since DMI pretreatment prevented the stress-induced structural plasticity but not the hormone level increase...

  13. Mitotic recombination induced by chemical and physical agents in the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    The treatment of diploid cultures of yeast with ultraviolet light (uv), γ-rays, nitrous acid (na) and ethyl methane sulphonate (ems) results in increases in cell death, mitotic gene conversion and crossing-over. Acridine orange (ao) treatment, in contrast, was effective only in increasing the frequency of gene conversion. The individual mutagens were effective in the order uv>na>γ-rays>ao>ems. Prior treatment of yeast cultures in starvation medium produced a significant reduction in the yield of induced gene conversion. The results have been interpreted on the basis of a general model of mitotic gene conversion which involves the post-replication repair of induced lesions involving de novo DNA synthesis without genetic exchange. In contrast mitotic crossing-over appears to involve the action of a repair system independent from excision or post-replication repair which involves genetic exchange between homologous chromosomes

  14. Chemical inducible promoter used to obtain transgenic plants with a silent marker and organisms and cells and methods of using same for screening for mutations

    Science.gov (United States)

    Zuo, Jianru; Chua, Nam-Hai

    2007-06-12

    Disclosed is a chemically inducible promoter for transforming plants or plant cells with genes which are regulatable by adding the plants or cells to a medium containing an inducer or by removing them from such medium. The promoter is inducible by a glucocorticoid, estrogen or inducer not endogenous to plants. Such promoters may be used with any plant genes that can promote shoot regeneration and development to induce shoot formation in the presence of a glucocorticoid, estrogen or inducer. The promoter may be used with antibiotic or herbicide resistance genes or other genes which are regulatable by the presence or absence of a given inducer. Also presented are organisms or cells comprising a gene wherein the natural promoter of the gene is disrupted and the gene is placed under the control of a transgenic inducible promoter. These organisms and cells and their progeny are useful for screening for conditional gain of function and loss of function mutations.

  15. Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges

    OpenAIRE

    Payne, Heather; Adamson, Andrew; Bahl, Amit; Borwell, Jonathan; Dodds, David; Heath, Catherine; Huddart, Robert; McMenemin, Rhona; Patel, Prashant; Peters, John L; Thompson, Andrew

    2013-01-01

    To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. A systema...

  16. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice

    OpenAIRE

    Jian-Hong Ye; Meng-Hua Liu; Xu-Lin Zhang; Jing-Yu He

    2015-01-01

    Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography -diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, signi...

  17. Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.

    Science.gov (United States)

    Ubillos, Luis; Freire, Teresa; Berriel, Edgardo; Chiribao, María Laura; Chiale, Carolina; Festari, María Florencia; Medeiros, Andrea; Mazal, Daniel; Rondán, Mariella; Bollati-Fogolín, Mariela; Rabinovich, Gabriel A; Robello, Carlos; Osinaga, Eduardo

    2016-04-01

    Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4(+) and CD8(+) T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c(+) His48(-) MHC II(+) cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti-T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth. PMID:26519949

  18. Chemical composition and deformation-induced stresses in ferroelectric films of barium-strontium titanate

    International Nuclear Information System (INIS)

    Influence of the ratio of cationic components and inner deformation-induced stresses on critical temperature (Tc) and dielectric characteristics of ferroelectric films BaxSr1-xTiO3 grown on α-Al2O3 [1012] and LaAlO3 substrates was studied. Diagnosis by means of ion backscattering permitted ascertaining the deficiency of barium in the films near the surface layer, as well as differences in their structural quality

  19. Use of silicate shells to prevent sintering during thermally induced chemical ordering of iron platinum nanoparticles

    Science.gov (United States)

    Reed, Dwayne Fitzgerald

    Its very high value of magnetocrystalline anisotropy makes the L1 0 phase of FePt a leading candidate for future high density magnetic recording systems. FePt nanoparticles can be prepared by a number of chemical methods. However, these particles have a face-centered cubic structure, with low anisotropy and are superparamagnetic. They must be heated to temperatures above 500 °C to obtain the chemically ordered L10 phase. However, during heating the particles coalesce to give twinned grains with large sizes (10-30 nm). Here we provide a solution to the sintering problem by developing a sol-gel procedure for coating the FePt particles with an amorphous silica shell. The silica shell prevents the FePt particles from agglomerating when heated to 700 °C to effect chemical ordering. FePt nanoparticles were prepared by the super-hydride reduction of platinum(II) acetylacetonate and iron(II) chloride in hot diphenyl ether in the presence of oleylamine and oleic acid capping ligands. The particles had an average diameter of 5-6 nm, a face-centered cubic structure and were superparamagnetic. The particles were coated using a microemulsion process producing a 6 nm silicon oxide shell with a single nanoparticle core-shell structure. The nanoparticles were heated to 700 °C for times of 30 min and 1hr to achieve L10 phase transformation. These samples were annealed in a tube furnace under 95% Ar/5% H2. Many procedures were found to be ineffective. They mostly consisted of biphasic reaction systems and several trials where reaction variables were altered in search of the appropriate conditions. This work has impacted the search for a higher density magnetic recording medium by allowing the study of FePt under a protected environment while achieving chemical ordering. If the L10 FePt nanoparticles will be used in magnetic recording, the particles will require a hard coating to prevent wear. In the course of the present work, it has been shown that the silicate shells

  20. In Vivo Screening of Chemically Modified RNA duplexes for their Ability to Induce Innate Immune Responses

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Bramsen, Jesper Bertram; Kjems, Jørgen; Wengel, Jesper; Lorenzen, Niels

    Due to their sequence specific gene targeting activity siRNAs are regarded as promising active compounds in gene medicine. But one serious problem with delivering siRNAs as treatment is the now well-established non-specific activities of some RNA duplexes. Cellular reactions towards double stranded...... protection against a fish pathogenic virus. This protection corresponded with an interferon response in the fish. Here we use this fish model to screen siRNAs containing various chemical modifications of the RNA backbone for their antiviral activity, the overall aim being identification of an siRNA form with...