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Sample records for aisi d3 tool

  1. Investment cast AISI H13 tooling for automotive applications

    SciTech Connect

    Maguire, M.C.; Baldwin, M.D.; Hochanadel, P.W.; Edwards, G.R.

    1995-07-01

    While many techniques exist for production of soft tooling, for die casting there is limited recent experience with cast tooling. The most common US alloy used for manufacture of die casting tooling is wrought AISI H13. If the performance of the cast material is comparable to the wrought counterpart, the use of investment cast HI 3 tooling directly from patterns made via rapid prototyping is of considerable interest. A metallurgical study of investment cast H13 was conducted to evaluate the mechanical behavior in simulated die casting applications. Variable thickness plate investment castings of AISI H13 hot work die steel were produced and characterized in the as-cast and heat-treated conditions. The characterization included light microscopy and mechanical testing. Wrought samples of standard and premium grade H13 were heat-treated and characterized similarly for comparison. Microstructural differences were observed in as-cast samples produced in different section thicknesses. Dendrite cell size and carbide morphology constituted the most prominent microstructural differences observed. After a full heat-treatment, microstructural differences between the wrought material and cast materials were slight regardless of section thickness.The mechanical properties of the cast and heat-treated material proved similar to the properties of the standard heat-treated wrought material. A thermal fatigue testing unit was to con-elate the heat checking susceptibility of H13 steel to its processing and consequent microstructural condition. Surface hardness decreased significantly with thermal cycling, and heat checking was observed in as few as 50 cycles. Thermal softening and thermal fatigue susceptibility were quantified and discussed relative to the microstructural conditions created by processing and heat-treatment. It was found that the premium grade wrought H13 steel provided the best overall resistance to heat checking.

  2. Modelling of Tool Wear and Residual Stress during Machining of AISI H13 Tool Steel

    NASA Astrophysics Data System (ADS)

    Outeiro, José C.; Umbrello, Domenico; Pina, José C.; Rizzuti, Stefania

    2007-05-01

    Residual stresses can enhance or impair the ability of a component to withstand loading conditions in service (fatigue, creep, stress corrosion cracking, etc.), depending on their nature: compressive or tensile, respectively. This poses enormous problems in structural assembly as this affects the structural integrity of the whole part. In addition, tool wear issues are of critical importance in manufacturing since these affect component quality, tool life and machining cost. Therefore, prediction and control of both tool wear and the residual stresses in machining are absolutely necessary. In this work, a two-dimensional Finite Element model using an implicit Lagrangian formulation with an automatic remeshing was applied to simulate the orthogonal cutting process of AISI H13 tool steel. To validate such model the predicted and experimentally measured chip geometry, cutting forces, temperatures, tool wear and residual stresses on the machined affected layers were compared. The proposed FE model allowed us to investigate the influence of tool geometry, cutting regime parameters and tool wear on residual stress distribution in the machined surface and subsurface of AISI H13 tool steel. The obtained results permit to conclude that in order to reduce the magnitude of surface residual stresses, the cutting speed should be increased, the uncut chip thickness (or feed) should be reduced and machining with honed tools having large cutting edge radii produce better results than chamfered tools. Moreover, increasing tool wear increases the magnitude of surface residual stresses.

  3. Modeling of the flow stress for AISI H13 Tool Steel during Hard Machining Processes

    NASA Astrophysics Data System (ADS)

    Umbrello, Domenico; Rizzuti, Stefania; Outeiro, José C.; Shivpuri, Rajiv

    2007-04-01

    In general, the flow stress models used in computer simulation of machining processes are a function of effective strain, effective strain rate and temperature developed during the cutting process. However, these models do not adequately describe the material behavior in hard machining, where a range of material hardness between 45 and 60 HRC are used. Thus, depending on the specific material hardness different material models must be used in modeling the cutting process. This paper describes the development of a hardness-based flow stress and fracture models for the AISI H13 tool steel, which can be applied for range of material hardness mentioned above. These models were implemented in a non-isothermal viscoplastic numerical model to simulate the machining process for AISI H13 with various hardness values and applying different cutting regime parameters. Predicted results are validated by comparing them with experimental results found in the literature. They are found to predict reasonably well the cutting forces as well as the change in chip morphology from continuous to segmented chip as the material hardness change.

  4. Surface modification of AISI H13 tool steel by laser cladding with NiTi powder

    NASA Astrophysics Data System (ADS)

    Norhafzan, B.; Aqida, S. N.; Chikarakara, E.; Brabazon, D.

    2016-04-01

    This paper presents laser cladding of NiTi powder on AISI H13 tool steel surface for surface properties enhancement. The cladding process was conducted using Rofin DC-015 diffusion-cooled CO2 laser system with wavelength of 10.6 µm. NiTi powder was pre-placed on H13 tool steel surface. The laser beam was focused with a spot size of 90 µm on the sample surface. Laser parameters were set to 1515 and 1138 W peak power, 18 and 24 % duty cycle and 2300-3500 Hz laser pulse repetition frequency. Hardness properties of the modified layer were characterized by Wilson Hardness tester. Metallographic study and chemical composition were conducted using field emission scanning electron microscope and energy-dispersive X-ray spectrometer (EDXS) analysis. Results showed that hardness of NiTi clad layer increased three times that of the substrate material. The EDXS analysis detected NiTi phase presence in the modified layer up to 9.8 wt%. The metallographic study shows high metallurgical bonding between substrate and modified layer. These findings are significant to both increased hardness and erosion resistance of high-wear-resistant components and elongating their lifetime.

  5. Microstructure and Mechanical Properties of Laser Clad and Post-cladding Tempered AISI H13 Tool Steel

    NASA Astrophysics Data System (ADS)

    Telasang, Gururaj; Dutta Majumdar, Jyotsna; Wasekar, Nitin; Padmanabham, G.; Manna, Indranil

    2015-05-01

    This study reports a detailed investigation of the microstructure and mechanical properties (wear resistance and tensile strength) of hardened and tempered AISI H13 tool steel substrate following laser cladding with AISI H13 tool steel powder in as-clad and after post-cladding conventional bulk isothermal tempering [at 823 K (550 °C) for 2 hours] heat treatment. Laser cladding was carried out on AISI H13 tool steel substrate using a 6 kW continuous wave diode laser coupled with fiber delivering an energy density of 133 J/mm2 and equipped with a co-axial powder feeding nozzle capable of feeding powder at the rate of 13.3 × 10-3 g/mm2. Laser clad zone comprises martensite, retained austenite, and carbides, and measures an average hardness of 600 to 650 VHN. Subsequent isothermal tempering converted the microstructure into one with tempered martensite and uniform dispersion of carbides with a hardness of 550 to 650 VHN. Interestingly, laser cladding introduced residual compressive stress of 670 ± 15 MPa, which reduces to 580 ± 20 MPa following isothermal tempering. Micro-tensile testing with specimens machined from the clad zone across or transverse to cladding direction showed high strength but failure in brittle mode. On the other hand, similar testing with samples sectioned from the clad zone parallel or longitudinal to the direction of laser cladding prior to and after post-cladding tempering recorded lower strength but ductile failure with 4.7 and 8 pct elongation, respectively. Wear resistance of the laser surface clad and post-cladding tempered samples (evaluated by fretting wear testing) registered superior performance as compared to that of conventional hardened and tempered AISI H13 tool steel.

  6. Wear and Adhesive Failure of Al2O3 Powder Coating Sprayed onto AISI H13 Tool Steel Substrate

    NASA Astrophysics Data System (ADS)

    Amanov, Auezhan; Pyun, Young-Sik

    2016-07-01

    In this study, an alumina (Al2O3) ceramic powder was sprayed onto an AISI H13 hot-work tool steel substrate that was subjected to sanding and ultrasonic nanocrystalline surface modification (UNSM) treatment processes. The significance of the UNSM technique on the adhesive failure of the Al2O3 coating and on the hardness of the substrate was investigated. The adhesive failure of the coating sprayed onto sanded and UNSM-treated substrates was investigated by a micro-scratch tester at an incremental load. It was found, based on the obtained results, that the coating sprayed onto the UNSM-treated substrate exhibited a better resistance to adhesive failure in comparison with that of the coating sprayed onto the sanded substrate. Dry friction and wear property of the coatings sprayed onto the sanded and UNSM-treated substrates were assessed by means of a ball-on-disk tribometer against an AISI 52100 steel ball. It was demonstrated that the UNSM technique controllably improved the adhesive failure of the Al2O3 coating, where the critical load was improved by about 31%. Thus, it is expected that the application of the UNSM technique to an AISI H13 tool steel substrate prior to coating may delay the adhesive failure and improve the sticking between the coating and the substrate thanks to the modified and hardened surface.

  7. Cytoscape tools for the web age: D3.js and Cytoscape.js exporters.

    PubMed

    Ono, Keiichiro; Demchak, Barry; Ideker, Trey

    2014-01-01

    In this paper we present new data export modules for Cytoscape 3 that can generate network files for Cytoscape.js and D3.js. Cytoscape.js exporter is implemented as a core feature of Cytoscape 3, and D3.js exporter is available as a Cytoscape 3 app. These modules enable users to seamlessly export network and table data sets generated in Cytoscape to popular JavaScript library readable formats. In addition, we implemented template web applications for browser-based interactive network visualization that can be used as basis for complex data visualization applications for bioinformatics research. Example web applications created with these tools demonstrate how Cytoscape works in modern data visualization workflows built with traditional desktop tools and emerging web-based technologies. This interactivity enables researchers more flexibility than with static images, thereby greatly improving the quality of insights researchers can gain from them.

  8. Cytoscape tools for the web age: D3.js and Cytoscape.js exporters

    PubMed Central

    Ono, Keiichiro; Demchak, Barry; Ideker, Trey

    2014-01-01

    In this paper we present new data export modules for Cytoscape 3 that can generate network files for Cytoscape.js and D3.js. Cytoscape.js exporter is implemented as a core feature of Cytoscape 3, and D3.js exporter is available as a Cytoscape 3 app. These modules enable users to seamlessly export network and table data sets generated in Cytoscape to popular JavaScript library readable formats. In addition, we implemented template web applications for browser-based interactive network visualization that can be used as basis for complex data visualization applications for bioinformatics research. Example web applications created with these tools demonstrate how Cytoscape works in modern data visualization workflows built with traditional desktop tools and emerging web-based technologies. This interactivity enables researchers more flexibility than with static images, thereby greatly improving the quality of insights researchers can gain from them. PMID:25520778

  9. Finite Element Modelling of the effect of tool rake angle on tool temperature and cutting force during high speed machining of AISI 4340 steel

    NASA Astrophysics Data System (ADS)

    Sulaiman, S.; Roshan, A.; Ariffin, M. K. A.

    2013-12-01

    In this paper, a Finite Element Method (FEM) based on the ABAQUS explicit software which involves Johnson-Cook material model was used to simulate cutting force and tool temperature during high speed machining (HSM) of AISI 4340 steel. In this simulation work, a tool rake angle ranging from 0° to 20° and a range of cutting speeds between 300 to 550 m/min was investigated. The purpose of this simulation analysis was to find optimum tool rake angle where cutting force is smallest as well as tool temperature is lowest during high speed machining. It was found that cutting forces to have a decreasing trend as rake angle increased to positive direction. The optimum rake angle observed between 10° and 18° due to decrease of cutting force as 20% for all simulated cutting speeds. In addition, increasing cutting tool rake angle over its optimum value had negative influence on tool's performance and led to an increase in cutting temperature. The results give a better understanding and recognition of the cutting tool design for high speed machining processes.

  10. Combining Aspirin with Cholecalciferol (Vitamin D3) – A Potential New Tool for Controlling Possum Populations

    PubMed Central

    Morgan, David R.; Arrow, Jane; Smith, Mark P.

    2013-01-01

    The introduced Australian brushtail possum is a major vertebrate pest in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Cholecalciferol (vitamin D3) is registered for use in controlling possums and despite its many advantages it is expensive and relatively inhumane. Combination of a high proportion of aspirin with a low proportion of cholecalciferol was effective in killing high proportions of groups of acclimatised, caged possums: this is attributed to both an unexpectedly high toxicity of the type of cholecalciferol used, and a proposed synergistic mechanism between the two compounds. Death was caused by localised damage to heart ventricles by aspirin, and inhibition of tissue repair by both aspirin and cholecalciferol. The observed toxicosis had lower impact on the welfare of possums than either compound administered alone, particularly aspirin alone. Residue analyses of bait remains in the GI tract suggested a low risk of secondary poisoning by either compound. The combination of cholecalciferol and aspirin has the potential to meet key requirements of cost-effectiveness and humaneness in controlling possum populations, but the effect of the combination in non-target species has yet to be tested. PMID:23950982

  11. Effects of Deep Cryogenic Treatment on the Wear Resistance and Mechanical Properties of AISI H13 Hot-Work Tool Steel

    NASA Astrophysics Data System (ADS)

    Çiçek, Adem; Kara, Fuat; Kıvak, Turgay; Ekici, Ergün; Uygur, İlyas

    2015-11-01

    In this study, a number of wear and tensile tests were performed to elucidate the effects of deep cryogenic treatment on the wear behavior and mechanical properties (hardness and tensile strength) of AISI H13 tool steel. In accordance with this purpose, three different heat treatments (conventional heat treatment (CHT), deep cryogenic treatment (DCT), and deep cryogenic treatment and tempering (DCTT)) were applied to tool steel samples. DCT and DCTT samples were held in nitrogen gas at -145 °C for 24 h. Wear tests were conducted on a dry pin-on-disk device using two loads of 60 and 80 N, two sliding velocities of 0.8 and 1 m/s, and a wear distance of 1000 m. All test results showed that DCT improved the adhesive wear resistance and mechanical properties of AISI H13 steel. The formation of small-sized and uniformly distributed carbide particles and the transformation of retained austenite to martensite played an important role in the improvements in the wear resistance and mechanical properties. After cleavage fracture, the surfaces of all samples were characterized by the cracking of primary carbides, while the DCT and DCTT samples displayed microvoid formation by decohesion of the fine carbides precipitated during the cryo-tempering process.

  12. Comparison of surface roughness and chip characteristics obtained under different modes of lubrication during hard turning of AISI H13 tool work steel.

    NASA Astrophysics Data System (ADS)

    Raj, Anil; Wins, K. Leo Dev; Varadarajan, A. S.

    2016-09-01

    Surface roughness is one of the important parameters, which not only affects the service life of a component but also serves as a good index of machinability. Near Dry Machining, methods (NDM) are considered as sustainable alternative for workshops trying to bring down their dependence on cutting fluids and the hazards associated with their indiscriminate usage. The present work presents a comparison of the surface roughness and chip characteristics during hard turning of AISI H13 tool work steel using hard metal inserts under two popular NDM techniques namely the minimal fluid application and the Minimum Quantity Lubrication technique(MQL) using an experiment designed based on Taguchi's techniques. The statistical method of analysis of variance (ANOVA) was used to determine the relative significance of input parameters consisting of cutting speed, feed and depth of cut on the attainable surface finish and the chip characteristics. It was observed that the performance during minimal fluid application was better than that during MQL application.

  13. Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status

    PubMed Central

    Hollis, Bruce W.; Wagner, Carol L.; Drezner, Mark K.; Binkley, Neil C.

    2007-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months. Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be. PMID:17218096

  14. Hot hardness characteristics of ausformed AISI M-50, Matrix 2, WD-65, modified AISI 440-C, and Super Nitralloy

    NASA Technical Reports Server (NTRS)

    Chevalier, J. L.; Dietrich, M. W.; Zaretsky, E. V.

    1973-01-01

    Short-term hot hardness studies were performed with ausformed AISI M-50, Matrix 2, WD-65, modified AISI 440-C (14-4-1) and case hardened Super Nitralloy. Hardness levels of each material were measured at elevated temperatures in an electric furnace with a low oxygen environment. Test temperatures ranged from 294 to 877 K. The hot hardness characteristics of the ausformed AISI-M-50, Matrix 2 WD-65, and modified AISI 440-C were the same as those determined for high-speed tool steels. Hot hardness for these steels can be predicted within one point Rockwell C. The hot hardness characteristics of both the case and core of Super Nitralloy were superior to AISI 52100 but inferior to the high-speed tool steels. The short-term Rockwell C hardness at temperature for the Super Nitralloy material between 294 and 769 K can be predicted within one point Rockwell C hardness.

  15. Effect of cryogenic treatment on microstructure, mechanical and wear behaviors of AISI H13 hot work tool steel

    NASA Astrophysics Data System (ADS)

    Koneshlou, Mahdi; Meshinchi Asl, Kaveh; Khomamizadeh, Farzad

    2011-01-01

    This paper focuses on the effects of low temperature (subzero) treatments on microstructure and mechanical properties of H13 hot work tool steel. Cryogenic treatment at -72 °C and deep cryogenic treatment at -196 °C were applied and it was found that by applying the subzero treatments, the retained austenite was transformed to martensite. As the temperature was decreased more retained austenite was transformed to martensite and it also led to smaller and more uniform martensite laths distributed in the microstructure. The deep cryogenic treatment also resulted in precipitation of more uniform and very fine carbide particles. The microstructural modification resulted in a significant improvement on the mechanical properties of the H13 tool steel.

  16. Wear and friction behavior of Zr implanted D3 steel

    SciTech Connect

    Akbas, N.; Saklakoglu, I.E.; Monteiro, O.R.; Brown, I.G.

    2001-08-23

    Multicharged, pure, high current and pulsed ion beams of Zr have been extracted from a metal vapor vacuum arc (MEVVA) source and implanted into AISI D3 (C: 2-2,35%, Mn: 0,60%, Si: 0,60%, Cr: 11-13,50%, Ni: 0,30%, W: 1%, V: 1%) tool steel samples at the 3,6.1016, 5.1016 and 1.1017 ions/cm2 doses. The wear resistance and friction coefficient have been estimated using pin-on-disc wear tests. Implantation of Zr decreased the wear loss and friction coefficient. RBS, AES and SEM Microprobe analyses were used as a guide for explanation of implantation's effects.

  17. NOTE: A software tool for 2D/3D visualization and analysis of phase-space data generated by Monte Carlo modelling of medical linear accelerators

    NASA Astrophysics Data System (ADS)

    Neicu, Toni; Aljarrah, Khaled M.; Jiang, Steve B.

    2005-10-01

    A computer program has been developed for novel 2D/3D visualization and analysis of the phase-space parameters of Monte Carlo simulations of medical accelerator radiation beams. The software is written in the IDL language and reads the phase-space data generated in the BEAMnrc/BEAM Monte Carlo code format. Contour and colour-wash plots of the fluence, mean energy, energy fluence, mean angle, spectra distribution, energy fluence distribution, angular distribution, and slices and projections of the 3D ZLAST distribution can be calculated and displayed. Based on our experience of using it at Massachusetts General Hospital, the software has proven to be a useful tool for analysis and verification of the Monte Carlo generated phase-space files. The software is in the public domain.

  18. AISI direct steelmaking program

    SciTech Connect

    Aukrust, E.

    1991-01-09

    AISI with co-funding from DOE has initiated a research and development program aimed at the development of a new process for direct steelmaking, and the program is discussed in this document. The project is expected to cost about $30 million over a three-year period, with the government providing approximately 77 percent of the funds and AISI the balance. In contrast to current steelmaking processes which are largely open and batch, the direct steelmaking process would be closed and continuous. Further, it would use coal directly, thereby avoiding the need for coke ovens. The second year of the Direct Steelmaking Program (November 29, 1989, through November 28, 1990) was a year of significant accomplishment. The various research programs proceeded essentially on schedule and the pilot plant, the centerpiece of the program, was completed about three months behind schedule but began operation in almost a picture-perfect manner. This report presents the last years accomplishments.

  19. Effect of Energy Input on the Characteristic of AISI H13 and D2 Tool Steels Deposited by a Directed Energy Deposition Process

    NASA Astrophysics Data System (ADS)

    Park, Jun Seok; Park, Joo Hyun; Lee, Min-Gyu; Sung, Ji Hyun; Cha, Kyoung Je; Kim, Da Hye

    2016-05-01

    Among the many additive manufacturing technologies, the directed energy deposition (DED) process has attracted significant attention because of the application of metal products. Metal deposited by the DED process has different properties than wrought metal because of the rapid solidification rate, the high thermal gradient between the deposited metal and substrate, etc. Additionally, many operating parameters, such as laser power, beam diameter, traverse speed, and powder mass flow rate, must be considered since the characteristics of the deposited metal are affected by the operating parameters. In the present study, the effect of energy input on the characteristics of H13 and D2 steels deposited by a direct metal tooling process based on the DED process was investigated. In particular, we report that the hardness of the deposited H13 and D2 steels decreased with increasing energy input, which we discuss by considering microstructural observations and thermodynamics.

  20. Surface fatigue and failure characteristics of hot-forged powder metal AISI 4620, AISI 4640, and machined AISI 4340 steel spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.

    1987-01-01

    Spur gear surface fatigue endurance tests were conducted to investigate hot forged powder metal AISI 4620 and 4640 steel for use as a gear material, to determine endurance characteristics and to compare the results with machined AISI 4340 and 9310 steel gear materials. The as-forged and unground AISI 4620 gear exhibited a 10 percent fatigue life that was approximately one-fourth of that for AISI 9310 and less than one-half that for the AISI 4340 gears. The forged and finish ground AISI 4620 gears exhibited a 10 percent life, approximately 70 percent that of AISI 9310 and slightly better than that of AISI 4340. The AISI 4640 hot forged gears had less fracture toughness and slightly less fatigue life than the AISI 4620 test gears.

  1. Surface fatigue and failure characteristics of hot forged powder metal AISI 4620, AISI 4640, and machined AISI 4340 steel spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.

    1986-01-01

    Spur gear surface fatigue endurance tests were conducted to investigate hot forged powder metal AISI 4620 and 4640 steel for use as a gear material, to determine endurance characteristics and to compare the results with machined AISI 4340 and 9310 steel gear materials. The as-forged and unground SISI 4620 gear exhibited a 10 percent fatigue life that was approximately one-fourth of that for AISI 9310 and less than one-half that for the AISI 4340 gears. The forged and finish ground AISI 4620 gears exhibited a 10 percent life, approximately 70 percent that of AISI 9310 and slightly better than that of AISI 4340. The AISI 4640 hot forged gears had less fracture toughness and slightly less fatigue life than the AISI 4620 test gears.

  2. Comparing the Formability of AISI 304 and AISI 202 Stainless Steels

    NASA Astrophysics Data System (ADS)

    du Toit, M.; Steyn, H. G.

    2012-07-01

    The formability of AISI 202 austenitic stainless steel was compared with that of type AISI 304 stainless steel. Type 202 is a low-nickel austenitic stainless steel alloyed with manganese and nitrogen. In this study, the formability of the two grades was examined using Erichsen cupping tests and room temperature uniaxial tensile tests performed at various angles to the rolling direction. AISI 202 appears to work-harden at a slightly higher rate than AISI 304, even though the austenite in type 202 is more stable than that in 304 with respect to the formation of deformation-induced α' martensite. Although both grades are predicted to be susceptible to earing during deep drawing, AISI 202 displays a higher work-hardening exponent, higher average normal anisotropy, and a higher limiting drawing ratio than AISI 304. Similar cup heights were measured during Erichsen cupping tests, confirming that the two grades have very similar deep drawing properties. The results of this investigation therefore suggest that AISI 202 is a suitable alternative for AISI 304 in applications requiring good deep drawing properties.

  3. Atomic diffusion in laser surface modified AISI H13 steel

    NASA Astrophysics Data System (ADS)

    Aqida, S. N.; Brabazon, D.; Naher, S.

    2013-07-01

    This paper presents a laser surface modification process of AISI H13 steel using 0.09 and 0.4 mm of laser spot sizes with an aim to increase surface hardness and investigate elements diffusion in laser modified surface. A Rofin DC-015 diffusion-cooled CO2 slab laser was used to process AISI H13 steel samples. Samples of 10 mm diameter were sectioned to 100 mm length in order to process a predefined circumferential area. The parameters selected for examination were laser peak power, pulse repetition frequency (PRF), and overlap percentage. The hardness properties were tested at 981 mN force. Metallographic study and energy dispersive X-ray spectroscopy (EDXS) were performed to observe presence of elements and their distribution in the sample surface. Maximum hardness achieved in the modified surface was 1017 HV0.1. Change of elements composition in the modified layer region was detected in the laser modified samples. Diffusion possibly occurred for C, Cr, Cu, Ni, and S elements. The potential found for increase in surface hardness represents an important method to sustain tooling life. The EDXS findings signify understanding of processing parameters effect on the modified surface composition.

  4. The D3 Middleware Architecture

    NASA Technical Reports Server (NTRS)

    Walton, Joan; Filman, Robert E.; Korsmeyer, David J.; Lee, Diana D.; Mak, Ron; Patel, Tarang

    2002-01-01

    DARWIN is a NASA developed, Internet-based system for enabling aerospace researchers to securely and remotely access and collaborate on the analysis of aerospace vehicle design data, primarily the results of wind-tunnel testing and numeric (e.g., computational fluid-dynamics) model executions. DARWIN captures, stores and indexes data; manages derived knowledge (such as visualizations across multiple datasets); and provides an environment for designers to collaborate in the analysis of test results. DARWIN is an interesting application because it supports high-volumes of data. integrates multiple modalities of data display (e.g., images and data visualizations), and provides non-trivial access control mechanisms. DARWIN enables collaboration by allowing not only sharing visualizations of data, but also commentary about and views of data. Here we provide an overview of the architecture of D3, the third generation of DARWIN. Earlier versions of DARWIN were characterized by browser-based interfaces and a hodge-podge of server technologies: CGI scripts, applets, PERL, and so forth. But browsers proved difficult to control, and a proliferation of computational mechanisms proved inefficient and difficult to maintain. D3 substitutes a pure-Java approach for that medley: A Java client communicates (though RMI over HTTPS) with a Java-based application server. Code on the server accesses information from JDBC databases, distributed LDAP security services, and a collaborative information system. D3 is a three tier-architecture, but unlike 'E-commerce' applications, the data usage pattern suggests different strategies than traditional Enterprise Java Beans - we need to move volumes of related data together, considerable processing happens on the client, and the 'business logic' on the server-side is primarily data integration and collaboration. With D3, we are extending DARWIN to handle other data domains and to be a distributed system, where a single login allows a user

  5. Vitamin D3 metabolism in dogs.

    PubMed

    Hazewinkel, H A W; Tryfonidou, M A

    2002-11-29

    Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs

  6. Laser Surface Hardening of AISI 1045 Steel

    NASA Astrophysics Data System (ADS)

    Li, Ruifeng; Jin, Yajuan; Li, Zhuguo; Qi, Kai

    2014-09-01

    The study investigates laser surface hardening in the AISI 1045 steel using two different types of industrial laser: a high-power diode laser (HPDL) and a CO2 laser, respectively. The effect of process parameters such as beam power, travel speed on structure, case depth, and microhardness was examined. In most cases, a heat-affected zone (HAZ) formed below the surface; a substantial increase in surface hardness was achieved. In addition, big differences were found between the hardened specimens after HPDL surface hardening and CO2 laser surface hardening. For HPDL, depths of the HAZ were almost equal in total HAZ o, without surface melting. For CO2 laser, the depths changed a lot in the HAZ, with surface melting in the center. To better understand the difference of laser hardening results when use these two types of laser, numerical (ANSYS) analysis of the heat conduction involved in the process was also studied. For HPDL method, a rectangular beam spot and uniform energy distribution across the spot were assumed, while for CO2 laser, a circular beam spot and Gaussian energy distribution were assumed. The results showed that the energy distribution variety altered the thermal cycles of the HAZ dramatically. The rectangular HPDL laser beam spot with uniform energy distribution is much more feasible for laser surface hardening.

  7. Vitamin D3 and brain development.

    PubMed

    Eyles, D; Brown, J; Mackay-Sim, A; McGrath, J; Feron, F

    2003-01-01

    Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain. PMID:12710973

  8. Colloquium on Large Scale Improvement: Implications for AISI

    ERIC Educational Resources Information Center

    McEwen, Nelly, Ed.

    2008-01-01

    The Alberta Initiative for School Improvement (AISI) is a province-wide partnership program whose goal is to improve student learning and performance by fostering initiatives that reflect the unique needs and circumstances of each school authority. It is currently ending its third cycle and ninth year of implementation. "The Colloquium on Large…

  9. Recovery and recrystallization in AISI 321 steel under static conditions

    NASA Astrophysics Data System (ADS)

    Kratochvíl, P.; Smola, B.; Stulíková, I.; Vostrý, P.; Jandoš, F.; Šedivec, J.

    1985-03-01

    Static softening of AISI 321 steel after cold and hot deformation characterizing the industrial thermomechanical treatment was studied by means of tensile tests and TEM. The deformation temperature, the strain and the grain size were the main parameters determining the final softening. The results can be applied for optimization of the solution annealing.

  10. Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia.

    PubMed

    Colby, Jennifer K; Abdulnour, Raja-Elie E; Sham, Ho Pan; Dalli, Jesmond; Colas, Romain A; Winkler, Jeremy W; Hellmann, Jason; Wong, Blenda; Cui, Ye; El-Chemaly, Souheil; Petasis, Nicos A; Spite, Matthew; Serhan, Charles N; Levy, Bruce D

    2016-07-01

    Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid-derived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid-initiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3-treated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel γ expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-κB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function. PMID:27171898

  11. "Scrubbing" Data for D3M

    ERIC Educational Resources Information Center

    Mercurius, Neil

    2005-01-01

    Data-driven decision-making (D3M) appears to be the new buzz phrase for this century, the information age. On the education front, teachers and administrators are engaging in data-centered dialog in grade-level meetings, lounges, hallways, and classrooms as they brainstorm toward closing the gap in student achievement. Clearly, such discussion…

  12. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  13. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  14. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  15. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  16. 42 CFR 52d.3 - Eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.3 Eligibility. To be eligible for a grant under this part, an applicant..., affiliated teaching hospital, or specialized cancer institute; and (b) Located in a State, the District...

  17. Primary Human Osteoblasts in Response to 25-Hydroxyvitamin D3, 1,25-Dihydroxyvitamin D3 and 24R,25-Dihydroxyvitamin D3

    PubMed Central

    van der Meijden, Karen; Lips, Paul; van Driel, Marjolein; Heijboer, Annemieke C.; Schulten, Engelbert A. J. M.; den Heijer, Martin; Bravenboer, Nathalie

    2014-01-01

    The most biologically active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has well known direct effects on osteoblast growth and differentiation in vitro. The precursor 25-hydroxyvitamin D3 (25(OH)D3) can affect osteoblast function via conversion to 1,25(OH)2D3, however, it is largely unknown whether 25(OH)D3 can affect primary osteoblast function on its own. Furthermore, 25(OH)D3 is not only converted to 1,25(OH)2D3, but also to 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) which may have bioactivity as well. Therefore we used a primary human osteoblast model to examine whether 25(OH)D3 itself can affect osteoblast function using CYP27B1 silencing and to investigate whether 24R,25(OH)2D3 can affect osteoblast function. We showed that primary human osteoblasts responded to both 25(OH)D3 and 1,25(OH)2D3 by reducing their proliferation and enhancing their differentiation by the increase of alkaline phosphatase, osteocalcin and osteopontin expression. Osteoblasts expressed CYP27B1 and CYP24 and synthesized 1,25(OH)2D3 and 24R,25(OH)2D3 dose-dependently. Silencing of CYP27B1 resulted in a decline of 1,25(OH)2D3 synthesis, but we observed no significant differences in mRNA levels of differentiation markers in CYP27B1-silenced cells compared to control cells after treatment with 25(OH)D3. We demonstrated that 24R,25(OH)2D3 increased mRNA levels of alkaline phosphatase, osteocalcin and osteopontin. In addition, 24R,25(OH)2D3 strongly increased CYP24 mRNA. In conclusion, the vitamin D metabolites 25(OH)D3, 1,25(OH)2D3 and 24R,25(OH)2D3 can affect osteoblast differentiation directly or indirectly. We showed that primary human osteoblasts not only respond to 1,25(OH)2D3, but also to 24R,25(OH)2D3 by enhancing osteoblast differentiation. This suggests that 25(OH)D3 can affect osteoblast differentiation via conversion to the active metabolite 1,25(OH)2D3, but also via conversion to 24R,25(OH)2D3. Whether 25(OH)D3 has direct actions on osteoblast function needs further

  18. Ultrasonic and metallographic studies on AISI 4140 steel exposed to hydrogen at high pressure and temperature

    NASA Astrophysics Data System (ADS)

    Oruganti, Malavika

    This thesis conducts an investigation to study the effects of hydrogen exposure at high temperature and pressure on the behavior of AISI 4140 steel. Piezoelectric ultrasonic technique was primarily used to evaluate surface longitudinal wave velocity and defect geometry variations, as related to time after exposure to hydrogen at high temperature and pressure. Critically refracted longitudinal wave technique was used for the former and pulse-echo technique for the latter. Optical microscopy and scanning electron microscopy were used to correlate the ultrasonic results with the microstructure of the steel and to provide better insight into the steel behavior. The results of the investigation indicate that frequency analysis of the defect echo, determined using the pulse-echo technique at regular intervals of time, appears to be a promising tool for monitoring defect growth induced by a high temperature and high pressure hydrogen-related attack.

  19. Dense plasma focus-assisted nitriding of AISI-304

    NASA Astrophysics Data System (ADS)

    Shafiq, M.; Asghar, M.; Ahmad, S.; Sadiq, M.; Qayyum, A.; Zakaullah, M.

    Nitrogen ion implantation into AISI-304 stainless steel is carried out using a dense plasma focus device, operated at a charging voltage of 18 kV (discharge energyD1.45 kJ) with nitrogen filling at optimum pressure of 0.75 mbar. AISI-304 stainless steel samples placed axially above the anode tip are exposed to the ions for 10, 20 and 30 focus shots. X-ray diffraction (XRD), Vickers's micro hardness tester, scanning electron microscopy, and energy dispersive X-ray spectroscopy are used to explore the ion induced changes in the crystallographic structures, surface morphology, elemental composition and surface hardness of the ion irradiated samples. The XRD pattern confirms the formation of an expanded austenite phase, owing to nitrogen incorporated into the existing iron lattice. The results of micro hardness tester show that the hardness is increased about three times at an axial distance of 5 cm for 20 shots.

  20. The aluminizing in powder technology of AISI 304 steel

    NASA Astrophysics Data System (ADS)

    Băitanu, D. B.; Găluşcă, D. G.; Achiţei, D. C.; Minciună, M. G.; Bakri Abdullah, Mohd Mustafa Al

    2016-06-01

    The paper presents a study about the aluminizing treatments applied to AISI 304 stainless steel, with the purpose to improve the corrosion resistance. The aluminizing is realized in a powder medium, composed by aluminium powder (with 99.95% purity), aluminium oxide Al2O3 and ammonium chloride NH4Cl. The structural characterization was made by scanning electronic microscopy to highlight the structure of layer after aluminizing, at different magnitudes.

  1. Fragmentation of primary coarse macrostructure of AISI 321 steel

    NASA Astrophysics Data System (ADS)

    Jandoš, F.; Mazanec, K.; Kasl, J.; Kuneš, J.

    1988-04-01

    Fragmentation of primary grains in an ingot of AISI 321 steel was studied under common hammer forging conditions, i.e. at a temperature gradient existing in the cross-section of the ingot. It has been found that recrystallization in the surface zone starts by deformation induced migration of large subgrains observed inside primary grains, that static recrystallization takes place by intragranular twinning and that the fragmentation of the primary macrostructure is conditioned by static recrystallization.

  2. Comparison of pitting fatigue life of ausforged and standard forged AISI M-50 and AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Bamberger, E. N.; Zaretsky, E. V.

    1975-01-01

    Standard forged and ausforged spur gears made of vacuum-induction-melted, consumable-electrode, vacuum-arc-remelted AISI M-50 steel were tested under conditions that produced fatigue pitting. The gears were 8.89 cm (3.5 in.) in pitch diameter and had tip relief. The M-50 standard forged and ausforged test results were compared with each other. They were then compared with results for machined vacuum-arc-remelted AISI 9310 gears tested under identical conditions. Both types of M-50 gears had lives approximately five times that of the 9310 gears. The life at which 10 percent of the M-50 ausforged gears failed was slightly less than that at which the M-50 standard forged gears failed. The ausforged gears had a slightly greater tendency to fail by tooth fracture than did the standard forged gears, most likely because of the better forging and grain flow pattern of standard forged gears.

  3. Automated D/3 to Visio Analog Diagrams

    2000-08-10

    ADVAD1 reads an ASCII file containing the D/3 DCS MDL input for analog points for a D/3 continuous database. It uses the information in the files to create a series of Visio files representing the structure of each analog chain, one drawing per Visio file. The actual drawing function is performed by Visio (requires Visio version 4.5+). The user can configure the program to select which fields in the database are shown on the diagrammore » and how the information is to be presented. This gives a visual representation of the structure of the analog chains, showing selected fields in a consistent manner. Updating documentation can be done easily and the automated approach eliminates human error in the cadding process. The program can also create the drawings far faster than a human operator is capable, able to create approximately 270 typical diagrams in about 8 minutes on a Pentium II 400 MHz PC. The program allows for multiple option sets to be saved to provide different settings (i.e., different fields, different field presentations, and /or different diagram layouts) for various scenarios or facilities on one workstation. Option sets may be exported from the Windows registry to allow duplication of settings on another workstation.« less

  4. White Layer Formation Due to Phase Transformation to Orthogonal machine of AISI 1045 Annealed Steel

    SciTech Connect

    Han, Sangil; Melkote, Shreyes N; Haluska, Dr. Michael S; Watkins, Thomas R

    2008-01-01

    It is commonly believed that the white layer formed during machining of steels is caused primarily by a thermally induced phase transformation resulting from rapid heating and quenching. As a result, it is often assumed that if the temperature at the tool flank-workpiece interface exceeds the nominal phase transformation temperature for the steel, a white layer forms. However, no attempt has been made to actually measure the temperatures produced at the tool flank-workpiece interface and correlate it with microstructural evidence of phase transformation. This paper aims to address these limitations through suitably designed experiments and analysis. Orthogonal machining tests were performed on AISI 1045 annealed steel at different cutting speeds and tool flank wear. During machining, temperature measurements at the tool flank-workpiece interface were made using an exposed thermocouple technique. Metallographic studies of the machined sub-surface and X-ray diffraction (XRD) measurements were performed to determine the presence and depth of white layer, and the presence of the retained austenite phase in the machined surface layer, respectively. Analysis of the data shows that the white layer can form due to phase transformation at temperatures below the nominal austenitization temperature of the steel. Possible causes of this result are presented.

  5. Investigations on Surface Milling of Hardened AISI 4140 Steel with Pulse Jet MQL Applicator

    NASA Astrophysics Data System (ADS)

    Bashir, Mahmood Al; Mia, Mozammel; Dhar, Nikhil Ranjan

    2016-06-01

    In this article, an experimental investigation was performed in milling hardened AISI 4140 steel of hardness 40 HRC. The machining was performed in both dry and minimal quantity lubricant (MQL) conditions, as part of neat machining, to make a strong comparison of the undertaken machining environments. The MQL was impinged int the form of pulse jet, by using the specially developed pulse-jet-attachment, to ensure that the cutting fluid can be applied in different timed pulses and quantities at critical zones. The tool wear, cutting force and surface roughness were taken as the quality responses while cutting speed, table feed rate and flow rate of the pulse were considered as influential factors. The depth of cut was kept constant at 1.50 mm because of its less significant effects and the straight oil was adopted as cutting fluid in pulse-jet-MQL. The effects of different factors, on the quality responses, are analyzed using ANOVA. It is observed that MQL applicator system exhibits overall better performance when compared to dry milling by reducing surface roughness, cutting force and prolonging tool life but a flow rate of 150 ml/h has tremendous effects on the responses. This investigation and afterward results are expected to aid the industrial practitioner and researcher to adopt the pulse-MQL in high speed milling to prolong tool life, reduce tool wear, diminish cutting force generation and promote better surface finish.

  6. Conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in renal slices from the rat

    SciTech Connect

    Armbrecht, H.J.; Zenser, T.V.; Davis, B.B.

    1981-07-01

    Isolated renal cortical slices were used to study the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25)(OH2)D3) by the rat kidney. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was linear with time (30-90 min) and tissue weight (40-250 mg). Production of 1,25-(OH)2D3 was greatest (134 +/- 17 pg/mg tissue.h) in animals fed a low calcium, vitamin D-deficient diet. The greatest 24,25-(OH)2D3 production (106 +/- 17 pg/mg tissue.h) was seen in animals fed a high calcium, vitamin D-replete diet, 1,25-(OH)2D3 production was reduced to 23% of maximum by the addition of 1.2% calcium or 0.8% strontium to the vitamin D-deficient, low calcium diet. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was greatly reduced in renal cortical slices that had been heated before incubation. Slices of renal medulla produced only small amounts of 1,25-(OH)2D3 compared to slices of renal cortex. These studies provide direct evidence for the production of 1,25-(OH)2D3 and 24,25-(OH)2D3 by the mammalian renal cortex. They also demonstrate that this production may be modulated by dietary calcium, strontium, and vitamin D.

  7. Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

    SciTech Connect

    Yamato, H.; Matsumoto, T.; Fukumoto, S.; Ikeda, K.; Ishizuka, S.; Ogata, E.

    1989-01-01

    Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected (1 beta-3H)1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of (3H)24,25-(OH)2D3 to (3H)1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level.

  8. Interactive initialization of 2D/3D rigid registration

    SciTech Connect

    Gong, Ren Hui; Güler, Özgür; Kürklüoglu, Mustafa; Lovejoy, John; Yaniv, Ziv

    2013-12-15

    Purpose: Registration is one of the key technical components in an image-guided navigation system. A large number of 2D/3D registration algorithms have been previously proposed, but have not been able to transition into clinical practice. The authors identify the primary reason for the lack of adoption with the prerequisite for a sufficiently accurate initial transformation, mean target registration error of about 10 mm or less. In this paper, the authors present two interactive initialization approaches that provide the desired accuracy for x-ray/MR and x-ray/CT registration in the operating room setting. Methods: The authors have developed two interactive registration methods based on visual alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the first approach, the operator uses a gesture based interface to align a volume rendering of the preoperative image to multiple x-rays. The second approach uses a tracked tool available as part of a navigation system. Preoperatively, a virtual replica of the tool is positioned next to the anatomical structures visible in the volumetric data. Intraoperatively, the physical tool is positioned in a similar manner and subsequently used to align a volume rendering to the x-ray images using an augmented reality (AR) approach. Both methods were assessed using three publicly available reference data sets for 2D/3D registration evaluation. Results: In the authors' experiments, the authors show that for x-ray/MR registration, the gesture based method resulted in a mean target registration error (mTRE) of 9.3 ± 5.0 mm with an average interaction time of 146.3 ± 73.0 s, and the AR-based method had mTREs of 7.2 ± 3.2 mm with interaction times of 44 ± 32 s. For x-ray/CT registration, the gesture based method resulted in a mTRE of 7.4 ± 5.0 mm with an average interaction time of 132.1 ± 66.4 s, and the AR-based method had mTREs of 8.3 ± 5.0 mm with interaction times of 58 ± 52 s. Conclusions: Based on the

  9. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes.

    PubMed

    Cheng, Chloe Y S; Slominski, Andrzej T; Tuckey, Robert C

    2014-10-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  10. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes

    PubMed Central

    Cheng, Chloe Y.S.; Slominski, Andrzej T.; Tuckey, Robert C.

    2014-01-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263 nm seen for 20(OH)D3, to 290 nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  11. Seawater piping systems designed with AISI 316 and RCP anodes

    SciTech Connect

    Valen, S.; Johnsen, R.; Gartland, P.O.; Drugli, J.M.

    1999-11-01

    Internal cathodic protection by resistor controlled anodes--Resistor controlled Cathodic Protection (RCP)--has been introduced as an alternative method for the prevention of localized corrosion of seawater transportation systems. More than 1000 RCP anodes have been installed in seawater piping systems made from highly alloyed stainless steel which previously had suffered from corrosion. The application of cheaper stainless steels like AISI 316 in combination with RCP anodes results in significant cost savings for the seawater system, and a few systems have been installed. This paper gives a short review of the theoretical background, and a presentation of the experience from some of the installations with these materials and RCP.

  12. Crack growth behavior of AISI-4340 steel during environmental exposure

    SciTech Connect

    Giannuzzi, L.A.

    1995-11-01

    AISI-4340 is observed to undergo stress corrosion cracking when subjected to a constant load during exposure to a 3.5% NaCl solution. Crack initiation, nucleation, and growth has been monitored as a function of time. Stepped regions consisting of fast and slow crack growth periods are shown to correspond to microstructural changes observed in the fracture surface of the steel. These regions of fast and slow crack rate variations with time show that the crack growth rates do not increase continuously with an increase in the stress intensity.

  13. Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

    PubMed Central

    2016-01-01

    The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy. PMID:25826710

  14. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice

    PubMed Central

    2015-01-01

    The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice. PMID:26203768

  15. Coated carbide drill performance under soluble coconut oil lubricant and nanoparticle enhanced MQL in drilling AISI P20

    NASA Astrophysics Data System (ADS)

    Jamil, N. A. M.; Azmi, A. I.; Fairuz, M. A.

    2016-02-01

    This research experimentally investigates the performance of a TiAlN coated carbide drill bit in drilling AISI P20 through two different kinds of lubricants, namely; soluble coconut oil (SCO) and nanoparticle-enhanced coconut oil (NECO) under minimum quantity lubrication system. The tool life and tool wear mechanism were studied using various cutting speeds of 50, 100 and 150 m/min with a constant feed of 0.01 mm/rev. Since the flank wear land was not regular along the cutting edge, the average flank wear (VB) was measured at several points using image analysis software. The drills were inspected using a scanning electron microscope to further elucidate the wear mechanism. The result indicates that drilling with the nanoparticle- enhanced lubricant was better in resisting the wear and improving the drill life to some extent

  16. Tribological properties of CrN coatings deposited by nitro-chromizing treatment on AISI D2 steel

    SciTech Connect

    Durmaz, M. Abakay, E.; Sen, U.; Sen, S.; Kilinc, B.

    2015-03-30

    In this work, the wear test of uncoated and chromium nitride coated AISI D2 cold work tool steel against alumina ball realized at 0.1 m/s sliding speeds and under the loads of 2.5N, 5N and 10N. Steel samples were nitrided at 575°C for 8 h in the first step of the coating process, and then chromium nitride coating was performed thermo-reactive deposition technique (TRD) in a powder mixture consisting of ferro-chromium, ammonium chloride and alumina at 1000°C for 2 h. Nitro-chromized samples were characterized by X-Ray diffraction analysis (XRD), scanning electron microscopy (SEM), micro-hardness and ball on disk wear tests. The coating layer formed on the AISI D2 steel was compact and homogeneous. X-ray studies showed that the phase formed in the coated layer is Cr{sub 2}N. The depth of the layer was 8.15 µm. The average hardness of the layer was 2160±15 HV{sub 0.025}. For uncoated and chromium nitride materials, wear rate increased with increasing load. The results of friction coefficient and wear rate of the tested materials showed that the CrN coating presents the lowest results.

  17. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  18. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  19. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  20. 21 CFR 582.5953 - Vitamin D 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D 3. (a) Product. Vitamin D3. (b) Conditions of use. This substance...

  1. 21 CFR 582.5953 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D3. 582.5953 Section 582.5953 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5953 Vitamin D3. (a) Product. Vitamin D3. (b) Conditions of use. This substance is...

  2. Effect of tip relief on endurance characteristics of super nitralloy and AISI M-50 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1974-01-01

    Tests were conducted with two groups of 8.89-centimeter (3.5-in.) pitch diameter spur gears with standard 20 deg involute profile with tip relief made of CVM Super-Nitralloy (5Ni-2Al) and CVM AISI M-50 at a temperature of 350 K (170 F). Super-Nitralloy gears with tip relief had a life 150 percent that of gears without tip relief. An increased scoring phenomenon was noted with the Super-Nitralloy gears with tip relief. Through-hardened AISI M-50 gears with tip relief failed due to tooth fracture. AISI M-50 gears without tip relief had a life approximately 40 times greater than the AISI M-50 gears with tip relief.

  3. Cosmic D- and DF-strings from D3D3: Black strings and BPS limit

    SciTech Connect

    Kim, Taekyung; Kim, Yoonbai; Kyae, Bumseok; Lee, Jungjai

    2008-03-15

    We study D- and DF-strings in a D3D3 system by using Dirac-Born-Infeld type action. In the presence of an electric flux from the transverse direction, we discuss gravitating thick D-string solutions of a spatial manifold, S{sup 2}xR{sup 1}, in which straight D-strings stretched along the R{sup 1} direction are attached to the south and north poles of the two-sphere. There is a horizon along its equator, which means the structure of black strings is formed. We also discuss the BPS limit for thin parallel D- and DF-strings in both flat and curved spacetime. We obtain the BPS sum rule for an arbitrarily-separated multistring configuration with a Gaussian type tachyon potential. At the site of each thin BPS D(F)-string, the pressure takes a finite value. We find that there exists a maximum deficit angle {pi} in the conical geometry induced by thin BPS D- and DF-strings.

  4. Fretting of AISI 9310 and selected fretting resistant surface treatments

    NASA Technical Reports Server (NTRS)

    Bill, R. C.

    1977-01-01

    Fretting wear experiments were conducted with uncoated AISI 9310 mating surfaces, and with combinations incorporating a selected coating to one of the mating surfaces. Wear measurements and SEM observations indicated that surface fatigue, as made evident by spallation and surface crack formation, is an important mechanism in promoting fretting wear to uncoated 9310. Increasing humidity resulted in accelerated fretting, and a very noticeable difference in nature of the fretting debris. Of the coatings evaluated, aluminum bronze with a polyester additive was most effective at reducing wear and minimizing fretting damage to the mating uncoated surface, by means of a selflubricating film that developed on the fretting surfaces. Chromium plate performed as an effective protective coating, itself resisting fretting and not accelerating damage to the uncoated surface.

  5. Simulation of Thermo-viscoplastic Behaviors for AISI 4140 Steel

    NASA Astrophysics Data System (ADS)

    Li, Hong-Bin; Feng, Yun-Li

    2016-04-01

    The thermo-viscoplastic behaviors of AISI 4140 steel are investigated over wide ranges of strain rate and deformation temperature by isothermal compression tests. Based on the experimental results, a unified viscoplastic constitutive model is proposed to describe the hot compressive deformation behaviors of the studied steel. In order to reasonably evaluate the work hardening behaviors, a strain hardening material constant (h0) is expressed as a function of deformation temperature and strain rate in the proposed constitutive model. Also, the sensitivity of initial value of internal variable s to the deformation temperature is discussed. Furthermore, it is found that the initial value of internal variable s can be expressed as a linear function of deformation temperature. Comparisons between the measured and predicted results confirm that the proposed constitutive model can give an accurate and precise estimate of the inelastic stress-strain relationships for the studied high-strength steel.

  6. Stress Ratio Effect on Ratcheting Behavior of AISI 4340 Steel

    NASA Astrophysics Data System (ADS)

    Divya Bharathi, K.; Dutta, K.

    2016-02-01

    Ratcheting is known as accumulation of plastic strain during asymmetric cyclic loading of metallic materials under non-zero mean stress. This phenomenon reduces fatigue life of engineering materials and thus limits the life prediction capacity of Coffin-Manson relationship. This study intends to investigate the ratcheting behavior in AISI 4340 steel which is mainly used for designing of railway wheel sets, axles, shafts, aircraft components and other machinery parts. The effect of stress ratio on the ratcheting behaviour in both annealed and normalised conditions were investigated for investigated steel. Ratcheting tests were done at different stress ratios of -0.4, -0.6 and -0.8. The results showed that the material responds to hardening behavior and nature of strain accumulation is dependent on the magnitude of stress ratio. The post ratcheted samples showed increase in tensile strength and hardness which increases with increasing stress ratio and these variations in tensile properties are correlated with the induced cyclic hardening.

  7. Texture evolution in thin-sheets on AISI 301 metastable stainless steel under dynamic loading

    SciTech Connect

    Kim, K.Y.; Kozaczek, K.; Kulkarni, S.M.; Bastias, P.C.; Hahn, G.T.

    1995-05-08

    The evolution of texture in thin sheets of metastable austenitic stainless steel AISI 301 is affected by external conditions such as loading rate and temperature, by inhomogeneous deformation phenomena such as twinning and shear band formation, and by the concurent strain induced phase transformation of the retained austenitc ({gamma}) into martensite ({alpha}). The present paper describes texture measurements on different gauges of AISI 301 prior and after uniaxial stretching under different conditions.

  8. A Life Study of Ausforged, Standard Forged and Standard Machined AISI M-50 Spur Gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Bamberger, E. N.; Zaretsky, E. V.

    1975-01-01

    Tests were conducted at 350 K (170 F) with three groups of 8.9 cm (3.5 in.) pitch diameter spur gears made of vacuum induction melted (VIM) consumable-electrode vacuum-arc melted (VAR), AISI M-50 steel and one group of vacuum-arc remelted (VAR) AISI 9310 steel. The pitting fatigue life of the standard forged and ausforged gears was approximately five times that of the VAR AISI 9310 gears and ten times that of the bending fatigue life of the standard machined VIM-VAR AISI M-50 gears run under identical conditions. There was a slight decrease in the 10-percent life of the ausforged gears from that for the standard forged gears, but the difference is not statistically significant. The standard machined gears failed primarily by gear tooth fracture while the forged and ausforged VIM-VAR AISI M-50 and the VAR AISI 9310 gears failed primarily by surface pitting fatigue. The ausforged gears had a slightly greater tendency to fail by tooth fracture than the standard forged gears.

  9. Metabolism and pharmacokinetics of 24,25-dihydroxyvitamin D3 in the vitamin D3-replete rat

    SciTech Connect

    Jarnagin, K.; Zeng, S.Y.; Phelps, M.; DeLuca, H.F.

    1985-11-05

    The time course of in vivo metabolism of 24,25-dihydroxyvitamin D3 in rats has been examined. Several tissues were surveyed in an effort to discover new metabolites of 24,25-dihydroxyvitamin D3 and to estimate the concentrations of previously identified metabolites. Rapidly growing male rats were dosed with 24,25-dihydroxyvitamin D3 orally until plasma concentrations of 24,25-dihydroxyvitamin D3 were at steady state. 24,25-Dihydroxyvitamin (3-TH)D3 was then administered. At 10 min and 1, 6, 15, 24, 96, and 192 h after dosing, the animals were killed, and plasma, liver, intestine, and bones were analyzed with a newly developed gradient straight-phase high performance liquid chromatography system. The high performance liquid chromatography system is capable of base-line resolution of most of the major vitamin D metabolites. 24,25-Dihydroxyvitamin D3 clearance from plasma, liver, and kidney but not intestine followed a two-compartment model. 24,25-Dihydroxyvitamin D3 disappeared from plasma with a half-life of 0.55 h (fast phase) and 73.8 h (slow phase). Only two lipid-soluble metabolites of 24,25-dihydroxyvitamin D3 were detected: 24-oxo-25-hydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3. These compounds circulate at very low concentrations in the plasma (50 pg/ml of plasma).

  10. Thermodynamic modeling and kinetics simulation of precipitate phases in AISI 316 stainless steels

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Busby, J. T.

    2014-05-01

    This work aims at utilizing modern computational microstructural modeling tools to accelerate the understanding of phase stability in austenitic steels under extended thermal aging. Using the CALPHAD approach, a thermodynamic database OCTANT (ORNL Computational Thermodynamics for Applied Nuclear Technology), including elements of Fe, C, Cr, Ni, Mn, Mo, Si, and Ti, has been developed with a focus on reliable thermodynamic modeling of precipitate phases in AISI 316 austenitic stainless steels. The thermodynamic database was validated by comparing the calculated results with experimental data from commercial 316 austenitic steels. The developed computational thermodynamics was then coupled with precipitation kinetics simulation to understand the temporal evolution of precipitates in austenitic steels under long-term thermal aging (up to 600,000 h) at a temperature regime from 300 to 900 °C. This study discusses the effect of dislocation density and difusion coefficients on the precipitation kinetics at low temperatures, which shed a light on investigating the phase stability and transformation in austenitic steels used in light water reactors.

  11. Prediction of Cutting Forces Using ANNs Approach in Hard Turning of AISI 52100 steel

    SciTech Connect

    Makhfi, Souad; Habak, Malek; Velasco, Raphael; Haddouche, Kamel; Vantomme, Pascal

    2011-05-04

    In this study, artificial neural networks (ANNs) was used to predict cutting forces in the case of machining the hard turning of AISI 52100 bearing steel using cBN cutting tool. Cutting forces evolution is considered as the key factors which affect machining. Predicting cutting forces evolution allows optimizing machining by an adaptation of cutting conditions. In this context, it seems interesting to study the contribution that could have artificial neural networks (ANNs) on the machining forces prediction in both numerical and experiment studies. Feed-forward multi-layer neural networks trained by the error back-propagation (BP) algorithm are used. Levenberg-Marquardt (LM) optimization algorithm was used for finding out weights. The training of the network is carried out with experimental machining data.The input dataset used are cutting speed, feed rate, cutting depth and hardness of the material. The output dataset used are cutting forces (Ft-cutting force, Fa- feed force and Fr- radial force).Results of the neural networks approach, in comparison with experimental data are discussed in last part of this paper.

  12. Quantifying Cutting and Wearing Behaviors of TiN- and CrN-Coated AISI 1070 Steel

    PubMed Central

    Cakan, Ahmet; Ozkaner, Vedat; Yildirim, Mustafa M.

    2008-01-01

    Hard coatings such as titanium nitride (TiN) and chromium nitride (CrN) are widely used in cutting and forming tools against wear and corrosion. In the present study, hard coating films were deposited onto AISI 1070 steels by a cathodic arc evaporation plating (CAVP) technique. These samples were subjected to wear in a conventional lathe for investigating the tribological behaviour of coating structure, and prenitrided subsurface composition was characterized using scanning electron microscopy (SEM), line scan analyses and X-ray diffraction (XRD). The wear properties of TiN- and CrN-coated samples were determined using an on-line monitoring system. The results show that TiN-coated samples demonstrate higher wear resistance than CrN-coated samples.

  13. Corrosion and microstructural analysis data for AISI 316L and AISI 347H stainless steels after exposure to a supercritical water environment

    PubMed Central

    Ruiz, A.; Timke, T.; van de Sande, A.; Heftrich, T.; Novotny, R.; Austin, T.

    2016-01-01

    This article presents corrosion data and microstructural analysis data of austenitic stainless steels AISI 316L and AISI 347H exposed to supercritical water (25 MPa, 550 °C) with 2000 ppb of dissolved oxygen. The corrosion tests lasted a total of 1200 h but were interrupted at 600 h to allow measurements to be made. The microstructural data have been collected in the grain interior and at grain boundaries of the bulk of the materials and at the superficial oxide layer developed during the corrosion exposure. PMID:27158647

  14. Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

    SciTech Connect

    Chien, Ellen Y.T.; Liu, Wei; Zhao, Qiang; Katritch, Vsevolod; Han, Gye Won; Hanson, Michael A.; Shi, Lei; Newman, Amy Hauck; Javitch, Jonathan A.; Cherezov, Vadim; Stevens, Raymond C.

    2010-11-30

    Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.

  15. HoxD3 accelerates wound healing in diabetic mice

    SciTech Connect

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

    2003-12-01

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

  16. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  17. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... (a) Product. 25-Hydroxyvitamin D3 (9,10-secocholesta-5,7,10(19)-triene-3β, 25-diol). (b) Conditions of use. This substance is generally recognized as safe as a source of vitamin D3 activity in feed...

  18. Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-D3) dilution in rats.

    PubMed

    Stimpson, Stephen A; Turner, Scott M; Clifton, Lisa G; Poole, James C; Mohammed, Hussein A; Shearer, Todd W; Waitt, Greg M; Hagerty, Laura L; Remlinger, Katja S; Hellerstein, Marc K; Evans, William J

    2012-06-01

    There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass. PMID:22422801

  19. Study on tempering behaviour of AISI 410 stainless steel

    SciTech Connect

    Chakraborty, Gopa; Das, C.R.; Albert, S.K.; Bhaduri, A.K.; Thomas Paul, V.; Panneerselvam, G.; Dasgupta, Arup

    2015-02-15

    Martensitic stainless steels find extensive applications due to their optimum combination of strength, hardness and wear-resistance in tempered condition. However, this class of steels is susceptible to embrittlement during tempering if it is carried out in a specific temperature range resulting in significant reduction in toughness. Embrittlement of as-normalised AISI 410 martensitic stainless steel, subjected to tempering treatment in the temperature range of 673–923 K was studied using Charpy impact tests followed by metallurgical investigations using field emission scanning electron and transmission electron microscopes. Carbides precipitated during tempering were extracted by electrochemical dissolution of the matrix and identified by X-ray diffraction. Studies indicated that temper embrittlement is highest when the steel is tempered at 823 K. Mostly iron rich carbides are present in the steel subjected to tempering at low temperatures of around 723 K, whereas chromium rich carbides (M{sub 23}C{sub 6}) dominate precipitation at high temperature tempering. The range 773–823 K is the transition temperature range for the precipitates, with both Fe{sub 2}C and M{sub 23}C{sub 6} types of carbides coexisting in the material. The nucleation of Fe{sub 2}C within the martensite lath, during low temperature tempering, has a definite role in the embrittlement of this steel. Embrittlement is not observed at high temperature tempering because of precipitation of M{sub 23}C{sub 6} carbides, instead of Fe{sub 2}C, preferentially along the lath and prior austenite boundaries. Segregation of S and P, which is widely reported as one of the causes for temper embrittlement, could not be detected in the material even through Auger electron spectroscopy studies. - Highlights: • Tempering behaviour of AISI 410 steel is studied within 673–923 K temperature range. • Temperature regime of maximum embrittlement is identified as 773–848 K. • Results show that type of

  20. Interactive client side data visualization with d3.js

    NASA Astrophysics Data System (ADS)

    Rodzianko, A.; Versteeg, R.; Johnson, D. V.; Soltanian, M. R.; Versteeg, O. J.; Girouard, M.

    2015-12-01

    Geoscience data associated with near surface research and operational sites is increasingly voluminous and heterogeneous (both in terms of providers and data types - e.g. geochemical, hydrological, geophysical, modeling data, of varying spatiotemporal characteristics). Such data allows scientists to investigate fundamental hydrological and geochemical processes relevant to agriculture, water resources and climate change. For scientists to easily share, model and interpret such data requires novel tools with capabilities for interactive data visualization. Under sponsorship of the US Department of Energy, Subsurface Insights is developing the Predictive Assimilative Framework (PAF): a cloud based subsurface monitoring platform which can manage, process and visualize large heterogeneous datasets. Over the last year we transitioned our visualization method from a server side approach (in which images and animations were generated using Jfreechart and Visit) to a client side one that utilizes the D3 Javascript library. Datasets are retrieved using web service calls to the server, returned as JSON objects and visualized within the browser. Users can interactively explore primary and secondary datasets from various field locations. Our current capabilities include interactive data contouring and heterogeneous time series data visualization. While this approach is very powerful and not necessarily unique, special attention needs to be paid to latency and responsiveness issues as well as to issues as cross browser code compatibility so that users have an identical, fluid and frustration-free experience across different computational platforms. We gratefully acknowledge support from the US Department of Energy under SBIR Award DOE DE-SC0009732, the use of data from the Lawrence Berkeley National Laboratory (LBNL) Sustainable Systems SFA Rifle field site and collaboration with LBNL SFA scientists.

  1. Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production

    SciTech Connect

    Vieth, R.; McCarten, K.; Norwich, K.H. )

    1990-05-01

    To understand the relationships among (1) the dose of 25-hydroxyvitamin D (25(OH)D) in vivo, (2) the activity of 1-hydroxylase in renal mitochondria, and (3) the production of 1,25-dihydroxyvitamin D (1,25(OH)2D) in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 (25(OH)D3). We followed the metabolism of intracardially administered (25-hydroxy-26,27-methyl-3H)cholecalciferol (25(OH)(3H)D3) for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-(26,27-methyl-3H)cholecalciferol (1,25(OH)2(3H)D3) as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2(3H)D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2(3H)D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

  2. The Surface Fatigue Life of Contour Induction Hardened AISI 1552 Gears

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Turza, Alan; Chaplin, Mike

    1995-01-01

    Two groups of spur gears manufactured from two different materials and heat treatments were endurance tested for surface fatigue life. One group was manufactured from AISI 1552 and was finished ground to a 0.4 micron (16 micro-in.) rms surface finish and then dual frequency contour induction hardened. The second group was manufactured from CEVM AISI 9310 and was carburized, hardened, and ground to a 0.4 micron (16 micro-in.) rms surface finish. The gear pitch diameter was 8.89 cm (3.5 in.). Test conditions were a maximum Hertz stress of 1.71 GPa (248 ksi), a bulk gear temperature of approximately 350 K (170 F) and a speed of 10,000 rpm. The lubricant used for the tests was a synthetic paraffinic oil with an additive package. The test results showed that the 10 percent surface fatigue (pitting) life of the contour hardened AISI 1552 test gears was 1.7 times that of the carburized and hardened AISI 9310 test gears. Also there were two early failures of the AISI 1552 gears by bending fatigue.

  3. Ferromagnetic properties of cold rolled AISI 304L steel

    NASA Astrophysics Data System (ADS)

    Tavares, S. S. M.; da Silva, M. R.; Neto, J. M.; Miraglia, S.; Fruchart, D.

    2002-04-01

    The ferromagnetic properties (coercive force, residual and saturation magnetisation) of a cold rolled AISI 304L stainless steel were measured as function of the applied deformation, using a vibrating sample magnetometer. The martensite volume fraction produced by deformation was calculated through the magnetisation saturation ( σs) value. A maximum amount of martensite (81%) was obtained by applying a true deformation ɛ=2.41 and a heat treatment at 400°C after rolling. The residual induction ( Br) and the squareness (=ratio between residual ( Br) and saturation ( Bs) inductions) increased, while the coercive field ( Hc) decreased with the amount of deformation. The heat treatment at 400°C promotes as well the increase of both Br and Br/ Bs and the decrease of Hc. The magnetic properties obtained in the most severely deformed samples ( Hc=23.08-23.63 kJ/m 3, Br=1.01-1.20 T and Bs=1.12-1.28 T) are comparable to that of some hard and semi-hard alloys used as magnets. The stability of the ferromagnetic martensite ( α') was investigated by thermomagnetic analysis. The starting ( As) and final ( Af) temperatures of the martensite phase ( α') transformation into austenite during heating were determined to As=430-440°C and Af=610-616°C.

  4. Investigations on the Predictability of Coining Stainless Steel AISI 410

    NASA Astrophysics Data System (ADS)

    Grobbink, S. J.; Klaseboer, G.; Post, J.; Huetink, J.

    2010-06-01

    Due to the increasing trend towards miniaturization, various industries demand the knowledge of materials forming on microscale. Forming has many advantages above machining such as high accuracy, low costs and strengthening by cold-working. However, a drawback of microforming is that it leads to problems caused by so-called size effects. A lot of research has been done on this topic, but only a minor part deals with the forming of high strength materials. In this study two channels with 0.25 mm width and 4.5 mm length are formed in stainless steel sheet AISI 410 with an initial sheet thickness 0.5 mm. The channels are formed by the coining process. The experiments have been repeated in which all dimensions are scaled down by a factor two, in order to check if size effects occur. Ring compression tests are used to determine a shear friction coefficient. A finite element model was build up and solved with MSC.Marc in order to gain a better understanding of the coining process. A size dependent material model known from literature and a conventional material model is used for the simulations. Both results are compared with the experimental results.

  5. The Forming of AISI 409 sheets for fan blade manufacturing

    SciTech Connect

    Foroni, F. D.; Menezes, M. A.; Moreira Filho, L. A.

    2007-04-07

    The necessity of adapting the standardized fan models to conditions of higher temperature has emerged due to the growth of concern referring to the consequences of the gas expelling after the Mont Blanc tunnel accident in Italy and France, where even though, with 100 fans in operation, 41 people died. The objective of this work is to present an alternative to the market standard fans considering a new technology in constructing blades. This new technology introduces the use of the stainless steel AISI 409 due to its good to temperatures of gas exhaust from tunnels in fire situation. The innovation is centered in the process of a deep drawing of metallic sheets in order to keep the ideal aerodynamic superficies for the fan ideal performance. Through the impression of circles on the sheet plane it is shown, experimentally, that, during the pressing process, the more deformed regions on the sheet plane of the blade can not reach the deformation limits of the utilized sheet material.

  6. Modeling the Flow Curve of AISI 410 Martensitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Momeni, A.; Dehghani, K.; Heidari, M.; Vaseghi, M.

    2012-11-01

    In the present study, hot deformation behavior of AISI 410 martensitic stainless steel was investigated and modeled after conducting compression tests at the temperature range of 900-1150 °C and strain rate range of 0.001-1 s-1. At the studied temperature and strain rates, the flow curves were typical of dynamic recrystallization (DRX) showing a hardening peak followed by a softening one, and a steady state. The flow curves up to the peaks were modeled using the Estrin and Mecking equation. The softening due to DRX was also considered to increase the consistency of the developed model. The experimental equation proposed by Cingara and McQueen was also used to model the work hardening region. The results showed that the phenomenological model based on the Estrin and Mecking equation resulted in a better model for the work hardening region. Based on the Avrami equation, a model was developed to estimate the flow softening due to DRX between the peak and the starting point of steady state. The average value of the Avrami exponent was determined as 2.2, and it decreased with the increasing Zener-Hollomon parameter.

  7. High-temperature oxidation behavior of aluminized AISI 4130 steel

    NASA Astrophysics Data System (ADS)

    Badaruddin, Mohammad; Wang, Chaur Jeng; Wardono, Herry; Tarkono, Asmi, Dwi

    2016-02-01

    AISI 4130 steel was dipped into a molten aluminum bath at 700°C for 16 s to produce an aluminide coating on the steel substrate. The coating, which consisted of an Al-rich layer and an FeAl3 and Fe2Al5 intermetallic layer, strongly adhered to the steel substrate. High-temperature oxidation of the bare steel and aluminized steel was performed by thermogravimetry at 850°C for 49 h in static air. The oxidation products were characterized by scanning electron microscopy and energy-dispersive spectroscopy. The aluminide coating could increase the oxidation resistance of the bare steel by a factor of ˜19. The increase in high-temperature oxidation resistance of the aluminized steel is attributed to the formation of protective alumina scale (α-Al2O3). Although iron oxide nodules grew on the aluminide coating surface, the oxidation rate of the aluminide coatings was very low. After 49 h of oxidation, agglomerates of α-Al2O3 fine grains grew on the rod-shaped FeAl phases.

  8. Abnormal grain growth in AISI 304L stainless steel

    SciTech Connect

    Shirdel, M.; Mirzadeh, H.; Parsa, M.H.

    2014-11-15

    The microstructural evolution during abnormal grain growth (secondary recrystallization) in 304L stainless steel was studied in a wide range of annealing temperatures and times. At relatively low temperatures, the grain growth mode was identified as normal. However, at homologous temperatures between 0.65 (850 °C) and 0.7 (900 °C), the observed transition in grain growth mode from normal to abnormal, which was also evident from the bimodality in grain size distribution histograms, was detected to be caused by the dissolution/coarsening of carbides. The microstructural features such as dispersed carbides were characterized by optical metallography, X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis, and microhardness. Continued annealing to a long time led to the completion of secondary recrystallization and the subsequent reappearance of normal growth mode. Another instance of abnormal grain growth was observed at homologous temperatures higher than 0.8, which may be attributed to the grain boundary faceting/defaceting phenomenon. It was also found that when the size of abnormal grains reached a critical value, their size will not change too much and the grain growth behavior becomes practically stagnant. - Highlights: • Abnormal grain growth (secondary recrystallization) in AISI 304L stainless steel • Exaggerated grain growth due to dissolution/coarsening of carbides • The enrichment of carbide particles by titanium • Abnormal grain growth due to grain boundary faceting at very high temperatures • The stagnancy of abnormal grain growth by annealing beyond a critical time.

  9. AISI waste oxide recycling program. Final technical report

    SciTech Connect

    Aukrust, E.; Downing, K.B.; Sarma, B.

    1995-08-01

    In March 1995 AISI completed a five-year, $60 million collaborative development program on Direct Steelmaking cost-shared by DOE under the Metals Initiative. This program defined an energy-efficient and environmentally-friendly technology to produce hot metal for steelmaking directly from coal and iron ore pellets without incurring the high capital costs and environmental problems associated with traditional coke oven and blast furnace technology. As it becomes necessary to replace present capacity, this new technology will be favored because of reduced capital costs, higher energy efficiency, and lower operating costs. In April 1994, having failed to move forward with a demonstration plant for direct ironmaking, despite substantial efforts by both Stelco and Geneva Steel, an alternative opportunity was sought to commercialize this new technology without waiting until existing ironmaking capacity needed to be replaced. Recycling and resource recovery of steel plant waste oxides was considered an attractive possibility. This led to approval of a ten-month, $8.3 million joint program with DOE on recycling steel plant waste oxides utilizing this new smelting technology. This highly successful trial program was completed in December 1994. The results of the pilot plant work and a feasibility study for a recycling demonstration plant are presented in this final technical report.

  10. Hot compression deformation behavior of AISI 321 austenitic stainless steel

    NASA Astrophysics Data System (ADS)

    Haj, Mehdi; Mansouri, Hojjatollah; Vafaei, Reza; Ebrahimi, Golam Reza; Kanani, Ali

    2013-06-01

    The hot compression behavior of AISI 321 austenitic stainless steel was studied at the temperatures of 950-1100°C and the strain rates of 0.01-1 s-1 using a Baehr DIL-805 deformation dilatometer. The hot deformation equations and the relationship between hot deformation parameters were obtained. It is found that strain rate and deformation temperature significantly influence the flow stress behavior of the steel. The work hardening rate and the peak value of flow stress increase with the decrease of deformation temperature and the increase of strain rate. In addition, the activation energy of deformation ( Q) is calculated as 433.343 kJ/mol. The microstructural evolution during deformation indicates that, at the temperature of 950°C and the strain rate of 0.01 s-1, small circle-like precipitates form along grain boundaries; but at the temperatures above 950°C, the dissolution of such precipitates occurs. Energy-dispersive X-ray analyses indicate that the precipitates are complex carbides of Cr, Fe, Mn, Ni, and Ti.

  11. QM Computations on Complete Nucleic Acids Building Blocks: Analysis of the Sarcin-Ricin RNA Motif Using DFT-D3, HF-3c, PM6-D3H, and MM Approaches.

    PubMed

    Kruse, Holger; Havrila, Marek; Šponer, Jiřı

    2014-06-10

    A set of conformations obtained from explicit solvent molecular dynamics (MD) simulations of the Sarcin-Ricin internal loop (SRL) RNA motif is investigated using quantum mechanical (QM, TPSS-D3/def2-TZVP DFT-D3) and molecular mechanics (MM, AMBER parm99bsc0+χol3 force field) methods. Solvent effects are approximated using implicit solvent methods (COSMO for DFT-D3; GB and PB for MM). Large-scale DFT-D3 optimizations of the full 11-nucleotide motif are compared to MM results and reveal a higher flexibility of DFT-D3 over the MM in the optimization procedure. Conformational energies of the SRL motif expose significant differences in the DFT-D3 and MM energy descriptions that explain difficulties in MD simulations of the SRL motif. The TPSS-D3 data are in excellent agreement with results obtained by the hybrid functionals PW6B95-D3 and M06-2X. Computationally more efficient methods such as PM6-D3H and HF-3c show promising but partly inconsistent results. It is demonstrated that large-scale DFT-D3 computations on complete nucleic acids building blocks are a viable tool to complement the picture obtained from MD simulations and can be used as benchmarks for faster computational methods. Methodological challenges of large-scale QM computations on nucleic acids such as missing solvent-solute interactions and the truncation of the studied systems are discussed. PMID:26580782

  12. The effect of microstructure on the thermal fatigue resistance of investment cast and wrought AISI H13 hot work die steel

    SciTech Connect

    Hochanadel, P.W.; Edwards, G.R.; Maguire, M.C.; Baldwin, M.D.

    1995-07-01

    Variable thickness plate investment castings of AISI H13 hot work die steel were pour and characterized in the as-cast and heat treated conditions. The characterization included light microscopy and mechanical testing. Wrought samples of standard and premium grade H13 steel were heat treated and characterized similarly for comparison. Microstructural differences were observed in as-cast samples poured to different section thicknesses. Dendrite cell size and carbide morphology constituted the most prominent microstructural differences observed. After a full heat treatment, however, Microstructural differences between the wrought material and cast materials were slight regardless of section thickness. The mechanical properties of the cast and heat treated material proved similar to the properties of the standard heat treated wrought material. A thermal fatigue testing unit was designed and built to correlate the heat checking susceptibility of AISI H13 steel to its processing and consequent microstructural condition. Surface hardness decreased significantly with thermal cycling, and heat checking was noticed in as few as 50 cycles. Thermal softening and thermal fatigue susceptibility were quantified and discussed relative to the microstructural conditions created by processing and heat treatment. It was found that the premium grade wrought H13 steel provided the best overall resistance to heat checking; however, the heat-treat cast and as-cast H13 tool steel (made from standard grade wrought H13 tool steel) provided comparable resistance to heat checking in terms Of area fraction of heat checking and maximum crack length.

  13. ACC deaminase activity in avirulent Agrobacterium tumefaciens D3.

    PubMed

    Hao, Youai; Charles, Trevor C; Glick, Bernard R

    2011-04-01

    Some plant-growth-promoting bacteria encode the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, which breaks down ACC, the direct precursor of ethylene biosynthesis in all higher plants, into ammonia and α-ketobutyrate and, as a result, reduces stress ethylene levels in plants caused by a wide range of biotic and abiotic stresses. It was previously shown that ACC deaminase can inhibit crown gall development induced by Agrobacterium tumefaciens and can partially protect plants from this disease. Agrobacterium tumefaciens D3 has been previously reported to contain a putative ACC deaminase structural gene (acdS) and a regulatory gene (acdR = lrpL). In the present study, it was found that A. tumefaciens D3 is an avirulent strain. ACC deaminase activity and its regulation were also characterized. Under gnotobiotic conditions, wild-type A. tumefaciens D3 was shown to be able to promote plant root elongation, while the acdS and lrpL double mutant strain A. tumefaciens D3-1 lost that ability. When co-inoculated with the virulent strain, A. tumefaciens C58, in wounded castor bean plants, both the wild-type A. tumefaciens D3 and the mutant A. tumefaciens D3-1 were found to be able to significantly inhibit crown gall development induced by A. tumefaciens C58. PMID:21491979

  14. Serum level of vitamin D3 in cutaneous melanoma

    PubMed Central

    de Oliveira, Renato Santos; de Oliveira, Daniel Arcuschin; Martinho, Vitor Augusto Melão; Antoneli, Célia Beatriz Gianotti; Marcussi, Ludmilla Altino de Lima; Ferreira, Carlos Eduardo dos Santos

    2014-01-01

    Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. PMID:25628199

  15. Induction of the Angiogenic Phenotype by Hox D3

    PubMed Central

    Boudreau, Nancy; Andrews, Catherine; Srebrow, Anabella; Ravanpay, Ali; Cheresh, David A.

    1997-01-01

    Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin αvβ3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin αvβ3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin αvβ3 and uPA. In fact, sustained expression of Hox D3 in vivo on the chick chorioallantoic membrane retained EC in this invasive state and prevented vessel maturation leading to vascular malformations and endotheliomas. Therefore, Hox D3 regulates EC gene expression associated with the invasive stage of angiogenesis. PMID:9314544

  16. Vitamin D3 and cardiovascular function in rats.

    PubMed Central

    Weishaar, R E; Simpson, R U

    1987-01-01

    We have previously identified a receptor for 1,25-dihydroxyvitamin D3 in myocardial cells (Simpson, R.U. 1983. Circulation. 68:239.). To establish the relevance of this observation, we evaluated the role of the prohormone vitamin D3 in regulating cardiovascular function. In rats maintained on a vitamin D3-deficient diet for nine weeks, increases in systolic blood pressure (BP) and serum creatine phosphokinase (CPK) were observed. These increases coincided with a reduction of serum calcium from 10.3 to 5.6 mg/dl. However, while serum calcium remained depressed throughout the study, increases in BP and serum CPK were transient. After nine weeks of vitamin D3-depletion, but not after six weeks, ventricular and vascular muscle contractile function were also markedly enhanced. The increase in ventricular contractile function could not be prevented by maintaining serum calcium at 9.0 mg/dl during the period of D3-depletion. These observations suggest a primary role for the vitamin D3-endocrine system in regulating cardiovascular function. PMID:3034981

  17. Vitamin D3: a helpful immuno-modulator

    PubMed Central

    Di Rosa, Michelino; Malaguarnera, Michele; Nicoletti, Ferdinando; Malaguarnera, Lucia

    2011-01-01

    The active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)2D3], is involved in calcium and phosphate metabolism and exerts a large number of biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive immunity and cell proliferation, and at the same time promotes insulin secretion, innate immunity and stimulates cellular differentiation. The role of vitamin D3 in immunoregulation has led to the concept of a dual function as both as an important secosteroid hormone for the regulation of body calcium homeostasis and as an essential organic compound that has been shown to have a crucial effect on the immune responses. Altered levels of vitamin D3 have been associated, by recent observational studies, with a higher susceptibility of immune-mediated disorders and inflammatory diseases. This review reports the new developments with specific reference to the metabolic and signalling mechanisms associated with the complex immune-regulatory effects of vitamin D3 on immune cells. PMID:21896008

  18. Surface fatigue life of CBN and vitreous ground carburized and hardened AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Patel, P. R.

    1988-01-01

    Spur gear surface endurance tests were conducted to investigate CBN ground AISI 9310 spur gears for use in aircraft applications, to determine their endurance characteristics and to compare the results with the endurance of standard vitreous ground AISI 9310 spur gears. Tests were conducted with VIM-VAR AISI 9310 carburized and hardened gears that were finish ground with either CBN or vitreous grinding methods. Test conditions were an inlet oil temeprature of 320 K (116 F), an outlet oil temperature of 350 K (170 F), a maximum Hertz stress of 1.71 GPa (248 ksi), and a speed of 10,000 rpm. The CBN ground gears exhibited a surface fatigue life that was slightly better than the vitreous ground gears. The subsurface residual stress of the CBN ground gears was approximately the same as that for the standard vitreous ground gears for the CBN grinding method used.

  19. Corrosion resistance of the AISI 304, 316 and 321 stainless steel surfaces modified by laser

    NASA Astrophysics Data System (ADS)

    Szubzda, B.; Antończak, A.; Kozioł, P.; Łazarek, Ł.; Stępak, B.; Łęcka, K.; Szmaja, A.; Ozimek, M.

    2016-02-01

    The article presents the analysis results of the influence of laser fluence on physical and chemical structure and corrosion resistance of stainless steel surfaces modified by irradiating with nanosecond-pulsed laser. The study was carried out for AISI 304, AISI 316 and AISI 321 substrates using Yb:glass fiber laser. All measurements were made for samples irradiated in a broad range of accumulated fluence (10÷400 J/cm2). The electrochemical composition (by EDX) and surface morphology (by SEM) of the prepared surfaces were carried out. Finally, corrosion resistance was analyzed by a potentiodynamic electrochemical test. The obtained results showed very high corrosion resistance for samples made by fluency of values lower than 100 J/cm2. In this case, higher values of corrosion potentials and breakdown potentials were observed. A correlation between corrosion phenomena, the range of laser power (fluence) and the results of chemical and structural tests were also found.

  20. Characterization of Structural Conditions of AISI 316 Analog Stainless Steel Irradiated in the BN-350 Reactor

    SciTech Connect

    Maksimkin, O. P.; Tsai, K V.; Turubarova, L. G.; Doronina, T. A.; Garner, Francis A.

    2004-08-24

    In several recently published studies conducted on a Soviet analog of AISI 321 stainless steel irradiated in either fast reactors or light water reactors, it was shown that the void swelling phenomenon extended to temperatures as low as {approx} 300 C, when produced by neutron irradiation at dpa rates in the range 10(-7 power) to 10(-8 power) dpa/sec. Other studies yielded similar results for AISI 316. In the current study a blanket duct assembly from BN-350, constructed from the Soviet analog of AISI 316, also exhibits swelling at dpa rates on the order of 10(-8 power) dpa/sec, with voids seen as low as 281 C and only 1.3 dpa. It appears that low-temperature swelling at low dpa rates occurs in 300 series stainless steels in general, and during irradiations conducted in either fast or mixed spectrum reactors.

  1. Coupled Multi-Electrode Investigation of Crevice Corrosion of AISI 316 Stainless Steel

    SciTech Connect

    F. Bocher; F. Presuel-Moreno; N.D. Budinasky; J.R. Scully

    2006-06-23

    Close packed coupled multi-electrodes arrays (MEA) simulating a planar electrode were used to measure the current evolution as a function of position during initiation and propagation of crevice corrosion of AISI 316 stainless steel. Scaling laws derived from polarization data enabled the use of rescaled crevices providing spatial resolution. Crevice corrosion of AISI 316 stainless steel in 0.6 M NaCl at 50 C was found to initiate close to the crevice mouth and to spread inwards with time. The local crevice current density increased dramatically over a short period to reach a limiting value.

  2. Effect of vitamin D3 on lifespan in Caenorhabditis elegans.

    PubMed

    Messing, Jennifer A; Heuberger, Roschelle; Schisa, Jennifer A

    2013-12-01

    Vitamin D is an essential micronutrient, necessary for human health. To determine if Caenorhabditis elegans (C. elegans) could function as an effective model to study the mechanisms of action of vitamin D, we asked if vitamin D3 affects C. elegans lifespan. Multiple factors positively impact lifespan in this system including dietary restriction and vitamin E. In addition, the C. elegans DAF-12 nuclear hormone receptor is homologous to the vitamin D receptor in humans and is therefore a candidate for a functional vitamin D receptor. It was hypothesized that vitamin D3 supplementation would increase the lifespan of C. elegans in a DAF-12-dependent manner. Dose-response curves were completed, and results indicate that exposure to 1,000 µg/ml vitamin D3 significantly increased the lifespan of wild-type worms by up to 39% (p<0.001). The daf-12 mutants exposed to 1,000 µg/ml vitamin D3 lived significantly longer than daf-12 controls exposed to 0 µg/ml (p<0.001), but among worms exposed to 1,000 µg/ml vitamin D3, wild type lived significantly longer than daf-12 (p<0.01). The data suggest that vitamin D3 can interact with multiple receptors, possibly implicating the NHR family of nuclear hormone receptors related to DAF-12. This research is the first to our knowledge to utilize C. elegans as a model to study the impact of vitamin D3 on longevity and supports the use of this model system to increase our understanding of vitamin D function at the cellular level, its role in cellular health, and its potential medicinal utility in humans.

  3. Local Reversion of Cold Formed AISI 301LN

    NASA Astrophysics Data System (ADS)

    Järvenpää, A.; Jaskari, M.; Hietala, M.; Mäntyjärvi, K.

    This study demonstrates applying laser heat treatment for reversion treatments of cold-formed AISI 301LN. Sheets were cold- rolled to final thicknesses of 1.5 and 3 mm (65pct reduction), having martensite fraction of 70-95%. Sheets were heated locally by a laser beam to various peak temperatures to obtain different degrees of martensite reversion to austenite. Mechanical properties and formability of grain-refined and coarse-grained structures were measured by tensile, bending and Erichsen cup tests. In addition to standard Erichsen cup test, additional interrupted tests were carried out, where cups were first stretched close to the critical strain. Drawn cups were then heated locally by a laser beam to revitalize the structure and thereby enhance the formability in the following cupping test until failure. Various structures were produced: completely reverted microstructures (T > 700 °C) with grain sizes 0.9 - 2 μm in addition to partially reverted structure (T < 700 °C) containing nano- and ultrafine-grained austenite (0.6 μm) with some martensite. Results showed that local laser heat treatment is suitable for the reversion treatment to refine the austenite grain size. Refinement of the austenitic structures increased strength properties and the formability was better than with coarse grained structures having the same strength. Especially the yield strength was significantly enhanced, being around 900 MPa in the strongest reverted structure compared to the 300-400 MPa of the coarse grained austenitic structure. It was demonstrated that the local laser treatment restored formability of the drawn cups, allowing stretching to be continued.

  4. Rapid tooling for functional prototyping of metal mold processes: Literature review on cast tooling

    SciTech Connect

    Baldwin, M.D.; Hochanadel, P.W.

    1995-11-01

    This report is a literature review on cast tooling with the general focus on AISI H13 tool steel. The review includes processing of both wrought and cast H13 steel along with the accompanying microstructures. Also included is the incorporation of new rapid prototyping technologies, such as Stereolithography and Selective Laser Sintering, into the investment casting of tool steel. The limiting property of using wrought or cast tool steel for die casting is heat checking. Heat checking is addressed in terms of testing procedures, theories regarding the mechanism, and microstructural aspects related to the cracking.

  5. D3-Brane Model Building and the Supertrace Rule.

    PubMed

    Bena, Iosif; Graña, Mariana; Kuperstein, Stanislav; Ntokos, Praxitelis; Petrini, Michela

    2016-04-01

    A common way to obtain standard-model-like Lagrangians in string theory is to place D3-branes inside flux compactifications. The bosonic and fermionic masses and couplings of the resulting gauge theory are determined by the ten-dimensional metric and the fluxes, respectively, and the breaking of supersymmetry is soft. However, not any soft-supersymmetry-breaking Lagrangian can be obtained this way since the string theory equations of motion impose certain relations between the soft couplings. We show that for D3-branes in background fluxes, these relations imply that the sums of the squares of the boson and of the fermion masses are equal and that, furthermore, one- and two-loop quantum corrections do not spoil this equality. This makes the use of D3-branes for constructing computationally controllable models for physics beyond the standard model problematic. PMID:27104696

  6. D3-Brane Model Building and the Supertrace Rule.

    PubMed

    Bena, Iosif; Graña, Mariana; Kuperstein, Stanislav; Ntokos, Praxitelis; Petrini, Michela

    2016-04-01

    A common way to obtain standard-model-like Lagrangians in string theory is to place D3-branes inside flux compactifications. The bosonic and fermionic masses and couplings of the resulting gauge theory are determined by the ten-dimensional metric and the fluxes, respectively, and the breaking of supersymmetry is soft. However, not any soft-supersymmetry-breaking Lagrangian can be obtained this way since the string theory equations of motion impose certain relations between the soft couplings. We show that for D3-branes in background fluxes, these relations imply that the sums of the squares of the boson and of the fermion masses are equal and that, furthermore, one- and two-loop quantum corrections do not spoil this equality. This makes the use of D3-branes for constructing computationally controllable models for physics beyond the standard model problematic.

  7. Taming supersymmetric defects in 3d-3d correspondence

    NASA Astrophysics Data System (ADS)

    Gang, Dongmin; Kim, Nakwoo; Romo, Mauricio; Yamazaki, Masahito

    2016-07-01

    We study knots in 3d Chern-Simons theory with complex gauge group {SL}(N,{{C}}), in the context of its relation with 3d { N }=2 theory (the so-called 3d-3d correspondence). The defect has either co-dimension 2 or co-dimension 4 inside the 6d (2,0) theory, which is compactified on a 3-manifold \\hat{M}. We identify such defects in various corners of the 3d-3d correspondence, namely in 3d {SL}(N,{{C}}) CS theory, in 3d { N }=2 theory, in 5d { N }=2 super Yang-Mills theory, and in the M-theory holographic dual. We can make quantitative checks of the 3d-3d correspondence by computing partition functions at each of these theories. This Letter is a companion to a longer paper [1], which contains more details and more results.

  8. Suntanning and cutaneous synthesis of vitamin D3.

    PubMed

    Matsuoka, L Y; Wortsman, J; Hollis, B W

    1990-07-01

    Skin tanning is the melanization of the epidermis induced by excessive sunlight exposure. Since melanin absorbs preferentially the wavelengths around 300 nm and the cutaneous synthesis of vitamin D3 is stimulated by the same wavelengths (290 to 320 nm, ultraviolet light B [UVB]), we investigated the effect of tanning on vitamin D3 formation. Vitamin D3 and 25 hydroxyvitamin D (25-OH-D) serum levels were measured during midwinter (untanned state) in seven healthy subjects. Blood was obtained immediately before whole body exposure to UVB in a phototherapy unit, and again 24 hours later. The study was repeated in the same subjects during midsummer (tanned state) using the same UVB dose. Serum vitamin D3 increased in the untanned state from 1.7 +/- 0.4 ng/ml (mean +/- SE) to 11 +/- 1.5 ng/ml following UVB (p less than 0.001). In the tanned state, basal serum vitamin D3 was significantly higher: 9.6 +/- 2.8 ng/ml (p less than 0.04 basal untanned versus basal tanned), and exhibited minimal rise after UVB to 14.3 +/- 4.1 ng/ml (p greater than 0.1 for tanned basal versus post UVB tanned). Tanning was also associated with significantly higher serum 25-OH-D levels: 22.5 +/- 2.9 ng/ml (untanned) versus 36.9 +/- 4.7 ng/ml (tanned) (p less than 0.02). Thus excessive solar exposure produces, besides erythema and tanning, the resetting of the vitamin D3 synthetic mechanism with blunting of the response to UVB.

  9. Vitamin D(3) receptor ablation alters mammary gland morphogenesis.

    PubMed

    Zinser, Glendon; Packman, Kathryn; Welsh, JoEllen

    2002-07-01

    Postnatal mammary gland morphogenesis is achieved through coordination of signaling networks in both the epithelial and stromal cells of the developing gland. While the major proliferative hormones driving pubertal mammary gland development are estrogen and progesterone, studies in transgenic and knockout mice have successfully identified other steroid and peptide hormones that impact on mammary gland development. The vitamin D(3) receptor (VDR), whose ligand 1,25-dihydroxyvitamin D(3) is the biologically active form of vitamin D(3), has been implicated in control of differentiation, cell cycle and apoptosis of mammary cells in culture, but little is known about the physiological relevance of the vitamin D(3) endocrine system in the developing gland. In these studies, we report the expression of the VDR in epithelial cells of the terminal end bud and subtending ducts, in stromal cells and in a subset of lymphocytes within the lymph node. In the terminal end bud, a distinct gradient of VDR expression is observed, with weak VDR staining in proliferative populations and strong VDR staining in differentiated populations. The role of the VDR in ductal morphogenesis was examined in Vdr knockout mice fed high dietary Ca(2+) which normalizes fertility, serum estrogen and neonatal growth. Our results indicate that mammary glands from virgin Vdr knockout mice are heavier and exhibit enhanced growth, as evidenced by higher numbers of terminal end buds, greater ductal outgrowth and enhanced secondary branch points, compared with glands from age- and weight-matched wild-type mice. In addition, glands from Vdr knockout mice exhibit enhanced growth in response to exogenous estrogen and progesterone, both in vivo and in organ culture, compared with glands from wild-type mice. Our data provide the first in vivo evidence that 1,25-dihydroxyvitamin D(3) and the VDR impact on ductal elongation and branching morphogenesis during pubertal development of the mammary gland. Collectively

  10. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels.

    PubMed

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  11. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels

    PubMed Central

    Xue, Ying; He, Xin; Li, Huan-De; Deng, Yang; Yan, Miao; Cai, Hua-Lin; Tang, Mi-Mi; Dang, Rui-Li; Jiang, Pei

    2015-01-01

    While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. PMID:26713090

  12. The Kinetics of Vitamin D3 in the Osteoblastic Cell

    PubMed Central

    Buchanan, James L; Gilbert, Robert; Ou, Yvonne; Nohe, Anja; Schaefer, Rachel

    2014-01-01

    Experimental evidience is presented on the translocation of vitamin D metabolite, 1,25-(OH)2D3, from the membrane to the nucleus in osteoblast progenitor cells. A mathematical model permitting traversal of the cytoplasm at either a fixed velocity or by diffusion is formulated in order to determine whether transport along the cytoskeletal tracks is more consistent with the observed spatial-temporal distribution than diffusion, and it is so found. The model includes reactions in the nucleus involving D3 to form other compounds, such as protegerin, and thus also makes predictions of the concentrations of these compounds in various regions of the cell. PMID:23775045

  13. Ghost-Free, Finite, Fourth-Order D=3 Gravity

    NASA Astrophysics Data System (ADS)

    Deser, S.

    2009-09-01

    Canonical analysis of a recently proposed linear+quadratic curvature gravity model in D=3 establishes its pure, irreducibly fourth derivative, quadratic curvature limit as both ghost-free and power-counting UV finite, thereby maximally violating standard folklore. This limit is representative of a generic class whose kinetic terms are conformally invariant in any dimension, but it is unique in simultaneously avoiding the transverse-traceless graviton ghosts plaguing D>3 quadratic actions as well as double pole propagators in its other variables. While the two-term model is also unitary, its additional mode’s second-derivative nature forfeits finiteness.

  14. Welding procedure specification: gas tungsten arc welding of AISI 41XX steels

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.

    1985-08-01

    Procedure WPS-126 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of AISI 4130 and 4142 steel (ASTM A519) (P-No: None), 0.438-in. wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No: None).

  15. Eddy Current Assessment of the Cold Rolled Deformation Behavior of AISI 321 Stainless Steel

    NASA Astrophysics Data System (ADS)

    Liu, Kunpeng; Zhao, Zihua; Zhang, Zheng

    2012-08-01

    Applicability of the eddy current (EC) technique in assessing martensite phase transformation during cold reduction in AISI 321 stainless steel was investigated. An empirical model based on measured EC parameters was developed for predicting the volume fraction of strain-induced martensite. Good agreement was found between the model-predicted and the experimental data.

  16. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  17. 21 CFR 172.380 - Vitamin D 3;.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  18. 21 CFR 172.380 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the United States Pharmacopeial.../federal-register/cfr/ibr-locations.html. (c) The additive may be used as follows: (1) At levels not to...-dehydrocholesterol produced from cholesterol and is purified by crystallization. (b) Vitamin D3 meets...

  19. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  20. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the... crystallization. (b) Vitamin D3 meets the specifications of the Food Chemicals Codex, 5th ed. (2004), pp....

  1. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  2. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  3. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  4. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRINKING WATER OF ANIMALS Listing of Specific Substances Affirmed as GRAS § 584.725 25-Hydroxyvitamin D3... drinking water of broiler chickens when used in accordance with the limitations in paragraph (c) of this... exceed 69 ppb in feed or 34.5 ppb in drinking water. (ii) Adequate use directions to ensure that...

  5. Quantum Electrodynamics in d=3 from the ε Expansion.

    PubMed

    Di Pietro, Lorenzo; Komargodski, Zohar; Shamir, Itamar; Stamou, Emmanuel

    2016-04-01

    We study quantum electrodynamics in d=3 coupled to N_{f} flavors of fermions. The theory flows to an IR fixed point for N_{f} larger than some critical number N_{f}^{c}. For N_{f}≤N_{f}^{c}, chiral-symmetry breaking is believed to take place. In analogy with the Wilson-Fisher description of the critical O(N) models in d=3, we make use of the existence of a fixed point in d=4-2ε to study the three-dimensional conformal theory. We compute, in perturbation theory, the IR dimensions of fermion bilinear and quadrilinear operators. For small N_{f}, a quadrilinear operator can become relevant in the IR and destabilize the fixed point. Therefore, the epsilon expansion can be used to estimate N_{f}^{c}. An interesting novelty compared to the O(N) models is that the theory in d=3 has an enhanced symmetry due to the structure of 3D spinors. We identify the operators in d=4-2ε that correspond to the additional conserved currents at d=3 and compute their infrared dimensions. PMID:27081967

  6. Quantum Electrodynamics in d=3 from the ε Expansion.

    PubMed

    Di Pietro, Lorenzo; Komargodski, Zohar; Shamir, Itamar; Stamou, Emmanuel

    2016-04-01

    We study quantum electrodynamics in d=3 coupled to N_{f} flavors of fermions. The theory flows to an IR fixed point for N_{f} larger than some critical number N_{f}^{c}. For N_{f}≤N_{f}^{c}, chiral-symmetry breaking is believed to take place. In analogy with the Wilson-Fisher description of the critical O(N) models in d=3, we make use of the existence of a fixed point in d=4-2ε to study the three-dimensional conformal theory. We compute, in perturbation theory, the IR dimensions of fermion bilinear and quadrilinear operators. For small N_{f}, a quadrilinear operator can become relevant in the IR and destabilize the fixed point. Therefore, the epsilon expansion can be used to estimate N_{f}^{c}. An interesting novelty compared to the O(N) models is that the theory in d=3 has an enhanced symmetry due to the structure of 3D spinors. We identify the operators in d=4-2ε that correspond to the additional conserved currents at d=3 and compute their infrared dimensions.

  7. A liposomal model that mimics the cutaneous production of vitamin D3. Studies of the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to vitamin D3

    NASA Technical Reports Server (NTRS)

    Tian, X. Q.; Holick, M. F.

    1999-01-01

    We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD3 to vitamin D3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found that a decrease in the hydrophilic interaction of the preD3 with liposomal phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3-3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which decreased the hydrophobic interaction of preD3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little difference among the rates of the conversion of preD3, its 3beta-acetate, and 25-hydroxy derivatives to their corresponding vitamin D3 compounds. We also determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes containing phosphatidylcholines with different carbon chain lengths. The rates of the reaction were found to be enhanced as the number of carbons (Cn) in the hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion, these results support our hypothesis that amphipathic interactions between preD3 and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc-conformer, the only conformer of preD3 that can convert to vitamin D3. The stronger these interactions were, the more preD3 was likely in its cZc conformation at any moment and the faster was the rate of its conversion to vitamin D3.

  8. A life study of AISI M-50 and Super Nitralloy spur gears with and without tip relief

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1973-01-01

    Tests were conducted at 170 F with groups of 3.5-in.-pitch-diameter spur gear with and without tip relief made of consumable-electrode vacuum melted (CVM) Spur Nitralloy (5Ni-2Al) and CVM AISI M-50 steel. The AISI M-50 gears without tip relief had lives approximately 50 percent longer than the Super Nitralloy gears without tip relief. However, the Super Nitralloy gears with tip relief had lives equal to the AISI M-50 gears without tip relief. The difference in lives were not statistically significant. All gears failed by classical pitting fatigue at the pitch circle. However, the AIAI M-50 gears with tip relief failed by tooth fracture. AISI M-50 gear sets without tip relief having a spalled gear tooth which were deliberately overrun after spalling had occurred, failed by tooth fracture.

  9. Swiss-cheese D3- D7 soft SUSY breaking

    NASA Astrophysics Data System (ADS)

    Misra, Aalok; Shukla, Pramod

    2010-03-01

    We address issues related to (i) a proposal for resolving a long-standing tension between large volume cosmology and phenomenology as regards reconciliation of requirements of different gravitino masses within the same string-theoretic framework, as well as (ii) evaluation of soft supersymmetry breaking terms and open-string moduli masses in the context of type IIB large volume compactifications involving orientifolds of the Swiss-cheese Calabi-Yau WCP[1,1,1,6,9] with a single mobile space-time filling D3-brane and stacks of D7-branes wrapping the "big" divisor Σ as well as supporting D7-brane fluxes. In addition, we also include perturbative α-corrections and non-perturbative world-sheet instanton corrections to the Kähler potential as well as Euclidean D3-instanton superpotential. First, using the toric data for the aforementioned Swiss-cheese Calabi-Yau and GLSM techniques, we obtain in the large volume limit, the geometric Kähler potential for the big (and small) divisor(s) in terms of derivatives of genus-two Siegel theta functions. Next, we show that as the mobile space-time filling D3-brane moves from a particular non-singular elliptic curve embedded in the Swiss-cheese Calabi-Yau to another non-singular elliptic curve, it is possible to obtain 10 12 GeV gravitino during the primordial inflationary era as well as, e.g., a TeV gravitino in the present era, within the same set up for the same volume of the Calabi-Yau stabilized at around 10ls6. Then by constructing local (i.e. localized around the location of the mobile D3-brane in the Calabi-Yau) appropriate involutively-odd harmonic one-form on the big divisor that lies in coker(H∂¯,-(0,1)(CY)→iH∂¯,-(0,1)(Σ)) and extremizing the potential, we show that it is possible to obtain an O(1)g from the wrapping of D7-branes on the big divisor due to competing contributions from the Wilson line moduli relative to the divisor volume modulus. To permit gaugino condensation, we take the rigid limit of the

  10. Nonperturbative gluon and ghost propagators in d = 3

    SciTech Connect

    Papavassiliou, Joannis

    2011-05-23

    We study the nonperturbative gluon and ghost propagators in d = 3 Yang-Mills, using the Schwinger-Dyson equations of the pinch technique. The use of the Schwinger mechanism leads to the dynamical generation of a gluon mass, which, in turn, gives rise to an infrared finite gluon propagator and ghost dressing function. The propagators obtained are in very good agreement with the results of SU(2) lattice simulations.

  11. Role of the D3 dopamine receptor in nicotine sensitization.

    PubMed

    Smith, Laura N; Bachus, Susan E; McDonald, Craig G; Smith, Robert F

    2015-08-01

    Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here, we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined (1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing regimen of nicotine and (2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. DRD3 antagonism only blocked the induction of sensitization in adolescents and did not block the expression of sensitization in either age group. Adolescents and adults showed opposite DRD1 mRNA responses to nicotine treatment, while no age- and nicotine-related changes in DRD2 mRNA were observed. These data reveal important age-dependent regulation of DRD1- and DRD3-related mRNAs during the course of nicotine exposure. Furthermore, they highlight a requirement for DRD3 signaling in the development of adolescent nicotine sensitization, suggesting it may represent an appropriate target in the prevention of nicotine dependence initiated at this age.

  12. A simultaneous 2D/3D autostereo workstation

    NASA Astrophysics Data System (ADS)

    Chau, Dennis; McGinnis, Bradley; Talandis, Jonas; Leigh, Jason; Peterka, Tom; Knoll, Aaron; Sumer, Aslihan; Papka, Michael; Jellinek, Julius

    2012-03-01

    We present a novel immersive workstation environment that scientists can use for 3D data exploration and as their everyday 2D computer monitor. Our implementation is based on an autostereoscopic dynamic parallax barrier 2D/3D display, interactive input devices, and a software infrastructure that allows client/server software modules to couple the workstation to scientists' visualization applications. This paper describes the hardware construction and calibration, software components, and a demonstration of our system in nanoscale materials science exploration.

  13. Dopamine D2/D3 receptor availability and venturesomeness.

    PubMed

    Bernow, Nina; Yakushev, Igor; Landvogt, Christian; Buchholz, Hans-Georg; Smolka, Michael N; Bartenstein, Peter; Lieb, Klaus; Gründer, Gerhard; Vernaleken, Ingo; Schreckenberger, Mathias; Fehr, Christoph

    2011-08-30

    The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-Venturesomeness-Empathy questionnaire (I7). Image processing and statistical analysis was performed on a voxel-by-voxel basis using statistical parametric mapping (SPM) software. The I7 subscale venturesomeness correlated positively with the D2/D3 receptor availability within the left temporal cortex and the thalamus. Measures on the I7 subscale impulsiveness and empathy did not correlate with the D2/D3 receptor availability in any brain region investigated. Our results suggest the involvement of extrastriatal dopaminergic neurotransmission in venturesomeness, a component of impulsivity. PMID:21689908

  14. Assessment of XM-19 as a Substitute for AISI 348 in ATR Service

    SciTech Connect

    F. A. Garner; L. R. Greenwood; R. E. Mizia; C. R. Tyler

    2007-11-01

    It has been proposed that XM-19 alloy be considered as a possible replacement steel for AISI 348 in the construction of Advanced Test Reactor (ATR) capsules. AISI 348 works well, but is currently very difficult to obtain commercially. The superior and desirable mechanical properties of XM-19 alloy have been proven in non-nuclear applications, but no data are available regarding its use in radiation environments. While most 300 series alloys will meet the conditions required in ATR , it cannot be confidently assumed that XM-19 can be substituted without prior qualification in a radiation test. Compared to AISI 348, XM-19 will have an enhanced tendency for phase instabilities due to its higher levels of Ni and, especially, Si. However, transmutation of important elemental components in the highly thermalized ATR spectrum may have a very pronounced effect on its performance during irradiation. Not only will strong transmutation of Mn to Fe reduce the ductility and strength advantages provided by the higher initial Mn content of XM-19, but the extensive loss of Mn will also release from solution much of the N upon which the higher strength of XM-19 depends. In addition, the combined influence of transmutation and Inverse Kirkendall processes may lead to gas-bubble-covered grain boundaries, producing a very fragile alloy after significant irradiation has accumulated. At present, there are no radiation data available to substantiate this possible scenario. An alternate proposal is therefore advanced. Since the response of AISI 348 and 347 to radiation are expected to be relatively indistinguishable, the AISI 347 might serve as an acceptable replacement. While AISI 348 is usually chosen for nuclear service in order to reduce the overall radioactivity arising from relatively small amounts of highly transmutable elements such as cobalt, these elements have very little effect on the radiation performance of the steel. In the proposed application, however, the activity

  15. Metabolism of 20-Hydroxyvitamin D3 and 20,23-Dihydroxyvitamin D3 by Rat and Human CYP24A1

    PubMed Central

    Tieu, Elaine W.; Li, Wei; Chen, Jianjun; Kim, Tae-Kang; Ma, Dejian; Slominski, Andrzej T.; Tuckey, Robert C.

    2015-01-01

    CYP11A1 hydroxylates vitamin D3 producing 20S-hydroxyvitamin D3 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)2D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20(OH)D3 can be metabolized by rat CYP24A1 to products including 20S,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20S,25-dihydroxyvitamin D3, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)2D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)2D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)2D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20S,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)2D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)2D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)2D3. We conclude that rat and human CYP24A1 metabolizes 20(OH)D3 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)2D3 undergoes multiple oxidations which include cleavage of the side chain. PMID:25727742

  16. Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D3 Metabolites

    PubMed Central

    Tuohimaa, Pentti; Wang, Jing-Huan; Khan, Sofia; Kuuslahti, Marianne; Qian, Kui; Manninen, Tommi; Auvinen, Petri; Vihinen, Mauno; Lou, Yan-Ru

    2013-01-01

    1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1−/−), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1−/−. By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment. PMID:24116037

  17. An experimental analysis of process parameters to manufacture micro-channels in AISI H13 tempered steel by laser micro-milling

    NASA Astrophysics Data System (ADS)

    Teixidor, D.; Ferrer, I.; Ciurana, J.

    2012-04-01

    This paper reports the characterization of laser machining (milling) process to manufacture micro-channels in order to understand the incidence of process parameters on the final features. Selection of process operational parameters is highly critical for successful laser micromachining. A set of designed experiments is carried out in a pulsed Nd:YAG laser system using AISI H13 hardened tool steel as work material. Several micro-channels have been manufactured as micro-mold cavities varying parameters such as scanning speed (SS), pulse intensity (PI) and pulse frequency (PF). Results are obtained by evaluating the dimensions and the surface finish of the micro-channel. The dimensions and shape of the micro-channels produced with laser-micro-milling process exhibit variations. In general the use of low scanning speeds increases the quality of the feature in both surface finishing and dimensional.

  18. Rolling-element fatigue life of AISI M-50 and 18-4-1 balls

    NASA Technical Reports Server (NTRS)

    Parker, R. J.; Zaretsky, E. V.

    1978-01-01

    Rolling element fatigue studies were conducted with AISI M-50, EFR 18-4-1, and VAR 18-4-1. Groups of 12.7 mm (1/2-in) diameter balls of each material were tested in the five ball fatigue tester. Test conditions included a load of 1540 N (347 lbf) giving a maximum Hertz stress of 5520 MPa (800 000 psi), a shaft speed of 10,700 rpm, and a contact angle of 30 deg. Tests were run at a race temperature of 339 K (150 F) with a type 2 ester lubricant. The rolling element fatigue life of AISI M-50 was not significantly different from that of EFR 18-4-1 or VAR 18-4-1 based on a statistical comparison of the test results.

  19. Behavior of AISI SAE 1020 Steel Implanted by Titanium and Exposed to Bacteria Sulphate Deoxidizer

    NASA Astrophysics Data System (ADS)

    Niño, Ely Dannier V.; Garnica, Hernán; Dugar-Zhabon, Veleriy; Castillo, Genis

    2014-05-01

    A hybrid technology to treat solid surfaces with the pulse high voltage and electric arc discharges of low pressure with a three-dimensional ion implantation technique (3DII) is applied. This technology is used to protect AISI SAE 1020 steel against a microbiological corrosion. The titanium ion implanted steel samples (coupons) are subjected to a medium of bacteria sulphate deoxidizer (BSD) which are very typical of the hydrocarbon industry and are potentially harmful for structures when are in contact with petroleum and some of its derivatives. The used technology aims to find an effective hybrid procedure to minimize the harmful effects of bacteria on AISI SAE 1020 steel. The hybrid technology efficiency of superficial titanium implantation is estimated through the measurements of the point corrosion characteristics obtained after testing both the treated and non-treated coupons. The three-dimensional surface structures of the samples are reconstructed with help of a confocal microscope.

  20. An investigation of the plastic fracture of AISI 4340 and 18 nickel - 200 grade maraging steels

    NASA Technical Reports Server (NTRS)

    Cox, T. B.; Low, J. R., Jr.

    1974-01-01

    The mechanisms of plastic fracture (dimpled rupture) in high-purity and commercial 18 Ni, 200 grade maraging steels and quenched and tempered AISI 4340 steels have been studied. Plastic fracture takes place in the maraging alloys through void initiation by fracture of titanium carbo-nitride inclusions and the growth of these voids until impingement results in coalescence and final fracture. The fracture of AISI 4340 steel at a yield strength of 200 ksi occurs by nucleation and subsequent growth of voids formed by fracture of the interface between manganese sulfide inclusions and the matrix. The growth of these inclusion-nucleated voids is interrupted long before coalescence by impingement, by the formation of void sheets which connect neighboring sulfide-nucleated voids.

  1. Radiation-induced evolution of austenite matrix in silicon-modified AISI 316 alloys

    SciTech Connect

    Garner, F.A.; Brager, H.R.

    1980-01-01

    The microstructures of a series of silicon-modified AISI 316 alloys irradiated to fast neutron fluences of about 2-3 and 10 x 10/sup 22/ n/cm/sup 2/ (E > 0.1 MeV at temperatures ranging from 400/sup 0/C to 600/sup 0/C have been examined. The irradiation of AISI 316 leads to an extensive repartition of several elements, particularly nickel and silicon, between the matrix and various precipitate phases. The segregation of nickel at void and grain boundary surfaces at the expense of other faster-diffusing elements is a clear indication that one of the mechanisms driving the microchemical evolution is the Inverse Kirkendall effect. There is evidence that at one sink this mechanism is in competition with the solute drag process associated with interstitial gradients.

  2. Vacancy clustering behavior in hydrogen-charged martensitic steel AISI 410 under tensile deformation

    NASA Astrophysics Data System (ADS)

    Sugita, K.; Mutou, Y.; Shirai, Y.

    2016-01-01

    The formation and accumulation of defects under tensile deformation of hydrogen- charged AISI 410 martensitic steels were investigated by using positron lifetime spectroscopy. During the deformation process, dislocations and vacancy-clusters were introduced and increased with increasing strains. Between hydrogen-charged and uncharged samples with the same tensile strains there was no significant difference in the dislocation density and monovacancy equivalent vacancy density.

  3. Stress corrosion cracking of AISI 321 stainless steel in acidic seawater

    NASA Astrophysics Data System (ADS)

    Huang, Yan-Liang; Hou, Bao-Rong; Cao, Chu-Nan; Lin, Hai-Chao

    1997-12-01

    The stress corrosion cracking (SCC) of AISI 321 stainless steel in acidic in acidic seawater was studied by slow strain rate (SSR) technique and fracture mechanics method. The fractured surface was characterized by cleavage fracture. The inhibiting effects of KI on SCC behavior were also covered in this detailed study which showed that they were mainly attributable to their inhibition on anodic reaction. The SCC mechanism study supported the unified mechanism of SCC and corrosion fatigue cracking (CFC).

  4. Recent update of the RPLUS2D/3D codes

    NASA Technical Reports Server (NTRS)

    Tsai, Y.-L. Peter

    1991-01-01

    The development of the RPLUS2D/3D codes is summarized. These codes utilize LU algorithms to solve chemical non-equilibrium flows in a body-fitted coordinate system. The motivation behind the development of these codes is the need to numerically predict chemical non-equilibrium flows for the National AeroSpace Plane Program. Recent improvements include vectorization method, blocking algorithms for geometric flexibility, out-of-core storage for large-size problems, and an LU-SW/UP combination for CPU-time efficiency and solution quality.

  5. Recombination of H(3+) and D(3+) ions with electrons

    NASA Technical Reports Server (NTRS)

    Johnsen, R.; Gougousi, T.; Golde, M. F.

    1994-01-01

    Flowing-afterglow measurements in decaying H3(+) or D3(+) plasmas suggest that de-ionization does not occur by simple binary recombination of a single ion species. We find that vibrational excitation of the ions fails to provide an explanation for the effect, contrary to an earlier suggestion. Instead, we suggest that collisional stabilization of H3** Rydberg molecules by ambient electrons introduces an additional dependence on electron density. The proposed mechanism would permit plasma de-ionization to occur without the need for dissociative recombination by the mechanism of potential-surface crossings.

  6. Experimental investigation of wear characteristics on TiCN-coated AISI 410 steel

    NASA Astrophysics Data System (ADS)

    Prabakaran, Vijayasarathi; Sivakumaran, Ilaiyavel; Palimar, Suresh Prabhu

    2016-04-01

    In this work, the dry sliding wear test of uncoated and multilayer TiCN-coated AISI 410 steel against high carbon steel disc recognized at 2.30267 ms-1 sliding speeds and under a three series load of 5, 10 and 20 N at room temperature. On account of the more coherent interface between TiCN and C probably found, there are high hardness and superior wear resistance. Compared to AISI 410 uncoated steel, the presence of C in the multilayer TiCN coatings leads to reduced coefficient of friction and wear loss. The multilayer TiCN coating is characterized by X-ray diffraction analysis, scanning electron microscopy, micro-hardness and pin-on-disc tribometer tests. The more grooving region, pits and ploughing ridge were examined on the worn surface of the AISI 410 uncoated steel. The result shows hard multilayer TiCN-coated particles viewing on the worn surface of the high carbon steel disc.

  7. Stoichiometric titanium dioxide ion implantation in AISI 304 stainless steel for corrosion protection

    NASA Astrophysics Data System (ADS)

    Hartwig, A.; Decker, M.; Klein, O.; Karl, H.

    2015-12-01

    The aim of this study is to evaluate the applicability of highly chemically inert titanium dioxide synthesized by ion beam implantation for corrosion protection of AISI 304 stainless steel in sodium chloride solution. More specifically, the prevention of galvanic corrosion between carbon-fiber reinforced plastic (CFRP) and AISI 304 was investigated. Corrosion performance of TiO2 implanted AISI 304 - examined for different implantation and annealing parameters - is strongly influenced by implantation fluence. Experimental results show that a fluence of 5 × 1016 cm-2 (Ti+) and 1 × 1017 cm-2 (O+) is sufficient to prevent pitting corrosion significantly, while galvanic corrosion with CFRP can already be noticeably reduced by an implantation fluence of 5 × 1015 cm-2 (Ti+) and 1 × 1016 cm-2 (O+). Surface roughness, implantation energy and annealing at 200 °C and 400 °C show only little influence on the corrosion behavior. TEM analysis indicates the existence of stoichiometric TiO2 inside the steel matrix for medium fluences and the formation of a separated metal oxide layer for high fluences.

  8. Nanoscale precipitates and comprehensive strengthening mechanism in AISI H13 steel

    NASA Astrophysics Data System (ADS)

    Mao, Wen-wen; Ning, An-gang; Guo, Han-jie

    2016-09-01

    The effects of heat treatment on the precipitates and strengthening mechanism in AISI H13 steel were investigated. The results showed that the presence of nanoscale precipitates favorably affected grain refinement and improved the yield strength. The volume fraction of precipitates increased from 1.05% to 2.85% during tempering, whereas the average precipitate size first decreased then increased during tempering. Contributions to the yield strength arising from the various mechanisms were calculated quantificationally, and the results demonstrated that grain refinement and dislocation density most strongly influenced the yield strength. In addition, under the interaction of average size and volume fraction, precipitates' contribution to the yield strength ranged from 247.9 to 378.5 MPa. Finally, a root-mean-square summation law of σ = σg + σs + (σd 2 + σp 2)1/2, where σg, σs, σd, and σp represent the contributions of fine-grain strengthening, solid-solution strengthening, dislocation strengthening, and precipitation strengthening, respectively, was confirmed as the most applicable for AISI H13 steel, which indicates a strong link between precipitates and dislocations in AISI H13 steel.

  9. 750 GeV diphotons from a D3-brane

    NASA Astrophysics Data System (ADS)

    Heckman, Jonathan J.

    2016-05-01

    Motivated by the recently reported diphoton excess at 750 GeV observed by both CMS and ATLAS, we study string-based particle physics models which can accommodate this signal. Quite remarkably, although Grand Unified Theories in F-theory tend to impose tight restrictions on candidate extra sectors, the case of a probe D3-brane near an E-type Yukawa point naturally leads to a class of strongly coupled models capable of accommodating the observed signature. In these models, the visible sector is realized by intersecting 7-branes, and the 750 GeV resonance is a scalar modulus associated with motion of the D3-brane in the direction transverse to the Standard Model 7-branes. Integrating out heavy 3-7 string messenger states leads to dimension five operators for gluon fusion production and diphoton decays. Due to the unified structure of interactions, these models also predict that there should be additional decay channels to ZZ and Zγ. We also comment on models with distorted unification, where both the production mechanism and decay channels can differ.

  10. The dopamine D3 receptor gene and posttraumatic stress disorder.

    PubMed

    Wolf, Erika J; Mitchell, Karen S; Logue, Mark W; Baldwin, Clinton T; Reardon, Annemarie F; Aiello, Alison; Galea, Sandro; Koenen, Karestan C; Uddin, Monica; Wildman, Derek; Miller, Mark W

    2014-08-01

    The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). The aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed White, non-Hispanic U.S. veterans and their trauma-exposed intimate partners (N = 491); 60.3% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants living in Detroit, Michigan; 23.6% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, 4 single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (OR range = 0.59 to 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (OR = 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors could potentially explain this association. PMID:25158632

  11. The Dopamine D3 Receptor Gene and Posttraumatic Stress Disorder

    PubMed Central

    Wolf, Erika J.; Mitchell, Karen S.; Logue, Mark W.; Baldwin, Clinton T.; Reardon, Annemarie F.; Aiello, Alison; Galea, Sandro; Koenen, Karestan C.; Uddin, Monica; Wildman, Derek; Miller, Mark W.

    2014-01-01

    The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). This aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed white, non-Hispanic veterans and their trauma-exposed intimate partners (N = 491); 60% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants; 24% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, four single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (odds ratio range: 0.59 – 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (odds ratio: 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors, could potentially explain this association. PMID:25158632

  12. Numerical modelling of tool wear in turning with cemented carbide cutting tools

    SciTech Connect

    Franco, P.; Estrems, M.; Faura, F.

    2007-04-07

    A numerical model is proposed for analysing the flank and crater wear resulting from the loss of material on cutting tool surface in turning processes due to wear mechanisms of adhesion, abrasion and fracture. By means of this model, the material loss along cutting tool surface can be analysed, and the worn surface shape during the workpiece machining can be determined. The proposed model analyses the gradual degradation of cutting tool during turning operation, and tool wear can be estimated as a function of cutting time. Wear-land width (VB) and crater depth (KT) can be obtained for description of material loss on cutting tool surface, and the effects of the distinct wear mechanisms on surface shape can be studied. The parameters required for the tool wear model are obtained from bibliography and experimental observation for AISI 4340 steel turning with WC-Co cutting tools.

  13. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS ENERGY AND WATER... RULEâ) Pt. 305, App. D3 Appendix D3 to Part 305—Water Heaters—Oil Range Information Capacity First...

  14. Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25[OH]D3) by the enzyme 1alpha-hydroxylase in monocytes upon activation by TLR...

  15. "big" Divisor D3/D7 Swiss-Cheese Phenomenology

    NASA Astrophysics Data System (ADS)

    Misra, Aalok

    We review progress made over the past couple of years in the field of Swiss-Cheese Phenomenology involving a mobile spacetime filling D3-brane and stack(s) of fluxed D7-branes wrapping the "big" (as opposed to the "small") divisor in (the orientifold of (a) Swiss-Cheese Calabi-Yau. The topics reviewed include reconciliation of large volume cosmology and phenomenology, evaluation of soft supersymmetry breaking parameters, one-loop RG-flow equations' solutions for scalar masses, obtaining fermionic (possibly first two generations' quarks/leptons) mass scales in the {O}(MeV--GeV)-regime as well as (first two generations') neutrino masses (and their one-loop RG flow) of around an eV. The heavy sparticles and the light fermions indicate the possibility of "split SUSY" large volume scenario.

  16. Modulation of 1alpha,25-dihydroxyvitamin D3-membrane associated, rapid response steroid binding protein expression in mouse odontoblasts by 1alpha,25-(OH)2D3.

    PubMed

    Teillaud, Christophe; Nemere, Ilka; Boukhobza, Florine; Mathiot, Claire; Conan, Nicole; Oboeuf, Martine; Hotton, Dominique; Macdougall, Mary; Berdal, Ariane

    2005-01-01

    The rapid, nongenomic effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3 have been related to a 1,25D3-membrane associated, rapid response steroid binding protein or 1,25D3-[MARRS]bp, with a molecular weight of 65 kDa, in several tissues and species. Currently, no information is available concerning the nongenomic responses to 1alpha,25-(OH)2D3 in dental tissues. In order to investigate the expression of 1,25D3-[MARRS]bp in dental cells, in the presence or absence of 1alpha,25-(OH)2D3, we have used rabbit polyclonal antibodies directed against the N-terminus of the 1,25D3-[MARRS]bp (Ab099) that recognizes the 1alpha,25-(OH)2D3 binding protein in chick intestinal basolateral membranes and a mouse odontoblast-like cell line (MO6-G3). Western blotting and flow cytometric analyses with Ab099 specifically detected 1,25D3-[MARRS]bp in MO6-G3 cells. Moreover, 1,25D3-[MARRS]bp was up-regulated, in vivo, in differentiated dental cells. Electron microscopic analysis confirmed the plasma membrane localization of this binding protein and also showed its intracellular presence. Incubation of MO6-G3 cells with different doses of 1alpha,25-(OH)2D3 for 36 h resulted in an inhibition of 1,25D3-[MARRS]bp expression with a maximal effect at 50 nM steroid. In addition, the culture media of MO6-G3 cells contains immunoreactive 1,25D3-[MARRS]bp. Immunogold positive membrane vesicle-like structures are present in the extracellular matrix of MO6-G3 cells. Altogether, these results indicate that the 1,25D3-[MARRS]bp expression in MO6-G3 cells is modulated by 1alpha,25-(OH)2D3. In conclusion, this 1alpha,25-(OH)2D3 binding protein could play an important role in the rapid, nongenomic responses to 1alpha,25-(OH)2D3 in dental cells.

  17. 6-s-cis locked analogues of the steroid hormone 1alpha, 25-dihydroxyvitamin D(3). Synthesis Of novel A-ring stereoisomeric 1, 25-dihydroxy-3-epi-19-nor-previtamin D(3) derivatives.

    PubMed

    Díaz, M; Ferrero, M; Fernández, S; Gotor, V

    2000-09-01

    Efficient syntheses of A-ring synthons 24 and 32 are described from hydroxy ester 16, which is easily available on a preparative scale from (-)-quinic acid. Key features of the syntheses were (a) the ability to selectively perform desilylations in the presence of p-nitrobenzoate esters and (b) the excellent yield and complete stereospecificity with which the configuration of alcohols 16, 18, and 26 could be inverted under Mitsunobu conditions. Thus, A-ring synthons 24 and 32 were both prepared in 35-38% yield (eight steps) from the common precursor 16. The coupling of A-ring synthons 24 and 32 with the appropriate CD-ring/side chain fragment 7 provides access to novel 6-s-cis locked analogues of steroid hormone 1alpha, 25-dihydroxyvitamin D(3): 1alpha, 25-dihydroxy-3-epi-19-nor-previtamin D(3) (37) and 1beta, 25-dihydroxy-3-epi-19-nor-previtamin D(3) (38), which are unable to undergo rearrangement to the respective vitamin D form by virtue of the absence of the C-19 methyl group. Compounds 37 and 38 can be used as tools for studying the genomic and nongenomic mechanisms of action of the previtamin form of the hormone 1alpha, 25-dihydroxyvitamin D(3).

  18. Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.

    PubMed

    van der Meijden, K; Bravenboer, N; Dirks, N F; Heijboer, A C; den Heijer, M; de Wit, G M J; Offringa, C; Lips, P; Jaspers, R T

    2016-11-01

    An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  19. Highly Selective Dopamine D3 Receptor (D3R) Antagonists and Partial Agonists Based on Eticlopride and the D3R Crystal Structure: New Leads for Opioid Dependence Treatment.

    PubMed

    Kumar, Vivek; Bonifazi, Alessandro; Ellenberger, Michael P; Keck, Thomas M; Pommier, Elie; Rais, Rana; Slusher, Barbara S; Gardner, Eliot; You, Zhi-Bing; Xi, Zheng-Xiong; Newman, Amy Hauck

    2016-08-25

    The recent and precipitous increase in opioid analgesic abuse and overdose has inspired investigation of the dopamine D3 receptor (D3R) as a target for therapeutic intervention. Metabolic instability or predicted toxicity has precluded successful translation of previously reported D3R-selective antagonists to clinical use for cocaine abuse. Herein, we report a series of novel and D3R crystal structure-guided 4-phenylpiperazines with exceptionally high D3R affinities and/or selectivities with varying efficacies. Lead compound 19 was selected based on its in vitro profile: D3R Ki = 6.84 nM, 1700-fold D3R versus D2R binding selectivity, and its metabolic stability in mouse microsomes. Compound 19 inhibited oxycodone-induced hyperlocomotion in mice and reduced oxycodone-induced locomotor sensitization. In addition, pretreatment with 19 also dose-dependently inhibited the acquisition of oxycodone-induced conditioned place preference (CPP) in rats. These findings support the D3R as a target for opioid dependence treatment and compound 19 as a new lead molecule for development. PMID:27508895

  20. Wear Evaluation of AISI 4140 Alloy Steel with WC/C Lamellar Coatings Sliding Against EN 8 Using Taguchi Method

    NASA Astrophysics Data System (ADS)

    Kadam, Nikhil Rajendra; Karthikeyan, Ganesarethinam

    2016-06-01

    The purpose of the experiments in this paper is to use the Taguchi methods to investigate the wear of WC/C coated nitrided AISI 4140 alloy steel. A study of lamellar WC/C coating which were deposited by a physical vapor deposition on nitrided AISI 4140 alloy steel. The investigation includes wear evaluation using Pin-on-disk configuration. When WC/C coated AISI 4140 alloy steel slides against EN 8 steel, it was found that carbon-rich coatings show much lower wear of the countersurface than nitrogen-rich coatings. The results were correlated with the properties determined from tribological and mechanical characterization, therefore by probably selecting the proper processing parameters the deposition of WC/C coating results in decreasing the wear rate of the substrate which shows a potential for tribological application.

  1. Endurance and failure characteristics of modified Vasco X-2, CBS 600 and AISI 9310 spur gears. [aircraft construction materials

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1980-01-01

    Gear endurance tests and rolling-element fatigue tests were conducted to compare the performance of spur gears made from AISI 9310, CBS 600 and modified Vasco X-2 and to compare the pitting fatigue lives of these three materials. Gears manufactured from CBS 600 exhibited lives longer than those manufactured from AISI 9310. However, rolling-element fatigue tests resulted in statistically equivalent lives. Modified Vasco X-2 exhibited statistically equivalent lives to AISI 9310. CBS 600 and modified Vasco X-2 gears exhibited the potential of tooth fracture occurring at a tooth surface fatigue pit. Case carburization of all gear surfaces for the modified Vasco X-2 gears results in fracture at the tips of the gears.

  2. A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin.

    PubMed

    Staunstrup, Nicklas Heine; Bak, Rasmus O; Cai, Yujia; Svensson, Lars; Petersen, Thomas K; Rosada, Cecilia; Stenderup, Karin; Bolund, Lars; Mikkelsen, Jacob Giehm

    2013-03-01

    Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.

  3. Association study of dopamine D3 receptor gene and schizophrenia

    SciTech Connect

    Kennedy, J.L.; Billett, E.A.; Macciardi, F.M.

    1995-12-18

    Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. 32 refs., 2 tabs.

  4. Ammonia Induces Autophagy through Dopamine Receptor D3 and MTOR.

    PubMed

    Li, Zhiyuan; Ji, Xinmiao; Wang, Wenchao; Liu, Juanjuan; Liang, Xiaofei; Wu, Hong; Liu, Jing; Eggert, Ulrike S; Liu, Qingsong; Zhang, Xin

    2016-01-01

    Hyperammonemia is frequently seen in tumor microenvironments as well as in liver diseases where it can lead to severe brain damage or death. Ammonia induces autophagy, a mechanism that tumor cells may use to protect themselves from external stresses. However, how cells sense ammonia has been unclear. Here we show that culture medium alone containing Glutamine can generate milimolar of ammonia at 37 degrees in the absence of cells. In addition, we reveal that ammonia acts through the G protein-coupled receptor DRD3 (Dopamine receptor D3) to induce autophagy. At the same time, ammonia induces DRD3 degradation, which involves PIK3C3/VPS34-dependent pathways. Ammonia inhibits MTOR (mechanistic target of Rapamycin) activity and localization in cells, which is mediated by DRD3. Therefore, ammonia has dual roles in autophagy: one to induce autophagy through DRD3 and MTOR, the other to increase autophagosomal pH to inhibit autophagic flux. Our study not only adds a new sensing and output pathway for DRD3 that bridges ammonia sensing and autophagy induction, but also provides potential mechanisms for the clinical consequences of hyperammonemia in brain damage, neurodegenerative diseases and tumors.

  5. 2D/3D registration algorithm for lung brachytherapy

    SciTech Connect

    Zvonarev, P. S.; Farrell, T. J.; Hunter, R.; Wierzbicki, M.; Hayward, J. E.; Sur, R. K.

    2013-02-15

    Purpose: A 2D/3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. Methods: The algorithm utilizes a rigid registration model based on a pixel/voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. Results: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. Conclusions: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

  6. D3-instantons, mock theta series and twistors

    NASA Astrophysics Data System (ADS)

    Alexandrov, Sergei; Manschot, Jan; Pioline, Boris

    2013-04-01

    The D-instanton corrected hypermultiplet moduli space of type II string theory compactified on a Calabi-Yau threefold is known in the type IIA picture to be determined in terms of the generalized Donaldson-Thomas invariants, through a twistorial construction. At the same time, in the mirror type IIB picture, and in the limit where only D3-D1-D(-1)-instanton corrections are retained, it should carry an isometric action of the S-duality group SL(2, {Z} ). We prove that this is the case in the one-instanton approximation, by constructing a holomorphic action of SL(2, {Z} ) on the linearized twistor space. Using the modular invariance of the D4-D2-D0 black hole partition function, we show that the standard Darboux coordinates in twistor space have modular anomalies controlled by period integrals of a Siegel-Narain theta series, which can be canceled by a contact transformation generated by a holomorphic mock theta series.

  7. Electrochemical Study of AISI C1018 Steel in Methanesulfonic Acid Containing an Acetylenic Alcohol-Based Corrosion Inhibitor Formulation.

    PubMed

    Finšgar, Matjaž; Jackson, Jennifer

    2016-10-01

    In this work, the electrochemical potentiodynamic behavior of AISI C1018 lower-grade steel material was investigated in 20 wt.% methanesulfonic acid (MSA) solutions with or without different components to design corrosion inhibitor formulations based on acetylenic alcohol, cinnamaldehyde, 1-dodecylpyridinium chloride, and methanol. MSA has recently been considered as a new potential acid to be used in the matrix stimulation procedure and in well cleaning. It is demonstrated that AISI C1018 steel MSA needs to be inhibited. Inhibition type is determined for single components as well as for formulations.

  8. Investigating early stages of biocorrosion with XPS: AISI 304 stainless steel exposed to Burkholderia species

    NASA Astrophysics Data System (ADS)

    Johansson, Leena-Sisko; Saastamoinen, Tuomas

    1999-04-01

    We have investigated the interactions of an exopolymer-producing bacteria, Burkholderia sp. with polished AISI 304 stainless steel substrates using X-ray photoelectron spectroscopy (XPS). Steel coupons were exposed to the pure bacteria culture in a specially designed flowcell for 6 h during which the experiment was monitored in situ with an optical microscope. XPS results verified the formation of biofilm containing extracellular polymer on all the samples exposed to bacteria. Sputter results indicated that some ions needed for metabolic processes were trapped within the biofilm. Changes in the relative Fe concentration and Fe 2p peak shape indicated that also iron had accumulated into the biofilm.

  9. Martensitic stainless steel AISI 420—mechanical properties, creep and fracture toughness

    NASA Astrophysics Data System (ADS)

    Brnic, J.; Turkalj, G.; Canadija, M.; Lanc, D.; Krscanski, S.

    2011-11-01

    In this paper some experimental results and analyses regarding the behavior of AISI 420 martensitic stainless steel under different environmental conditions are presented. That way, mechanical properties like ultimate tensile strength and 0.2 percent offset yield strength at lowered and elevated temperatures as well as short-time creep behavior for selected stress levels at selected elevated temperatures of mentioned material are shown. The temperature effect on mentioned mechanical properties is also presented. Fracture toughness was calculated on the basis of Charpy impact energy. Experimentally obtained results can be of importance for structure designers.

  10. AISI/DOE Advanced Process Control Program Vol. 6 of 6: Temperature Measurement of Galvanneal Steel

    SciTech Connect

    S.W. Allison; D.L. Beshears; W.W. Manges

    1999-06-30

    This report describes the successful completion of the development of an accurate in-process measurement instrument for galvanneal steel surface temperatures. This achievement results from a joint research effort that is a part of the American Iron and Steel Institute's (AISI) Advanced Process Control Program, a collaboration between the U.S> Department of Energy and fifteen North American Steelmakers. This three-year project entitled ''Temperature Measurement of Galvanneal Steel'' uses phosphor thermography, and outgrowth of Uranium enrichment research at Oak Ridge facilities. Temperature is the controlling factor regarding the distribution of iron and zinc in the galvanneal strip coating, which in turn determines the desired product properties

  11. Prediction of Phase Transformation and Hardness Distribution of AISI 1045 Steel After Spot Continual Induction Hardening

    NASA Astrophysics Data System (ADS)

    Zhu, Shengxiao; Wang, Zhou; Qin, Xunpeng; Mao, Huajie; Gao, Kai

    2015-10-01

    An numerical and experimental study of spot continual induction hardening (SCIH) for AISI 1045 steel was carried out to gain a better understanding of this non-stationary and transverse flux induction hardening treatment. The SCIH device was set up by assembling the single-turn coil inductor to a five-axis cooperating computer numerical control system. The influence of inductor velocity, input current, and quenching medium on temperature field was estimated via the SCIH model, and the simulated micro-hardness and microstructure were validated by experimental verification. The heating delay phenomenon appearing in the SCIH process had been analyzed.

  12. Experimental Design and Data collection of a finishing end milling operation of AISI 1045 steel

    PubMed Central

    Dias Lopes, Luiz Gustavo; de Brito, Tarcísio Gonçalves; de Paiva, Anderson Paulo; Peruchi, Rogério Santana; Balestrassi, Pedro Paulo

    2016-01-01

    In this Data in Brief paper, a central composite experimental design was planned to collect the surface roughness of an end milling operation of AISI 1045 steel. The surface roughness values are supposed to suffer some kind of variation due to the action of several factors. The main objective here was to present a multivariate experimental design and data collection including control factors, noise factors, and two correlated responses, capable of achieving a reduced surface roughness with minimal variance. Lopes et al. (2016) [1], for example, explores the influence of noise factors on the process performance. PMID:26909374

  13. Wear behavior of AISI 1090 steel modified by pulse plasma technique

    SciTech Connect

    Ayday, Aysun; Durman, Mehmet

    2012-09-06

    AISI 1090 steel was pulse plasma treated (PPT) using a Molybdenum electrode. Two different pulse numbers were chosen to obtain modified layers of 20{+-}5 {mu}m thickness. The dry sliding wear studies performed on this steel with and without PPT against an alumina ball counterpart showed that the PPT improved the wear resistance. The pulse number of the PPT modified layer was found to be highly influential in imparting the wear resistance to this steel, due to enhancement of surface hardness depending on treatment time.

  14. Study of passive films formed on AISI 304 stainless steel by impedance measurements and photoelectrochemistry

    SciTech Connect

    Simoes, A.M.P.; Ferreiro, M.G.S. ); Rondot, B.; Belo, M. . Centre d'Etudes de Chimie Metallurgique)

    1990-01-01

    Moss-Schottky plots and photoelectrochemical measurements were made on films formed at different potentials on AISI 304 stainless steel in a borate/boric acid solution, pH 9.2. The results allowed the determination of the semiconductive properties and band structure of the films, which account for the existence of two kinds of films depending on the formation potential. For potentials below 0 V (SCE), the results point out for a film with an inverse spinel structure constituted by Cr-substituted magnetite with two donor levels. Above 0 V only one donor level is detected, which should be Fe{sup 2 +} on tetrahedral sites.

  15. The structural characterization of some biomaterials, type AISI 310, used in medicine

    NASA Astrophysics Data System (ADS)

    Minciuna, M. G.; Vizureanu, P.; Hanganu, C.; Achitei, D. C.; Popescu, D. C.; Focsaneanu, S. C.

    2016-06-01

    Orthopedics biomaterials are intended for implantation in the human body and substituted or help to repair of bones, cartilage or organ transplant, and tendons. At the end of the 20th century, the availability of materials for the manufacture implants used in medicine has been the same as for other industrial applications. The most used metals for manufacturing the orthopedics implants are: stainless steels, cobalt-chrome-molybdenum alloys, titanium and his alloys. The structural researches which are made in this paper, offer a complete analysis of AISI310 stainless steels, using: optical spectrometry, X-ray diffraction and scanning electronic microscopy.

  16. Microstructural Evolution and Wear Resistance of Friction Stir-Processed AISI 52100 Steel

    NASA Astrophysics Data System (ADS)

    Seraj, R. A.; Abdollah-zadeh, A.; Hajian, M.; Kargar, F.; Soltanalizadeh, R.

    2016-07-01

    Friction stir processing (FSP) was successfully applied on AISI 52100 steel. The influence of process parameters on the microstructure and mechanical properties of the material was evaluated. It was observed that the initial ferritic-pearlitic microstructure of the base metal is transformed to the martensitic microstructure with retained austenite in the stir zone. The results also showed that microhardness and wear resistance of the FSP samples are, respectively, at least 2 and 15 times higher than those of the base metal. The improvement of the mechanical properties of FSP samples was attributed to their microstructural characteristics. The mechanisms controlling the wear behavior of the base metal and FSP samples were also discussed.

  17. Measurements on cracktips in stainless steel AISI 321 by using a new positron microprobe

    NASA Astrophysics Data System (ADS)

    Haaks, M.; Bennewitz, K.; Bihr, H.; Männig, U.; Zamponi, C.; Maier, K.

    1999-08-01

    High resolution positron microscopy provides a new method for non-destructive investigations of plastic deformation with spatial resolution in the micron range. As positron annihilation is highly sensitive to lattice defects, low concentrations of dislocations are detectable, so that the plastic zone in front of a cracktip appears larger than in comparable metallographic methods. To demonstrate this, a plastic zone in the common stainless steel AISI 321 is imaged with the Bonn Positron Microprobe (BPM) with a spatial resolution of 20 μm.

  18. Exposure to Cigarette Smoke Reduces Vitamin D3 in the Blood Stream and Respiratory Tract

    MedlinePlus

    ... respiratory tract Share | Exposure to cigarette smoke reduces vitamin D3 in the blood stream and respiratory tract ... be understood as to how smoke causes inflammation. Vitamin D3 has anti-inflammatory and anti-bacterial effects. ...

  19. Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains.

    PubMed Central

    Sasaki, J; Mikami, A; Mizoue, K; Omura, S

    1991-01-01

    To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25-hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25-dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25-hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP-1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3. PMID:1746944

  20. Dopamine D3 Receptor Inactivation Attenuates Cocaine-Induced Conditioned Place Preference in Mice

    PubMed Central

    Song, Rui; Zhang, Hai-Ying; Peng, Xiao-Qing; Su, Rui-Bin; Yang, Ri-Fang; Li, Jin; Xi, Zheng-Xiong; Gardner, Eliot L.

    2013-01-01

    The dopamine (DA) D3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D3 receptor-knockout (D3−/−) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D3−/− mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D3Rs by YQA-14, a novel DA D3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D3−/− mice. These findings suggest that: 1) D3Rs play an important role in mediating cocaine’s rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction. PMID:23643749

  1. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  2. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  3. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  4. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  5. 42 CFR 51d.3 - Who is eligible for an award under this subpart?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Who is eligible for an award under this subpart? 51d.3 Section 51d.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS MENTAL HEALTH AND SUBSTANCE ABUSE EMERGENCY RESPONSE PROCEDURES § 51d.3 Who is eligible for...

  6. Surface Treatments for Improved Performance of Spinel-coated AISI 441 Ferritic Stainless Steel

    SciTech Connect

    Stevenson, Jeffry W.; Riel, Eric M.; Stephens, Elizabeth V.; Khaleel, Mohammad A.

    2013-01-01

    Ferritic stainless steels are promising candidates for IT-SOFC interconnect applications due to their low cost and resistance to oxidation at SOFC operating temperatures. However, steel candidates face several challenges; including long term oxidation under interconnect exposure conditions, which can lead to increased electrical resistance, surface instability, and poisoning of cathodes due to volatilization of Cr. To potentially extend interconnect lifetime and improve performance, a variety of surface treatments were performed on AISI 441 ferritic stainless steel coupons prior to application of a protective spinel coating. The coated coupons were then subjected to oxidation testing at 800 and 850°C in air, and electrical testing at 800°C in air. While all of the surface-treatments resulted in improved surface stability (i.e., increased spallation resistance) compared to untreated AISI 441, the greatest degree of improvement (through 20,000 hours of testing at 800°C and 14,000 hours of testing at 850°C) was achieved by surface blasting.

  7. Pitting and Intergranular Corrosion Resistance of AISI Type 301LN Stainless Steels

    NASA Astrophysics Data System (ADS)

    Ningshen, S.; Kamachi Mudali, U.

    2010-03-01

    The pitting and intergranular corrosion (IGC) resistance of AISI type 301LN stainless steels were evaluated using ASTM methods, anodic polarization, and electrochemical impedance techniques. The IGC results indicated that the microstructure of the samples after sensitization heat treatment at 675 °C for 1 h shows step or dual structure for both imported and indigenous materials indicating insignificant Cr23C6 precipitation. The results of immersion tests in boiling 6% copper sulfate + 16% sulfuric acid + copper solution for 24 h followed by the bend test (ASTM A262 Practice-E method) indicated no crack formation in any of the tested specimens. Pitting corrosion resistance carried out in 6% FeCl3 solution at different temperatures of 22 ± 2 and 50 ± 2 °C (ASTM G 48) up to the period of 72 h revealed pitting corrosion attack in all the investigated alloys. The potentiodynamic anodic polarization results in 0.5 M NaCl revealed variation in passive current density and pitting potential depending on the alloy chemistry and metallurgical condition. The passive film properties studied by electrochemical impedance spectroscopy (EIS) correlated well with the polarization results. The x-ray diffraction (XRD) results revealed the presence of austenite (γ) and martensite (α') phases depending on the material condition. The suitability of three indigenously developed AISI type 301LN stainless steels were compared with imported type 301LN stainless steel and the results are highlighted in this article.

  8. Niobium boride layers deposition on the surface AISI D2 steel by a duplex treatment

    SciTech Connect

    Kon, O.; Pazarlioglu, S.

    2015-03-30

    In this paper, we investigated the possibility of deposition of niobium boride layers on the surface of AISI D2 steel by a duplex treatment. At the first step of duplex treatment, boronizing was performed on AISI D2 steel samples at 1000{sup o}C for 2h and then pre-boronized samples niobized at 850°C, 900°C and 950°C using thermo-reactive deposition method for 1–4 h. The presence of the niobium boride layers such as NbB, NbB{sub 2} and Nb{sub 3}B{sub 4} and also iron boride phases such as FeB, Fe{sub 2}B were examined by X-ray diffraction analysis. Scanning electron microscope (SEM) and micro-hardness measurements were realized. Experimental studies showed that the depth of the coating layers increased with increasing temperature and times and also ranged from 0.42 µm to 2.43 µm, depending on treatment time and temperature. The hardness of the niobium boride layer was 2620±180 HV{sub 0.005}.

  9. Effects of biofilm formation on the electrochemical behavior of AISI 304 SS in board machine environment

    SciTech Connect

    Carp, L.; Hakkarainen, T.; Raaska, L.

    1999-11-01

    The electrochemical behavior of and biofilm formation on AISI 304 stainless steel were studied in board machine environment with natural bacteria population. Open circuit potentials, redox-potential as well as different electrochemical measurements were performed. The biofilms formed were analyzed by microbial cultivation and by epifluorescence microscopy. The results of the measurements were compared with those performed both in sterilized white water and in artificial white water. The anodic polarization behavior of just immersed specimens was very similar in biotic (real), artificial and abiotic (sterilized) white water. Pitting initiated at very low potentials and continued to very negative values. The initiation of pitting became more difficult when the immersion time increased to 7 or 8 days in real, artificial or sterilized water. When the immersion time further increased, the pitting nucleated more easily in sterilized white water as well as in artificial white water than in biotic white water. In the laboratory equipment it was possible to maintain the biofilm already formed in the board mill, but the amount of sulfate reducing bacteria decreased and the amount of biofilm did not further increase. The composition and structure of the biofilm formed in laboratory differed from that formed in board mill conditions. The preliminary results indicate that the formation of biofilm in biotic white water rather inhibits than enhances the pitting corrosion of type AISI 304 stainless steel.

  10. Void Swelling Of Aisi 321 Analog Stainless Steel Irradiated At Low Dpa Rates In The Bn-350 Reactor

    SciTech Connect

    Maksimkin, O. P.; Tsai, K. V.; Turubarova, L. G.; Doronina, T. A.; Garner, Francis A.

    2006-03-01

    In several recently published studies conducted on a Soviet analog of AISI 321 stainless steel irradiated in either fast reactors or light water reactors, it was shown that the void swelling phenomenon extended to temperatures as low as ~300ºC or less, when produced by neutron irradiation at dpa rates in the range 10-7 to 10-8 dpa/sec. Other studies yielded similar results for AISI 316 and the Russian analog of AISI 316. In the current study a blanket duct assembly from BN-350, constructed from the Soviet analog of AISI 321, also exhibits swelling at dpa rates on the order of 10-8 dpa/sec, with voids seen as low as 281oC and only 0.65 dpa. It appears that low-temperature swelling occurs at low dpa rates in 300 series stainless steels in general, and also occurs during irradiations conducted in either fast or mixed spectrum reactors. Therefore it is expected that a similar behavior will be observed in fusion devices as well.

  11. Void Swelling of AISI 321 Analog Stainless Steel Irradiated at Low DPA Rates in the BN-350 Reactor

    SciTech Connect

    Maksimkin, O. P.; Tsai, K. V.; Turubarova, L. G.; Doronina, T. A.; Garner, Francis A.

    2007-08-01

    In several recently published studies conducted on a Soviet analog of AISI 321 stainless steel irradiated in either fast reactors or light water reactors, it was shown that the void swelling phenomenon extended to temperatures as low as ~300ºC or less, when produced by neutron irradiation at dpa rates in the range 10-7 to 10-8 dpa/sec. Other studies yielded similar results for AISI 316 and the Russian analog of AISI 316. In the current study a blanket duct assembly from BN-350, constructed from the Soviet analog of AISI 321, also exhibits swelling at dpa rates on the order of 10-8 dpa/sec, with voids seen as low as 281C and only 0.65 dpa. It appears that low-temperature swelling occurs at low dpa rates in 300 series stainless steels in general, and also occurs during irradiations conducted in either fast or in mixed spectrum reactors as shown in other studies.

  12. Surface fatigue life and failure characteristics of EX-53, CBS 1000M, and AISI 9310 gear materials

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.

    1985-01-01

    Spur gear endurance tests and rolling-element surface fatigue tests are conducted to investigate EX-53 and CBS 1000M steels for use as advanced application gear materials, to determine their endurance characteristics, and to compare the results with the standard AISI 9310 gear material. The gear pitch diameter is 8.89 cm (3.50 in). Gear test conditions are an oil inlet temperature of 320 K (116 F), an oil outlet temperature of 350 K (170 F), a maximum Hertz stress of 1.71 GPa (248 ksi), and a speed of 10,000 rpm. Bench-type rolling-element fatigue tests are conducted at ambient temperature with a bar specimen speed of 12,500 rpm and a maximum Hertz stress of 4.83 GPa (700 ksi). The EX-53 test gears have a surface fatigue life of twice that of the AISI 9310 spur gears. The CBS 1000M test gears have a surface fatigue life of more than twice that of the AISI 9310 spur gears. However, the CBS 1000M gears experience a 30-percent tooth fracture failure which limits its use as a gear material. The rolling-contact fatigue lines of RC bar specimens of EX-53 and ASISI 9310 are approximately equal. However, the CBS 1000M RC specimens have a surface fatigue life of about 50 percent that of the AISI 9310.

  13. Studies on the determination of surface deuterium in AISI 1062, 4037, and 4140 steels by secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Sastri, V. S.; Donepudi, V. S.; McIntyre, N. S.; Johnston, D.; Revie, R. W.

    1988-12-01

    The concentration of deuterium at the surface of cathodically charged high strength steels AISI 1062, 4037, and 4140 has been determined by secondary ion mass spectrometry (SIMS). The beneficial effects of pickling in NAP (a mixture of nitric, acetic, and phosphoric acids) to remove surfacebound deuterium have been observed.

  14. Effects of Ultrasonic Nanocrystal Surface Modification (UNSM) on Residual Stress State and Fatigue Strength of AISI 304

    NASA Astrophysics Data System (ADS)

    Cherif, A.; Pyoun, Y.; Scholtes, B.

    2010-03-01

    The effects of a new mechanical surface treatment method, called ultrasonic nanocrystal surface modification (UNSM), on near-surface microstructures and residual stress states as well as on the fatigue behavior of an austenitic steel AISI 304 are investigated and discussed. The results are compared with consequences of other mechanical surface treatment methods such as deep rolling or shot peening.

  15. Void swelling of AISI 321 analog stainless steel irradiated at low dpa rates in the BN-350 reactor

    NASA Astrophysics Data System (ADS)

    Maksimkin, O. P.; Tsai, K. V.; Turubarova, L. G.; Doronina, T.; Garner, F. A.

    2007-08-01

    In several recently published studies conducted on a Soviet analog of AISI 321 stainless steel irradiated in either fast reactors or light water reactors, it was shown that the void swelling phenomenon extended to temperatures as low as ˜300 °C or less, when produced by neutron irradiation at dpa rates in the range 10 -7-10 -8 dpa/s. Other studies yielded similar results for AISI 316 and the Russian analog of AISI 316. In the current study a blanket assembly duct from BN-350, constructed from the Soviet analog of AISI 321, also exhibits swelling at dpa rates on the order of 10 -8 dpa/s, with voids seen as low as 281 °C and only 0.65 dpa. It appears that low-temperature swelling occurs at low dpa rates in 300 series stainless steels in general, and also occurs during irradiations conducted in either fast or in mixed spectrum reactors as shown in other studies.

  16. Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation

    SciTech Connect

    Webb, A.R.; DeCosta, B.R.; Holick, M.F.

    1989-05-01

    Exposure to sunlight initiates the formation of vitamin D3 in skin as the UV B radiation in the solar spectrum causes the photoconversion of 7-dehydrocholesterol to previtamin D3. A heat-induced isomerization then converts previtamin D3 to vitamin D3 over a period of days. A number of irradiation products of vitamin D3 are known to form upon irradiation with high intensity UV radiation, but the effect of subsequent exposures to sunlight on the vitamin D3 formed in skin is not known. To investigate this phenomenon, human skin containing vitamin D3 was exposed to sunlight in Boston. A model system of (/sup 3/H)vitamin D3 in methanol was also used to study the effects of sunlight on vitamin D3 throughout the year. Vitamin D3 proved to be exquisitely sensitive to sunlight, and once formed in the skin, exposure to sunlight resulted in its rapid photodegradation to a variety of photoproducts, including 5,6-transvitamin D3, suprasterol I, and suprasterol II.

  17. Photoactivable analogs for labeling 25-hydroxyvitamin D3 serum binding protein and for 1,25-dihydroxyvitamin D3 intestinal receptor protein

    NASA Technical Reports Server (NTRS)

    Kutner, A.; Link, R. P.; Schnoes, H. K.; DeLuca, H. F.

    1986-01-01

    3-Azidobenzoates and 3-azidonitrobenzoates of 25-hydroxyvitamin D3 as well as 3-deoxy-3-azido-25-hydroxyvitamin D3 and 3-deoxy-3-azido-1,25-dihydroxyvitamin D3 were prepared as photoaffinity labels for vitamin D serum binding protein and 1,25-dihydroxyvitamin D3 intestinal receptor protein. The compounds prepared were easily activated by short- or long-wavelength uv light, as monitored by uv and ir spectrometry. The efficacy of the compounds to compete with 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for the binding site of serum binding protein and receptor, respectively, was studied to evaluate the vitamin D label with the highest affinity for the protein. The presence of an azidobenzoate or azidonitrobenzoate substituent at the C-3 position of 25-OH-D3 significantly decreased (10(4)- to 10(6)-fold) the binding activity. However, the labels containing the azido substituent attached directly to the vitamin D skeleton at the C-3 position showed a high affinity, only 20- to 150-fold lower than that of the parent compounds with their respective proteins. Therefore, 3-deoxy-3-azidovitamins present potential ligands for photolabeling of vitamin D proteins and for studying the structures of the protein active sites.

  18. Effect of treatment by a pulsed magnetic field on the hardness and fracture strength of a hypereutectoid tool steel

    NASA Astrophysics Data System (ADS)

    Vorob'ev, R. A.; Dubinskii, V. N.

    2014-08-01

    Using samples of quenched U10A tool steel (AISI/SAE W1-1.0C steel), the possibility of selecting a regime of the magnetic pulsed treatment that provides a simultaneous increase of the Vickers hardness and fracture resistance (the load that induces a crack nucleation from the indent) that would insure an increase in the steel ductility and resistance of tools produced from it has been demonstrated.

  19. Further Characterization of Quinpirole-Elicited Yawning as a Model of Dopamine D3 Receptor Activation in Male and Female Monkeys

    PubMed Central

    Martelle, Susan E.; Nader, Susan H.; Czoty, Paul W.; John, William S.; Duke, Angela N.; Garg, Pradeep K.; Garg, Sudha; Newman, Amy H.

    2014-01-01

    The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [11C]PHNO ([11C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [11C]PHNO, and the ability of quinpirole (0.01–0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) self-administration and found that monkeys with experience self-administering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds. PMID:24876234

  20. Further characterization of quinpirole-elicited yawning as a model of dopamine D3 receptor activation in male and female monkeys.

    PubMed

    Martelle, Susan E; Nader, Susan H; Czoty, Paul W; John, William S; Duke, Angela N; Garg, Pradeep K; Garg, Sudha; Newman, Amy H; Nader, Michael A

    2014-08-01

    The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [(11)C]PHNO ([(11)C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [(11)C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) self-administration and found that monkeys with experience self-administering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds.

  1. Further characterization of quinpirole-elicited yawning as a model of dopamine D3 receptor activation in male and female monkeys.

    PubMed

    Martelle, Susan E; Nader, Susan H; Czoty, Paul W; John, William S; Duke, Angela N; Garg, Pradeep K; Garg, Sudha; Newman, Amy H; Nader, Michael A

    2014-08-01

    The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [(11)C]PHNO ([(11)C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [(11)C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) self-administration and found that monkeys with experience self-administering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds. PMID:24876234

  2. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3.

    PubMed

    Connelly, Sandra J; Walling, Kelly; Wilbert, Steven A; Catlin, Diane M; Monaghan, Cailin E; Hlynchuk, Sofiya; Meehl, Pamela G; Resch, Lauren N; Carrera, J Valerie; Bowles, Stephanie M; Clark, Michael D; Tan, Loraine T; Cody, Jeremy A

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3.

  3. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3

    PubMed Central

    Walling, Kelly; Wilbert, Steven A.; Catlin, Diane M.; Monaghan, Cailin E.; Hlynchuk, Sofiya; Meehl, Pamela G.; Resch, Lauren N.; Carrera, J. Valerie; Bowles, Stephanie M.; Clark, Michael D.

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID:26147286

  4. The cutaneous photosynthesis of previtamin D3: a unique photoendocrine system

    SciTech Connect

    Holick, M.F.

    1981-07-01

    The skin has been recognized as the site for the sun-mediated photosynthesis of vitamin D3; until recently, however, very little was known about either the sequence of events leading to the formation of vitamin D3 in human skin or the factors that regulate the synthesis of this hormone. It is now established that, during exposure to sunlight, the cutaneous reservoir of 7-dehydrocholesterol (principally in the stratum Malpighii) converts to previtamin D3. Once this thermally labile previtamin is formed, it undergoes a temperature-dependent isomerization to vitamin D3 over a period of 3 days. The plasma vitamin-D binding protein preferentially translocates vitamin D3 from the skin into the circulation. During prolonged exposure to the sun, the accumulation of previtamin D3 is limited to about 10 to 15% of the original 7-dehydrocholesterol content because the previtamin photoisomerizes to 2 biologically inert photoproducts, lumisterol3 and tachysterol3. Increases in either latitude or the melanin concentration in the skin diminish the epidermal synthesis of previtamin D3. A single total body exposure to 3 minimal erythemal doses of ultraviolet radiation increased the vitamin-D3 levels in the serum 25-hydroxyvitamin-D levels after 7 days. The unique mechanism for the cutaneous synthesis, storage, and steady release of vitamin D3 into the circulation prompted an investigation into the potential therapeutic benefits of using the skin as the site for the synthesis and absorption of vitamin-D3 metabolites.

  5. 1,25(OH)2D3 increases membrane associated protein kinase C in MDBK cells.

    PubMed

    Simboli-Campbell, M; Franks, D J; Welsh, J

    1992-01-01

    To determine whether 1,25-dihydroxycholecalciferol [1,25(OH)2D3] affects protein kinase C (PKC) activity in kidney, as has been demonstrated in HL-60 cells we measured 1,25(OH)2D3 binding, PKC activity and PKC immunoreactivity in Madin Darby bovine kidney (MDBK) cells, a normal renal epithelial cell line derived from bovine kidney. Our data demonstrate that MDBK cells exhibit specific high affinity binding for 1,25(OH)2D3, indicating the presence of the vitamin D receptor (VDR). Treatment of MDBK cells with 1,25(OH)2D3 for 24 h increased membrane PKC activity and immunoreactivity. The effect of 1,25(OH)2D3 was dose-dependent, with a peak effect observed at 10(-7)M 1,25(OH)2D3. The 1,25(OH)2D3 induced increase in membrane PKC was paralleled by a comparable decrease in cytosolic PKC activity and amount. Although time course studies were consistent with a VDR mediated effect of 1,25(OH)2D3 on PKC protein synthesis, total PKC activity was not increased by 1,25(OH)2D3, suggesting an effect on PKC translocation or localization. These results suggest that 1,25(OH)2D3 modulates PKC mediated events in kidney, a classic target for this steroid hormone.

  6. The influence of latitude on the concentration of vitamin D3 and 25-hydroxy-vitamin D3 in Australian red meat.

    PubMed

    Liu, Jerry; Greenfield, Heather; Strobel, Norbert; Fraser, David R

    2013-10-01

    There is little information on the vitamin D content of Australian red meat or on the possible influence of latitude on this content. To determine the content of vitamin D3 and 25-hydroxy-vitamin D3 (25OHD3), lamb and beef were analysed from 34° S with LC-IT-MS. To investigate the possible influence of latitude on vitamin D in meat, the lean meat and fat from five cuts of beef were analysed from 17° S and 41° S. Lamb contained 0.10μg vitamin D3/100g and 0.20μg 25OHD3/100g lean meat, while beef contained 0.12μg vitamin D3 and 0.27μg 25OHD3/100g (lean meat). Latitude had no effect on the vitamin D3 (P=0.21) or 25OHD3 (P=0.29) content of lean beef, but fat from cattle in the 17° S latitude group contained significantly higher (P<0.01) concentrations of vitamin D3 than fat from the 41° S group of cattle.

  7. Influence of alumina and titanium dioxide coatings on abrasive wear resistance of AISI 1045 steel

    NASA Astrophysics Data System (ADS)

    Santos, A.; Remolina, A.; Marulanda, J.

    2016-02-01

    This project aims to compare the behaviour of an AISI 1045 steel's abrasive wear resistance when is covered with aluminium oxide (Al2O3) or Titanium dioxide (TiO2), of nanometric size, using the technique of thermal hot spray, which allows to directly project the suspension particles on the used substrate. The tests are performed based on the ASTM G65-04 standard (Standard Test Method for Measuring Abrasion Using the Dry Sand/Rubber Apparatus). The results show that the amount of, lost material increases linearly with the travelled distance; also determined that the thermal treatment of hardening-tempering and the alumina and titanium dioxide coatings decrease in average a 12.9, 39.6 and 29.3% respectively the volume of released material during abrasive wear test.

  8. Effect of five lubricants on life of AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1985-01-01

    Spur-gear surface fatigue tests were conducted with five lubricants using a single lot of consumable-electrode vacuum melted (CVM) AISI 9310 spur gears. The lot of gears was divided into five groups, each of which was tested with a different lubricant. The test lubricants are classified as either a synthetic hydrocarbon, mineral oil, or ester-based lubricant. All five lubricants have imilar viscosity and pressure-viscosity coefficients. A pentaerythritol base stock without sufficient antiwear additives produced a surface fatigue life pproximately 22 percent that of the same base stock with chlorine and phosphorus type additives. The presence of sulfur type antiwear additives in the lubricant did not appear to affect the surface fatigue life of the gears tested. No statistical difference in the 10-percent surface fatigue life was produced with four of the five lubricants.

  9. Effect of Plasma Nitriding Temperatures on Characteristics of Aisi 201 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Gao, Yuxin; Zheng, Shaomei

    2016-10-01

    Samples of AISI 201 austenitic stainless steel were produced by plasma nitriding at 350∘C, 390∘C, 420∘C, 450∘C and 480∘C for 5h. Systematic characterization of the nitrided layer was carried out in terms of micrograph observations, phase identification, chemical composition depth profiling, surface microhardness measurements and electrochemical corrosion tests. The results show that the surface hardness and the layer thickness increased with increasing temperature. XRD indicated that a single S-phase layer was formed during low temperature (≤420∘C), while Cr2N or CrN phase was formed besides S-phase when nitrided at 450∘C and 480∘C. The specimen treated at 390∘C presents a much enhanced corrosion resistance compared to the untreated substrate. The corrosion resistance deteriorated for samples treated above 450∘C due to the formation of chromium nitrides.

  10. Roughness Reduction in AISI 316L Stainless Steel after Surface Mechanical Attrition Treatment (SMAT)

    NASA Astrophysics Data System (ADS)

    Arifvianto, B.; Suyitno, Suyitno; Mahardika, M.

    2011-12-01

    Surface mechanical attrition treatment (SMAT) enhances the strength of metals by generating nanocrystallites at the surface layer. During the treatment, multiple impacts of milling balls are subjected to the treated surface. Consequently, the structure and roughness of the treated surface are also modified. In this paper, the effect of SMAT on the surface structure and roughness of an initially rough AISI 316L stainless steel is investigated. The SMAT was conducted for 0-20 minutes. The surface morphology, roughness, and volume loss due to the SMAT were studied. The result shows a decreasing roughness by the SMAT. An apparently deformed structure is also observed after 15 minutes of the treatment. However, no significant change in the volume loss is reported due to this treatment. Deformation by the multiple impacts is proposed to be the mechanism of the roughness reduction instead of microcutting by the milling balls during the SMAT.

  11. Acoustic emission studies on welded and thermally treated AISI 304 stainless steel during tensile deformation

    SciTech Connect

    Mukherjee, P.; Barat, P.; Jayakumar, T.; Kalyanasundaram, P.; Rajagopalan, C.; Raj, B.

    1997-10-15

    The present investigations are planned to study the influence of prior martensites formed due to cold treatment as 77K in AISI 304 SS welded specimens, on strain-induced martensites occurred during tensile deformation using AE technique. AE parameters like count rate and root mean square (r.m.s.) voltage have been used to characterize AE activities generated during tensile deformation process in as-welded and welded-treated samples. Frequency spectrum analysis of AE signals captured from the samples has been done to understand the dynamic behavior of the martensite phase formation. Tensile properties of these samples have also been reported. Volume fraction of the magnetic phase (martensite and delta ferrite) formed in these samples are measured before and after straining. X-ray diffraction (XRD) technique has been used to support the presence of delta ferrite (formed during welding) and martensite in the weld region.

  12. Residual Stresses in LENS-Deposited AISI 410 Stainless Steel Plates

    SciTech Connect

    Wang, L; Felicellli, S D; Pratt, Phillip R

    2008-01-01

    The residual stress in thin plate components deposited by the laser engineered net shaping (LENS{reg_sign}) process was investigated experimentally and numerically. Neutron diffraction mapping was used to characterize the residual stress in LENS-deposited AISI 410 stainless steel thin wall plates. Using the commercial welding software SYSWELD, a thermo-mechanical three-dimensional finite element model was developed, which considers also the effect of metallurgical phase transformations. The model was employed to predict the temperature history and the residual stress field during the LENS process. Several simulations were performed with the geometry and process parameters that were used to build the experimental samples. The origin of the residual stress distribution is discussed based on the thermal histories of the samples, and the modeling results are compared with measurements obtained by neutron diffraction mapping.

  13. Improving electrochemical properties of AISI 1045 steels by duplex surface treatment of plasma nitriding and aluminizing

    NASA Astrophysics Data System (ADS)

    Haftlang, Farahnaz; Habibolahzadeh, Ali; Sohi, Mahmoud Heydarzadeh

    2015-02-01

    Improvement in electrochemical behavior of AISI 1045 steel after applying aluminum nitride coating was investigated in 3.5% NaCl solution, using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) analyses. Aluminum nitride coating was applied on the steel surface by duplex treatment of pack aluminizing and plasma nitriding. Some specimens were plasma nitrided followed by aluminizing (PN-Al), while the others were pack aluminized followed by plasma nitriding (Al-PN). Topological and structural studies of the modified surfaces were conducted using scanning electron microscope (SEM) equipped by energy dispersive X-ray spectroscope (EDS), and X-ray diffractometer (XRD). The electrochemical measurements showed that the highest corrosion and polarization (Rp) resistances were obtained in PN-Al specimens, having single phase superficial layer of AlN. Pitting mechanism was dominant reason of lower corrosion resistance in the Al-PN specimens.

  14. Comparisons of modified Vasco X-2 and AISI 9310 gear steels

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1980-01-01

    Endurance tests were conducted with four groups of spur gears manufactured from three heats of consumable electrode vacuum melted (CVM) modified Vasco X-2. Endurance tests were also conducted with gears manufactured from CVM AISI 9310. Bench type rolling element fatigue tests were conducted with both materials. Hardness measurements were made to 811 K. There was no statistically significant life difference between the two materials. Life differences between the different heats of modified Vasco X-2 can be attributed to heat treat variation and resultant hardness. Carburization of gear flanks only can eliminate tooth fracture as a primary failure mode for modified Vasco X-2. However, a tooth surface fatigue spall can act as a nucleus of a tooth fracture failure for the modified Vasco X-2.

  15. Microstructure and Texture Evolutions in AISI 1050 Steel by Flow Forming

    SciTech Connect

    Bedekar, Vikram; Pauskar, Praveen; Shivpuri, Rajiv; Howe, Jane Y

    2014-01-01

    Hot rolled and annealed AISI 1050 steel cylindrical coupons were flow formed at different levels of deformation (66% and 90% wall thickness reduction). TEM studies revealed development of ultra fine (sub) grain cell structure due to severe plastic deformation. The transverse subgrain size changed from 10 m (beginning) to 300nm (66% deformation) to 40nm (90% deformation). EBSD study revealed decreased recrystallization fraction at 90% deformation compared with 66% deformation due to orientation pinning from preferred orientation along {002} planes. No evidence of dislocation pinning or cracking was observed on any samples. The aim of the present work is to study the deformation behaviour and microstructural evolution during conventional flow forming process. The study also sheds light on the strengthening behaviour and structural changes during severe straining.

  16. Pitting fatigue characteristics of AISI M-50 and super nitralloy spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Chevalier, J. L.; Zaretsky, E. V.

    1973-01-01

    Two groups of 3.50-in. pitch-diameter spur gears, without tip relief, made from consumable-electrode vacuum-melted (CVM) AISI M-50 steel and CVM super nitralloy (5Ni-2A1) were tested under conditions which produced fatigue pitting. The M-50 gears had fatigue lives approximately 50 percent longer than the super nitralloy gears. Both groups of gears failed by classical rolling-element fatigue at the pitch circle. When the gears were overrun past initial spall formation, the spalled M-50 gear teeth failed by fatigue fracture. The M-50 material had higher wear than the super nitralloy material. Differences in fatigue life and wear were not considered statistically significant.

  17. Aluminum diffusion in Al-implanted AISI 321 stainless steel using accelerator-based characterization techniques

    NASA Astrophysics Data System (ADS)

    Noli, F.; Misaelides, P.; Bethge, K.

    1998-04-01

    The aluminum diffusion in near-surface layers of Al-implanted AISI 321 austenitic stainless steel (Fe/Cr18/Ni8/Ti) was studied using ion beam analysis techniques. The implanted samples were investigated at temperatures between 450°C and 650°C (treatment times up to 144 h in vacuum and in air). The Al-profiles were determined by the 992 keV resonance of the 27Al(p,γ) 28Si nuclear reaction as well as by 4He +-Rutherford Backscattering Spectrometry (RBS). The experimental diffusion coefficients, obtained during this study using Fick's second law, were compared with corresponding literature concerning the aluminum diffusion in other relevant metallic materials. The determination of the depth profiles contributes to the interpretation of the high temperature oxidation behavior of Al-implanted stainless steel surfaces.

  18. Influence of Laser Peening on Phase Transformation and Corrosion Resistance of AISI 321 steel

    NASA Astrophysics Data System (ADS)

    Karthik, D.; Swaroop, S.

    2016-07-01

    The objective of this study is to investigate the influence of laser peening without coating (LPwC) on austenitic to martensitic (γ → α') phase transformation and corrosion behavior of austenitic stainless steel AISI 321 in 3.5% NaCl environment. Results indicate that LPwC induces a large compressive residual stresses of nearly -854 MPa and γ → α' phase transformation of about 18% (volume fraction). Microstructures of peened surface confirmed the γ → α' phase transformation and showed no grain refinement. Hardness increased slightly with a case depth of 900 μm. Despite the smaller surface roughness introduced, corrosion resistance improved after peening due to compressive residual stresses.

  19. Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs.

    PubMed

    Pich, Emilio Merlo; Collo, Ginetta

    2015-09-01

    Dopamine D3 receptors have been pharmacologically engaged in humans since the development of the first antipsychotics and ergot-derivative dopamine (DA) agonists, even without knowing it. These agents were generally non-selective, developed primarily to target D2 receptors. In the last 10 years the understanding of the clinical implication of D3 receptors has been progressing also due to the identification of D3 gene polymorphisms, the use of more selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A new specific neuroplasticity role of D3 receptor regarding dendrite arborisation outgrowth in dopaminergic neurons was also proposed to support, at least in part, the slowing of disease observed in subjects with Parkinson׳s Disease treated with DA agonists. Similar mechanisms could be at the basis of the antidepressant-like effects observed with DA agonists when co-administered with standard of care. Severe adverse event occurring with the use of anti-parkinsonian DA agonists in predisposed subjects, i.e., impulse control disorders, are now suggested to be putatively related to overactive D3 receptors. Not surprisingly, blockade of D3 receptors was proposed as treatment for addictive disorders, a goal that could be potentially achieved by repositioning buspirone, an anxiolytic drug with D3-preferential antagonistic features, or with novel selective D3 antagonists or partial agonists currently in development for schizophrenia. At the moment ABT-925 is the only selective D3 antagonist tested in schizophrenic patients in Phase II, showing an intriguing cognitive enhancing effects supported by preclinical data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could be effective in a subpopulation of patients with a polymorphism on the D3 receptor, opening to a possible personalised medicine approach. PMID:26298833

  20. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.

  1. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.

    PubMed

    Holick, M F

    1995-08-01

    Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis. PMID:8579891

  2. System-dependent dispersion coefficients for the DFT-D3 treatment of adsorption processes on ionic surfaces.

    PubMed

    Ehrlich, Stephan; Moellmann, Jonas; Reckien, Werner; Bredow, Thomas; Grimme, Stefan

    2011-12-01

    Dispersion-corrected density functional theory calculations (DFT-D3) were performed for the adsorption of CO on MgO and C(2) H(2) on NaCl surfaces. An extension of our non-empirical scheme for the computation of atom-in-molecules dispersion coefficients is proposed. It is based on electrostatically embedded M(4)X(4) (M=Na, Mg) clusters that are used in TDDFT calculations of dynamic dipole polarizabilities. We find that the C(MM)(6) dispersion coefficients for bulk NaCl and MgO are reduced by factors of about 100 and 35 for Na and Mg, respectively, compared to the values of the free atoms. These are used in periodic DFT calculations with the revPBE semi-local density functional. As demonstrated by calculations of adsorption potential energy curves, the new C(6) coefficients lead to much more accurate energies (E(ads)) and molecule-surface distances than with previous DFT-D schemes. For NaCl/C(2) H(2) we obtained at the revPBE-D3(BJ) level a value of E(ads) =-7.4 kcal mol(-1) in good agreement with experimental data (-5.7 to -7.1 kcal mol(-1)). Dispersion-uncorrected DFT yields an unbound surface state. For the MgO/CO system, the computed revPBE-D3(BJ) value of E(ads) =-4.1 kcal mol(-1) is also in reasonable agreement with experimental results (-3.0 kcal mol(-1)) when thermal corrections are taken into account. Our new dispersion correction also improves computed lattice constants of the bulk systems significantly compared to plain DFT or previous DFT-D results. The extended DFT-D3 scheme also provides accurate non-covalent interactions for ionic systems without empirical adjustments and is suggested as a general tool in surface science.

  3. N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)-butyl)-heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonistsγ

    PubMed Central

    Newman, Amy Hauck; Grundt, Peter; Cyriac, George; Deschamps, Jeffrey R.; Taylor, Michelle; Kumar, Rakesh; Ho, David; Luedtke, Robert R.

    2009-01-01

    In the present report, the D3 receptor pharmacophore is modified in the 2,3-diCl-and 2-OCH3-phenyl piperazine class of compounds with the goal to improve D3 receptor affinity and selectivity. This extension of structure-activity relationships (SAR) has resulted in the identification of the first enantioselective D3 antagonists (R- and S-22) to be reported, wherein enantioselectivity is more pronounced at D3 than at D2, and that a binding region on the second extracellular loop (E2) may play a role in both enantioselectivity and D3 receptor selectivity. Moreover, we have discovered some of the most D3-selective compounds reported to date that show high affinity (Ki =1 nM) for D3 and ∼400-fold selectivity over the D2 receptor subtype. Several of these analogues showed exquisite selectivity for D3 receptors over >60 other receptors further underscoring their value as in vivo research tools. These lead compounds also have appropriate physical characteristics for in vivo exploration and therefore will be useful in determining how intrinsic activity at D3 receptors tested in vitro is related to behaviors in animal models of addiction and other neuropsychiatric disorders. PMID:19331412

  4. Experimental and numerical study on plasma nitriding of AISI P20 mold steel

    NASA Astrophysics Data System (ADS)

    Nayebpashaee, N.; Vafaeenezhad, H.; Kheirandish, Sh.; Soltanieh, M.

    2016-09-01

    In this study, plasma nitriding was used to fabricate a hard protective layer on AISI P20 steel, at three process temperatures (450°C, 500°C, and 550°C) and over a range of time periods (2.5, 5, 7.5, and 10 h), and at a fixed gas N2:H2 ratio of 75vol%:25vol%. The morphology of samples was studied using optical microscopy and scanning electron microscopy, and the formed phase of each sample was determined by X-ray diffraction. The elemental depth profile was measured by energy dispersive X-ray spectroscopy, wavelength dispersive spectroscopy, and glow dispersive spectroscopy. The hardness profile of the samples was identified, and the microhardness profile from the surface to the sample center was recorded. The results show that ɛ-nitride is the dominant species after carrying out plasma nitriding in all strategies and that the plasma nitriding process improves the hardness up to more than three times. It is found that as the time and temperature of the process increase, the hardness and hardness depth of the diffusion zone considerably increase. Furthermore, artificial neural networks were used to predict the effects of operational parameters on the mechanical properties of plastic mold steel. The plasma temperature, running time of imposition, and target distance to the sample surface were all used as network inputs; Vickers hardness measurements were given as the output of the model. The model accurately reproduced the experimental outcomes under different operational conditions; therefore, it can be used in the effective simulation of the plasma nitriding process in AISI P20 steel.

  5. Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.

    PubMed

    Soeters, Maarten R; Serlie, Mireille J; Sauerwein, Hans P; Duran, Marinus; Ruiter, Jos P; Kulik, Willem; Ackermans, Mariëtte T; Minkler, Paul E; Hoppel, Charles L; Wanders, Ronald J A; Houten, Sander M

    2012-07-01

    Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid β-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.

  6. Methamphetamine-induced locomotor activity and behavioral sensitization: are dopamine d3 receptors involved?

    PubMed

    Jones, C D; Bartee, J A; Leite-Browning, M L; Blackshear, M A

    2007-05-15

    Drug sensitization is a behavioral phenomenon that occurs following repeated administration of methamphetamine (METH) and similar CNS stimulants. The mechanism of drug sensitization is unknown, but is believed to be due to downregulation of dopamine D3 receptors. It is hypothesized that repeated administration of dopamine D3 agonists results in downregulation of D3 receptors in methamphetamine-induced (METH-IND) sensitization. Furthermore, repeated administration of dopamine D3 antagonists and METH cause upregulation of D3 receptors and block METH-IND sensitization. The objective of this study was to determine the role of D3 receptors in METH-IND sensitization. To test these hypotheses, male mice received chronic injections (i.p.) of 2 mg/kg of the dopamine D3 agonist, PD128907 plus 0.5 mg/kg of METH or 8 mg/kg of D3 antagonist, U99194A and 0.5 mg\\kg of METH daily for 7-days. Drugs were withdrawn on day 8, and METH-IND sensitization was determined on day 18. Locomotor activity was measured for 75 minutes immediately after METH administration in an activity monitor. Acute administration of PD128907 decreased METH-IND locomotion, p < 0. 01, and acute U99194A increased it. However, chronic administration of these drugs did not alter the locomotor effects of METH (p > 0.05). These findings support in-part the hypothesis that dopamine D3 receptors are downregulated in METH-IND sensitization.

  7. Formation of fatty acid esterified vitamin D3 in rat skin by exposure to ultraviolet radiation

    SciTech Connect

    Takada, K.

    1983-04-01

    The formation of fatty acid esters of vitamin D3 was demonstrated in rat skin exposed to artificial ultraviolet rays by using multi-dimensional high-performance liquid chromatography, ultraviolet spectrophotometry, and gas-liquid chromatography-mass spectrometry. This result indicated that the fatty acid esters of 7-dehydrocholesterol in rat skin (at least 80% of 7-dehydrocholesterol in rat skin is esterified) is also isomerized into vitamin D3 ester in vivo. The initial percentage of the esterified form was 84.3% and this did not significantly change up to the time when about half of the skin total vitamin D3 disappeared (2 days). Consequently, it was speculated that the vitamin D3 ester was delivered into the blood circulation from skin without having been hydrolyzed. This was supported by the presence of vitamin D3 ester in rat plasma exposed to ultraviolet radiation. In addition, in connection with the study of the restriction of vitamin D3 synthesis, distribution of total vitamin D3 in rat skin exposed to ultraviolet irradiation in vivo was compared with that in isolated skin exposed to ultraviolet radiation. The dermal layer of the isolated skin contained about 4 times more total vitamin D3 than that of in vivo skin. This finding suggests not only that ultraviolet rays could not penetrate deeply into the in vivo skin, but that the restriction of cutaneous synthesis of vitamin D3 observed in vivo may arise from this reduced penetration of ultraviolet rays.

  8. Characterization of the translocation process of vitamin D3 from the skin into the circulation.

    PubMed

    Tian, X Q; Chen, T C; Lu, Z; Shao, Q; Holick, M F

    1994-08-01

    The cutaneous synthesis of vitamin D3 and the subsequent translocation of vitamin D3 into the circulation are two key steps in the vitamin D endocrine system. To study the kinetic aspects of cutaneous synthesis and translocation of vitamin D3, both in vitro and in vivo chicken models have been developed. To assess the capacity of chicken skin to generate vitamin D3, the concentrations of 7-dehydrocholesterol (7-DHC) in different skin areas were determined. It was found that the highest concentration of 7-DHC was in the leg skin (3524 +/- 937 ng cm-2), which was about 30 times greater than that in the back (120 +/- 62 ng cm-2). Whole body exposure of chickens to UV-B radiation (0.5 J cm-2) resulted in the production of previtamin D3 (preD3) in the skin of the legs and feet (43 +/- 7 and 54 +/- 17 ng cm-2, respectively), whereas no preD3 was detected in the back skin. In vitro, at 40 C, the forward (k1) and reverse (k2) rate constants of the preD3<-->vitamin D3 reaction in the leg skin were greatly increased compared to those in n-hexane (k1, 0.367 vs. 0.0369 h-1; k2, 0.042 vs. 0.0059 h-1). In vivo, the determined rate constants k1, k2, and k3 for the consecutive reactions preD3<-->vitamin D3-->vitamin D3 were 0.257, 0.034, and 0.114 h-1, respectively. To evaluate the circulating concentration of vitamin D3 in response to UV-B radiation, chicken legs were irradiated. The time course revealed a 4-fold increase in the circulating concentration of vitamin D3, with a peak about 30 h postradiation. No appreciable amount of preD3 could be detected in the circulation in the early hours after UV-B radiation, suggesting the existence of a process responsible for the specific translocation of vitamin D3 from the skin into the circulation. PMID:8033813

  9. Photoaffinity labeling of the rat plasma vitamin D binding protein with (26,27-3H)-25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate)

    SciTech Connect

    Ray, R.; Holick, S.A.; Hanafin, N.; Holick, M.F.

    1986-08-26

    It is well recognized that the vitamin D binding protein (DBP) is important for the transport of vitamin D, 25-hydroxyvitamin D (25-OH-D), and its metabolites. In an attempt to better understand the molecular-binding properties of this ubiquitous protein, we designed and synthesized a photoaffinity analogue of 25-OH-D3 and its radiolabeled counterpart. This analogue, 25-hydroxyvitamin D3 3 beta-(N-(4-azido-2-nitrophenyl)glycinate) (25-OH-D3-ANG), was recognized by the rat DBP and was about 10 times less active than 25-OH-D3 in terms of binding. Incubation of (/sup 3/H)25-OH-D3 or (/sup 3/H)25-OH-D3-ANG with rat DBP revealed that both compounds were specifically bound to a protein with a sedimentation coefficient of 4.1 S. Each was displaced with a 500-fold excess of 25-OH-D3. When (/sup 3/H)25-OH-D3-ANG was exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3, there was no displacement of tritium from the 4.1S peak. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of (/sup 3/H)25-OH-D3-ANG exposed to UV radiation in the presence of rat DBP followed by the addition of a 500-fold excess of 25-OH-D3 revealed one major band with a molecular weight of 52 000. These data provide strong evidence that (/sup 3/H)25-OH-D3-ANG was covalently linked to the rat DBP. This photoaffinity probe should provide a valuable tool for the analysis of the binding site on this transport protein.

  10. Experimental Evaluation and Optimization of Flank Wear During Turning of AISI 4340 Steel with Coated Carbide Inserts Using Different Cutting Fluids

    NASA Astrophysics Data System (ADS)

    Lawal, S. A.; Choudhury, I. A.; Nukman, Y.

    2015-01-01

    The understanding of cutting fluids performance in turning process is very important in order to improve the efficiency of the process. This efficiency can be determined based on certain process parameters such as flank wear, cutting forces developed, temperature developed at the tool chip interface, surface roughness on the work piece, etc. In this study, the objective is to determine the influence of cutting fluids on flank wear during turning of AISI 4340 with coated carbide inserts. The performances of three types of cutting fluids were compared using Taguchi experimental method. The results show that palm kernel oil based cutting fluids performed better than the other two cutting fluids in reducing flank wear. Mathematical models for cutting parameters such as cutting speed, feed rate, depth of cut and cutting fluids were obtained from regression analysis using MINITAB 14 software to predict flank wear. Experiments were conducted based on the optimized values to validate the regression equations for flank wear and 5.82 % error was obtained. The optimal cutting parameters for the flank wear using S/N ratio were 160 m/min of cutting speed (level 1), 0.18 mm/rev of feed (level 1), 1.75 mm of depth of cut (level 2) and 2.97 mm2/s palm kernel oil based cutting fluid (level 3). ANOVA shows cutting speed of 85.36 %; and feed rate 4.81 %) as significant factors.

  11. Serum 25-Hydroxyvitamin D3 and Mammography Density among Mexican Women.

    PubMed

    Amadou, Amina; Biessy, Carine; Rinaldi, Sabina; Fedirko, Veronika; Assi, Nada; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

    2016-01-01

    Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3-32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = -0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = -0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels. PMID:27564705

  12. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.

    PubMed

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  13. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  14. Condensin II Subunit dCAP-D3 Restricts Retrotransposon Mobilization in Drosophila Somatic Cells

    PubMed Central

    Schuster, Andrew T.; Sarvepalli, Kavitha; Murphy, Eain A.; Longworth, Michelle S.

    2013-01-01

    Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1) higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2) increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin II influences local

  15. Condensin II subunit dCAP-D3 restricts retrotransposon mobilization in Drosophila somatic cells.

    PubMed

    Schuster, Andrew T; Sarvepalli, Kavitha; Murphy, Eain A; Longworth, Michelle S

    2013-10-01

    Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1) higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2) increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin II influences local

  16. Serum 25–Hydroxyvitamin D3 and Mammography Density among Mexican Women

    PubMed Central

    Amadou, Amina; Biessy, Carine; Rinaldi, Sabina; Fedirko, Veronika; Assi, Nada; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

    2016-01-01

    Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25−hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3–32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = −0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = −0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels. PMID:27564705

  17. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle

    SciTech Connect

    Simpson, R.U.; Thomas, G.A.; Arnold, A.J.

    1985-07-25

    Cytosols from cultured myoblast cells prepared in high salt possesses receptor like proteins for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) that sediment in the 3.2 S region of sucrose gradients. These receptors were characterized as having high affinity for 1,25-(OH)2D3 and are in low capacity. Analog competition for receptor binding revealed that 1,25-(OH)2D3 was more potent than 24,25-(OH)2D3, or 25-(OH)2D3 for displacement of 1,25-(OH)2(TH)D3 from these 3.2 S region sedimenting receptors. Furthermore, the receptor proteins had affinity for DNA and eluted from Sephacryl S-200 as a macromolecule with Stokes radius (Rs) of 32 A. High salt cytosol from collagenase-dispersed skeletal muscle cells was also found to possess a 3.2 S 1,25-(OH)2D3 receptor-like protein. The 1,25-(OH)2D3 receptor concentration was found to down-regulate by 50-70% when cells were stimulated to differentiate to myotubes by lowering fetal calf serum to 5% of the medium. Moreover, the authors demonstrated that 1,25-(OH)2D3 can inhibit DNA synthesis and cell proliferation of the G-8 myoblast cells in a dose-dependent manner. The data support the possibility that muscle is a target tissue for 1,25-(OH)2D3 and the hormone may act to initiate terminal differentiation of myoblast cells.

  18. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

  19. Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves.

    PubMed

    Zimmerman, Duane R; Koszewski, Nicholas J; Hoy, Derrel A; Goff, Jesse P; Horst, Ronald L

    2015-04-01

    Leaves of the Solanum glaucophyllum (Sg) plant, indigenous to South America, have long been known for their calcinogenic toxicity in ruminant animals. It was determined the leaves contained glycosidic derivatives of 1,25-dihydroxyvitamin D3 (1,25D3) and liberation of the free hormone by rumen bacterial populations elicited a hypercalcemic response. Our interest in the leaves is predicated on the concept that the glycoside forms of 1,25D3 would target release of the active hormone in the lower gut of non-ruminant mammals. This would provide a means of delivering 1,25D3 directly to the colon, where the hormone has been shown to have beneficial effects in models of inflammatory bowel disease (IBD) and colon cancer. We fed mice for 10 days with variable amounts of Sg leaf. Feeding 7-333μg leaf/day produced no changes in plasma Ca(2+) and 1,25D3 concentrations, and only at ≥1000μg leaf/day did these values become significantly elevated compared to controls. Gene expression studies from colon tissue indicated a linear relationship between the amount of leaf consumed and expression of the Cyp24a1 gene. In contrast, Cyp24a1 gene expression in the duodenums and ileums of these mice was unchanged compared to controls. One of the major 1,25D3-glycosides was isolated from leaves following extraction and purification by Sep-Pak cartridges and HPLC fractionation. Ultraviolet absorbance was consistent with modification of the 1-hydroxyl group, and positive ion ESI mass spectrometry indicated a diglycoside of 1,25D3. 2-Dimensional NMR analyses were carried out and established the C1 proton of the A-ring was interacting with a C1' sugar proton, while the C3 proton of the A-ring was linked with a second C1' sugar proton. The structure of the isolated compound is therefore consistent with a β-linked 1,3-diglycoside of 1,25D3. Thus, Sg leaf administered to mice at up to 333 ug/day can elicit colon-specific enhancement of Cyp24a1 gene expression without inducing hypercalcemia, and

  20. Application of high resolution 2D/3D spectral induced polarization (SIP) in metalliferous ore exploration

    NASA Astrophysics Data System (ADS)

    Chen, R.; Zhao, X.; Yao, H.; He, X.; Zeng, P.; Chang, F.; Yang, Y.; Zhang, X.; Xi, X.; He, L.

    2015-12-01

    Induced polarization (IP) is a powerful tool in metalliferous ore exploration. However, there are many sources, such as clay and graphite, which can generate IP anomaly. Spectral induced polarization (SIP) measures IP response on a wide frequency range. This method provides a way to discriminate IP response generated by metalliferous ore or other objects. The best way to explore metalliferous ore is 3D SIP exploration. However, if we consider the exploration cost and efficiency, we can use SIP profiling to find an anomaly, and then use 2D/3D SIP sounding to characterize the anomaly. Based on above idea, we used a large-scale distributed SIP measurement system which can realize 800 sounding sites in one direction at the same time. This system can be used for SIP profiling, 2D/3D SIP sounding with high efficiency, high resolution, and large depth of investigation (> 1000 m). Qiushuwan copper - molybdenum deposit is located in Nanyang city, Henan province, China. It is only a middle-size deposit although over 100 holes were drilled and over 40 years of exploration were spent because of very complex geological setting. We made SIP measurement over 100 rock and ore samples to discriminate IP responses of ore and rock containing graphite. Then we carried out 7 lines of 2D SIP exploration with the depth of investigation great than 1000 m. The minimum electode spacing for potential difference is only 20 m. And we increase the spacing of current electodes at linear scale. This acquisition setting ensures high density data acquired and high quality data acquisition. Modeling and inversion result proves that we can get underground information with high resolution by our method. Our result shows that there exists a strong SIP response related to ore body in depth > 300 m. Pseudo-3D inversion of five 2D SIP sounding lines shows the location and size of IP anomaly. The new drillings based our result found a big copper-molybdenum ore body in new position with depth > 300 m and

  1. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED... Part 305—Water Heaters—Oil Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  2. Comparison of analysis of vitamin D3 in foods using ultraviolet and mass spectrometric detection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A method for analysis of vitamin D3 in commonly fortified foods and in fish, which contains endogenous vitamin D3, was developed by combining the best aspects of two official methods. The ethyl ether/petroleum ether extraction procedure from AOAC 992.26 was combined with the chromatographic separat...

  3. Dopamine D3 Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony

    PubMed Central

    Lemercier, Clément E.; Schulz, Steffen B.; Heidmann, Karin E.; Kovács, Richard; Gerevich, Zoltan

    2016-01-01

    Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D3 receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D3 receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D3 receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D3 receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D3 receptors. Investigating the underlying cellular mechanisms for these effects showed that D3 receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D3 receptors may impair cognition and how, in converse, D3 antagonists may exert pro-cognitive and antipsychotic effects. PMID:26779018

  4. 26 CFR 53.4941(d)-3 - Exceptions to self-dealing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Exceptions to self-dealing. 53.4941(d)-3...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(d)-3 Exceptions to self-dealing. (a) General rule. In general, a transaction described in section 4941(d)(2)...

  5. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE CONCERNING... Part 305—Water Heaters—Oil Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  6. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED... Part 305—Water Heaters—Oil Range Information CAPACITY FIRST HOUR RATING Range of Estimated...

  7. Medication Discovery for Addiction: Translating the Dopamine D3 Receptor Hypothesis

    PubMed Central

    Newman, Amy Hauck; Blaylock, Brandi L.; Nader, Michael A.; Bergman, Jack; Sibley, David R.; Skolnick, Phil

    2013-01-01

    The dopamine D3 receptor (D3R) has been investigated as a potential target for medication development to treat substance use disorders (SUDs) with a particular focus on cocaine and methamphetamine. Currently, there are no approved medications to treat cocaine and methamphetamine addiction and thus developing pharmacotherapeutics to compliment existing behavioral strategies is a fundamental goal. Novel compounds with high affinity and D3R selectivity have been evaluated in numerous animal models of drug abuse and favorable outcomes in nonhuman primate models of self-administration and relapse have provided compelling evidence to advance these agents into the clinic. One approach is to repurpose drugs that share the D3R mechanism and already have clinical utility, and to this end buspirone has been identified as a viable candidate for clinical trials. A second, but substantially more resource intensive and risky approach involves the development of compounds that exclusively target D3R, such as GSK598809 and PG 619. Clinical investigation of these drugs or other novel D3R-selective agents will provide a better understanding of the role D3R plays in addiction and whether or not antagonists or partial agonists that are D3R selective are effective in achieving abstinence in this patient population. PMID:22781742

  8. On the breakdown of asymptotic Poincare invariance in D = 3 Einstein gravity

    NASA Technical Reports Server (NTRS)

    Deser, S.

    1985-01-01

    It is shown through a series of calculations that neither momentum nor boosts are definable for finite energy solutions of Einstein gravity in D = 3. The contrast between the effects of Lorentz transformations on the corresponding metrics for D = 3 and D = 4 gravity is demonstrated, and some comparisons with the vector gauge treatment of the problem are offered.

  9. 16 CFR Appendix D3 to Part 305 - Water Heaters-Oil

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Water Heaters-Oil D3 Appendix D3 to Part 305... Part 305—Water Heaters—Oil Range Information CAPACITY FIRST HOUR RATING Range of Estimated Annual... DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS...

  10. D3D augmented reality imaging system: proof of concept in mammography

    PubMed Central

    Douglas, David B; Petricoin, Emanuel F; Liotta, Lance; Wilson, Eugene

    2016-01-01

    Purpose The purpose of this article is to present images from simulated breast microcalcifications and assess the pattern of the microcalcifications with a technical development called “depth 3-dimensional (D3D) augmented reality”. Materials and methods A computer, head display unit, joystick, D3D augmented reality software, and an in-house script of simulated data of breast microcalcifications in a ductal distribution were used. No patient data was used and no statistical analysis was performed. Results The D3D augmented reality system demonstrated stereoscopic depth perception by presenting a unique image to each eye, focal point convergence, head position tracking, 3D cursor, and joystick fly-through. Conclusion The D3D augmented reality imaging system offers image viewing with depth perception and focal point convergence. The D3D augmented reality system should be tested to determine its utility in clinical practice. PMID:27563261

  11. Functional Regulation of Dopamine D3 Receptor through Interaction with PICK1

    PubMed Central

    Zheng, Mei; Zhang, Xiaohan; Min, Chengchun; Choi, Bo-Gil; Oh, In-Joon; Kim, Kyeong-Man

    2016-01-01

    PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine D3 receptors (D3R), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine D2 receptor (D2R) and D3R in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of D2R were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of D3R were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on D3R functions. PMID:27169823

  12. Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin

    SciTech Connect

    MacLaughlin, J.A.; Anderson, R.R.; Holick, M.F.

    1982-05-28

    The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.

  13. Surface fatigue life of M50NiL and AISI 9310 spur gears and R C bars

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Bamberger, Eric N.

    1991-01-01

    Spur gear endurance tests and rolling element surface fatigue tests were conducted to study vacuum induction melted, vacuum arc remelted (VIM-VAR) M50NiL steel for use as a gear steel in advanced aircraft applications, to determine its endurance characteristics, and to compare the results with those for standard VAR and VIM-VAR AISI 9310 gear material. Tests were conducted with spur gears and rolling contact bars manufactured from VIM-VAR M50NiL and VAR and VIM-VAR AISI 9310. The gear pitch diameter was 8.9 cm. Gear test conditions were an inlet oil temperature of 320 K, and outlet oil temperature of 350 K, a maximum Hertz stress of 1.71 GPa, and a speed of 10000 rpm. Bench rolling element fatigue tests were conducted at ambient temperatures with a bar speed of 12,500 rpm and a maximum Hertz stress of 4.83 GPa. The VIM-VAR M50NiL gears had a surface fatigue life that was 4.5 and 11.5 times that for VIM-VAR and VAR AISI 9310 gears, respectively. The surface fatigue life of the VIM-VAR M50NiL rolling contact bars was 13.2 and 21.6 times that for the VIM-VAR and VAR AISI 9310, respectively. The VIM-VAR M50NiL material was shown to have good resistance to fracture through a fatigue spall and superior fatigue life to both other gears.

  14. Effect of coatings obtanied by sputtering of chromium catode on the corrosion resistance of AISI H13 steel

    NASA Astrophysics Data System (ADS)

    Sandoval, A.; Peña, D.; Piratoba, U.

    2013-11-01

    Corrosion resistance of coatings obtained by sputtering a chromium target were evaluated. The films were deposited on substrates of disk-shaped AISI H13 steel. By means of potentiodynamic polarization curves were able to determine the current density vs. potential for the coated and uncoated substrate and the difference in the corrosion potential Ecorr. All samples with coating showed an increase in Ecorr respect to substrate. The electrochemical tests were conducted in an electrolytic solution of 3% NaCl.

  15. Softening during and after the hot deformation of the AISI 321 steel with respect to practical applications

    NASA Astrophysics Data System (ADS)

    Havela, L.; Kratochvíl, P.; Lukáč, P.; Smola, B.; Svobodová, A.

    1988-04-01

    The softening processes during and after the hot deformation (850 1180 ‡C) in AISI 321 stainless steel were studied with respect to true strains ɛ D and true strain ratesdot \\varepsilon _D . The analysis of deformation curves indicates the occurrence of dynamic recrystallization for values of Zener-Hollomon parameter Z≈1015 s-1. The retardation of static recrystallization by fine Ti(N, C) precipitates is documented by microstructure studies and by variations of annealing conditions.

  16. Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans.

    PubMed

    Clark, Richard V; Walker, Ann C; O'Connor-Semmes, Robin L; Leonard, Michael S; Miller, Ram R; Stimpson, Stephen A; Turner, Scott M; Ravussin, Eric; Cefalu, William T; Hellerstein, Marc K; Evans, William J

    2014-06-15

    Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19-30 yr, 70-84 yr), 15 postmenopausal women (51-62 yr, 70-84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA.

  17. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS. PMID:26943970

  18. Sequence conservation of the 12D3 gene in Mexican isolates of Babesia bovis.

    PubMed

    Perez, J; Javier Perez, J; Vargas, P; Antonio Alvarez, J; Rojas, C; Figueroa, J V

    2010-04-01

    The 12D3 antigen present in Babesia bovis has been evaluated as a recombinant vaccine candidate and the 12d3 coding sequence has been reported for an Australian and an USA (Texas) isolate of B. bovis. However, no approach has been conducted to perform analysis of 12d3 sequence conservation on a larger number of B. bovis isolates. This could provide important information to determine whether a recombinant vaccine containing this antigen could be widely used. This study reports the cloning and sequencing analysis of the 12d3 coding region in 20 different B. bovis isolates collected from various geographical regions in the tropics and subtropics of Mexico. Comparative analysis of the consensus nucleotide sequences obtained for each isolate revealed a high degree of conservation (94-99% sequence identity) among the 12d3 alleles present in the Mexican isolates when compared with the 12d3 ORF sequences from the Texan (T2Bo) B. bovis isolate. Similarly, BLASTX sequence homology search showed a high percent identity (93-99%) of the deduced amino acid 12D3 sequence as compared with the T2Bo isolate sequence. The high level of sequence conservation in 12d3 among the 20 B. bovis isolates collected from geographically distant locations in Mexico suggests that there exists a minimal bovine-host immunological pressure which could be translated into antigenic diversity or variation, and most probably this is reflected in the non-inmunodominant characteristic of the 12D3 antigen as it has been previously described in the literature. 12D3 antigen can be considered as a viable candidate for inclusion in a recombinant vaccine for cattle babesiosis caused by B. bovis in Mexico.

  19. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism

    PubMed Central

    Slominski, Andrzej; Semak, Igor; Zjawiony, Jordan; Wortsman, Jacobo; Li, Wei; Szczesniewski, Andre; Tuckey, Robert C.

    2008-01-01

    We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in isolated adrenal mitochondria can metabolize vitamin D3. The major products of the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22-dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely arising from further metabolism of dihydroxycholecalciferol. Based on NMR analysis and known properties of P450scc we propose that hydroxylation of vitamin D3 by P450scc occurs sequentially and stereospecifically with initial formation of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3, indicating that modification of C25 protected it against P450scc action. Adrenal mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition showed that the three major metabolites, but not the others, resulted from P450scc action. It therefore appears that non-P450scc enzymes present in the adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude that purified P450scc in a reconstituted system or P450scc in adrenal mitochondria can add one hydroxyl group to vitamin D3 with subsequent hydroxylation being observed for reconstituted enzyme but not for adrenal mitochondria. Additional vitamin D3 metabolites arise from the action of other enzymes in adrenal mitochondria. These findings appear to define novel metabolic pathways involving vitamin D3 that remain to be characterized. PMID:16098191

  20. Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas

    PubMed Central

    Tang, Jean Y.; Xiao, Tony Zheng; Oda, Yuko; Chang, Kris S.; Shpall, Elana; Wu, Angela; So, Po-Lin; Hebert, Jennifer; Bikle, Daniel; Epstein, Ervin H.

    2011-01-01

    Constitutive Hedgehog (HH) signaling underlies several human tumors, including basal cell carcinoma (BCC). Recently, Bijlsma et al (Bijlsma MF, et al. (2006) PLoS Biol 4: 1397–1410) reported a new biologic function for vitamin D3 in suppressing HH signaling in an in vitro model system. Based on that work, we have assessed effects of vitamin D3 on HH signaling and proliferation of murine BCCs in vitro and in vivo. We find that indeed in BCC cells, vitamin D3 blocks both proliferation and HH signaling as assessed by mRNA expression of the HH target gene Gli1. These effects of vitamin D3 on Gli1 expression and on BCC cell proliferation are comparable to the effects of cyclopamine, a known inhibitor of the HH pathway. These results are specific for vitamin D3, since the precursor 7-dehydrocholesterol and the downstream products 25-hydroxy vitamin D3 [25(OH)D] and 1,25-dihydroxy vitamin D3 [1,25(OH)2D] are considerably less effective in reducing either Gli1 mRNA or cellular proliferation. Moreover, these effects seem to be independent of the vitamin D receptor (VDR) since shRNA knock down of VDR does not abrogate the anti HH effects of D3 despite reducing expression of the VDR target gene 24-hydroxylase. Finally, topical vitamin D3 treatment of existing murine BCC tumors significantly decreases Gli1 and Ki67 staining. Thus, topical vitamin D3 acting via its HH inhibiting effect may hold promise as an effective anti-BCC agent. PMID:21436386

  1. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS.

  2. Formation of Expanded Austenite on a Cold-Sprayed AISI 316L Coating by Low-Temperature Plasma Nitriding

    NASA Astrophysics Data System (ADS)

    Adachi, Shinichiro; Ueda, Nobuhiro

    2015-12-01

    Low-temperature plasma nitriding at temperatures below 450 °C is commonly applied to austenitic stainless steels to enhance wear resistance, while maintaining corrosion resistance, by forming expanded austenite (known as the S-phase). In this work, low-temperature plasma nitriding of cold-sprayed AISI 316L coatings was examined. A cold-spray technique was developed to produce metal coatings with less oxidation. However, the cold-sprayed AISI 316L coating obtained by use of nitrogen gas as propellant contained many interconnected pores and cracks, and was, consequently, unsuitable as an anticorrosive coating. Therefore, laser post-treatment was used to modify the coating and increase its density to similar to that of bulk steel. The anticorrosive performance of this coating on a carbon steel substrate in NaCl solution was substantially improved. Subsequent low-temperature plasma nitriding enhanced the wear resistance by two orders of magnitude. It is concluded that cold-sprayed AISI 316L coatings treated by laser post-treatment and subsequent low-temperature plasma nitriding could be used as protective coatings under severe wear and corrosion conditions.

  3. Plasma nitriding process by direct current glow discharge at low temperature increasing the thermal diffusivity of AISI 304 stainless steel

    SciTech Connect

    Prandel, L. V.; Somer, A.; Assmann, A.; Camelotti, F.; Costa, G.; Bonardi, C.; Jurelo, A. R.; Rodrigues, J. B.; Cruz, G. K.

    2013-02-14

    This work reports for the first time on the use of the open photoacoustic cell technique operating at very low frequencies and at room temperature to experimentally determine the thermal diffusivity parameter of commercial AISI304 stainless steel and AISI304 stainless steel nitrided samples. Complementary measurements of X-ray diffraction and scanning electron microscopy were also performed. The results show that in standard AISI 304 stainless steel samples the thermal diffusivity is (4.0 {+-} 0.3) Multiplication-Sign 10{sup -6} m{sup 2}/s. After the nitriding process, the thermal diffusivity increases to the value (7.1 {+-} 0.5) Multiplication-Sign 10{sup -6} m{sup 2}/s. The results are being associated to the diffusion process of nitrogen into the surface of the sample. Carrying out subsequent thermal treatment at 500 Degree-Sign C, the thermal diffusivity increases up to (12.0 {+-} 2) Multiplication-Sign 10{sup -6} m{sup 2}/s. Now the observed growing in the thermal diffusivity must be related to the change in the phases contained in the nitrided layer.

  4. Correlation between characteristics of grain boundary carbides and creep-fatigue properties in AISI 321 stainless steel

    NASA Astrophysics Data System (ADS)

    Min, Kyung Seon; Nam, Soo Woo

    2003-11-01

    The effects of the interfacial relationships between grain boundary carbides and neighboring grains on the creep-fatigue behaviors have been investigated in AISI 321 stainless steel. The contacting interfacial planes between grain boundary TiC and neighboring grains are found to have lower Miller indices than those between Cr 23C 6 and neighboring grains. From this observation, it is suggested that the interfacial free energy between grain boundary TiC and grains is lower than that between Cr 23C 6 and grains. Creep-fatigue life of TiC aged AISI 321 stainless steel is observed to be longer than that of Cr 23C 6 aged AISI 321 stainless steel. The differences in creep-fatigue life are based on the stronger cavitation resistance of TiC compared with that of Cr 23C 6. From the interfacial relationships between the grain boundary carbides and the neighboring grains, it is verified that formation and growth of grain boundary cavities at TiC carbides are more retarded than those at Cr 23C 6 carbides, thus extending the creep-fatigue life of the steel.

  5. The tensile properties of AISI 316L and OPTIFER in various conditions irradiated in a spallation environment

    NASA Astrophysics Data System (ADS)

    Chen, J.; Rödig, M.; Carsughi, F.; Dai, Y.; Bauer, G. S.; Ullmaier, H.

    2005-08-01

    Tensile specimens, prepared from AISI 316L austenitic stainless steel in three conditions (solution-annealed, cold-worked and electron-beam welded) and from OPTIFER martensitic stainless steel in tempered condition, were irradiated in the Swiss spallation neutron source (SINQ) at 90-400 °C to displacement doses from 3 dpa to 11 dpa. The mechanical properties were measured by tensile testing at room temperature and 250 °C, respectively, and subsequent metallographic analysis was employed. The tensile results indicated that the strength of AISI 316L-SA is quite similar or a little higher than in 316L-EBW but elongation of SA 316L is somewhat larger than EBW for both unirradiated and irradiated samples. The cold-worked specimens revealed much higher strength but almost zero strain-to-necking after irradiation. The results from OPTIFER samples showed that irradiation hardening increases with dose, which is accompanied by a dramatic reduction of uniform elongation beginning at very low dose. The metallographic analysis showed that the samples of AISI 316L-EBW failed in the welded zone.

  6. VizieR Online Data Catalog: H2 d3{Pi}u excitation by elec

    NASA Astrophysics Data System (ADS)

    Liu, X.; Shemansky, D. E.; Yoshii, J.; Johnson, P. V.; Malone, C. P.; Ajello, J. M.

    2016-05-01

    Electron-impact excitation of H2 triplet states plays an imp role in the heating of outer planet upper thermospheres. The d3{Pi}u state is the third ungerade triplet state, and the d3{Pi}u-a3{Sigma}g+ emission is the largest cascade channel for the a3{Sigma}g+ state. Accurate energies of the d3{Pi}u-(v, J) levels are calculated from an ab initio potential energy curve. Radiative lifetimes of the d3{Pi}u(v,J) levels are obtained by an accurate evaluation of the d3{Pi}u-a3{Sigma}g+ transition probabilities. The emission yields are determined from experimental lifetimes and calculated radiative lifetimes and are further verified by comparing experimental and synthetic d3{Pi}u-a3{Sigma}g+ spectra at 20eV impact energy. Spectral analysis revealed that multipolar components beyond the dipolar term are required to model the X1{Sigma}g+-d3{Pi}u excitation, and significant cascade excitation occurs at the d3{Pi}u (v=0,1) levels. Kinetic energy (Ek) distributions of H atoms produced via predissociation of the 3{Pi}u state and the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ cascade dissociative emission are obtained. Predissociation of the d3{Pi}u state produces H atoms with an average Ek of 2.3+/-0.4 eV/atom, while the Ekdistribution of the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ channel is similar to that of the X1{Sigma}g+-a3{Sigma}g+-b3{Sigma}u+ channel and produces H(1s) atoms with an average Ek of 1.15+/-0.05eV/atom. On average, each H2 excited to the d3{Pi}u state in an H2-dominated atmosphere deposits 3.3+/-0.4eV into the atmosphere, while each H2directly excited to the a3{Sigma}g+ state gives 2.2-2.3eV to the atmosphere. The spectral distribution of the calculated a3{Sigma}g+-b3{Sigma}u+ continuum emission due to the X1{Sigma}g+-d3{Pi}u excitation is significantly different from that of direct a3{Sigma}g+ excitation. (2 data files).

  7. Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

    PubMed Central

    Chalkley, S. R.; Richmond, J.; Barltrop, D.

    1998-01-01

    OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25- dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6- 145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium

  8. Estimation and fortification of vitamin D3 in pasteurized process cheese.

    PubMed

    Upreti, P; Mistry, V V; Warthesen, J J

    2002-12-01

    The objective of this study was to develop methods for the estimation and fortification of vitamin D3 in pasteurized Process cheese. Vitamin D3 was estimated using alkaline saponification at 70 degrees C for 30 min, followed by extraction with petroleum ether:diethyl ether (90:10 vol/vol) and HPLC. The retention time for vitamin D3 was approximately 9 min. A standard curve with a correlation coefficient of 0.972 was prepared for quantification of vitamin D3 in unknown samples. In the second phase of the study, pasteurized Process cheeses fortified with commercial water- or fat-dispersible forms of vitamin D3 at a level of 100 IU per serving (28 g) were manufactured. There was no loss of vitamin D3 during Process cheese manufacture, and the vitamin was uniformly distributed. No losses of the vitamin occurred during storage of the fortified cheeses over a 9-mo period at 21 to 29 degrees C and 4 to 6 degrees C. There was an approximately 25 to 30% loss of the vitamin when cheeses were heated for 5 min in an oven maintained at 232 degrees C. Added vitamin D3 did not impart any off flavors to the Process cheeses as determined by sensory analysis. There were no differences between the water- and fat-dispersible forms of the vitamin in the parameters measured in fortified cheeses.

  9. Fusion product studies via fast ion D-D and D-3He fusion on JET

    NASA Astrophysics Data System (ADS)

    Sharapov, S. E.; Hellsten, T.; Kiptily, V. G.; Craciunescu, T.; Eriksson, J.; Fitzgerald, M.; Girardo, J.-B.; Goloborod'ko, V.; Hellesen, C.; Hjalmarsson, A.; Johnson, T.; Kazakov, Y.; Koskela, T.; Mantsinen, M.; Monakhov, I.; Nabais, F.; Nocente, M.; Perez von Thun, C.; Rimini, F.; Santala, M.; Schneider, M.; Tardocchi, M.; Tsalas, M.; Yavorskij, V.; Zoita, V.; Contributors, JET

    2016-11-01

    Dedicated fast ion D-D and D-3He fusion experiments were performed on JET with carbon wall (2008) and ITER-like wall (2014) for testing the upgraded neutron and energetic ion diagnostics of fusion products. Energy spectrum of D-D neutrons was the focus of the studies in pure deuterium plasmas. A significant broadening of the energy spectrum of neutrons born in D-D fast fusion was observed, and dependence of the maximum D and D-D neutron energies on plasma density was established. Diagnostics of charged products of aneutronic D-3He fusion reactions, 3.7 MeV alpha-particles similar to those in D-T fusion, and 14.6 MeV protons, were the focus of the studies in D-3He plasmas. Measurements of 16.4 MeV gamma-rays born in the weak secondary branch of D(3He, γ)5Li reaction were used for assessing D-3He fusion power. For achieving high yield of D-D and D-3He reactions at relatively low levels of input heating power, an acceleration of D beam up to the MeV energy range was used employing 3rd harmonic (f=3{{f}CD} ) ICRH technique. These results were compared to the techniques of D beam injection into D-3He mixture, and 3He-minority ICRH in D plasmas.

  10. Homology Modeling of Dopamine D2 and D3 Receptors: Molecular Dynamics Refinement and Docking Evaluation

    PubMed Central

    Platania, Chiara Bianca Maria; Salomone, Salvatore; Leggio, Gian Marco; Drago, Filippo; Bucolo, Claudio

    2012-01-01

    Dopamine (DA) receptors, a class of G-protein coupled receptors (GPCRs), have been targeted for drug development for the treatment of neurological, psychiatric and ocular disorders. The lack of structural information about GPCRs and their ligand complexes has prompted the development of homology models of these proteins aimed at structure-based drug design. Crystal structure of human dopamine D3 (hD3) receptor has been recently solved. Based on the hD3 receptor crystal structure we generated dopamine D2 and D3 receptor models and refined them with molecular dynamics (MD) protocol. Refined structures, obtained from the MD simulations in membrane environment, were subsequently used in molecular docking studies in order to investigate potential sites of interaction. The structure of hD3 and hD2L receptors was differentiated by means of MD simulations and D3 selective ligands were discriminated, in terms of binding energy, by docking calculation. Robust correlation of computed and experimental Ki was obtained for hD3 and hD2L receptor ligands. In conclusion, the present computational approach seems suitable to build and refine structure models of homologous dopamine receptors that may be of value for structure-based drug discovery of selective dopaminergic ligands. PMID:22970199

  11. Detection of D-^3He Fusion γ-Rays using Gas Cherenkov Detectors

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Herrmann, H. W.; Mack, J. M.; Young, C. S.; Hale, G. M.; Evans, S. C.; Sedillo, T. J.; Cahill, A.; Horsfield, C. J.; Rubery, M. S.; Grafil, E.; Stoeffl, W.; Waugh, C.; Rinderknecht, H. G.; Frenje, J. A.; Petrasso, R. D.; Miller, E. Kirk

    2012-10-01

    The high-energy γ-ray from ^3He(d,γ)^5Li reactions has drawn the attention of the nuclear physics and fusion community as a diagnostic signature to study the ^5Li nuclear structure and the D-^3He fusion reaction. In the past, the D-^3He γ-rays have been measured via accelerator-based beam-target experiments and recently in tokamak-based fusion reactors. In this work, we report the detection of D-^3He fusion γ-rays generated from inertial confinement fusion (ICF) implosions at the OMEGA laser facility. The γ-ray signal observed using Gas Cherenkov Detectors (GCD) is proportional to the independently measured 14.7-MeV fusion proton yield and provides a high-bandwidth alternative to fusion protons for D-^3He burn-history measurements. By comparing γ-rays from D-^3He and D-T implosions, we were able to examine (1) similarities in the γ-ray spectra of D-^3He and D-T and (2) disparities in the γ-to-particle branching ratios of D-^3He and D-T. This experimental work motivates further theoretical investigation of the multichannel ^5Li- and ^5He-system.

  12. Structural basis for stabilization of the hypervariable D3 domain of Salmonella flagellin upon filament formation.

    PubMed

    Muskotál, Adél; Seregélyes, Csaba; Sebestyén, Anett; Vonderviszt, Ferenc

    2010-11-01

    The hypervariable D3 domain of Salmonella flagellin, composed of residues 190-283, is situated at the outer surface of flagellar filaments. A flagellin mutant deprived of the complete D3 domain (ΔD3_FliC) exhibited a significantly decreased thermal stability (T(m) 41.9 °C) as compared to intact flagellin (T(m) 47.3 °C). However, the stability of filaments formed from ΔD3_FliC subunits was virtually identical with that of native flagellar filaments. While D3 comprises the most stable part of monomeric flagellin playing an important role in the stabilization of the other two (D1 and D2) domains, the situation is reversed in the polymeric state. Upon filament formation, ordering of the disordered terminal regions of flagellin in the core part of the filament results in the stabilization of the radially arranged D1 and D2 domains, and there is a substantial increase of stability even in the distant outermost D3 domain, which is connected to D2 via a pair of short antiparallel β-strands. Our experiments revealed that crosslinking the ends of the isolated D3 domain through a disulfide bridge gives rise to a stabilization effect reminiscent of that observed upon polymerization. It appears that the short interdomain linker between domains D2 and D3 serves as a stabilization center that facilitates propagation of the conformational signal from the filament core to the outer part of filament. Because D3 is a largely independent part of flagellin, its replacement by heterologous proteins or domains might offer a promising approach for creation of various fusion proteins possessing polymerization ability.

  13. 1,25-Dihydroxyvitamin-D3 Induces Avian β-Defensin Gene Expression in Chickens

    PubMed Central

    Zhang, Guolong; Ouyang, Linghua; Robinson, Kelsy; Tang, Yanqiang; Zhu, Qing; Li, Diyan; Hu, Yaodong; Liu, Yiping

    2016-01-01

    Host defense peptides (HDPs) play a critical role in innate immunity. Specific modulation of endogenous HDP synthesis by dietary compounds has been regarded as a novel approach to boost immunity and disease resistance in animal production. 1,25-dihydroxy vitamin D3 (1,25D3) is well known as a powerful HDP inducer in humans, but limited information about the effect of 1,25D3 on HDPs in poultry is available. Here, we sought to examine whether 1,25D3 could stimulate avian β-defensin (AvBD) expression in chickens. We used chicken embryo intestinal epithelial cells (CEIEPCs) and peripheral blood mononuclear cells (PBMCs) to study the effect of 1,25D3 on the expression of AvBDs. We observed that 1,25D3 is able to up-regulate the expression of several AvBDs in CEIEPCs and PBMCs, whereas it increased the amounts of AvBD4 mRNA in CEIEPCs only in the presence of lipopolysaccharide (LPS). On the other hand, LPS treatment not only inhibited the expression of CYP24A1 but also altered the expression pattern of VDR in CEIEPCs. Furthermore, AvBDs were not directly regulated by 1,25D3, as cycloheximide completely blocked 1,25D3-induced expression of AvBDs. Our observations suggest that 1,25D3 is capable of inducing AvBD gene expression and is a potential antibiotic alternative through augmentation of host innate immunity as well as disease control in chickens. PMID:27135828

  14. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile.

    PubMed

    Kiss, Béla; Horváth, Attila; Némethy, Zsolt; Schmidt, Eva; Laszlovszky, István; Bugovics, Gyula; Fazekas, Károly; Hornok, Katalin; Orosz, Szabolcs; Gyertyán, István; Agai-Csongor, Eva; Domány, György; Tihanyi, Károly; Adham, Nika; Szombathelyi, Zsolt

    2010-04-01

    Cariprazine {RGH-188; trans-N-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-N',N'-dimethylurea hydrochloride}, a novel candidate antipsychotic, demonstrated approximately 10-fold higher affinity for human D(3) versus human D(2L) and human D(2S) receptors (pKi 10.07, 9.16, and 9.31, respectively). It displayed high affinity at human serotonin (5-HT) type 2B receptors (pK(i) 9.24) with pure antagonism. Cariprazine had lower affinity at human and rat hippocampal 5-HT(1A) receptors (pK(i) 8.59 and 8.34, respectively) and demonstrated low intrinsic efficacy. Cariprazine displayed low affinity at human 5-HT(2A) receptors (pK(i) 7.73). Moderate or low affinity for histamine H(1) and 5-HT(2C) receptors (pK(i) 7.63 and 6.87, respectively) suggest cariprazine's reduced propensity for adverse events related to these receptors. Cariprazine demonstrated different functional profiles at dopamine receptors depending on the assay system. It displayed D(2) and D(3) antagonism in [(35)S]GTPgammaS binding assays, but stimulated inositol phosphate (IP) production (pEC(50) 8.50, E(max) 30%) and antagonized (+/-)-quinpirole-induced IP accumulation (pK(b) 9.22) in murine cells expressing human D(2L) receptors. It had partial agonist activity (pEC(50) 8.58, E(max) 71%) by inhibiting cAMP accumulation in Chinese hamster ovary cells expressing human D(3) receptors and potently antagonized R(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphtalene HBr (7-OH-DPAT)-induced suppression of cAMP formation (pK(b) 9.57). In these functional assays, cariprazine showed similar (D(2)) or higher (D(3)) antagonist-partial agonist affinity and greater (3- to 10-fold) D(3) versus D(2) selectivity compared with aripiprazole. In in vivo turnover and biosynthesis experiments, cariprazine demonstrated D(2)-related partial agonist and antagonist properties, depending on actual dopaminergic tone. The antagonist-partial agonist properties of cariprazine at D(3) and D(2) receptors, with very high

  15. Modulation of the Bovine Innate Immune Response by Production of 1alpha,25-Dihydroxyvitamin D3 in Bovine Monocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In cattle, the kidney has been the only known site for production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) from 25-hydroxyvitamin D3 25(OH)D3 by 1alpha-hydroxylase (1alpha-OHase). However, recent studies have shown that human monocytes express 1alpha-OHase and produce 1,25(OH)2D3 in response to to...

  16. Retinoid X receptor:vitamin D3 receptor heterodimers promote stable preinitiation complex formation and direct 1,25-dihydroxyvitamin D3-dependent cell-free transcription.

    PubMed Central

    Lemon, B D; Fondell, J D; Freedman, L P

    1997-01-01

    The numerous members of the steroid/nuclear hormone receptor superfamily act as direct transducers of circulating signals, such as steroids, thyroid hormone, and vitamin or lipid metabolites, and modulate the transcription of specific target genes, primarily as dimeric complexes. The receptors for 9-cis retinoic acid and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], RXR and VDR, respectively, as members of this superfamily, form a heterodimeric complex and bind cooperatively to vitamin D responsive elements (VDREs) to activate or repress the transcription of a multitude of genes which regulate a variety of physiological functions. To directly investigate RXR- and VDR-mediated transactivation, we developed a cell-free transcription system for 1,25(OH)2D3 signaling by utilizing crude nuclear extracts and a G-free cassette-based assay. Transcriptional enhancement in vitro was dependent on purified, exogenous RXR and VDR and was responsive to physiological concentrations of 1,25(OH)2D3. We found that RXR and VDR transactivated selectively from VDRE-linked templates exclusively as a heterodimeric complex, since neither receptor alone enhanced transcription in vitro. By the addition of low concentrations of the anionic detergent Sarkosyl to limit cell-free transcription to a single round and the use of agarose gel mobility shift experiments to assay factor complex assembly, we observed that 1,25(OH)2D3 enhanced RXR:VDR-mediated stabilization or assembly of preinitiation complexes to effect transcriptional enhancement from VDRE-linked promoter-containing DNA. PMID:9121440

  17. Novel Mechanism of Negative Regulation of 1,25-Dihydroxyvitamin D3-induced 25-Hydroxyvitamin D3 24-Hydroxylase (Cyp24a1) Transcription

    PubMed Central

    Seth-Vollenweider, Tanya; Joshi, Sneha; Dhawan, Puneet; Sif, Said; Christakos, Sylvia

    2014-01-01

    The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) β and cooperate with VDR and C/EBPβ in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription. PMID:25324546

  18. Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is regulated by protein palmitoylation

    SciTech Connect

    Kong, Chen; Lange, Jeffrey J.; Samovski, Dmitri; Su, Xiong; Liu, Jialiu; Sundaresan, Sinju; Stahl, Philip D.

    2013-05-03

    Highlights: •Hominoid-specific oncogene TBC1D3 is targeted to plasma membrane by palmitoylation. •TBC1D3 is palmitoylated on two cysteine residues: 318 and 325. •TBC1D3 palmitoylation governs growth factors-induced TBC1D3 degradation. •Post-translational modifications may regulate oncogenic properties of TBC1D3. -- Abstract: Expression of the hominoid-specific oncoprotein TBC1D3 promotes enhanced cell growth and proliferation by increased activation of signal transduction through several growth factors. Recently we documented the role of CUL7 E3 ligase in growth factors-induced ubiquitination and degradation of TBC1D3. Here we expanded our study to discover additional molecular mechanisms that control TBC1D3 protein turnover. We report that TBC1D3 is palmitoylated on two cysteine residues: 318 and 325. The expression of double palmitoylation mutant TBC1D3:C318/325S resulted in protein mislocalization and enhanced growth factors-induced TBC1D3 degradation. Moreover, ubiquitination of TBC1D3 via CUL7 E3 ligase complex was increased by mutating the palmitoylation sites, suggesting that depalmitoylation of TBC1D3 makes the protein more available for ubiquitination and degradation. The results reported here provide novel insights into the molecular mechanisms that govern TBC1D3 protein degradation. Dysregulation of these mechanisms in vivo could potentially result in aberrant TBC1D3 expression and promote oncogenesis.

  19. The Synthesis of Active Metabolites and Analogues of Vitamin D3

    NASA Astrophysics Data System (ADS)

    Yakhimovich, R. I.

    1980-04-01

    The literature date on the synthesis of the active metabolites and analogues of vitamin D3 (cholecalciferol), which play an important role in regulating the homeostatis of calcium in the organism, are reviewed. The bibliography includes 150 references.

  20. Effect of Surface Integrity of Hard Turned AISI 52100 Steel on Fatigue Performance

    SciTech Connect

    Lara-Curzio, Edgar; Watkins, Thomas R; Allard Jr, Lawrence Frederick; Riester, Laura

    2007-01-01

    This paper addresses the relationship between surface integrity and fatigue life of hard turned AISI 52100 steel (60-62 HRC), with grinding as a benchmark. The impact of superfinishing on the fatigue performance of hard turned and ground surfaces is also discussed. Specifically, the surface integrity and fatigue life of the following five distinct surface conditions are examined: hard turned with continuous white layer, hard turned with no white layer, ground, and superfinished hard turned and ground specimens. Surface integrity of the specimens is characterized via surface topography measurement, metallography, residual stress measurements, transmission electron microscopy (TEM), and nano-indentation tests. High cycle tension-tension fatigue tests show that the presence of white layer does not adversely affect fatigue life and that, on average, the hard turned surface performs as well or better than the ground surface. The effect of superfinishing is to exaggerate these differences in performance. The results obtained from this study suggest that the effect of residual stress on fatigue life is more significant than the effect of white layer. For the hard turned surfaces, the fatigue life is found to be directly proportional to both the surface compressive residual stress and the maximum compressive residual stress. Possible explanations for the observed effects are discussed.

  1. Effect of shot peening on surface fatigue life of carburized and hardened AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, D. P.; Zaretsky, E. V.

    1982-01-01

    Surface fatigue tests were conducted on two groups of AISI 9310 spur gears. Both groups were manufactured with standard ground tooth surfaces, with the second group subjected to an additional shot peening process on the gear tooth flanks. The gear pitch diameter was 8.89 cm (3.5 in.). Test conditions were a gear temperature of 350 K (170 F), a maximum Hertz stress of 1.71 billion N/sq m (248,000 psi), and a speed of 10,000 rpm. The shot peened gears exhibited pitting fatigue lives 1.6 times the life of standard gears without shot peening. Residual stress measurements and analysis indicate that the longer fatigue life is the result of the higher compressive stress produced by the shot peening. The life for the shot peened gear was calculated to be 1.5 times that for the plain gear by using the measured residual stress difference for the standard and shot peened gears. The measured residual stress for the shot peened gears was much higher than that for the standard gears.

  2. Characterization of irradiated AISI 316L stainless steel disks removed from the Spallation Neutron Source

    SciTech Connect

    Vevera, Bradley J; Hyres, James W; McClintock, David A; Riemer, Bernie

    2014-01-01

    Irradiated AISI 316L stainless steel disks were removed from the Spallation Neutron Source (SNS) for post-irradiation examination (PIE) to assess mechanical property changes due to radiation damage and erosion of the target vessel. Topics reviewed include high-resolution photography of the disk specimens, cleaning to remove mercury (Hg) residue and surface oxides, profile mapping of cavitation pits using high frequency ultrasonic testing (UT), high-resolution surface replication, and machining of test specimens using wire electrical discharge machining (EDM), tensile testing, Rockwell Superficial hardness testing, Vickers microhardness testing, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The effectiveness of the cleaning procedure was evident in the pre- and post-cleaning photography and permitted accurate placement of the test specimens on the disks. Due to the limited amount of material available and the unique geometry of the disks, machine fixturing and test specimen design were critical aspects of this work. Multiple designs were considered and refined during mock-up test runs on unirradiated disks. The techniques used to successfully machine and test the various specimens will be presented along with a summary of important findings from the laboratory examinations.

  3. Phase Transformations During the Low-Temperature Nitriding of AISI 2205 Duplex Stainless Steel

    NASA Astrophysics Data System (ADS)

    Yan, Jing; Gu, Tan; Qiu, Shaoyu; Wang, Jun; Xiong, Ji; Fan, Hongyuan

    2015-02-01

    Liquid nitriding of type AISI 2205 duplex stainless steel was conducted at 723 K (450 °C), using one type of novel low-temperature liquid chemical thermo-treatment. The transformation of the nitrided surface microstructure was systematically studied. Experimental results revealed that a nitrided layer formed on the sample surface with the thickness ranging from 3 to 28 μm, depending on nitriding time. After the 2205 duplex stainless steel was subjected to liquid nitriding 723 K (450 °C) for less than 8 hours, the pre-existing ferrite region on the surface transformed into the expanded austenite (S phase) by the infusion of nitrogen atoms, most of which stay in the interstitial sites. Generally, the dominant phase of the nitrided layer was the expanded austenite. When the nitriding time prolonged up to 16 hours, some pre-existing ferrite in expanded austenite was decomposed and ɛ-nitride precipitated subsequently. When the treatment time went up to 40 hours, large amount of ɛ-nitride and CrN precipitates were observed in the pre-existing ferritic region in the expanded austenite. Furthermore, many nitrides precipitated from the pre-austenite region. Acicular nitride was identified by transmission electron microscopy. The thickness of the nitrided layer increased with increasing nitriding time. The growth of the nitrided layer is mainly due to nitrogen diffusion in accordance with the expected parabolic rate law. Liquid nitriding effectively increased the surface hardness of 2205 duplex stainless steel by a factor of 3.

  4. Effect of Austenitizing Heat Treatment on the Microstructure and Hardness of Martensitic Stainless Steel AISI 420

    NASA Astrophysics Data System (ADS)

    Barlow, L. D.; Du Toit, M.

    2012-07-01

    The effect of austenitizing on the microstructure and hardness of two martensitic stainless steels was examined with the aim of supplying heat-treatment guidelines to the user that will ensure a martensitic structure with minimal retained austenite, evenly dispersed carbides and a hardness of between 610 and 740 HV (Vickers hardness) after quenching and tempering. The steels examined during the course of this examination conform in composition to medium-carbon AISI 420 martensitic stainless steel, except for the addition of 0.13% vanadium and 0.62% molybdenum to one of the alloys. Steel samples were austenitized at temperatures between 1000 and 1200 °C, followed by oil quenching. The as-quenched microstructures were found to range from almost fully martensitic structures to martensite with up to 35% retained austenite after quenching, with varying amounts of carbides. Optical and scanning electron microscopy was used to characterize the microstructures, and X-ray diffraction was employed to identify the carbide present in the as-quenched structures and to quantify the retained austenite contents. Hardness tests were performed to determine the effect of heat treatment on mechanical properties. As-quenched hardness values ranged from 700 to 270 HV, depending on the amount of retained austenite. Thermodynamic predictions (using the CALPHAD™ model) were employed to explain these microstructures based on the solubility of the carbide particles at various austenitizing temperatures.

  5. Investigation of Low-Cycle Bending Fatigue of AISI 9310 Steel Spur Gears

    NASA Technical Reports Server (NTRS)

    Handschuh, Robert F.; Krantz, Timothy L.; Lerch, Bradley A.; Burke, Christopher S.

    2007-01-01

    An investigation of the low-cycle bending fatigue of spur gears made from AISI 9310 gear steel was completed. Tests were conducted using the single-tooth bending method to achieve crack initiation and propagation. Tests were conducted on spur gears in a fatigue test machine using a dedicated gear test fixture. Test loads were applied at the highest point of single tooth contact. Gear bending stresses for a given testing load were calculated using a linear-elastic finite element model. Test data were accumulated from 1/4 cycle to several thousand cycles depending on the test stress level. The relationship of stress and cycles for crack initiation was found to be semi-logarithmic. The relationship of stress and cycles for crack propagation was found to be linear. For the range of loads investigated, the crack propagation phase is related to the level of load being applied. Very high loads have comparable crack initiation and propagation times whereas lower loads can have a much smaller number of cycles for crack propagation cycles as compared to crack initiation.

  6. Effect of two synthetic lubricants on life of AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Shimski, John

    1991-01-01

    Spur-gear fatigue tests were conducted with two lubricants using a single lot of consumable-electrode vacuum-melted (CVM) AISI 9310 spur gears. The gears were case carburized and hardened to Rockwell C60. The gear pitch diameter was 8.89 cm. The lot of gears was divided into two groups, each of which was tested with a different lubricant. The test lubricants can be classified as synthetic polyol-ester-based lubricants. One lubricant was 30 percent more viscous that the other. Both lubricants have similar pressure viscosity coefficients. Test conditions included a bulk gear temperature of 350 K, a maximum Hertz stress of 1.71 GPa at the pitch line, and a speed of 10,000 rpm. The surface fatigue life of gears tested with one lubricant was approximately 2.4 times that for gears tested with the other lubricant. The lubricant with the 30 percent higher viscosity gave a calculated elastohydrodynamic (EHD) film thickness that was 20 percent higher than the other lubricant. This increased EHD film thickness is the most probable reason for the improvement in surface fatigue life of gears tested with this lubricant over gears tested with the less viscous lubricant.

  7. Investigation of Low-Cycle Bending Fatigue of AISI 9310 Steel Spur Gears

    NASA Technical Reports Server (NTRS)

    Handschuh, Robert F.; Krantz, Timothy L.; Lerch, Bradley A.; Burke, Christopher S.

    2007-01-01

    An investigation of the low-cycle bending fatigue of spur gears made from AISI 9310 gear steel was completed. Tests were conducted using the single-tooth bending method to achieve crack initiation and propagation. Tests were conducted on spur gears in a fatigue test machine using a dedicated gear test fixture. Test loads were applied at the highest point of single tooth contact. Gear bending stresses for a given testing load were calculated using a linear-elastic finite element model. Test data were accumulated from 1/4 cycle to several thousand cycles depending on the test stress level. The relationship of stress and cycles for crack initiation was found to be semilogarithmic. The relationship of stress and cycles for crack propagation was found to be linear. For the range of loads investigated, the crack propagation phase is related to the level of load being applied. Very high loads have comparable crack initiation and propagation times whereas lower loads can have a much smaller number of cycles for crack propagation cycles as compared to crack initiation.

  8. Influence of grain size on ultrasonic spectral parameters in AISI type 316 stainless steel

    SciTech Connect

    Kumar, A.; Jayakumar, T.; Palanichamy, P.; Raj, B.

    1999-01-08

    The grain size of a material is an important engineering parameter which influences the mechanical properties such as fatigue, creep, yield strength, impact transition temperature, etc. The reliability of the ultrasonic methods for grain size measurement, particularly amplitude based measurements are highly dependent upon the couplant condition. Therefore, application of these methods may be difficult for some practical applications, where uniform couplant condition can not be maintained. Therefore, it would be useful if a simplified method is developed, which could be used on-line and is free from the above mentioned limitations of the other methods. The shift in the spectral peak frequency has been used for microstructural characterization in carbon steel and for evaluation of structural variations induced by tensile deformation in SUS304 stainless steel. The spectral peak frequency in SUS304 steel was found to increase with increase in the tensile elongation. This was attributed to formation and growth of martensite structures due to tensile deformation resulting in smaller crystalline grains, thus reducing the attenuation due to ultrasonic scattering. The peak frequency has also been found to shift with the change in the grain size in Inconel 600 and copper. In the present study, the shift in the spectral peak frequency and the change in full width at half maximum (FWHM) of the autopower spectrum are correlated with the grain size in AISI type 316 austenitic stainless steel, a widely used structural material in nuclear, chemical, fertilizer and many other industries.

  9. Effect of superheat on the solidification structures of AISI 310S austenitic stainless steel

    SciTech Connect

    Ozbayraktar, S.; Koursaris, A.

    1996-04-01

    An experimental study was carried out to investigate the evolution of macrostructure and microstructure in AISI 310S stainless steel during solidification. Experimental findings suggested that the macrostructure a/nd the microstructure of the cast material responded differently to variations in casting temperature. As the casting temperature decreased, the macrostructure was refined, as expected, but the microstructure coarsened. A relationship was established between the proportion of equiaxed zone and superheat as follows: pct equiaxed zone = a + b ln (1/{Delta}T), where a and b are constants. The relationship between grain width and superheat could be expressed by the equation: gw = e(c+d/{Delta}T), where c and d are constants determined by the distance from the edge of the ingot. The relationship between primary arm spacing and superheat could be expressed by the equation: {lambda}{sub 1} = p + q ln (1/{Delta}T), where p and q are constants determined by the distance from the edge of the ingot. The parameter grain width ratio has been introduced to describe the relationship between the shape and the nucleation and growth kinetics of the columnar grains.

  10. Computational Modeling of Microstructural-Evolution in AISI 1005 Steel During Gas Metal Arc Butt Welding

    NASA Astrophysics Data System (ADS)

    Grujicic, M.; Ramaswami, S.; Snipes, J. S.; Yavari, R.; Arakere, A.; Yen, C.-F.; Cheeseman, B. A.

    2013-05-01

    A fully coupled (two-way), transient, thermal-mechanical finite-element procedure is developed to model conventional gas metal arc welding (GMAW) butt-joining process. Two-way thermal-mechanical coupling is achieved by making the mechanical material model of the workpiece and the weld temperature-dependent and by allowing the potential work of plastic deformation resulting from large thermal gradients to be dissipated in the form of heat. To account for the heat losses from the weld into the surroundings, heat transfer effects associated with natural convection and radiation to the environment and thermal-heat conduction to the adjacent workpiece material are considered. The procedure is next combined with the basic physical-metallurgy concepts and principles and applied to a prototypical (plain) low-carbon steel (AISI 1005) to predict the distribution of various crystalline phases within the as-welded material microstructure in different fusion zone and heat-affected zone locations, under given GMAW-process parameters. The results obtained are compared with available open-literature experimental data to provide validation/verification for the proposed GMAW modeling effort.

  11. Linking anisotropy with Fe3C distribution in AISI 1045 steel

    NASA Astrophysics Data System (ADS)

    Shen, Ke-chang; Li, Gui-hua; Sun, Yi-min; Wang, Yong-gang; Li, Ying-jie; Cao, Guang-hui; Wang, Wei-min

    2015-12-01

    The anisotropy of the microstructure, thermal expansion behavior, corrosion resistance and magnetic properties of AISI 1045 steel was investigated. The distribution of Fe3C lamellae in the investigation plane parallel to the radial directions of molds was observed to differ from that in the investigation plane perpendicular to the radial directions by transmission electron microscopy. The lattice constants a 0 of α-Fe deduced from the XRD patterns of samples prepared using a sand (S)-mold and cut parallel to the radial direction of the mold (S//) and using a metal (M)-mold and cut parallel to the radial direction (M//), the corrosion resistance measured using an electrochemical workstation, and the magnetic permeability obtained by vibrating sample magnetometry also indicated the existence of anisotropy in the tested samples. The anisotropic change of corrosion potential ( E corr), pitting potential ( E pit) and magnetic permeability ( µ) of the samples was observed to depend on the orientation factor F 200 of α-Fe in the measured samples, which is controlled by the distribution of Fe3C lamellae in the eutectoid structure.

  12. An Electrochemical Processing Strategy for Improving Tribological Performance of Aisi 316 Stainless Steel Under Grease Lubrication

    NASA Astrophysics Data System (ADS)

    Zou, Jiaojuan; Li, Maolin; Lin, Naiming; Zhang, Xiangyu; Qin, Lin; Tang, Bin

    2014-12-01

    In order to improve the tribological performance of AISI 316 stainless steel (316 SS) under grease lubrication, electrochemical processing was conducted on it to obtain a rough (surface texturing-like) surface by making use of the high sensitivity of austenitic stainless steel to pitting corrosion in Cl--rich environment. Numerous corrosion pits or micro-ditches acted as micro-reservoirs on the obtained surface. While the grease could offer consistent lubrication, and then improve the tribological performance of 316 SS. Tribological behaviors of raw 316 SS and the treated sample were measured using a reciprocating type tribometer sliding against GCr15 steel counterpart under dry and grease lubrication conditions. The results showed that the mass losses of the two samples were in the same order of magnitude, and the raw sample exhibited lower friction coefficient in dry sliding. When the tests were conducted under grease lubrication condition, the friction coefficients and mass losses of the treated sample were far lower than those of the raw 316 SS. The tribological performance of 316 SS under grease lubrication was drastically improved after electrochemical processing.

  13. Fe-Based Amorphous Coatings on AISI 4130 Structural Steel for Corrosion Resistance

    NASA Astrophysics Data System (ADS)

    Katakam, Shravana; Santhanakrishnan, S.; Dahotre, Narendra B.

    2012-06-01

    The current study focuses on synthesizing a novel functional coating for corrosion resistance applications, via laser surface alloying. The iron-based (Fe48Cr15Mo14Y2C15B) amorphous precursor powder is used for laser surface alloying on AISI 4130 steel substrate, with a continuous wave ytterbium Nd-YAG fiber laser. The corrosion resistance of the coatings is evaluated for different processing conditions. The microstructural evolution and the response of the microstructure to the corrosive environment is studied using x-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Microstructural studies indicate the presence of face-centered cubic Fe-based dendrites intermixed within an amorphous matrix along with fine crystalline precipitates. The corrosion resistance of the coatings decrease with an increase in laser energy density, which is attributed to the precipitation and growth of chromium carbide. The enhanced corrosion resistance of the coatings processed with low energy density is attributed to the self-healing mechanism of this amorphous system.

  14. The Meta-Lax method of stress reduction in welds. [ASTM A36; AISI 4140

    SciTech Connect

    Smith, S.M.

    1992-07-31

    This study is the second phase of ongoing research into the mechanics and feasibility of using the Meta-Lax method of vibratory stress relief in place of thermal methods of stress relief. The first phase of this research revealed results that were similar to, and even superior to those achieved using thermal methods. The testing here was designed to eliminate the effects of interbead tempering by utilizing single pass bead-on-plate welds only. A metallurgical explanation for the success of the Meta-Lax method was not found. No significant structure or chemical changes were noted when used with ASTM A36 or AISI 4140 materials, and the phenomena noted in phase I was apparently due to interbead tempering. The theory of accelerated aging has been proposed and studies exist which observed dislocation motion as a result of vibratory treatment. It is evident that the vibratory stress relief system does not impart sufficient energy to bring about the magnitude of change seen with thermal methods. however the physical improvement is a reality, and vibratory methods should be evaluated further.

  15. Nano- and Macro-wear of Bio-carbo-nitrided AISI 8620 Steel Surfaces

    NASA Astrophysics Data System (ADS)

    Arthur, Emmanuel Kwesi; Ampaw, Edward; Zebaze Kana, M. G.; Adetunji, A. R.; Olusunle, S. O. O.; Adewoye, O. O.; Soboyejo, W. O.

    2015-12-01

    This paper presents the results of an experimental study of nano- and macro-scale wear in a carbo-nitrided AISI 8620 steel. Carbo-nitriding is carried out using a novel method that involves the use of dried, cyanide-containing cassava leaves, as sources of carbon and nitrogen. These are used in a pack cementation that is used to diffuse carbon and nitrogen into case layers at intermediate temperatures [673.15 K, 723.15 K, 773.15 K, and 823.15 K (400 °C, 450 °C, 500 °C, and 550 °C)]. Nano- and macro-scale wear properties are studied in the case-hardened surfaces, using a combination of nano-scratch and pin-on-disk experiments. The measured wear volumes (at both nano- and macro-length scales) are shown to increase with decreasing pack cyaniding temperature. The nano- and macro-wear resistances are also shown to be enhanced by the in situ diffusion of carbon and nitrogen from cyanide-containing bio-processed waste. The underlying wear mechanisms are also elucidated via atomic force microscopy and scanning electron microscopy observations of the wear tracks. The implications of the results are discussed for the design of hardened carbo-nitrided steel surfaces with improved wear resistance.

  16. Some Temperature Effects on AISI-304 Nitriding in an Inductively Coupled RF Plasma

    SciTech Connect

    Valencia-Alvarado, R.; Barocio, S. R.; Mercado-Cabrera, A.; Pena-Eguiluz, R.; Munoz-Castro, A. E.; Piedad-Beneitez, A. de la; Rosa-Vazquez, J. de la; Lopez-Callejas, R.; Godoy-Cabrera, O. G.

    2006-12-04

    Some recent results obtained from nitriding AISI 304 stainless steel samples, 1.2 cm in diameter and 0.5 cm thick are reported here in the case of an 85% hydrogen and 15% nitrogen mixture work gas. The process was carried out from 300 to 400 W for (13.56 MHz) inductively coupled plasma within a 60 cm long pyrex glass tube 3.5 cm in diameter where the samples were biased up to -300 V with respect to earth. The resulting hardness appears to be a function of the substrate temperature which varied from 200 deg. C at a 0 V bias to 550 deg. C at -300 V. The plasma density at 400 W reached 3x1010 cm-3 with a 4 eV electron temperature. Prior to nitriding, all the samples were polished with 0.05 {mu}m diamond paste, leading to a 30 nm average roughness (Ra). After nitriding at -300 V, the Ra rose until {approx}400 nm while hardness values of 1500 HV under 300 g loads were measured. X ray diffraction indicates that the extended phase amplitude ({gamma}N), Fe and Cr nitride depends on the substrate temperature.

  17. Microstructure and oxidation behavior of high strength steel AISI 410 implanted with nitrogen ion

    NASA Astrophysics Data System (ADS)

    Bandriyana, Ismoyo, Agus Hadi; Sujitno, Tjipto; Dimyati, A.

    2016-04-01

    Surface treatment by implantation with nitrogen-ion was performed on the commercial feritic high strength steel AISI 410 which is termed for high temperature applications. The aim of this research was focused on the surface modification to improve its high temperature oxidation property in the early stages. Ion implantation was carried out at acceleration energy of 100 KeV and ion current 10 mA for 30, 60 and 90 minutes. The samples were subjected to the high temperature oxidation test by means of thermogravimetry in a magnetic suspension balance (MSB) at 500 °C for 5 hours. The scanning electron microscopy (SEM), X-ray diffraction spectrometry (XRD) and Vickers Hardness measurement were used for sample characterization. The formation of ferro-nitride phase after implantation did not occur, however a thin layer considered to contain nitrogen interstitials was detected. The oxidation of both samples before and after implantation followed parabolic kinetics indicating inward growth of oxide scale characteristically due to diffusion of oxygen anions towards matrix surface. After oxidation test relativelly stable oxide scales were observed. Oxidation rates decreased proportionally with the increasing of implantation time due to the formation of oxide layer which is considered to be effectiv inhibitor for the oxygen diffusion.

  18. Structural analysis and intergranular corrosion tests of AISI 316L steel.

    PubMed

    Stonawská, Z; Svoboda, M; Sozańska, M; Krístková, M; Sojka, J; Dagbert, C; Hyspecká, L

    2006-10-01

    Pure AISI 316L steel is investigated after solution heat treatment (1050 degrees C/H(2)O) and structural sensitization (650 degrees C). Two quite different intergranular corrosion tests are used to determine the degree of structural sensitization due to the precipitation of secondary phases along the grain boundaries (mainly the M(23)C(6) and sigma-phase): the oxalic acid etch test and the electrochemical potentio-kinetic reactivation test. Generally, the dissolution of chromium-rich carbides (M(23)C(6)) is provoked by oxalic acid etch tests, whereas the chromium-depleted zones, in the vicinity of chromium-rich carbides (M(23)C(6)), are attacked by electrochemical potentio-kinetic reactivation tests. Both intergranular corrosion tests are used to determine the maximum degree of structural sensitization. Thus structural analysis by carbon replicas reveals the Laves phase, and both the M(23)C(6) and (Cr,Mo)(x)(Fe,Ni)(y) phases. The results of intergranular corrosion tests are related to the findings of the structural analysis.

  19. Spinodal decomposition in AISI 316L stainless steel via high-speed laser remelting

    NASA Astrophysics Data System (ADS)

    Chikarakara, Evans; Naher, Sumsun; Brabazon, Dermot

    2014-05-01

    A 1.5 kW CO2 pulsed laser was used to melt the surface of AISI 316L stainless steel with a view to enhancing the surface properties for engineering applications. A 90 μm laser beam spot size focused onto the surface was used to provide high irradiances (up to 23.56 MW/cm2) with low residence times (as low as 50 μs) in order to induce rapid surface melting and solidification. Variations in microstructure at different points within the laser treated region were investigated. From this processing refined lamellar and nodular microstructures were produced. These sets of unique microstructures were produced within the remelted region when the highest energy densities were selected in conjunction with the lowest residence times. The transformation from the typical austenitic structure to much finer unique lamellar and nodular structures was attributed to the high thermal gradients achieved using these selected laser processing parameters. These structures resulted in unique characteristics including elimination of cracks and a reduction of inclusions within the treated region. Grain structure reorientation between the bulk alloy and laser-treated region occurred due to the induced thermal gradients. This present article reports on microstructure forms resulting from the high-speed laser surface remelting and corresponding underlying kinetics.

  20. Effect of welding parameters on the heat-affected zone of AISI409 ferritic stainless steel

    NASA Astrophysics Data System (ADS)

    Ranjbarnodeh, Eslam; Hanke, Stefanie; Weiss, Sabine; Fischer, Alfons

    2012-10-01

    One of the main problems during the welding of ferritic stainless steels is severe grain growth within the heat-affected zone (HAZ). In the present study, the microstructural characteristics of tungsten inert gas (TIG) welded AISI409 ferritic stainless steel were investigated by electron backscattered diffraction (EBSD), and the effects of welding parameters on the grain size, local misorientation, and low-angle grain boundaries were studied. A 3-D finite element model (FEM) was developed to predict the effects of welding parameters on the holding time of the HAZ above the critical temperature of grain growth. It is found that the base metal is not fully recrystallized. During the welding, complete recrystallization is followed by severe grain growth. A decrease in the number of low-angle grain boundaries is observed within the HAZ. FEM results show that the final state of residual strains is caused by competition between welding plastic strains and their release by recrystallization. Still, the decisive factor for grain growth is heat input.

  1. Deposition of titanium nitride on AISI-304 in a plasma focus environment

    NASA Astrophysics Data System (ADS)

    Zeb, S.; Qayyum, A.; Shafiq, M.; Zakaullah, M.

    2008-05-01

    Polycrystalline, smooth, and hard thin films of TiN are successfully deposited on AISI-304 substrates using a 1.5kJ Mather-type dense plasma focus device charged at 18kV. The purpose of this study is to investigate the structural and mechanical properties of the TiN thin films in terms of ion dose and substrate position to establish the optimum deposition conditions. The films are analyzed using XRD, SEM, electron microprobe and micro-hardness testing. XRD confirms the deposition of a polycrystalline TiN thin film together with the emergence of an iron chromium nickel phase. The surface hardness-in comparison to the unexposed substrate-is found to increase up to 250% when a film is deposited using 30 focus shots at an axial distance of 6cm. SEM micrographs show that the quality of the film is improved with an increasing number of focus shots. The constituent elements of the film are also confirmed by electron microprobe.

  2. Surface characterisation and corrosion behaviour of SiC-coated AISI 321 stainless steel

    NASA Astrophysics Data System (ADS)

    Misaelides, P.; Noli, F.; Riviere, J. P.; Delafond, J.

    1997-07-01

    The influence of SiC-coatings on the corrosion properties of AISI 321 austenitic stainless steel (Fe/Cr18/Ni8/Ti) in 1N H 2SO 4 was studied. SiC-coatings of various thicknesses (100-800 nm) were prepared at room temperature (RT) or at temperatures up to 750°C by ion beam sputtering of a SiC-target. The growing films could be continuously bombarded with a 160 keV Ar + ion beam and the role of this Dynamic Ion Mixing (DIM) on both the structure and corrosion resistance was investigated. The chemical composition of the coatings was determined by Rutherford Backscattering (RBS) using 1.8 MeV α-particles and by Nuclear Reaction Analysis (NRA). Transmission Electron Microscopy (TEM) observations were also performed for the determination of the microstructural state of the samples. The characterisation shows, that for all the deposition temperatures the DIM-treatment promotes the crystallisation of the β-SiC phase. It was also found, that the corrosion resistance of the stainless steel is considerably improved when the coatings are deposited by DIM regardless of the deposition temperature. The possible mechanisms are discussed and it is suggested that the interface mixing along with the coating densification effect are responsible for the improvement of the corrosion resistance.

  3. Fabrication of spectrally selective solar surfaces by the thermal treatment of austenitic stainless steel aisi 321

    SciTech Connect

    Sharma, V.C.

    1981-05-19

    The spectrally selective solar surfaces have been produced after heating the austenitic stainless steel aisi 321 at a firing temperature of 843* K. And for firing times ranging from 10 to 20 minutes. The heating was carried out in a constant temperature oven under normal atmospheric conditions. The optimum values of solar absorptance alpha S and near-normal emittance epsilon S were found to be alpha S 0.92+0.02, epsilon S 0.22 + or - 0.02 respectively. The corresponding values for the unheated steel were 0.50 + or - 0.02 and 0.22 + or - 0.22. Severe temperature treatments like quenching in liquid nitrogen at 77* K. Produced no adverse visible affect on the quality of the selective surfaces. It shows that the thermal coatings so produced are very tough and durable. The value of solar absorptance and near-normal thermal emittance remained unchanged after quenching in liquod nitrogen. The thermal coatings so produced not only offer a technical advantage but also economic advantage over any of the existing techniques for the manufacture of stainless steel solar panels.

  4. Effect of lubricant extreme-pressure additives on surface fatigue life of AISI 9310 spur gears

    NASA Technical Reports Server (NTRS)

    Scibbe, H. W.; Townsend, D. P.; Aron, P. R.

    1984-01-01

    Surface fatigue tests were conducted with AISI 9310 spur gears using a formulated synthetic tetraester oil (conforming to MIL-L-23699 specifications) as the lubricant containing either sulfur or phosphorus as the EP additive. Four groups of gears were tested. One group of gears tested without an additive in the lubricant acted as the reference oil. In the other three groups either a 0.1 wt % sulfur or phosphorus additive was added to the tetraester oil to enhance gear surface fatigue life. Test conditions included a gear temperature of 334 K (160 F), a maximum Hertz stress of 1.71 GPa (248 000 psi), and a speed of 10,000 rpm. The gears tested with a 0.1 wt % phosphorus additive showed pitting fatigue life 2.6 times the life of gears tested with the reference tetraester based oil. Although fatigue lives of two groups of gears tested with the sulfur additive in the oil showed improvement over the control group gear life, the results, unlike those obtained with the phosphorus oil, were not considered to be statistically significant.

  5. Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.

    PubMed Central

    Nunn, J D; Katz, D R; Barker, S; Fraher, L J; Hewison, M; Hendy, G N; O'Riordan, J L

    1986-01-01

    We have examined the effects of 1,25(OH)2D3 on T-cell populations isolated by buoyant density and E rosetting from human tonsils. Cell proliferation was assessed by measuring the incorporation of 125iododeoxyuridine; interleukin-2 (IL-2) production was measured using an IL-2-dependent cell line, and the number of 1,25(OH)2D3 receptors was measured by whole-cell nuclear association assay. At a concentration of 10(-7) M, 1,25(OH)2D3 inhibited mitogen-induced T-cell proliferation in all E+ T-cell populations. This effect was more pronounced in the cells from the intermediate and high density layers and was reflected both in cell proliferative responses and in relative IL-2 synthesis. By adding the 1,25(OH)2D3 during the course of the mitogen assay, we demonstrated that activation of the T cell precedes the 1,25(OH)2D3-mediated inhibition. Cells that had been preincubated with mitogen in the presence of the 1,25(OH)2D3 were refractory to further stimulation by mitogens. Receptors for 1,25(OH)2D3 could not be detected in unstimulated T cells. However, activation led to the expression of high-affinity receptors for 1,25(OH)2D3. Co-incubation of the cells with mitogen and 1,25(OH)2D3 increased the number of receptors compared with mitogen alone. The effects provide further evidence for the hypothesis that 1,25(OH)2D3 is an important potential modulator of the immune system through its action on T cells. Taking our observations in conjunction with the known capacity of monocytes to hydroxylate the precursor metabolite (and thus synthesize the active form of cholecalciferol), the results support the suggestion that 1,25(OH)2D3 plays a role as a local mediator of mononuclear phagocyte-T cell interaction in human lymphomedullary tissues. PMID:3026959

  6. Dopamine D3 autoreceptor inhibition enhances cocaine potency at the dopamine transporter.

    PubMed

    McGinnis, Molly M; Siciliano, Cody A; Jones, Sara R

    2016-09-01

    Cocaine is a commonly abused central nervous system stimulant that enhances dopamine (DA) neurotransmission through its ability to block dopamine transporters (DATs). Recent evidence suggests there may be an interaction between DATs and D2/D3 autoreceptors that modulates cocaine's effects. The purpose of this study was to explore how D2/D3 autoreceptors modulate the ability of cocaine to inhibit DA uptake through DATs on pre-synaptic DA terminals. Using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from male and female C57BL/6J mice, we first sought to examine the effects of global autoreceptor blockade using the non-selective D2/D3 autoreceptor antagonist, raclopride. We found that the ability of cocaine to inhibit DA uptake was increased by raclopride and that this effect was consistent across sexes. Furthermore, using D2 (L-741,626) or D3 (SB-277011-A) autoreceptor selective antagonists, we discovered that blockade of D3, but not D2, autoreceptors was responsible for the increased cocaine potency. Alterations in cocaine potency were attributable to alterations in uptake inhibition, rather than cocaine effects on vesicular DA release, suggesting that these results may be a product of a functional D3/DAT interaction apart from the canonical inhibitory actions of D3 autoreceptors on DA release. In addition, application of D2 (sumanirole) and D3 (PD 128907) autoreceptor-specific agonists had inverse effects, whereby D2 autoreceptor activation decreased cocaine potency and D3 autoreceptor activation had no effect. Together, these data show that DA autoreceptors dynamically regulate cocaine potency at the DAT, which is important for understanding cocaine's rewarding and addictive properties. We propose a model whereby presynaptic dopamine autoreceptors dynamically modulate cocaine potency through two separate mechanisms. We demonstrate that D2 agonists decrease cocaine potency, whereas D3 antagonists increase cocaine potency

  7. A new approach to the learning of dental morphology, function, and esthetics: the "2D-3D-4D" concept.

    PubMed

    Magne, Pascal

    2015-01-01

    A concept is proposed for an approach to the learning of dental morphology and occlusion. Dental morphology, function, and esthetics should reflect a fundamental driving force, that is, the faithful emulation of the natural dentition's structural (functional, mechanical) and esthetic properties. The innovative part of the proposed approach is the emphasis on visual arts and the 2D-3D-4D aspect that starts with drawing (2D/3D) and continues with partial wax-up exercises that are followed by labial waxups and, finally, full wax-ups using innovative technical aids (electric waxers, prefabricated wax patterns, etc). Finally, the concept of layers (4D) and the histoanatomy of enamel/dentin and optical depth are taught through the realization of layering exercises (advanced acrylic mock-ups and composite resin restorations). All these techniques and materials are not only used to teach morphology and occlusion, but also constitute essential tools that will be of significant use for the student dentists and dental technologists in their future daily practice. The clinical significance of the presented methodology should allow not only students but also practicing dentists and dental technologists to help their youngest collaborators to develop a deep sense of morphology, function, and esthetics.

  8. Variability of pre-vitamin D3 effectiveness of UV appliances for skin tanning.

    PubMed

    Sayre, Robert M; Dowdy, John C; Shepherd, James G

    2010-07-01

    While there is limited documentation that certain indoor tanning lamps effectively produce vitamin D, the diversity of such devices has not been extensively surveyed. This study compares the spectral effectiveness of a variety of tanning units, and solar spectra, for ultraviolet (UV) photosynthesis of pre-vitamin D3 (preD3) and UV induced erythema. Well-established techniques exist for the calculation of spectral effectiveness for photobiological responses that have defined action spectra. Using spectroradiometric data from sunlamp measurements, and standard solar reference spectra, we computed effective irradiances using the CIE action spectrum for the production of preD3 in human skin and the ISO/CIE human erythema reference action spectrum. We found, as with sunlight at different times or latitude, the preD3 and erythemal effectiveness of sunlamps varied as a function of the UV-B proportion of the spectrum. Ratios of sunlamp preD3 to erythemal effectiveness ranged from approximately 0.5 to nearly 2.0, similar to ratios for sunlight. Optimal risk to benefit conditions for preD3 from solar UV exposure occurs under high solar altitude, low zenith angle, midday midsummer sunlight. Analogous optimal preD3 exposure conditions are provided by low to intermediate pressure sunlamps with greater UV-B spectral overlap with the preD3 action spectrum. Similar to low altitude or high latitude sunlight, high pressure tanning units, filtered for negligible UV-B emissions, have insignificant vitamin D benefit. We conclude that while vitamin D can be made by both UVB exposure from indoor tanning units and by exposure UVB from sunlight, the effect is also comparably variable. Unlike sunlight, indoor tanning offers privacy and environmental conditions for practical full body exposure, lowering the requisite exposure per skin surface area, and device timers limit the potential of overexposure. Guidance for optimal use of tanning sources for vitamin D benefit is needed.

  9. Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides

    PubMed Central

    Jiang, Jiang; Chen, Guojun; Shuler, Franklin D.; Wang, Chi-Hwa; Xie, Jingwei

    2015-01-01

    Purpose This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. Methods 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes’ lysis solution. Results AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around 10 times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. Conclusions plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity. PMID:25773720

  10. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    DOE PAGES

    Volkow, N. D.; Wang, G. -J.; Logan, J.; Alexoff, D.; Fowler, J. S.; Thanos, P. K.; Wong, C.; Casado, V.; Ferre, S.; Tomasi, D.

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release inmore » striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.« less

  11. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

    PubMed

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-01-01

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

  12. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

    PubMed

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

  13. Blood mineral, hormone, and osteocalcin responses of multiparous Jersey cows to an oral dose of 25-hydroxyvitamin D3 or vitamin D3 before parturition.

    PubMed

    Taylor, M S; Knowlton, K F; McGilliard, M L; Seymour, W M; Herbein, J H

    2008-06-01

    Twenty-seven multiparous Jersey cows were randomly assigned to receive an oral bolus containing corn starch (control, CON), corn starch plus 15 mg of 25-hydroxyvitamin D(3) (25-OH), or 15 mg of cholecalciferol (D(3)) at 6 d before expected parturition. Cows were maintained in individual box stalls from 20 d before expected parturition and fed a common diet. Jugular blood samples were collected at -14, -13, -5, -4, -3, -2, -1 d before expected calving, at calving, and at 1, 3, 5, 7, 9, 11, 13, 28, 56, and 84 d postcalving. After calving, cows were housed in 1 pen in a free-stall barn and consumed a common diet. Colorimetric assays were used to analyze Ca, P, and Mg concentrations in serum. Serum concentrations of osteocalcin (OC), an indicator of bone formation, serum 25-hydroxyvitamin D(3), and parathyroid hormone (PTH) were determined in samples obtained from d -5 through d 13. The 9 control multiparous cows and 5 untreated primiparous cows were used to evaluate the effect of parity on the variables that were measured. There was no effect of parity on Ca, PTH, or 25-OH concentration. Compared with second-lactation cows and older cows (>2 lactations), first-lactation cows had greater serum OC (22.3, 32.0, and 48.3 ng/mL, respectively), indicating that younger animals were forming more bone. Blood Ca, P, and Mg decreased near the time of calving and then increased over time. Serum 25-hydroxyvitamin D(3) was greater for cows dosed with 25-OH (119.0 ng/mL) compared with those dosed with D(3) (77.5 ng/mL) or CON (69.3 ng/mL). Cows dosed with 25-OH tended to have lower serum PTH concentration, but treatments did not affect serum Ca, P, or Mg. Serum OC was greater in second-lactation cows compared with cows entering their third or fourth lactation but OC was unaffected by treatment. Although results indicated a 60% increase in serum 25-hydroxyvitamin D(3) due to a single oral dose of 25-OH before calving, the amount administered in this study apparently was not

  14. Synthesis, Pharmacological Evaluation and Molecular Modeling Studies of Triazole Containing Dopamine D3 Receptor Ligands

    PubMed Central

    Peng, Xin; Wang, Qi; Mishra, Yogesh; Xu, Jinbin; Reichert, David E.; Malik, Maninder; Taylor, Michelle; Luedtke, Robert R.; Mach, Robert H.

    2015-01-01

    A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D2 and D3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D3 receptors and moderate selectivity for the dopamine D3 versus D2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D2 and D3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D3 receptors. PMID:25556097

  15. Dopamine D3 receptor gene locus: Association with schizophrenia, as well age of onset

    SciTech Connect

    Nimgsonkar, V.L.; Zhang, X.R.; Brar, J.S.

    1994-09-01

    Genetic factors are clearly involved in the etiology of schizophrenia, but their specific nature is unknown. If the genetic etiology is multifactorial or polygenic, the role of specific genes as susceptibility factors can be directly evaluated by examining allelic variation at these loci among cases in comparison with controls. Two studies have independently demonstrated an association of schizophrenia with homozygosity at the dopamine D3 receptor gene (D3RG) locus, using a biallelic polymorphism in the first exon of D3RG. These results are important because D3RG is a favored candidate gene. Three other studies have identified associations among sub-groups of patients, but the majority were negative. The present study involved patients with schizophrenia (DSM-III-R criteria) of Caucasian or African-American ethnicity (n=130). Two groups of controls, matched for ethnicity, were used: adults screened for schizophrenia (n=128) and unselected neonates (n=160). Multivariate analysis revealed an association between allele no. 1 homozygosity and schizophrenia in comparison with adult, but not neonatal controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.7, C.I. 1.8, 104.3). An association of the D3RG locus with age of onset (AOO) was also noted. The discrepancies in earlier studies may due to variations in control groups, differencies in mean AOO among different cohorts, or ethnic variations in susceptibility attributable to D3RG.

  16. Purification and properties of D(-)-3-hydroxybutyrate-dimer hydrolase from Zoogloea ramigera I-16-M.

    PubMed

    Tanaka, Y; Saito, T; Fukui, T; Tanio, T; Tomita, K

    1981-08-01

    D(-)-3-Hydroxybutyrate-dimer hydrolase from Zoogloea ramigera I-16-M was purified 7000-fold to electrophoretic homogeneity. The molecular weight of the purified enzyme was 28 000 as determined by Sephadex G-100 gel filtration, and 30 000 as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The isoelectric point was at pH 5.7. The pH optimum for the enzyme reaction was 8.0. The dimer hydrolase was stereospecific for D(-)-3-[D(-)-3-hydroxybutyryloxy]butyric acid (DD-dimer) but also hydrolyzed D(-)-3-[L(+)-3-hydroxybutyryloxy]butyric acid (DL-dimmer) and L(+)-3-[D(-)-3-hydroxybutyryloxy]butyric acid (LD-dimer) at reduced rates. However, the enzyme did not attack L(+)-3-[L(+)-3-hydroxybutyryloxy]butyric acid (LL-dimer) at all. In addition, the purified hydrolase hydrolyzed several oligomeric esters of D(-)-3-hydroxybutyric acid (DDD-dimer, DDDD-tetramer and DDDDD-pentamer) faster than DD-dimer. Time course experiments with these oligomers and analysis of hydrolytic products of DDD-tetramer methyl ester with the hydrolase indicated that the enzyme attached these substrates from the free hydroxyl terminus releasing monomer units one at a time.

  17. Occurrence of Vitamin 25(OH)D3 Insufficiency in Young Women with Metabolic Syndrome

    PubMed Central

    Rogal, Karolina; Mankowska, Aneta

    2011-01-01

    Vitamin D insufficiency is prevalent and may be associated with higher risk for metabolic syndrome. Low serum 25-hydroxyvitamin D3 is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in the pathogenesis of obesity and type 2 diabetes. This study examined the vitamin 25(OH)D3 concentration and its relationship with the metabolic syndrome among 52 young women aged 20-40 yrs with overweight and obese. As defined by revised International Diabetes Federation (IDF 2005) criteria, 27 of the 52 women had the metabolic syndrome (52%). Women with MS had significantly lower mean concentration of vitamin 25(OH)D3. Vitamin D insufficiency was more prevalent in women with MS, compared with those who did not fulfill the criteria for this syndrome (63% vs 37%, respectively) as well as among women with metabolic syndrome mild deficiency occurred much more frequently than in without MS (58% vs 26%, respectively). When serum concentrations of 25(OH)D3 were categorized in tertiles, there was a decreasing prevalence of MS in women with increasing concentrations of 25(OH)D3. The study findings suggest that insufficiency of vitamin 25(OH)D3 is more common in women with excessive body weight and metabolic syndrome than in women with excessive body weight without metabolic syndrome.

  18. EFFECTS OF SMOKING ON D2/D3 STRIATAL RECEPTOR AVAILABILITY IN ALCOHOLICS AND SOCIAL DRINKERS

    PubMed Central

    Albrecht, Daniel S.; Kareken, David A.; Yoder, Karmen K.

    2013-01-01

    Objective Studies have reported lower striatal D2/D3 receptor availability in both alcoholics and cigarette smokers relative to healthy controls. These substances are commonly co-abused, yet the relationship between comorbid alcohol/tobacco abuse and striatal D2/D3 receptor availability has not been examined. We sought to determine the degree to which dual abuse of alcohol and tobacco is associated with lower D2/D3 receptor availability. Method Eighty-one subjects (34 nontreatment-seeking alcoholic smokers [NTS-S], 21 social-drinking smokers [SD-S], and 26 social-drinking non-smokers [SD-NS]) received baseline [11C]raclopride scans. D2/D3 binding potential (BPND ≡ Bavail/KD) was estimated for ten anatomically defined striatal regions of interest (ROIs). Results Significant group effects were detected in bilateral pre-commissural dorsal putamen, bilateral pre-commissural dorsal caudate; and bilateral post-commissural dorsal putamen. Post-hoc testing revealed that, regardless of drinking status, smokers had lower D2/D3 receptor availability than non-smoking controls. Conclusions Chronic tobacco smokers have lower striatal D2/D3 receptor availability than non-smokers, independent of alcohol use. Additional studies are needed to identify the mechanisms by which chronic tobacco smoking is associated with striatal dopamine receptor availability. PMID:23649848

  19. Treatment of vitiligo vulgaris with the combination therapy of topical steroid and vitamin D3 compound.

    PubMed

    Konishi, Yoko; Yamanaka, Keiichi; Mizutani, Hitoshi

    2012-01-01

    We report here two cases of vitiligo vulgaris successfully treated with the combination therapy of topical steroid and vitamin D3 compound and currently maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae or telangiectasia on the exposed areas. The best-known mechanism of topical vitamin D3 analog is the enhancement of keratinocytes differentiation and anti-proliferative effects. Vitamin D3 analog is also reported to suppress T-cell mediated immunity, T-cell skin recruitment, and skin infiltration via down-regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3 compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes are one of the causes. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The topical combination therapy is a simple, effective and safe option for vitiligo vulgaris in sun-exposed areas.

  20. Evolution of chemical bonding and electron density rearrangements during D(3h) → D(3d) reaction in monolayered TiS2: a QTAIM and ELF study.

    PubMed

    Ryzhikov, Maxim R; Slepkov, Vladimir A; Kozlova, Svetlana G; Gabuda, Svyatoslav P

    2014-08-15

    Monolayered titanium disulfide TiS2, a prospective nanoelectronic material, was previously shown to be subject to an exothermic solid-state D3h -D3d reaction that proceeds via a newly discovered transition state. Here, we study the reaction in detail using topological methods of quantum chemistry (quantum theory of atoms in molecules and electron localization function analysis) and show how electron density and chemical bonding between the atoms change in the course of the reaction. The reaction is shown to undergo a series of topological catastrophes, associated with elementary chemical events such as break and formation of bonds (including the unexpected formation of S-S bonding between sulfur layers), and rearrangement of electron density of outer valence and core shells.

  1. Structural evidence for enhancement of sequential vitamin D3 hydroxylation activities by directed evolution of cytochrome P450 vitamin D3 hydroxylase.

    PubMed

    Yasutake, Yoshiaki; Fujii, Yoshikazu; Nishioka, Taiki; Cheon, Woo-Kwang; Arisawa, Akira; Tamura, Tomohiro

    2010-10-01

    Vitamin D(3) hydroxylase (Vdh) isolated from actinomycete Pseudonocardia autotrophica is a cytochrome P450 (CYP) responsible for the biocatalytic conversion of vitamin D(3) (VD(3)) to 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)VD(3)) by P. autotrophica. Although its biological function is unclear, Vdh is capable of catalyzing the two-step hydroxylation of VD(3), i.e. the conversion of VD(3) to 25-hydroxyvitamin D(3) (25(OH)VD(3)) and then of 25(OH)VD(3) to 1α,25(OH)(2)VD(3), a hormonal form of VD(3). Here we describe the crystal structures of wild-type Vdh (Vdh-WT) in the substrate-free form and of the highly active quadruple mutant (Vdh-K1) generated by directed evolution in the substrate-free, VD(3)-bound, and 25(OH)VD(3)-bound forms. Vdh-WT exhibits an open conformation with the distal heme pocket exposed to the solvent both in the presence and absence of a substrate, whereas Vdh-K1 exhibits a closed conformation in both the substrate-free and substrate-bound forms. The results suggest that the conformational equilibrium was largely shifted toward the closed conformation by four amino acid substitutions scattered throughout the molecule. The substrate-bound structure of Vdh-K1 accommodates both VD(3) and 25(OH)VD(3) but in an anti-parallel orientation. The occurrence of the two secosteroid binding modes accounts for the regioselective sequential VD(3) hydroxylation activities. Moreover, these structures determined before and after directed evolution, together with biochemical and spectroscopic data, provide insights into how directed evolution has worked for significant enhancement of both the VD(3) 25-hydroxylase and 25(OH)VD(3) 1α-hydroxylase activities.

  2. Active vitamin D3, 1,25-(OH)2D3, protects against macrovasculopathy in a rat model of type 2 diabetes mellitus.

    PubMed

    Ma, R; Deng, X L; Du, G L; Li, C; Xiao, S; Aibibai, Y; Zhu, J

    2016-01-01

    To investigate the protective effect of the active form of vitamin D3, 1,25-(OH)2D3, on macrovasculopathy in rats with type 2 diabetes mellitus (T2DM), 8-week-old male Sprague-Dawley rats were randomly divided into control group, T2DM group, and treatment group. The T2DM model was established after 6 weeks by administering an intraperitoneal injection of streptozotocin (30 mg/kg). 1,25-(OH)2D3 was administered by gavage to rats in the treatment group, and an equal volume of peanut oil was administered to rats in the T2DM group. Fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterols were measured in all rats. The morphology of the thoracic aorta was examined, and the expression of tumor necrosis factor alpha (TNF-α), endothelin (ET), endothelial nitric oxide synthase (eNOS), CD54, and CD106 in the thoracic aorta was determined by immunohistochemistry. The expression of FPG, TG, TC, and LDL-C in rats from the T2DM and treatment groups was significantly elevated compared with rats from the control group (P < 0.05). Compared with that in control group, the expression of TNF-α, ET, eNOS, and CD106 was significantly upregulated in the T2DM group and the treatment group, while the expression of CD54 was increased only in the T2DM group (P < 0.05). Moreover, the levels of TNF-α, CD54, and CD106 in rats from the treatment group were lower than those in the T2DM group (P < 0.05). These data suggest that 1,25-(OH)2D3 may protect the macrovessels from injury in T2DM rats by inhibiting the expression of TNF-α, CD54, and CD106. PMID:27323139

  3. Effects of pharmacological doses of Vitamin D3 on mineral balance and profiles of plasma Vitamin D3 metabolites in horses.

    PubMed

    Harmeyer, Johein; Schlumbohm, Christina

    2004-05-01

    Metabolism and functions of Vitamin D in horses differ from those in humans, pigs and rats. In horses, calcidiol and calcitriol concentrations in blood plasma are remarkably low (<10 nmol L(-1); 20-40 pmol L(-1), respectively). When a toxic amount of Vitamin D(3) is administered, the responsiveness of calcium and calcitriol concentrations in blood plasma is much reduced compared to the other domestic animal species but inorganic phosphate (Pi) response is much more marked, leading to an increase of the Ca x Pi product. Also, soft tissue calcifications have been observed to develop in horses during Vitamin D(3) intoxication. It was suggested that the elevation of the Ca x Pi product may play a causative role in this calcification process. To test this assumption, two horses were treated with 40,000 IU kg(-1) of Vitamin D(3) whilst dietary uptake of Ca and Pi was restricted to prevent or to diminish the increase of the Ca x Pi product. Distribution, number and severity of calcification centres were considerably less in these horses than in the control animals of a previous experiment which had received the same amount of Vitamin D(3) but where Ca and Pi intake was not restricted. It appears from these findings that in horses, the increase of the Ca x Pi product in blood plasma during a Vitamin D intoxication contributes to the soft tissue calcifications. It is further concluded that in the event of a Vitamin D intoxication, it is recommended to restrict the Ca and Pi uptake immediately. The authors believe that this may help to prevent or at least diminish soft tissue calcifications which are often fatal to the horse due to nephrocalcinosis.

  4. Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy.

    PubMed

    Morales, Eva; Gascon, Mireia; Martinez, David; Casas, Maribel; Ballester, Ferran; Rodríguez-Bernal, Clara L; Ibarluzea, Jesus; Marina, Loreto Santa; Espada, Mercedes; Goñi, Fernando; Vizcaino, Esther; Grimalt, Joan O; Sunyer, Jordi

    2013-07-01

    Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3±1.5weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient=-1.59, 95% CI -3.27, 0.08, p trend=0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [-0.50 (-1.94, 0.94)], quartile Q3 vs. Q1 [-1.56 (-3.11, -0.02)] and quartile Q4 vs. Q1 [-1.21 (-2.80, 0.38)], p trend=0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p'-DDE, p,p'-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.

  5. A protective role of dietary vitamin D3 in rat colon carcinogenesis.

    PubMed

    Mokady, E; Schwartz, B; Shany, S; Lamprecht, S A

    2000-01-01

    The aim of the present work was to gain insight into a putative anticancer effect of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis. Male rats were assigned to three different dietary groups. The dietary regimens were based on a standard murine-defined diet (AIN-76A) or a stress diet containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio, and either low or high vitamin D3 content. Colorectal cancer was induced by administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in DMH-treated rats and in respective weight- and age-matched dietary control groups. Colonic epithelial proliferation was assessed by determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd) incorporation into crypt cell DNA, and the mean labeling index along the colonic crypt continuum. Maintenance of rats on the stress diet either unmodified or supplemented with vitamin D3 in the absence of carcinogen treatment provoked a time-dependent rise in colonic TK activity and hyperproliferation of colonic epithelium. DMH treatment of rats maintained on the standard diet caused a marked increase in the proliferative indexes of colonic epithelium and in expansion of the crypt proliferative compartment. TK activity and the crypt mitotic zone were significantly augmented in the animal group fed the stress diet. Supplementary vitamin D3 abrogated the stress diet-enhanced colonic responses to the carcinogenic insult. Colon tumor multiplicity was fourfold higher in animals fed the stress diet than in animals maintained on a standard diet. The marked rise in colonic tumor multiplicity and adenocarcinoma incidence in rats fed the stress diet was obliterated by supplemental dietary vitamin D3. Cumulatively, the present results indicate that dietary vitamin D3 impedes the neoplastic process in murine large intestine and strengthen the

  6. Regioselective synthesis of isotopically labeled Δ9-tetrahydrocannabinolic acid A (THCA-A-D3) by reaction of Δ9-tetrahydrocannabinol-D3 with magnesium methyl carbonate.

    PubMed

    Roth, Nadine; Wohlfarth, Ariane; Müller, Michael; Auwärter, Volker

    2012-10-10

    For the reliable quantification of Δ9-tetrahydrocannabinolic acid A (THCA-A), the biogenetic precursor of Δ9-tetrahydrocannabinol (THC), in biological matrices by LC-MS/MS and GC-MS(/MS), an isotopically labeled internal standard was synthesized starting from Δ9-tetrahydrocannabinol-D(3) (THC-D(3)). Synthesis strategy was based on a method reported by Mechoulam et al. in 1969 using magnesium methyl carbonate (MMC) as carboxylation reagent for the synthesis of cannabinoid acids. Preliminary experiments with THC to optimize yield of the product (THCA-A) resulted in the synthesis of the positional isomer tetrahydrocannabinolic acid B (THCA-B) as a byproduct. Using the optimized conditions for the desired isomer, THCA-A-D(3) was prepared and isolated with a yield of approx. 10% after two synthesis cycles. Isotope purity was estimated to be >99% by relative abundance of the molecular ions. The synthesized compound proved to be suitable as an internal standard for quantification of THCA-A in serum and hair samples of cannabis consumers.

  7. Effects of Ti-C:H coating and plasma nitriding treatment on tribological, electrochemical, and biocompatibility properties of AISI 316L.

    PubMed

    Kao, W H; Su, Y L; Horng, J H; Zhang, K X

    2016-08-01

    Ti-C:H coatings were deposited on original, nitrided, and polished-nitrided AISI 316L stainless steel substrates using a closed field unbalanced magnetron sputtering system. Sliding friction wear tests were performed in 0.89 wt.% NaCl solution under a load of 30 N against AISI 316L stainless steel, Si3N4, and Ti6Al4V balls, respectively. The electrochemical properties of the various specimens were investigated by means of corrosion tests performed in 0.89 wt.% NaCl solution at room temperature. Finally, the biocompatibility properties of the specimens were investigated by performing cell culturing experiments using purified mouse leukemic monocyte macrophage cells (Raw264.7). In general, the results showed that plasma nitriding followed by Ti-C:H coating deposition provides an effective means of improving the wear resistance, anti-corrosion properties, and biocompatibility performance of AISI 316L stainless steel.

  8. Vitamin D2 is much less effective than vitamin D3 in humans.

    PubMed

    Armas, Laura A G; Hollis, Bruce W; Heaney, Robert P

    2004-11-01

    Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

  9. 1,25(OH)2D3 dependent overt hyperactivity phenotype in klotho-hypomorphic mice

    PubMed Central

    Leibrock, Christina B.; Voelkl, Jakob; Kuro-o, Makoto; Lang, Florian; Lang, Undine E

    2016-01-01

    Klotho, a protein mainly expressed in kidney and cerebral choroid plexus, is a powerful regulator of 1,25(OH)2D3 formation. Klotho-deficient mice (kl/kl) suffer from excessive plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations, leading to severe soft tissue calcification and accelerated aging. NH4Cl treatment prevents tissue calcification and premature ageing without affecting 1,25(OH)2D3-formation. The present study explored the impact of excessive 1,25(OH)2D3 formation in NH4Cl-treated kl/kl-mice on behavior. To this end kl/kl-mice and wild-type mice were treated with NH4Cl and either control diet or vitamin D deficient diet (LVD). As a result, plasma 1,25(OH)2D3-, Ca2+- and phosphate-concentrations were significantly higher in untreated and in NH4Cl-treated kl/kl-mice than in wild-type mice, a difference abrogated by LVD. In each, open field, dark-light box, and O-maze NH4Cl-treated kl/kl-mice showed significantly higher exploratory behavior than untreated wild-type mice, a difference abrogated by LVD. The time of floating in the forced swimming test was significantly shorter in NH4Cl treated kl/kl-mice compared to untreated wild-type mice and to kl/kl-mice on LVD. In wild-type animals, NH4Cl treatment did not significantly alter 1,25(OH)2D3, calcium and phosphate concentrations or exploratory behavior. In conclusion, the excessive 1,25(OH)2D3 formation in klotho-hypomorphic mice has a profound effect on murine behavior. PMID:27109615

  10. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms

    SciTech Connect

    Scheven, B.A.; Hamilton, N.J. )

    1990-01-01

    The effects of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on osteoclast formation were examined in intact fetal long bones of different ages/developmental stages maintained in organ culture using a chemically defined medium with or without the presence of serum. Besides stimulating bone resorption, RA and 1,25-(OH)2D3 increased the number of osteoclasts in 19-day-old fetal rat tibiae. Likewise, these bone-resorbing agents induced and stimulated osteoclast formation in 19- and 18-day-old metatarsal bones which were osteoclast-free at the beginning of the culture. The response to 1,25-(OH)2D3 was greatly enhanced by 10% fetal bovine serum (FBS) irrespective of the developmental stage of the long bone. The response to RA was not. Light microscopic autoradiography after labeling of the cultures with tritiated thymidine showed that both RA and 1,25-(OH)2D3 induced osteoclast differentiation from proliferating and postmitotic precursors. However, neither agent was able to stimulate proliferation of osteoclast progenitor cells in the older bones (19 days). Studies on the formation of osteoclast-like (tartrate-resistant acid phosphatase positive) cells in bone marrow cultures indicated that FBS was a potent inducer of osteoclast-like cell formation. In the presence of FBS, 1,25-(OH)2D3 significantly stimulated this response, but RA did not. The results demonstrate that although both RA and 1,25-(OH)2D3 stimulate osteoclast formation from proliferating and postmitotic precursors in long bones in vitro, they do so by different mechanisms.

  11. Analyses of oxide films grown on AISI 304L stainless steel and Incoloy 800HT exposed to supercritical water environment

    NASA Astrophysics Data System (ADS)

    Fulger, Manuela; Mihalache, Maria; Ohai, Dumitru; Fulger, Stefan; Valeca, Serban Constantin

    2011-08-01

    Supercritical water (SCW) is being considered as a cooling medium for the next generation nuclear reactors because it provides high thermal efficiency and plant simplification. However, materials corrosion has been identified as a critical problem due to the oxidative nature of supercritical water. Thus, for safety using of these nuclear reactor systems a systematic study of candidate materials corrosion is needed. As in other high temperature environments, corrosion in SCW occurs by the growth of an oxide layer on the materials surface. The current work aims to evaluate oxidation behavior of AISI 304L SS and Incoloy 800HT in water at supercritical temperatures in the range 723-873 K under a pressure of 25 MPa for up to 1680 h. After exposure to deaerated supercritical water, the samples were investigated using gravimetry, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and electrochemical impedance spectroscopy (EIS). Oxide films grown on these materials have a layered structure with an outer layer consisting of a mixture of iron oxide/iron-nickel spinel oxides and an inner layer consisting of chromium oxide in the case of Incoloy 800HT and nickel-chromium spinel oxide in the case of AISI 304L SS. The mass gains for Incoloy 800HT at all temperatures were small, while comparatively with AISI 304L SS which exhibited higher oxidation rates. In the same time the results obtained by EIS indicate the best corrosion resistance of oxides grown on Incoloy 800HT surface.

  12. The action spectrum for vitamin D3: initial skin reaction and prolonged exposure.

    PubMed

    van Dijk, Arjan; den Outer, Peter; van Kranen, Henk; Slaper, Harry

    2016-07-01

    Vitamin D3 photosynthesis in the skin is formulated as a set of reaction equations, including side-reactions to lumisterol, tachysterol and toxisterols, and the accompanying reverse reactions, isomerisation of previtamin D3 to vitamin D3 and photodegradation of vitamin D3. The solution of this set is given for the stationary irradiance spectrum. The effective action spectrum for the instantaneous vitamin D3 production changes shape as a function of exposure, and therefore, no single action spectrum can be used. We assessed the action spectrum for unexposed skin and for skin that has been exposed to 7.5 Standard Erythemal Doses (SED). We constructed two new estimates: (1) the RIVM action spectrum, based on absorption spectra, quantum yields and skin transmission spectra, and (2) the modified QUT action spectrum, which is adjusted for self-absorption and skin transmission. For previously unexposed skin, the modified QUT action spectrum gives a qualitatively similar, but larger estimate than the RIVM action spectrum. We have not been able to solve the lack of quantitative agreement between the vitamin D production estimates from the three action spectrum estimates (RIVM, modified QUT and CIE). All new action spectra have stronger emphasis on the short wavelengths than the CIE action spectrum. We showed that, for wavelengths larger than 300 nm, the bandwidth that was used in the experiment that formed the basis of the CIE action spectrum, gives a red-shift of about 1 nm. Generally, with the formation of previtamin D3, the return reaction to provitamin D3 limits the production of vitamin D3. After some exposure, the new action spectrum has negative values for the longer wavelengths in the UVB. For the RIVM action spectrum, this happens after 7.5 SED, for the modified QUT action spectrum already after 1.25 SED, and after 7.5 SED the net production rate is largely cancelled. Thus prolonged exposure of previously unexposed skin saturates vitamin D3 formation. For maximum

  13. Impact of Vitamin D3 Dietary Supplement Matrix on Clinical Response

    PubMed Central

    Finnell, John S.; Bhandiwad, Anup; Oberg, Erica; Suhaila, Lena; Bradley, Ryan

    2014-01-01

    Context: As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. Objective: To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. Setting and Design: A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. Results: In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. Conclusions: Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements. PMID:24684456

  14. Syntheses of 24R,25-dihydroxy-(6,19,19-3H)vitamin D3 and 24R,25-dihydroxy-(6,19,19-2H)vitamin D3

    SciTech Connect

    Yamada, S.; Shimizu, M.; Fukushima, K.; Niimura, K.; Maeda, Y. )

    1989-08-01

    24R,25-Dihydroxy-(6,19,19-3H)vitamin D3 with a specific activity of 54 Ci/mmol and 24R,25-dihydroxy-(6,19,19-2H)vitamin D3 with 2.6 deuterium atoms/mol were synthesized in four steps starting from 24R,25-Dihydroxyvitamin D3 via its sulfur dioxide adduct.

  15. Evaluation of a photolabile derivative of 1,25-dihydroxyvitamin D3 as a photoaffinity probe for 1,25-dihydroxyvitamin-D3 receptor in chick intestinal cytosol

    SciTech Connect

    Ray, R.; Rose, S.; Holick, S.A.; Holick, M.F.

    1985-10-15

    The authors evaluated the viability of 1 alpha, 25-dihydroxyvitamin D3-3 beta-(N-(4-azido-2-nitrophenyl)glycinate) (1,25-(OH)2-D3-ANG), an analog of 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH)2-D3) as a photoaffinity probe for 1,25-(OH)2-D3 receptor in chick intestinal cytosol. A competitive-binding assay revealed that chick intestinal cytosolic 1,25-(OH)2- D3 receptor bound to 1,25-(OH)2-D3-ANG approximately 20-times less effectively than it did to 1,25-(OH)2-D3. Irradiation of 1,25-(OH)2-D3- ANG in the presence of chick intestinal cytosolic preparation significantly diminished subsequent binding to /sup 3/H-1,25-(OH)2-D3, suggesting that the photoaffinity analog was covalently attached to the receptor. Therefore the nitroarylazide derivative of 1,25-(OH)2-D3 may be a valuable photoaffinity probe for the characterization of the 1,25-(OH)2-D3 receptor.

  16. Machining Performance and Surface Integrity of AISI D2 Die Steel Machined Using Electrical Discharge Surface Grinding Process

    NASA Astrophysics Data System (ADS)

    Choudhary, Rajesh; Kumar, Harmesh; Singh, Shankar

    2013-12-01

    The aim of this study is to establish optimum machining conditions for EDSG of AISI D2 die steel through an experimental investigation using Taguchi Methodology. To achieve combined grinding and electrical discharge machining, metal matrix composite electrodes (Cu-SiCp) were processed through powder metallurgy route. A rotary spindle attachment was developed to perform the EDSG experimental runs on EDM machine. Relationships were developed between various input parameters such as peak current, speed, pulse-on time, pulse-off time, abrasive particle size, and abrasive particle concentration, and output characteristics such as material removal rate and surface roughness. The optimized parameters were further validated by conducting confirmation experiments.

  17. Mechanical behavior of AISI 304SS determined by miniature test methods after neutron irradiation to 28 dpa

    SciTech Connect

    Ellen M. Rabenberg; Brian J. Jaques; Bulent H. Sencer; Frank A. Garner; Paula D. Freyer; Taira Okita; Darryl P. Butt

    2014-05-01

    The mechanical properties of AISI 304 stainless steel irradiated for over a decade in the Experimental Breeder Reactor (EBR-II) were measured using miniature mechanical testing methods. The shear punch method was used to evaluate the shear strengths of the neutron-irradiated steel and a correlation factor was empirically determined to predict its tensile strength. The strength of the stainless steel slightly decreased with increasing irradiation temperature, and significantly increased with increasing dose until it saturated above approximately 5 dpa. Ferromagnetic measurements were used to observe and deduce the effects of the stress-induced austenite to martensite transformation as a result of shear punch testing.

  18. Formation of amorphous Ti alloy layers by excimer laser mixing of Ti on AISI 304 stainless-steel surfaces

    NASA Astrophysics Data System (ADS)

    Jervis, T. R.; Nastasi, M.; Zocco, T. G.; Martin, J. A.

    1988-07-01

    We used excimer laser radiation at 308 nm to mix thin layers of Ti into AISI 304 stainless steel. Different numbers of shots at a fluence about twice the threshold for melting varied the amount of mixing. When mixing is sufficiently complete, an amorphous surface layer is formed with Ti substituting for Fe on a one-to-one basis in the alloy. The laser mixing process, unlike Ti ion implantation, does not result in high incorporation of C in the processed layer, although some C from surface and interface contamination is incorporated into the surface layer.

  19. Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa

    PubMed Central

    Tasegian, Anna; Curcio, Francesco; Dalla Ragione, Laura; Rossetti, Francesca; Cataldi, Samuela; Codini, Michela; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Albi, Elisabetta

    2016-01-01

    Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders. PMID:26903713

  20. Dopamine D3 Receptor Alterations in Cocaine-Dependent Humans Imaged with [11C](+)PHNO

    PubMed Central

    Matuskey, David; Gallezot, Jean-Dominique; Pittman, Brian; Williams, Wendol; Wanyiri, Jane; Gaiser, Edward; Lee, Dianne E.; Hannestad, Jonas; Lim, Keunpoong; Zheng, Minq-Qiang; Lin, Shu-fei; Labaree, David; Potenza, Marc N.; Carson, Richard E.; Malison, Robert T.; Ding, Yu-Shin

    2014-01-01

    Background Evidence from animal models and postmortem human studies points to the importance of the dopamine D3 receptor (D3R) in cocaine dependence (CD). The objective of this pilot study was to use the D3R-preferring radioligand [11C](+)PHNO to compare receptor availability in groups with and without CD. Methods Ten medically healthy, non-treatment seeking CD subjects (mean age 41±8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41±6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region. Results BPND in CD subjects was higher in D3R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%, P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r = + 0.83; p =0.008) and pallidum (r = + 0.67; p = 0.03) correlated with years of cocaine use. Conclusions Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D3R as a medication development target in CD. PMID:24717909

  1. Constrained superfields from an anti-D3-brane in KKLT

    NASA Astrophysics Data System (ADS)

    Vercnocke, Bert; Wrase, Timm

    2016-08-01

    The KKLT construction of dS vacua [1] relies on an uplift term that arises from an anti-D3-brane. It was argued by Kachru, Pearson and Verlinde [2] that this anti-D3-brane is an excited state in a supersymmetric theory since it can decay to a supersymmetric ground state. Hence the anti-D3-brane breaks supersymmetry spontaneously and one should be able to package all the world-volume fields on the anti-D3-brane into a four dimensional {N} = 1 supersymmetric action. Here we extend previous results and identify the constrained superfields that correspond to all the degrees of freedom on the anti-D3-brane. In particular, we show explicitly that the four 4D worldvolume spinors give rise to constrained chiral multiplets S and Y i , i = 1 , 2 , 3 that satisfy S 2 = SY i = 0. We also conjecture (and provide evidence in a forthcoming publication) that the vector field A μ and the three scalars ϕ i give rise to a field strength multiplet W α and three chiral multiplets H i that satisfy the constraints S{W}_{α }={overline{D}}_{overset{\\cdot }{α }}(S{overline{H}}^i)=0 . This is the first time that such constrained multiplets appear in string theory constructions.

  2. Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa.

    PubMed

    Tasegian, Anna; Curcio, Francesco; Dalla Ragione, Laura; Rossetti, Francesca; Cataldi, Samuela; Codini, Michela; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Albi, Elisabetta

    2016-01-01

    Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders. PMID:26903713

  3. Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation.

    PubMed

    Arnardottir, Hildur H; Dalli, Jesmond; Norling, Lucy V; Colas, Romain A; Perretti, Mauro; Serhan, Charles N

    2016-09-15

    Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rvs) are a new family from the endogenous specialized proresolving mediators (SPMs) that actively stimulate resolution of inflammation. In this study, using lipid mediator metabololipidomics with murine joints we found a temporal regulation of endogenous SPMs during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series Rvs, for example, RvD1, RvD2, RvD3, and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared with self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis patients compared with healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores, and edema. Taken together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. PMID:27534559

  4. Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa.

    PubMed

    Tasegian, Anna; Curcio, Francesco; Dalla Ragione, Laura; Rossetti, Francesca; Cataldi, Samuela; Codini, Michela; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Albi, Elisabetta

    2016-01-01

    Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders.

  5. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth.

    PubMed

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-03-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg(-1) body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties. PMID:27025264

  6. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth.

    PubMed

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-03-30

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg(-1) body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties.

  7. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth

    PubMed Central

    Abbassy, Mona A; Watari, Ippei; Bakry, Ahmed S; Ono, Takashi; Hassan, Ali H

    2016-01-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C+D group (normal rats injected with calcitonin and vitamin D3), the diabetic C+D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mg·kg−1 body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C+D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties. PMID:27025264

  8. Investigation of AISI 441 Ferritic Stainless Steel and Development of Spinel Coatings for SOFC Interconnect Applications

    SciTech Connect

    Yang, Zhenguo; Xia, Guanguang; Wang, Chong M.; Nie, Zimin; Templeton, Joshua D.; Singh, Prabhakar; Stevenson, Jeffry W.

    2008-05-30

    As part of an effort to develop cost-effective ferritic stainless steel-based interconnects for solid oxide fuel cell (SOFC) stacks, both bare and spinel coated AISI 441 were studied in terms of metallurgical characteristics, oxidation behavior, and electrical performance. The conventional melt metallurgy used for the bulk alloy fabrication leads to significant processing cost reduction and the alloy chemistry with the presence of minor alloying additions of Nb and Ti facilitate the strengthening by precipitation and formation of Laves phase both inside grains and along grain boundaries during exposure in the intermediate SOFC operating temperature range. The Laves phase formed along the grain boundaries also ties up Si and prevents the formation of an insulating silica layer at the scale/metal interface during prolonged exposure. The substantial increase in ASR during long term oxidation due to oxide scale growth suggested the need for a conductive protection layer, which could also minimize Cr evaporation. In particular, Mn1.5Co1.5O4 based surface coatings on planar coupons drastically improved the electrical performance of the 441, yielding stable ASR values at 800ºC for over 5,000 hours. Ce-modified spinel coatings retained the advantages of the unmodified spinel coatings, and also appeared to alter the scale growth behavior beneath the coating, leading to a more adherent scale. The spinel protection layers appeared also to improve the surface stability of 441 against the anomalous oxidation that has been observed for ferritic stainless steels exposed to dual atmosphere conditions similar to SOFC interconnect environments. Hence, it is anticipated that, compared to unmodified spinel coatings, the Ce-modified coatings may lead to superior structural stability and electrical performance.

  9. Morphology, topography, and hardness of diffusion bonded sialon to AISI 420 at different bonding time

    NASA Astrophysics Data System (ADS)

    Ibrahim, Nor Nurulhuda Md.; Hussain, Patthi; Awang, Mokhtar

    2015-07-01

    Sialon and AISI 420 martensitic stainless steel were diffusion bonded in order to study the effect of bonding time on reaction layer's growth. Joining of these materials was conducted at 1200°C under a uniaxial pressure of 17 MPa in a vacuum ranging from 5.0 to 8.0×10-6 Torr with bonding time varied for 0.5, 2, and 3 h. Thicker reaction layer was formed in longer bonded sample since the elements from sialon could diffuse further into the steel. Sialon retained its microstructure but it was affected at the initial contact with the steel to form the new interface layer. Diffusion layer grew toward the steel and it was segregated with the parent steel as a result of the difference in properties between these regions. The segregation formed a stream-like structure and its depth decreased when the bonding time was increased. The microstructure of the steel transformed into large grain size with precipitates. Prolonging the bonding time produced more precipitates in the steel and reduced the steel thickness as well. Interdiffusions of elements occurred between the joined materials and the concentrations were decreasing toward the steel and vice versa. Silicon easily diffused into the steel because it possessed lower ionization potential compared to nitrogen. Formation of silicide and other compounds such as carbides were detected in the interface layer and steel grain boundary, respectively. These compounds were harmful due to silicide brittleness and precipitation of carbides in the grain boundary might cause intergranular corrosion cracking. Sialon retained its hardness but it dropped very low at the interface layer. The absence of crack at the joint in all samples could be contributed from the ductility characteristic of the reaction layer which compensated the residual stress that was formed upon the cooling process.

  10. Fatigue life improvements of the AISI 304 stainless steel ground surfaces by wire brushing

    NASA Astrophysics Data System (ADS)

    Ben Fredj, Nabil; Ben Nasr, Mohamed; Ben Rhouma, Amir; Sidhom, Habib; Braham, Chedly

    2004-10-01

    The surface and subsurface integrity of metallic ground components is usually characterized by an induced tensile residual stress, which has a detrimental effect on the fatigue life of these components. In particular, it tends to accelerate the initiation and growth of the fatigue cracks. In this investigation, to deliberately generate compressive residual stresses into the ground surfaces of the AISI 304 stainless steel (SS), wire brushing was applied. It was found that under the experimental conditions selected in this investigation, while the surface roughness was slightly improved by the brushing process, the surface residual stress shifted from a tensile stress (σ‖=+450 MPa) to a compressive stress (σ‖=-435 MPa). On the other hand, the work-hardened deformation layer was almost two times deeper after wire brushing. Concerning the fatigue life, an improvement of 26% in terms of endurance limit at 2×106 cycles was realized. Scanning electron microscope (SEM) observations of the fatigue fracture location and size were carried out to explain the fatigue life improvement. It was found that the enhancement of the fatigue strength could be correlated with the distribution and location of the fatigue fracture nucleation sites. Concerning the ground surfaces, it was seen that the fatigue cracks initiated at the bottom of the grinding grooves and were particularly long (150-200 µm). However, the fatigue cracks at the brushed surfaces were shorter (20-40 µm) and appeared to initiate sideways to the plowed material caused by the wire brushing. The results of the wire-brushed surface characterization have shown that significant advantages can be realized regarding surface integrity by the application of this low-cost process compared to shot peening.

  11. In vivo imaging of cerebral dopamine D3 receptors in alcoholism.

    PubMed

    Erritzoe, David; Tziortzi, Andri; Bargiela, David; Colasanti, Alessandro; Searle, Graham E; Gunn, Roger N; Beaver, John D; Waldman, Adam; Nutt, David J; Bani, Massimo; Merlo-Pich, Emilio; Rabiner, Eugenii A; Lingford-Hughes, Anne

    2014-06-01

    Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [(11)C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [(11)C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [(11)C]PHNO binding between the groups at baseline. However, baseline [(11)C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5 ± 4 vs 13.7 ± 2.9, p = 0.040), a region in which the [(11)C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [(11)C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic

  12. An evaluation of the effects of added vitamin D3 in maternal diets on sow and pig performance.

    PubMed

    Flohr, J R; Tokach, M D; Dritz, S S; DeRouchey, J M; Goodband, R D; Nelssen, J L; Bergstrom, J R

    2014-02-01

    A total of 84 sows (PIC 1050) and their litters were used to determine the effects of supplementing maternal diet with vitamin D3 on sow and pig performance, serum 25-hydroxyvitamin D3 (25(OH)D3), milk vitamin D3, neonatal bone mineralization, and neonatal tissue vitamin D3. After breeding, sows were randomly assigned to 1 of 3 dietary vitamin D3 treatments (1,500, 3,000, or 6,000 IU/kg of complete diets). Sows were bled on d 0 and 100 of gestation and at farrowing and weaning (d 21). Pig BW was recorded at birth and weaning, and serum was collected from 2 pigs/litter at birth, on d 10 and at weaning. A total of 54 pigs (18/treatment) were euthanized at birth and necropsied to sample bones and tissues. Sow and suckling pig performance and neonatal bone ash and bone density did not differ among maternal vitamin D3 treatments; however, sow 25(OH)D3 and milk vitamin D3 increased (linear, P < 0.01) with increasing maternal vitamin D3 supplementation. Piglet serum 25(OH)D3 increased (quadratic, P < 0.03) with increased maternal vitamin D3. Neonatal kidney vitamin D3 tended (quadratic, P = 0.08) to decrease with increasing maternal vitamin D3, but liver vitamin D3 tended (linear, P = 0.09) to increase with increasing maternal vitamin D3. At weaning, a subsample of 180 pigs (PIC 327 × 1050) were used in a 3 × 2 split plot design for 35 d to determine the effects of maternal vitamin D3 and 2 levels of dietary vitamin D3 (1,800 or 18,000 IU/kg) from d 0 to 10 postweaning on nursery growth and serum 25(OH)D3. Overall (d 0 to 35), nursery ADG and G:F were not affected by either concentration of vitamin D3, but ADFI tended (quadratic, P < 0.06) to decrease with increasing maternal vitamin D3 as pigs from sows fed 3,000 IU had lower ADFI compared with pigs from sows fed 1,500 or 6,000 IU/kg. Nursery pig serum 25(OH)D3 increased with increasing maternal vitamin D3 (weaning) on d 0 (linear, P < 0.01), and maternal × diet interactions (P < 0.01) were observed on d 10 and 21

  13. Therapeutic Targeting of the Cyclin D3:CDK4/6 Complex in T Cell Leukemia

    PubMed Central

    Sawai, Catherine; Freund, Jacquelyn; Oh, Philmo; Ndiaye-Lobry, Delphine; Bretz, Jamieson C.; Strikoudis, Alexandros; Genesca, Lali; Trimarchi, Thomas; Kelliher, Michelle A.; Clark, Marcus; Soulier, Jean; Chen-Kiang, Selina; Aifantis, Iannis

    2012-01-01

    SUMMARY D-type cyclins form complexes with cyclin dependent kinases (CDK4/6), and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27Kip1 and Rb is sufficient to rescue the development of Ccnd3−/− thymocytes. Furthermore, we show that a small molecule targeting the kinase function of cyclin D3:CDK4/6 inhibits both cell cycle entry in human T cell acute lymphoblastic leukemia (T-ALL) and disease progression in animal models of T-ALL. These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor. PMID:23079656

  14. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  15. SpreaD3: Interactive Visualization of Spatiotemporal History and Trait Evolutionary Processes.

    PubMed

    Bielejec, Filip; Baele, Guy; Vrancken, Bram; Suchard, Marc A; Rambaut, Andrew; Lemey, Philippe

    2016-08-01

    Model-based phylogenetic reconstructions increasingly consider spatial or phenotypic traits in conjunction with sequence data to study evolutionary processes. Alongside parameter estimation, visualization of ancestral reconstructions represents an integral part of these analyses. Here, we present a complete overhaul of the spatial phylogenetic reconstruction of evolutionary dynamics software, now called SpreaD3 to emphasize the use of data-driven documents, as an analysis and visualization package that primarily complements Bayesian inference in BEAST (http://beast.bio.ed.ac.uk, last accessed 9 May 2016). The integration of JavaScript D3 libraries (www.d3.org, last accessed 9 May 2016) offers novel interactive web-based visualization capacities that are not restricted to spatial traits and extend to any discrete or continuously valued trait for any organism of interest. PMID:27189542

  16. SpreaD3: Interactive Visualization of Spatiotemporal History and Trait Evolutionary Processes.

    PubMed

    Bielejec, Filip; Baele, Guy; Vrancken, Bram; Suchard, Marc A; Rambaut, Andrew; Lemey, Philippe

    2016-08-01

    Model-based phylogenetic reconstructions increasingly consider spatial or phenotypic traits in conjunction with sequence data to study evolutionary processes. Alongside parameter estimation, visualization of ancestral reconstructions represents an integral part of these analyses. Here, we present a complete overhaul of the spatial phylogenetic reconstruction of evolutionary dynamics software, now called SpreaD3 to emphasize the use of data-driven documents, as an analysis and visualization package that primarily complements Bayesian inference in BEAST (http://beast.bio.ed.ac.uk, last accessed 9 May 2016). The integration of JavaScript D3 libraries (www.d3.org, last accessed 9 May 2016) offers novel interactive web-based visualization capacities that are not restricted to spatial traits and extend to any discrete or continuously valued trait for any organism of interest.

  17. 77 FR 41795 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and ] Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended.... Implementation of this determination will be made by U.S. Citizenship and Immigration Services (USCIS),...

  18. 76 FR 2130 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as... Immigration Services (USCIS), in consultation with U.S. Immigration and Customs Enforcement (ICE), or by...

  19. 76 FR 2131 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as.... Implementation of this determination will be made by U.S. Citizenship and Immigration Services (USCIS),...

  20. 76 FR 14418 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as... determination will be made by U.S. Citizenship and Immigration Services (USCIS), in consultation with...

  1. 76 FR 14419 - Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and Nationality Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... SECURITY Office of the Secretary Exercise of Authority Under Section 212(d)(3)(B)(i) of the Immigration and...(d)(3)(B)(i) of the Immigration and Nationality Act (INA), 8 U.S.C. 1182(d)(3)(B)(i), as amended, as.... Citizenship and Immigration Services (USCIS), in consultation with U.S. Immigration and Customs...

  2. Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders

    PubMed Central

    Sikoglu, Elif M.; Navarro, Ana A. Liso; Starr, Debra; Dvir, Yael; Nwosu, Benjamin Udoka; Czerniak, Suzanne M.; Rogan, Ryan C.; Castro, Martha C.; Edden, Richard A. E.; Frazier, Jean A.

    2015-01-01

    Abstract Objective: We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD). Methods: The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6–17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation. Results: Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=−3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=−2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14). Conclusions: Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry. PMID:26091195

  3. Stability of Vitamin D3 in fortified yoghurt and yoghurt drink (Doogh)

    PubMed Central

    Jafari, Tina; Askari, Gholamreza; Mirlohi, Maryam; Javanmard, Shaghayegh Haghjooy; Faghihimani, Elham; Fallah, Aziz A

    2016-01-01

    Background: Vitamin D deficiency and insufficiency are recognized as a worldwide problem with serious consequences. Fortification of foods with Vitamin D is a certain approach to improve serum Vitamin D status if the stability of vitamin in the foodstuffs was controlled. The purpose of this study was to examine the stability of Vitamin D3 added to low-fat yogurt and yogurt drink “Doogh” during the products shelf-life. Materials and Methods: Two kinds of Vitamin D3, water- and oil-dispersible forms, suitable for food fortification, were compared to find out whether they show different stability in the products. The products were packed in opaque or translucent containers. The content of Vitamin D3 was determined by high performance liquid chromatography method. Results: Vitamin D was not affected by the heat treatment (pasteurization) and other processes (homogenization and fermentation). Both water- and oil-dispersible forms were stable during the shelf-life of yogurt samples packed in opaque containers. The Vitamin D3 content of yogurt fortified with water-dispersible form and packed in translucent containers was not stable during the shelf-life and significantly reduced after 1, 2, and 3 weeks of storage compared to the day 0. The Vitamin D3 content of samples fortified with the oil-dispersible form packed in the same container was only stable after 1-week and significantly reduced after 2 and 3 weeks of storage. The Vitamin D3 content of Doogh packed in the opaque containers remained stable during the shelf-life while it was not stable in the samples packed in translucent containers. Conclusion: The results suggested that both forms of Vitamin D are suitable for fortification, and opaque container is a better choice for packaging of the product. PMID:27110549

  4. Current perspectives on selective dopamine D3 receptor antagonists as pharmacotherapeutics for addictions and related disorders

    PubMed Central

    Heidbreder, Christian A.; Newman, Amy H.

    2011-01-01

    Repeated exposure to drugs of abuse produces long-term molecular and neurochemical changes that may explain the core features of addiction, such as the compulsive seeking and taking of the drug, as well as the risk of relapse. A growing number of new molecular and cellular targets of addictive drugs have been identified, and rapid advances are being made in relating those targets to specific behavioral phenotypes in animal models of addiction. In this context, the pattern of expression of the dopamine (DA) D3 receptor in the rodent and human brain and changes in this pattern in response to drugs of abuse have contributed primarily to direct research efforts toward the development of selective DA D3 receptor antagonists. Growing preclinical evidence indicates that these compounds may actually regulate the motivation to self-administer drugs and disrupt drug-associated cue-induced craving. This report will be divided into three parts. First, preclinical evidence in support of the efficacy of selective DA D3 receptor antagonists in animal models of drug addiction will be reviewed. The effects of mixed DA D2/D3 receptor antagonists will not be discussed here because most of these compounds have low selectivity at the D3 versus D2 receptor, and their efficacy profile is related primarily to functional antagonism at D2 receptors and possibly interactions with other neurotransmitter systems. Second, major advances in medicinal chemistry for the identification and optimization of selective DA D3 receptor antagonists and partial agonists will be analyzed. Third, translational research from preclinical efficacy studies to so-called proof-of-concept studies for drug addiction indications will be discussed. PMID:20201845

  5. Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders

    PubMed Central

    Seo, Joon H.; Kuzhikandathil, Eldo V.

    2015-01-01

    Several studies have shown that repeated stressful experiences during childhood increases the likelihood of developing depression- and anxiety-related disorders in adulthood; however, the underlying mechanisms are not well understood. We subjected drd3-EGFP and drd3-null mice to daily, two hour restraint stress episodes over a five day period during preadolescence (postnatal day 35 to 39), followed by social isolation. When these mice reached adulthood (post-natal day > 90), we assessed locomotor behavior in a novel environment, and assessed depression-related behavior in the Porsolt Forced Swim test. We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood. Adult male mice subjected to restraint stress during preadolescence exhibited both anxiety- and depression-related behaviors; however, adult female mice subjected to preadolescent restraint stress exhibited only depression-related behaviors. The development of preadolescent stress-derived psychiatric disorders was blocked by D3 receptor selective antagonist, SB 277011-A, and absent in D3 receptor null mice. Adult male mice that experienced stress during preadolescence exhibited a loss of D3 receptor expression and function in the amygdala but not in hippocampus or nucleus accumbens. In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus. Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood. PMID:26619275

  6. RUNX2 Mutation Impairs 1α,25-Dihydroxyvitamin D3 mediated Osteoclastogenesis in Dental Follicle Cells.

    PubMed

    Wang, X Z; Sun, X Y; Zhang, C Y; Yang, X; Yan, W J; Ge, L H; Zheng, S G

    2016-01-01

    Cleidocranial dysplasia (CCD), a skeletal disorder characterized by delayed permanent tooth eruption and other dental abnormalities, is caused by heterozygous RUNX2 mutations. As an osteoblast-specific transcription factor, RUNX2 plays a role in bone remodeling, tooth formation and tooth eruption. To investigate the crosstalk between RUNX2 and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) in human dental follicle cells (hDFCs) during osteoclast formation, we established a co-culture system of hDFCs from CCD patient and healthy donors with peripheral blood mononuclear cells (PBMCs). Expression of the osteoclast-associated genes and the number of TRAP(+) cells were reduced in CCD hDFCs, indicating its suppressed osteoclast-inductive ability, which was reflected by the downregulated RANKL/OPG ratio. In addition, 1α,25-(OH)2D3-stimulation elevated the expression of osteoclast-related genes, as well as RANKL mRNA levels and RANKL/OPG ratios in control hDFCs. Conversely, RUNX2 mutation abolished this 1α,25-(OH)2D3-induced RANKL gene activation and osteoclast formation in CCD hDFCs. Therefore, RUNX2 haploinsufficiency impairs dental follicle-induced osteoclast formation capacity through RANKL/OPG signaling, which may be partially responsible for delayed permanent tooth eruption in CCD patients. Furthermore, this abnormality was not rescued by 1α,25-(OH)2D3 application because 1α,25-(OH)2D3-induced RANKL activation in hDFCs is mediated principally via the RUNX2-dependent pathway. PMID:27068678

  7. Protective effects of vitamin D3 against d-galactosamine-induced liver injury in rats.

    PubMed

    Colakoglu, Neriman; Kuloglu, Tuncay; Ozan, Enver; Kocaman, Nevin; Dabak, Durrin Ozlem; Parlak, Gozde

    2016-08-01

    In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage. PMID:27291692

  8. 1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

    PubMed Central

    Meredith, Anna; Boroomand, Seti; Carthy, Jon; Luo, Zongshu; McManus, Bruce

    2015-01-01

    Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. PMID:26061181

  9. Implementation of the thermonuclear process in D3He-9Be plasma on the basis of a Z pinch with an ultrafast laser ignition

    NASA Astrophysics Data System (ADS)

    Voronchev, V. T.; Kukulin, V. I.

    2010-01-01

    A new concept of inertial-magnetic confinement fusion is proposed. This concept is based on a high-current Z pinch combined with a femtosecond laser. The fusion target is composed of a D3He fuel contained under a high pressure inside a sealed cylindrical capsule made from metallic 9Be. An electric discharge along the capsule preheats the target and transforms it into a state of compressed liner. A subsequent TW femtosecond-laser pulse focused on a target end face causes ultrafast cold ignition of a small portion of the D3He fuel. This laser impact generates energetic electrons and ions, which trigger a nuclear-physics mechanism of a catalytic heating of the fuel and also creates a detonation shock wave capable of propagating along the plasma filament. It is shown that the self-sustaining fusion burn wave can appear in the D3He-9Be plasma, in which case the bulk of the energy release is carried by nonradioactive ions, with the energy gain being in excess of 50. The possibility of probing the fusion process by means of gamma-ray spectroscopy is also discussed. The radiative-capture reactions 3He( d, γ), D( d, γ), and 3He(3He, γ) naturally accompanying the burning of the D3He fuel are shown to serve as a convenient diagnostic tool. A nuclear “marker” of D3He fusion on the basis of the detection of monochromatic gamma rays produced in the reaction 9Be( α, γn), which is induced in the liner beryllium shell by energetic fusion alpha particles, is also examined.

  10. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study.

    PubMed

    Mathangi Ramakrishnan, K; Babu, M; Lakshmi Madhavi, M S

    2015-09-30

    Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  11. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).

    PubMed

    Shapiro, Alice C; Adlis, Susan A; Robien, Kim; Kirstein, Mark N; Liang, Shuang; Richter, Sara A; Lerner, Rachel E

    2016-02-01

    The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL). PMID:26868123

  12. Nonperturbative gluon and ghost propagators for d=3 Yang-Mills theory

    SciTech Connect

    Aguilar, A. C.; Binosi, D.; Papavassiliou, J.

    2010-06-15

    We study a manifestly gauge-invariant set of Schwinger-Dyson equations to determine the nonperturbative dynamics of the gluon and ghost propagators in d=3 Yang-Mills theory. The use of the well-known Schwinger mechanism, in the Landau gauge leads to the dynamical generation of a mass for the gauge boson (gluon in d=3), which, in turn, gives rise to an infrared finite gluon propagator and ghost dressing function. The propagators obtained from the numerical solution of these nonperturbative equations are in very good agreement with the results of SU(2) lattice simulations.

  13. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).

    PubMed

    Shapiro, Alice C; Adlis, Susan A; Robien, Kim; Kirstein, Mark N; Liang, Shuang; Richter, Sara A; Lerner, Rachel E

    2016-02-01

    The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

  14. Expression of nephronectin is enhanced by 1α,25-dihydroxyvitamin D3.

    PubMed

    Hiranuma, Katsuhiro; Yamada, Atsushi; Kurosawa, Tamaki; Aizawa, Ryo; Suzuki, Dai; Saito, Yoshiro; Nagahama, Ryo; Ikehata, Mikiko; Tsukasaki, Masayuki; Morimura, Naoko; Chikazu, Daichi; Maki, Koutaro; Shirota, Tatsuo; Takami, Masamichi; Yamamoto, Matsuo; Iijima, Takehiko; Kamijo, Ryutaro

    2016-09-01

    The extracellular matrix protein nephronectin (Npnt), also called POEM, is considered to play critical roles as an adhesion molecule in development and functions of various tissues, such as the kidneys, liver, and bone. In the present study, we examined the molecular mechanism of Npnt gene expression and found that vitamin D3 (1α,25-dihydroxyvitamin D3,VD 3) strongly enhanced Npnt mRNA expression in MC3T3-E1 cells from a mouse osteoblastic cell line. The VD 3-induced increase in Npnt expression is both time- and dose-dependent and is mediated by the vitamin D receptor (VDR). PMID:27642554

  15. Autocrine TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in breast cells.

    PubMed

    Yang, L; Yang, J; Venkateswarlu, S; Ko, T; Brattain, M G

    2001-09-01

    In this study, we address whether TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGFbeta was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGFbeta. MCF7L TGFbetaRII-transfected cells, which have autocrine TGFbeta activity, were more sensitive to EB1089 than MCF7L cells. TGFbeta neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGFbeta signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGFbeta isoforms and/or TGFbeta receptors was induced by the analogs in the vitamin D3 and TGFbeta sensitive cells. Vitamin D3 analogs did not induce TGFbeta or TGFbeta receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGFbeta activity through increasing expression of TGFbeta isoforms and/or TGFbeta receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGFbeta signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGFbeta signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also

  16. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study

    PubMed Central

    Mathangi Ramakrishnan, K.; Babu, M.; Lakshmi Madhavi, M.S.

    2015-01-01

    Summary Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  17. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    PubMed

    Boyan, Barbara D; Hyzy, Sharon L; Pan, Qingfen; Scott, Kayla M; Coutts, Richard D; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  18. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    PubMed Central

    Boyan, Barbara D.; Hyzy, Sharon L.; Pan, Qingfen; Scott, Kayla M.; Coutts, Richard D.; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  19. Swelling and creep observed in AISI 304 fuel pin cladding from three MOX fuel assemblies irradiated in EBR-II

    NASA Astrophysics Data System (ADS)

    Garner, F. A.; Makenas, B. J.; Chastain, S. A.

    2011-06-01

    Three 37-pin MOX-fueled experimental subassemblies were irradiated in EBR-II with fuel pin cladding constructed from annealed AISI 304 stainless steel. Analysis of the swelling and irradiation creep of the cladding showed that the terminal swelling rate of AISI 304 stainless steel appears to be ˜1%/dpa and that swelling is very reproducible for identical irradiation conditions. The swelling at a given neutron fluence is rather sensitive to both irradiation temperature and especially to the neutron flux, however, with the primary influence residing in the transient regime. As the neutron flux increases the duration of the transient regime is increased in agreement with other recent studies. The duration of the transient regime is also decreased by increasing irradiation temperature. In these assemblies swelling reached high levels rather quickly, reducing the opportunity for fuel pin cladding interaction and thereby reducing the contribution of irradiation creep to the total deformation. It also appears that in this swelling-before-creep scenario that the well-known "creep disappearance" phenomenon was operating strongly.

  20. Effect of Filler Metals on the Weldability and Mechanical Properties of Multi-pass PCGTA Weldments of AISI 316L

    NASA Astrophysics Data System (ADS)

    Devendranath Ramkumar, K.; Maruthi Mohan Reddy, P.; Raja Arjun, B.; Choudhary, Ayush; Srivastava, Anubhav; Arivazhagan, N.

    2015-04-01

    The influence of filler metals on the microstructure, mechanical properties, and corrosion behavior of AISI 316L welds was investigated. Pulsed current gas tungsten arc welding was employed to join the AISI 316L plates using two different fillers ER2553 and ERNiCr-3. Microstructures studies showed the presence of different forms of austenite on employing ER2553 filler and formation of migrated grain boundaries at the weld zone while using ERNiCr-3 filler. Tensile studies corroborated that the tensile strength was greater for the weldments employing ER2553 filler. Charpy V-notch studies ascertained that the impact toughness was greater for ER2553 weldments as compared to the parent metal. Potentiodynamic polarization curves clearly inferred that the weld zone of ER2553 exhibited better corrosion resistance among the various coupons tested. It was concluded from the study that ER2553 exhibited better mechanical and corrosion properties and could be adopted to achieve optimal properties compared to over-alloyed filler.

  1. Influence of Surface Preparation on the Kinetics of Controlled Gas-Nitrided AISI H13 Steels Used in Extrusion Dies

    NASA Astrophysics Data System (ADS)

    Akhtar, S. S.; Arif, A. F. M.; Yilbas, B. S.; Sheikh, A. K.

    2010-04-01

    In the aluminum extrusion practice, gas nitriding represents an important factor in enhancing the service life of AISI H13 steel dies. It is observed that if the die-bearing surface is not adequately prepared before nitriding, a nonuniform and shallow nitrided layer develops with reduced hardening effect. The focus of this paper is to investigate the influence of different surface conditions in terms of roughness on the kinetics of nitrided layer developed during gas-nitriding process under controlled nitriding potential. Four samples made of AISI H13 steel properly heat treated (quenched and tempered) were considered: without surface preparation, ground, polished, and lapped. All the samples were gas nitrided under the same conditions and examined after being nitrided. The nitrided layers were characterized using different techniques including optical microscopy, scanning electron microscopy, x-ray diffraction analysis, energy dispersive spectrometry mapping, and microhardness analysis. It was found that the surface preparation prior to nitriding significantly enhanced the nitriding kinetics, which in turn resulted in even and deep nitrided case depth. This provided high load-bearing capacity due to increased and deep hardening effect as compared to unprepared sample. A thinner and uniform compound layer with well-resolved phases was achieved in comparison with unprepared sample.

  2. Co/LaCrO 3 composite coatings for AISI 430 stainless steel solid oxide fuel cell interconnects

    NASA Astrophysics Data System (ADS)

    Shaigan, Nima; Ivey, Douglas G.; Chen, Weixing

    Rapidly decreasing electronic conductivity, chromium volatility and poisoning of the cathode material are the major problems associated with inevitable growth of chromia on ferritic stainless steel interconnects of solid oxide fuel cells (SOFC). This work evaluates the performance of a novel, electrodeposited composite Co/LaCrO 3 coating for AISI 430 stainless steel. The oxidation behaviour of the Co/LaCrO 3-coated AISI 430 substrates is studied in terms of scale microstructure and growth kinetics. Area-specific resistance (ASR) of the coated substrates has also been tested. The results showed that the Co/LaCrO 3 coating forms a triple-layer scale consisting of a chromia-rich subscale, a Co-Fe spinel mid-layer and a Co 3O 4 spinel top layer at 800 °C in air. This scale is protective, acts as an effective barrier against chromium migration into the outer oxide layer and exhibits a low, stable ASR of ∼0.02 Ω cm 2 after 900 h at 800 °C in air.

  3. Improving the Adhesion Resistance of the Boride Coatings to AISI 316L Steel Substrate by Diffusion Annealing

    NASA Astrophysics Data System (ADS)

    Campos-Silva, I.; Bernabé-Molina, S.; Bravo-Bárcenas, D.; Martínez-Trinidad, J.; Rodríguez-Castro, G.; Meneses-Amador, A.

    2016-07-01

    In this study, new results about the practical adhesion resistance of boride coating/substrate system formed at the surface of AISI 316 L steel and improved by means of a diffusion annealing process are presented. First, the boriding of AISI 316 L steel was performed by the powder-pack method at 1173 K with different exposure times (4-8 h). The diffusion annealing process was conducted on the borided steels at 1273 K with 2 h of exposure using a diluent atmosphere of boron powder mixture. The mechanical behavior of the boride coating/substrate system developed by both treatments was established using Vickers and Berkovich tests along the depth of the boride coatings, respectively. Finally, for the entire set of experimental conditions, the scratch tests were performed with a continuously increasing normal force, in which the practical adhesion resistance of the boride coating/substrate system was represented by the critical load. The failure mechanisms developed over the surface of the scratch tracks were analyzed; the FeB-Fe2B/substrate system exhibited an adhesive mode, while the Fe2B/substrate system obtained by the diffusion annealing process showed predominantly a cohesive failure mode.

  4. High temperature oxidation behavior of austenitic stainless steel AISI 304 in steam of nanofluids contain nanoparticle ZrO2

    SciTech Connect

    Prajitno, Djoko Hadi Syarif, Dani Gustaman

    2014-03-24

    The objective of this study is to evaluate high temperature oxidation behavior of austenitic stainless steel SS 304 in steam of nanofluids contain nanoparticle ZrO{sub 2}. The oxidation was performed at high temperatures ranging from 600 to 800°C. The oxidation time was 60 minutes. After oxidation the surface of the samples was analyzed by different methods including, optical microscope, scanning electron microscope (SEM) and X-ray diffraction (XRD). X-ray diffraction examination show that the oxide scale formed during oxidation of stainless steel AISI 304 alloys is dominated by iron oxide, Fe{sub 2}O{sub 3}. Minor element such as Cr{sub 2}O{sub 3} is also appeared in the diffraction pattern. Characterization by optical microscope showed that cross section microstructure of stainless steel changed after oxidized with the oxide scale on the surface stainless steels. SEM and x-ray diffraction examination show that the oxide of ZrO{sub 2} appeared on the surface of stainless steel. Kinetic rate of oxidation of austenite stainless steel AISI 304 showed that increasing oxidation temperature and time will increase oxidation rate.

  5. Wear behavior of the surface alloyed AISI 1020 steel with Fe-Nb-B by TIG welding technique

    SciTech Connect

    Kilinc, B. Durmaz, M.; Abakay, E.; Sen, U.; Sen, S.

    2015-03-30

    Weld overlay coatings also known as hardfacing is a method which involves melting of the alloys and solidification for applied coatings. Recently hardfacing by welding has become a commonly used technique for improvement of material performance in extreme (high temperature, impact/abrasion, erosion, etc.) conditions.In the present study, the coatings were produced from a mixture of ferrous niobium, ferrous boron and iron powders in the ranges of -45µm particle size with different ratio. Fe{sub 12}Nb{sub 5}B{sub 3} and Fe{sub 2}NbBalloys were coated on the AISI 1020 steel surface by TIG welding. The phases formed in the coated layer are Fe{sub 2}B, NbB{sub 2}, NbFeB and Fe0,2 Nb{sub 0,8} phases. The hardness of the presence phases are changing between 1689±85 HV{sub 0.01}, and 181±7 HV{sub 0.1}. Microstructural examinations were realized by optical and scanning electron microscopy. The wear and friction behaviors of Fe{sub 12}Nb{sub 5}B{sub 3} and Fe2NbB realized on the AISI 1020 steel were investigated by the technique of TIG welding by using ball-on-disk arrangement against alumina ball.

  6. Improving the Adhesion Resistance of the Boride Coatings to AISI 316L Steel Substrate by Diffusion Annealing

    NASA Astrophysics Data System (ADS)

    Campos-Silva, I.; Bernabé-Molina, S.; Bravo-Bárcenas, D.; Martínez-Trinidad, J.; Rodríguez-Castro, G.; Meneses-Amador, A.

    2016-09-01

    In this study, new results about the practical adhesion resistance of boride coating/substrate system formed at the surface of AISI 316 L steel and improved by means of a diffusion annealing process are presented. First, the boriding of AISI 316 L steel was performed by the powder-pack method at 1173 K with different exposure times (4-8 h). The diffusion annealing process was conducted on the borided steels at 1273 K with 2 h of exposure using a diluent atmosphere of boron powder mixture. The mechanical behavior of the boride coating/substrate system developed by both treatments was established using Vickers and Berkovich tests along the depth of the boride coatings, respectively. Finally, for the entire set of experimental conditions, the scratch tests were performed with a continuously increasing normal force, in which the practical adhesion resistance of the boride coating/substrate system was represented by the critical load. The failure mechanisms developed over the surface of the scratch tracks were analyzed; the FeB-Fe2B/substrate system exhibited an adhesive mode, while the Fe2B/substrate system obtained by the diffusion annealing process showed predominantly a cohesive failure mode.

  7. Interleukin-1α mediates the antiproliferative effects of 1,25-dihydroxyvitamin D3 in prostate progenitor/stem cells.

    PubMed

    Maund, Sophia L; Barclay, Wendy W; Hover, Laura D; Axanova, Linara S; Sui, Guangchao; Hipp, Jason D; Fleet, James C; Thorburn, Andrew; Cramer, Scott D

    2011-08-01

    Vitamin D(3) is a promising preventative and therapeutic agent for prostate cancer, but its implementation is hampered by a lack of understanding about its mechanism of action. Upon treatment with 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3), vitamin D(3)], the metabolically active form of vitamin D(3), adult prostate progenitor/stem cells (PrP/SC) undergo cell-cycle arrest, senescence, and differentiation to an androgen receptor-positive luminal epithelial cell fate. Microarray analyses of control- and vitamin D(3)-treated PrP/SCs revealed global gene expression signatures consistent with induction of differentiation. Interestingly, one of the most highly upregulated genes by vitamin D(3) was the proinflammatory cytokine interleukin-1α (IL-1α). Systems biology analyses supported a central role for IL-1α in the vitamin D(3) response in PrP/SCs. siRNA-mediated knockdown of IL-1α abrogated vitamin D(3)-induced growth suppression, establishing a requirement for IL-1α in the antiproliferative effects of vitamin D(3) in PrP/SCs. These studies establish a system to study the molecular profile of PrP/SC differentiation, proliferation, and senescence, and they point to an important new role for IL-1α in vitamin D(3) signaling in PrP/SCs.

  8. Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals.

    PubMed

    Holick, M F; Tian, X Q; Allen, M

    1995-04-11

    The photoproduction of vitamin D in the skin was essential for the evolutionary development of terrestrial vertebrates. During exposure to sunlight, previtamin D3 formed in the skin is isomerized to vitamin D3 (calciol) by a temperature-dependent process. Since early land vertebrates were poikilothermic, the relatively slow conversion of previtamin D3 to vitamin D3 at ambient temperature put them at serious risk for developing vitamin D deficiency, thus leading to a poorly mineralized skeleton that could have ultimately halted further evolutionary development of vertebrates on land. We evaluated the rate of isomerization of previtamin D3 to vitamin D3 in the skin of iguanas and found the isomerization rate was enhanced by 1100% and 1700% at 25 degrees C and 5 degrees C, respectively. It is likely that the membrane entrapment of previtamin D3 in its s-cis,s-cis conformation is responsible for the markedly enhanced conversion of previtamin D3 to vitamin D3. The membrane-enhanced production of vitamin D3 ensures the critical supply of vitamin D3 to poikilothermic animals such as iguanas.

  9. Ultraviolet radiation and Vitamin D3 in amphibian health, behaviour, diet and conservation.

    PubMed

    Antwis, R E; Browne, R K

    2009-10-01

    Amphibians are currently suffering a period of mass extinction with approximately 20% of species under severe threat and more than 120 species already extinct. In light of this crisis there is an urgency to establish viable ex situ populations and also find the causes of in situ declines. The role of ultraviolet radiation and Vitamin D(3) in amphibian health directly influences both ex situ and in situ populations. Vitamin D(3) can be photosynthesised endogenously via UV-B radiation (UV-B), or acquired through the diet, and then metabolised to calcitriol the biologically active hormonal form. Although, there is a lack of literature concerning Vitamin D(3) requirements and calcitriol synthesis in amphibians, amphibians are likely to have similar Vitamin D(3) requirements and metabolic processes as other vertebrates due to the phylogenetically conservative nature of calcitriol biosynthesis. Deficiencies in calcitriol in amphibians result in nutritional metabolic bone disease (NMBD) and could compromise reproduction and immunity. However, excess biologically active UV radiation has also proven detrimental across all three amphibian life stages and therefore could impact both in situ and ex situ populations. Here we review the role and necessity of UV-B and calcitriol in amphibians and the potential for negative impacts due to excessive exposure to UV radiation. We also identify priorities for research that could provide critical information for maintaining healthy in ex situ and in situ populations of amphibians. PMID:19555772

  10. Black holes as D3-branes on Calabi-Yau threefolds

    NASA Astrophysics Data System (ADS)

    Bertolini, Matteo; Frè, Pietro; Iengo, Roberto; Scrucca, Claudio A.

    1998-07-01

    We show how an extremal Reissner-Nordström black hole can be obtained by wrapping a dyonic D3-brane on a Calabi-Yau manifold. In the orbifold limit T6/Z3, we explicitly show the correspondence between the solution of the supergravity equations of motion and the D-brane boundary state description of such a black hole.

  11. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease

    PubMed Central

    Grove, Megan L.; Naj, Adam; Vronskaya, Maria; DeStefano, Anita L.; Brody, Jennifer A.; Smith, Albert V.; Amin, Najaf; Sims, Rebecca; Ibrahim-Verbaas, Carla A.; Choi, Seung-Hoan; Lopez, Oscar L.; Beiser, Alexa; Ikram, M. Arfan; Garcia, Melissa E.; Hayward, Caroline; Ripatti, Samuli; Franks, Paul W.; Hallmans, Göran; Rolandsson, Olov; Jansson, Jan-Håkon; Porteous, David J.; Salomaa, Veikko; Eiriksdottir, Gudny; Rice, Kenneth M.; Bellen, Hugo J.; Levy, Daniel; Uitterlinden, Andre G.; Emilsson, Valur; Rotter, Jerome I.; Aspelund, Thor; O’Donnell, Christopher J.; Fitzpatrick, Annette L.; Launer, Lenore J.; Hofman, Albert; Wang, Li-San; Williams, Julie; Schellenberg, Gerard D.; Boerwinkle, Eric; Psaty, Bruce M.; Seshadri, Sudha; Shulman, Joshua M.; Gudnason, Vilmundur; van Duijn, Cornelia M.

    2016-01-01

    We performed an exome-wide association analysis in 1393 late-onset Alzheimer’s disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5–15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade. PMID:27764101

  12. Dopamine D3 Receptor Antagonists as Potential Therapeutics for the Treatment of Neurological Diseases

    PubMed Central

    Maramai, Samuele; Gemma, Sandra; Brogi, Simone; Campiani, Giuseppe; Butini, Stefania; Stark, Holger; Brindisi, Margherita

    2016-01-01

    D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists. Recent research efforts were devoted to the conception of chemical templates possibly endowed with a multi-target profile, especially with regards to other G-protein-coupled receptors (GPCRs). A comprehensive overview of the recent literature in the field is herein provided. In particular, the evolution of the chemical templates has been tracked, according to the growing advancements in both the structural information and the refinement of the key pharmacophoric elements. The receptor/multireceptor affinity and functional profiles for the examined compounds have been covered, together with their most significant pharmacological applications. PMID:27761108

  13. Treatment of an intramammary bacterial infection with 25-hydroxyvitamin D3

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases, such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihyd...

  14. Clinicopathological Studies on Vitamin D(3) Toxicity and Therapeutic Evaluation of Aloe vera in Rats.

    PubMed

    Chavhan, Sambhaji G; Brar, R S; Banga, H S; Sandhu, H S; Sodhi, S; Gadhave, P D; Kothule, V R; Kammon, A M

    2011-01-01

    A study was conducted to examine the clinical signs, hematological, biochemical and histopathological changes in vitamin D(3) toxicity at a dose rate 2 mg/kg b.wt. of vitamin D(3) and to assess the protective effect of Aloe vera in vitamin D(3) toxicity. The clinical signs observed were anorexia, progressive weight loss, difficulty in movement and respiration, diarrhea, epistaxis, subnormal body temperature and nervous signs before death. Mortality was observed in treated rats between day 10 and day 19 of treatment. The gross postmortem changes observed were severe emaciation, white chalky deposits on epicardial surface of heart, pin point white deposits on cortical surface of kidneys with pale yellow discoloration and diffused white deposits on serosal surface of stomach and intestine with bloody ingesta in lumen. The hematological changes included non-significant increase in hemoglobin and total leukocyte count and significant increase in relative neutrophil count. The biochemical changes observed were significant increase in plasma concentration of calcium, phosphorus and blood urea nitrogen, whereas a significant decrease in the concentration of albumin and total plasma protein was observed. The histopathological lesions included calcification of various organs, viz., tongue, stomach, intestines, kidney, heart, aorta, larynx, trachea, lungs, spleen, choroid plexus arteries of brain and vas deferens. The Aloe vera juice (2.5% in drinking water) has no protective effect on vitamin D(3) toxicity (2 mg/kg b.wt.). PMID:21430919

  15. Parkin expression profile in dopamine d3 receptor knock-out mice brains.

    PubMed

    D'Agata, Velia; Tiralongo, Adriana; Castorina, Alessandro; Leggio, Gian Marco; Micale, Vincenzo; Carnazza, Maria Luisa; Drago, Filippo

    2009-02-01

    Patients affected by autosomic recessive juvenile parkinsonism (ARJP) exhibit parkin gene mutations with brain decrease in dopamine D2/D3 binding sites. To date, there are no data indicating whether the reduction in dopamine D3 receptors (DRD3) may be associated with the expression of specific parkin variants. In the present study we investigated parkin expression profile in DRD3 knock-out mice brains. RT-PCR analysis was performed to assess qualitative changes in parkin isoforms' distribution pattern and in exons' expression both in wild type controls and dopamine D3 receptor's knock-out mice. Real-time PCR was performed to quantify single exons mRNA. Results demonstrated that exons 1, 2, 4, 6, 7, 8, were more expressed in wild type compared to dopamine D3 receptor KO mice brains while some other (3, 9, 10) were lower expressed. The expression levels of exons 5, 11 and 12 did not change in both animal groups. Our analysis was confirmed by western blot, which showed that parkin protein levels were influenced by the absence of DRD3.

  16. Ultraviolet radiation and Vitamin D3 in amphibian health, behaviour, diet and conservation.

    PubMed

    Antwis, R E; Browne, R K

    2009-10-01

    Amphibians are currently suffering a period of mass extinction with approximately 20% of species under severe threat and more than 120 species already extinct. In light of this crisis there is an urgency to establish viable ex situ populations and also find the causes of in situ declines. The role of ultraviolet radiation and Vitamin D(3) in amphibian health directly influences both ex situ and in situ populations. Vitamin D(3) can be photosynthesised endogenously via UV-B radiation (UV-B), or acquired through the diet, and then metabolised to calcitriol the biologically active hormonal form. Although, there is a lack of literature concerning Vitamin D(3) requirements and calcitriol synthesis in amphibians, amphibians are likely to have similar Vitamin D(3) requirements and metabolic processes as other vertebrates due to the phylogenetically conservative nature of calcitriol biosynthesis. Deficiencies in calcitriol in amphibians result in nutritional metabolic bone disease (NMBD) and could compromise reproduction and immunity. However, excess biologically active UV radiation has also proven detrimental across all three amphibian life stages and therefore could impact both in situ and ex situ populations. Here we review the role and necessity of UV-B and calcitriol in amphibians and the potential for negative impacts due to excessive exposure to UV radiation. We also identify priorities for research that could provide critical information for maintaining healthy in ex situ and in situ populations of amphibians.

  17. Voltammetric determination of vitamin D3 with a rotating glassy carbon electrode.

    PubMed

    Hernández Méndez, J; Sánchez Pérez, A; Delgado Zamarreño, M; Hernández Garcia, M L

    1988-01-01

    A voltamperometric study (DC and DP) on the electroanalytical behaviour of vitamin D(3) in a methanolic solution using LiClO(4) as the supporting electrolyte and working with a glassy carbon electrode was carried out. Vitamin D(3) exhibits an oxidation wave (DC) or peak (DP) at potentials close to +1.1 V (versus SCE). The optimum experimental conditions for the best reproducibility of the voltamperometric signal were determined and the different parameters affecting the electrochemical process were studied. The electrochemical process was seen to be irreversible and, under certain conditions, adsorption of vitamin D(3) onto the electrode surface was observed. A voltamperometric procedure for the determination of vitamin D(3) in a concentration range of 2 x 10(-6) - 2 x 10(-4) M is proposed. The detection limit is of the order of 2 x 10(-6) M and the relative standard deviations are 1.1% (DC) and 2.6% (DP), respectively.

  18. Validation for 2D/3D registration I: A new gold standard data set

    SciTech Connect

    Pawiro, S. A.; Markelj, P.; Pernus, F.; Gendrin, C.; Figl, M.; Weber, C.; Kainberger, F.; Noebauer-Huhmann, I.; Bergmeister, H.; Stock, M.; Georg, D.; Bergmann, H.; Birkfellner, W.

    2011-03-15

    Purpose: In this article, the authors propose a new gold standard data set for the validation of two-dimensional/three-dimensional (2D/3D) and 3D/3D image registration algorithms. Methods: A gold standard data set was produced using a fresh cadaver pig head with attached fiducial markers. The authors used several imaging modalities common in diagnostic imaging or radiotherapy, which include 64-slice computed tomography (CT), magnetic resonance imaging using Tl, T2, and proton density sequences, and cone beam CT imaging data. Radiographic data were acquired using kilovoltage and megavoltage imaging techniques. The image information reflects both anatomy and reliable fiducial marker information and improves over existing data sets by the level of anatomical detail, image data quality, and soft-tissue content. The markers on the 3D and 2D image data were segmented using ANALYZE 10.0 (AnalyzeDirect, Inc., Kansas City, KN) and an in-house software. Results: The projection distance errors and the expected target registration errors over all the image data sets were found to be less than 2.71 and 1.88 mm, respectively. Conclusions: The gold standard data set, obtained with state-of-the-art imaging technology, has the potential to improve the validation of 2D/3D and 3D/3D registration algorithms for image guided therapy.

  19. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    PubMed

    Lan, Nan; Luo, Guangyan; Yang, Xiaoqiong; Cheng, Yuanyuan; Zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  20. Clinicopathological Studies on Vitamin D(3) Toxicity and Therapeutic Evaluation of Aloe vera in Rats.

    PubMed

    Chavhan, Sambhaji G; Brar, R S; Banga, H S; Sandhu, H S; Sodhi, S; Gadhave, P D; Kothule, V R; Kammon, A M

    2011-01-01

    A study was conducted to examine the clinical signs, hematological, biochemical and histopathological changes in vitamin D(3) toxicity at a dose rate 2 mg/kg b.wt. of vitamin D(3) and to assess the protective effect of Aloe vera in vitamin D(3) toxicity. The clinical signs observed were anorexia, progressive weight loss, difficulty in movement and respiration, diarrhea, epistaxis, subnormal body temperature and nervous signs before death. Mortality was observed in treated rats between day 10 and day 19 of treatment. The gross postmortem changes observed were severe emaciation, white chalky deposits on epicardial surface of heart, pin point white deposits on cortical surface of kidneys with pale yellow discoloration and diffused white deposits on serosal surface of stomach and intestine with bloody ingesta in lumen. The hematological changes included non-significant increase in hemoglobin and total leukocyte count and significant increase in relative neutrophil count. The biochemical changes observed were significant increase in plasma concentration of calcium, phosphorus and blood urea nitrogen, whereas a significant decrease in the concentration of albumin and total plasma protein was observed. The histopathological lesions included calcification of various organs, viz., tongue, stomach, intestines, kidney, heart, aorta, larynx, trachea, lungs, spleen, choroid plexus arteries of brain and vas deferens. The Aloe vera juice (2.5% in drinking water) has no protective effect on vitamin D(3) toxicity (2 mg/kg b.wt.).

  1. Biliary excretion of radioactivity after intravenous administration of (3H)25-hydroxyvitamin D3 in man

    SciTech Connect

    Ledger, J.E.; Watson, G.J.; Compston, J.E.

    1986-04-01

    The biliary excretion of radioactivity after intravenous (3H)25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than (3H)25-hydroxyvitamin D3. No free (3H)25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following (3H)25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.

  2. [Prednisolone, 1 alpha hydroxyvitamin D3 and androgens in the management in patients with refractory anemias].

    PubMed

    Yoshida, Y; Yamagishi, M

    1988-04-01

    In a cooperative trial, 99 patients with refractory anemias were treated according to a standard protocol consisting of successive administration of prednisolone (PSL), 1 alpha hydroxyvitamin D3 (D3) and androgens. The primary objective of this protocol was to ameliorate peripheral cytopenia and to assess the value of the 3 drugs, claimed to be of some value, in the management of patients with refractory anemias. In principle, patients were initially treated with oral PSL 40-60 mg/day. Patients not responding to PSL within 4 weeks had an 8-week trial of D3 starting with 1 microgram/day, increasing to 3 micrograms/day. Those not responding to either of the two were given AS. Although the number of evaluable courses is limited as yet for each drug, the preliminary results suggest 1) a slight to moderate increase in hemoglobin in 20-25% of patients on PSL, 2) a partial increase in granulocyte and/or platelets and a reduction of marrow blasts in 10-20% of patients during the administration of D3 and 3) the effects are poorer in cases of severe cytopenia. In addition, the improvement was mostly transient. The treatment was well tolerated in the majority of patients.

  3. Downregulation of Runx2 by 1,25-Dihydroxyvitamin D3 Induces the Transdifferentiation of Osteoblasts to Adipocytes

    PubMed Central

    Kim, Jung Ha; Seong, Semun; Kim, Kabsun; Kim, Inyoung; Jeong, Byung-Chul; Kim, Nacksung

    2016-01-01

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) indirectly stimulates bone formation, but little is known about its direct effect on bone formation. In this study, we observed that 1,25(OH)2D3 enhances adipocyte differentiation, but inhibits osteoblast differentiation during osteogenesis. The positive role of 1,25(OH)2D3 in adipocyte differentiation was confirmed when murine osteoblasts were cultured in adipogenic medium. Additionally, 1,25(OH)2D3 enhanced the expression of adipocyte marker genes, but inhibited the expression of osteoblast marker genes in osteoblasts. The inhibition of osteoblast differentiation and promotion of adipocyte differentiation mediated by 1,25(OH)2D3 were compensated by Runx2 overexpression. Our results suggest that 1,25(OH)2D3 induces the transdifferentiation of osteoblasts to adipocytes via Runx2 downregulation in osteoblasts. PMID:27213351

  4. Abrasive Wear Resistance of Tool Steels Evaluated by the Pin-on-Disc Testing

    NASA Astrophysics Data System (ADS)

    Bressan, José Divo; Schopf, Roberto Alexandre

    2011-05-01

    Present work examines tool steels abrasion wear resistance and the abrasion mechanisms which are one main contributor to failure of tooling in metal forming industry. Tooling used in cutting and metal forming processes without lubrication fails due to this type of wear. In the workshop and engineering practice, it is common to relate wear resistance as function of material hardness only. However, there are others parameters which influences wear such as: fracture toughness, type of crystalline structure and the occurrence of hard precipitate in the metallic matrix and also its nature. In the present investigation, the wear mechanisms acting in tool steels were analyzed and, by normalized tests, wear resistance performance of nine different types of tool steels were evaluated by pin-on-disc testing. Conventional tool steels commonly used in tooling such as AISI H13 and AISI A2 were compared in relation to tool steels fabricated by sintering process such as Crucible CPM 3V, CPM 9V and M4 steels. Friction and wear testing were carried out in a pin-on-disc automated equipment which pin was tool steel and the counter-face was a abrasive disc of silicon carbide. Normal load of 5 N, sliding velocity of 0.45 m/s, total sliding distance of 3000 m and room temperature were employed. The wear rate was calculated by the Archard's equation and from the plotted graphs of pin cumulated volume loss versus sliding distance. Specimens were appropriately heat treated by quenching and three tempering cycles. Percentage of alloying elements, metallographic analyses of microstructure and Vickers microhardness of specimens were performed, analyzed and correlated with wear rate. The work is concluded by the presentation of a rank of tool steel wear rate, comparing the different tool steel abrasion wear resistance: the best tool steel wear resistance evaluated was the Crucible CPM 9V steel.

  5. Welding procedure specification. Supplement 1. Records of procedure qualification tests. Gas tungsten arc welding of AISI 41XX steels. [4130 and 4142

    SciTech Connect

    Wodtke, C.H.; Frizzell, D.R.

    1986-06-01

    Procedure WPS-126 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of AISI 4130 and 4142 steel (ASTM A519) (P-No: None), 0.438-inch wall pipe; filler metal is AMS 6457, Class 4130 MC (F-, A-No: None).

  6. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

    Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D; Wang, Xuewei; Lanza, Ian R; Schaible, Niccole S; Salisbury, Jeffrey L; Nair, K Sreekumaran; Terzic, Andre; Sieck, Gary C; Kumar, Rajiv

    2016-01-15

    Muscle weakness and myopathy are observed in vitamin D deficiency and chronic renal failure, where concentrations of the active vitamin D3 metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), are low. To evaluate the mechanism of action of 1α,25(OH)2D3 in skeletal muscle, we examined mitochondrial oxygen consumption, dynamics, and biogenesis and changes in expression of nuclear genes encoding mitochondrial proteins in human skeletal muscle cells following treatment with 1α,25(OH)2D3. The mitochondrial oxygen consumption rate (OCR) increased in 1α,25(OH)2D3-treated cells. Vitamin D3 metabolites lacking a 1α-hydroxyl group (vitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3) decreased or failed to increase OCR. 1α-Hydroxyvitamin D3 did not increase OCR. In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-like) decreased. Phosphorylated pyruvate dehydrogenase (PDH) (Ser-293) and PDH kinase 4 (PDK4) decreased in 1α,25(OH)2D3-treated cells. There was a trend to increased PDH activity in 1α,25(OH)2D3-treated cells (p = 0.09). 83 nuclear mRNAs encoding mitochondrial proteins were changed following 1α,25(OH)2D3 treatment; notably, PDK4 mRNA decreased, and PDP2 mRNA increased. MYC, MAPK13, and EPAS1 mRNAs, which encode proteins that regulate mitochondrial biogenesis, were increased following 1α,25(OH)2D3 treatment. Vitamin D receptor-dependent changes in the expression of 1947 mRNAs encoding proteins involved in muscle contraction, focal adhesion, integrin, JAK/STAT, MAPK, growth factor, and p53 signaling pathways were observed following 1α,25(OH)2D3 treatment. Five micro-RNAs were induced or repressed by 1α,25(OH)2D3. 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which are likely to influence muscle strength. PMID:26601949

  7. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells.

    PubMed

    Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D; Wang, Xuewei; Lanza, Ian R; Schaible, Niccole S; Salisbury, Jeffrey L; Nair, K Sreekumaran; Terzic, Andre; Sieck, Gary C; Kumar, Rajiv

    2016-01-15

    Muscle weakness and myopathy are observed in vitamin D deficiency and chronic renal failure, where concentrations of the active vitamin D3 metabolite, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), are low. To evaluate the mechanism of action of 1α,25(OH)2D3 in skeletal muscle, we examined mitochondrial oxygen consumption, dynamics, and biogenesis and changes in expression of nuclear genes encoding mitochondrial proteins in human skeletal muscle cells following treatment with 1α,25(OH)2D3. The mitochondrial oxygen consumption rate (OCR) increased in 1α,25(OH)2D3-treated cells. Vitamin D3 metabolites lacking a 1α-hydroxyl group (vitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3) decreased or failed to increase OCR. 1α-Hydroxyvitamin D3 did not increase OCR. In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-like) decreased. Phosphorylated pyruvate dehydrogenase (PDH) (Ser-293) and PDH kinase 4 (PDK4) decreased in 1α,25(OH)2D3-treated cells. There was a trend to increased PDH activity in 1α,25(OH)2D3-treated cells (p = 0.09). 83 nuclear mRNAs encoding mitochondrial proteins were changed following 1α,25(OH)2D3 treatment; notably, PDK4 mRNA decreased, and PDP2 mRNA increased. MYC, MAPK13, and EPAS1 mRNAs, which encode proteins that regulate mitochondrial biogenesis, were increased following 1α,25(OH)2D3 treatment. Vitamin D receptor-dependent changes in the expression of 1947 mRNAs encoding proteins involved in muscle contraction, focal adhesion, integrin, JAK/STAT, MAPK, growth factor, and p53 signaling pathways were observed following 1α,25(OH)2D3 treatment. Five micro-RNAs were induced or repressed by 1α,25(OH)2D3. 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which are likely to influence muscle strength.

  8. The inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on xanthine oxidase.

    PubMed

    Lin, Suyun; Zhang, Guowen; Liao, Yijing; Gong, Deming

    2016-06-15

    Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout.

  9. The inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on xanthine oxidase.

    PubMed

    Lin, Suyun; Zhang, Guowen; Liao, Yijing; Gong, Deming

    2016-06-15

    Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout. PMID:27241164

  10. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Tay, Sen Hee; Ho, Chung Shun; Ho, Roger Chun-Man; Mak, Anselm

    2015-01-01

    Objectives Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction. Methods Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry. Results In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs. Conclusions Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients. PMID:26636681

  11. Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma

    PubMed Central

    Hamilton, James P.; Potter, James J.; Koganti, Lahari; Meltzer, Stephen J.; Mezey, Esteban

    2014-01-01

    Aim Thioredoxin-interacting protein (TXNIP) promotes oxidative stress by inactivating thioredoxin (TXN). This protein is involved in diverse disease processes, including insulin resistance, atherosclerosis and carcinogenesis. The aim of the present study was to measure the expression and function of TXNIP in in vitro models of liver disease, as well as in primary human hepatocellular carcinoma (HCC) tissue specimens. In addition, we wanted to determine the effects of vitamin D3-induced TXNIP stimulation in HCC-derived cell lines. Methods TXNIP expression was measured by quantitative reverse transcription polymerase chain reaction and western blots. TXNIP expression was stimulated by vitamin D exposure and by transfection. Cell proliferation, apoptosis and reactive oxygen species were determined by standard assays. Results TXNIP expression levels were low in HCC cell lines, and vitamin D3 stimulated TXNIP expression in vitro. In HCC cells transfected with a TXNIP expression vector or treated with exogenous vitamin D3, there was a reduction in cell proliferation and an increase in apoptosis. Cells expressing TXNIP were markedly susceptible to oxidative injury induced by cobalt chloride or bacterial lipopolysaccharide. TXNIP expression was reduced or absent in a majority of primary human HCC specimens relative to matching, non-cancerous liver tissue. Conclusion TXNIP expression is low or absent in human HCC specimens and HCC-derived cell lines. Vitamin D3 stimulates TXNIP expression, resulting in diminished proliferation and enhanced apoptosis. Liver cells expressing TXNIP are primed for oxidative injury. These findings suggest that stimulation of TXNIP expression, by factors such as vitamin D3, may attenuate carcinogenesis in patients with chronic liver disease. PMID:24451003

  12. Vitamin D3 Supplementation and Childhood Diarrhea: A Randomized Controlled Trial

    PubMed Central

    Maroof, Zabihullah; Chandramohan, Daniel; Bruce, Jane; Mughal, M. Zulf; Bhutta, Zulfiqar; Walraven, Gijs; Masher, Mohammad I.; Ensink, Jeroen H.J.; Manaseki-Holland, Semira

    2013-01-01

    OBJECTIVE: To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. METHODS: This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100 000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. RESULTS: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28–3.59) and 3.59 per child-year (95% CI, 3.44–3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98–1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98–1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. CONCLUSIONS: Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases. PMID:24019420

  13. Serum Vitamin D3 Level in Patients with Female Pattern Hair Loss

    PubMed Central

    Banihashemi, Mahnaz; Nahidi, Yalda; Meibodi, Naser Tayyebi; Jarahi, Lida; Dolatkhah, Mojgan

    2016-01-01

    Background: Female pattern hair loss (FPHL) is the most common cause of alopecia in women, characterized by diffuse nonscarring hair loss in frontal, central, and parietal areas of the scalp. Pathophysiology of FPHL is still not well known, and it is probably a multifactorial genetic trait. FPHL is also observed in women without increased androgen levels, which raises the likelihood of androgen-independent mechanisms and explains the lack of response to antiandrogen treatments in some patients. Vitamin D is a factor that has recently been considered in dealing with these patients. The purpose of this study was to evaluate the serum levels of Vitamin D in patients with FPHL and compare it with healthy controls. Methods: In this case-control study, 45 women with FPHL were evaluated as well as the same number of healthy women matched for age, hours spent under sunlight per day, and body mass index. Serum 25(OH) D3 level was measured using ELISA. Results: 60% of FPHL patients were in 15–30 years old age group with the mean standard deviation (SD) age of 29.11 (7.30) years. In the majority of patients (66.7%), severity of hair loss was Ludwig I. Mean (SD) serum Vitamin D3 level in patient and control group was 13.45 (8.40) and 17.16 (8.96), respectively. T-test showed a significant difference between the two groups in terms of Vitamin D3 serum levels (P = 0.04). Conclusions: This study indicated the correlation between the incidence of FPHL and decreased serum levels of Vitamin D3. It is recommended to evaluate serum Vitamin D3 levels as well as other hormone assays in these patients. PMID:27625563

  14. Serum Vitamin D3 Level in Patients with Female Pattern Hair Loss

    PubMed Central

    Banihashemi, Mahnaz; Nahidi, Yalda; Meibodi, Naser Tayyebi; Jarahi, Lida; Dolatkhah, Mojgan

    2016-01-01

    Background: Female pattern hair loss (FPHL) is the most common cause of alopecia in women, characterized by diffuse nonscarring hair loss in frontal, central, and parietal areas of the scalp. Pathophysiology of FPHL is still not well known, and it is probably a multifactorial genetic trait. FPHL is also observed in women without increased androgen levels, which raises the likelihood of androgen-independent mechanisms and explains the lack of response to antiandrogen treatments in some patients. Vitamin D is a factor that has recently been considered in dealing with these patients. The purpose of this study was to evaluate the serum levels of Vitamin D in patients with FPHL and compare it with healthy controls. Methods: In this case-control study, 45 women with FPHL were evaluated as well as the same number of healthy women matched for age, hours spent under sunlight per day, and body mass index. Serum 25(OH) D3 level was measured using ELISA. Results: 60% of FPHL patients were in 15–30 years old age group with the mean standard deviation (SD) age of 29.11 (7.30) years. In the majority of patients (66.7%), severity of hair loss was Ludwig I. Mean (SD) serum Vitamin D3 level in patient and control group was 13.45 (8.40) and 17.16 (8.96), respectively. T-test showed a significant difference between the two groups in terms of Vitamin D3 serum levels (P = 0.04). Conclusions: This study indicated the correlation between the incidence of FPHL and decreased serum levels of Vitamin D3. It is recommended to evaluate serum Vitamin D3 levels as well as other hormone assays in these patients.

  15. Ion microprobe analysis of bone surface elements: Effects of 1,25(OH)2D3

    SciTech Connect

    Bushinsky, D.A.; Chabala, J.M.; Levi-Setti, R. )

    1989-12-01

    When neonatal mouse calvariae are incubated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) there is net calcium efflux from the bone into the medium. The effect of this enhanced cell-mediated Ca efflux on the relative concentrations of mineral 23Na, 39K, and 40Ca has not previously been studied. We used an imaging scanning ion microprobe, utilizing secondary ion mass spectrometry, to compare the relative ion concentrations of Na, K, and Ca on the surface, subsurface, and cross-section of cultured bone incubated in the presence of 1,25(OH)2D3 with the ion concentrations in similar regions of bone incubated in unaltered control medium. Changes in mineral ion concentration were correlated with net fluxes of Na, K, and Ca relative to bone. Calvariae incubated in control medium (24 h at pH approximately 7.40) have abundant surface Na and K relative to Ca (Na/Ca, 85 and K/Ca, 68), whereas the subsurface has less Na/Ca (21) and K/Ca (23), and on cross section the ratios of both Na/Ca (2.0) and K/Ca (1.9) decrease further. After incubation with 10(-8) M 1,25(OH)2D3, there is a significant increase in bone surface Na/Ca (154) and K/Ca (141) without a change in these ratios on the subsurface and a small fall in both ratios on cross section. The linear relationship between Na/Ca and K/Ca across the three regions of bone observed in control calvariae did not change with 1,25(OH)2D3 treatment. As determined by flux measurements there is a net efflux of Ca but not Na or K from bone.

  16. Association of serum 25(OH) vitamin D3 concentration with severity of multiple sclerosis

    PubMed Central

    Shahbeigi, Saeed; Pakdaman, Hosein; Fereshtehnejad, Seyed-Mohammad; Nikravesh, Elham; Jalilzadeh, Roghie

    2012-01-01

    Background There is a known inverse association between solar radiation and the prevalence of multiple sclerosis (MS). Some studies have investigated the link between vitamin D and MS. The aim of this study was to investigate the possible association between serum 25(OH) vitamin D3 concentration and the severity of disease in Iranian patients with MS. Methods Patients with relapsing–remitting MS underwent neurological examination, including measurement of Expanded Disability Status Scale (EDSS) score, and were categorized by disease severity into mild (0 ≤ EDSS ≤3), moderate (3.5 ≤ EDSS ≤5.5) and severe (6 ≤ EDSS). Serum concentrations of 25(OH) vitamin D3, calcium, phosphorus, magnesium and parathyroid hormone were also measured. Results A total of 78 (73.1% female) patients with MS were evaluated. The mean (± standard deviation) of age was 33.9 ± 9.2 years. The mean (± standard error) serum concentrations of 25(OH) vitamin D3 were 36.6 ± 5.1 mg/dL, 50.1 ± 12.6 mg/dL and 19.8 ± 6.5 mg/dL in patients with mild, moderate and severe disease, respectively. There was a statistically significant inverse correlation between 25(OH) vitamin D3 concentration and EDSS score (P = 0.016, r= –0.273 by Spearman rank correlation test), which was observed in women only (P = 0.021, r = –0.305). Receiver operating characteristic curve analysis suggested that a serum 25(OH) vitamin D3 concentration cutoff of 16.5 mg/dL could differentiate patients with mild/moderate MS from severe disease with 74.6% accuracy. Conclusion Our findings further support the association between vitamin D and disease severity in MS. PMID:24250862

  17. Prediction Of Abrasive And Diffusive Tool Wear Mechanisms In Machining

    NASA Astrophysics Data System (ADS)

    Rizzuti, S.; Umbrello, D.

    2011-01-01

    Tool wear prediction is regarded as very important task in order to maximize tool performance, minimize cutting costs and improve the quality of workpiece in cutting. In this research work, an experimental campaign was carried out at the varying of cutting conditions with the aim to measure both crater and flank tool wear, during machining of an AISI 1045 with an uncoated carbide tool P40. Parallel a FEM-based analysis was developed in order to study the tool wear mechanisms, taking also into account the influence of the cutting conditions and the temperature reached on the tool surfaces. The results show that, when the temperature of the tool rake surface is lower than the activation temperature of the diffusive phenomenon, the wear rate can be estimated applying an abrasive model. In contrast, in the tool area where the temperature is higher than the diffusive activation temperature, the wear rate can be evaluated applying a diffusive model. Finally, for a temperature ranges within the above cited values an adopted abrasive-diffusive wear model furnished the possibility to correctly evaluate the tool wear phenomena.

  18. Effects of AISI 316L corrosion products in in vitro bone formation.

    PubMed

    Morais, S; Sousa, J P; Fernandes, M H; Carvalho, G S; de Bruijn, J D; van Blitterswijk, C A

    1998-06-01

    Rat bone marrow cells were cultured in experimental conditions that favour the proliferation and differentiation of osteoblastic cells (i.e., 2.52 x 10(-4) mol l(-1) ascorbic acid, 10(-2) mol l(-1) beta-glycerophosphate and 10(-8) mol l(-1) dexamethasone) in the absence and in the presence of stainless-steel corrosion products, for a period of 18 days. An AISI 316L stainless-steel slurry (SS) was obtained by electrochemical means and the concentrations of the major metal ions, determined by atomic absorption spectrometry, were 8.78 x 10(-3) mol l(-1) of Fe, 4.31 x 10(-3) mol l(-1) of Cr and 2.56 x 10(-3) mol l(-1) of Ni. Bone marrow cells were exposed to 0.01, 0.1 and 1% of the SS and at the end of the incubation period, control and treated cultures were evaluated by histochemical assays for the identification of the presence of alkaline phosphatase and also calcium and phosphate deposition. Cultures were further observed by scanning electron microscopy. Levels of total and ionised calcium and phosphorus in the culture media collected from control and metal exposed cell cultures were also quantified. Histochemical staining showed that control cultures presented a strong reaction for the presence of alkaline phosphatase and exhibited formation of calcium and phosphates deposits. The presence of 0.01% SS caused no detectable biological effects in these cultures, 0.1% SS impaired osteoblastic behaviour and, 1% SS resulted in cell death. In the absence of bone cells, levels of total and ionised calcium and phosphorus in the control and metal added culture medium were similar throughout the incubation period. A significant decrease in the levels of ionised calcium and phosphorus were observed in the culture medium of control cultures and also in cultures exposed to 0.01% SS after two weeks of incubation, an event related with the formation of mineral calcium phosphate deposits in these cultures. In cultures grown in the presence of 0.1 and 1% SS corrosion products

  19. N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl) piperazine-1-yl)-butyl)-aryl carboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity

    PubMed Central

    Banala, Ashwini K.; Levy, Benjamin A.; Khatri, Sameer S.; Furman, Cheryse A.; Roof, Rebecca A.; Mishra, Yogesh; Griffin, Suzy A.; Sibley, David R.; Luedtke, Robert R.; Newman, Amy Hauck

    2011-01-01

    N-(3-fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)-butyl)-aryl carboxamides were prepared and evaluated for binding and function at dopamine D3 (D3R) and D2 receptors (D2R). In this series, we discovered some of the most D3R selective compounds reported to date, (e.g. 8d and 8j >1000-fold D3R-selective over D2R.) In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by >100-fold (e.g. D3RKi for 15b = 393 v. for 8j = 2.6 nM) resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R. PMID:21495689

  20. P elements inserted in the vicinity of or within the Drosophila snRNP SmD3 gene nested in the first intron of the Ornithine Decarboxylase Antizyme gene affect only the expression of SmD3.

    PubMed Central

    Schenkel, Heide; Hanke, Susanne; De Lorenzo, Cécilia; Schmitt, Rolf; Mechler, Bernard M

    2002-01-01

    The Drosophila gene for snRNP SmD3 (SmD3) is contained in reverse orientation within the first intron of the Ornithine Decarboxylase Antizyme (AZ) gene. Previous studies show that two closely linked P elements cause the gutfeeling phenotype characterized by embryonic lethality and aberrant neuronal and muscle cell differentiation. However, the exact nature of the gene(s) affected in the gutfeeling phenotype remained unknown. This study shows that a series of P inserts located within the 5'-untranslated region (5'-UTR) of SmD3 or its promoter affects only the expression of SmD3. Our analysis reveals that the gutfeeling phenotype associated with P elements inserted in the 5'-UTR of SmD3 results from amorphic or strongly hypomorphic mutations. In contrast, P inserts in the SmD3 promoter region reduce the expression of SmD3 without abolishing it and produce larval lethality with overgrown imaginal discs, brain hemispheres, and hematopoietic organs. The lethality of these mutations could be rescued by an SmD3+ transgene. Finally, inactivation of AZ was obtained by complementing with SmD3+ the deficiency Df(2R)guf(lex47) that uncovers both SmD3 and AZ. Interestingly, AZ inactivation causes a new phenotype characterized by late larval lethality and atrophy of the brain, imaginal discs, hematopoietic organs, and salivary glands. PMID:12072471

  1. Surface fatigue life of carburized and hardened M50NiL and AISI 9310 spur gears and rolling-contact test bars

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.; Bamberger, Eric N.

    1989-01-01

    Spur gear endurance tests and rolling-element surface tests were conducted to investigate vacuum-induction-melted, vacuum-arc-melted (VIM-VAR) M50NiL steel for use as a gear steel in advanced aircraft applications, to determine its endurance characteristics, and to compare the results with those for standard VAR and VIM-VAR AISI 9310 gear material. Tests were conducted with spur gears and rolling-contact bars manufactured from VIM-VAR M50NiL and VAR and VIM-VAR AISI 9310. The gear pitch diameter was 8.9 cm (3.5 in.). Gear test conditions were an inlet oil temperature of 320 K (116 F), and outlet oil temperature of 350 K (170 F), a maximum Hertz stress of 1.71 GPa (248 ksi), and a speed of 10,000 rpm. Bench rolling-element fatigue tests were conducted at ambient temperatures with a bar speed of 12,500 rpm and a maximum Hertz stress of 4.83 GPA (700 ksi). The VIM-VAR M50NiL gears had a surface fatigue life that was 4.5 and 11.5 times that for VIM-VAR and VAR AISI 9310 gears, respectively. The surface fatigue life of the VIM-VAR M50NiL rolling-contact bars was 13.2 and 21.6 times that for the VIM-VAR and VAR AISI 9310, respectively. The VIM-VAR M50NiL material was shown to have good resistance to fracture through a fatigue spall and to have fatigue life far superior to that of both VIM-VAR and VAR AISI 9310 gears and rolling-contact bars.

  2. Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro

    PubMed Central

    Pande, Vivek V.; Chousalkar, Kapil C.; Bhanugopan, Marie S.; Quinn, Jane C.

    2015-01-01

    The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3 deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)2D3 during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3 during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)2D3 with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)2D3 than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3 is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry. PMID:26500277

  3. Evaluation of static pressure drops and PM10 and TSP emissions for modified 1D-3D cyclones

    SciTech Connect

    Holt, G.A.; Baker, R.V.; Hughs, S.E.

    1999-12-01

    Five modifications of a standard 1D3D cyclone were tested and compared against the standard 1D3D design in the areas of particulate emissions and static pressure drop across the cyclone. The modifications to the 1D3D design included a 2D2D inlet, a 2D2D air outlet, a D/3 trash exit, an expansion chamber with a D/3 trash exit, and a tapered air outlet duct. The 1D3D modifications that exhibited a significant improvement in reducing both PM10 and total suspended particulate (TSP) emissions were the designs with the 2D2D inlet and air exhaust combined with either the conical D/3 tail cone or the expansion chamber. In reference to the standard 1D3D cyclone, the average reduction in PM10 emissions was 24 to 29% with a 29 to 35% reduction observed in TSP emissions. The modifications with the tapered air outlets did not show any significant improvements in controlling PM10 emissions. However, the modification with the tapered air outlet/expansion chamber combination exhibited statistical significance in reducing TSP emissions by 18% compared to the 1D3D cyclone. All modifications tested exhibited lower static pressure drops than the standard 1D3D.

  4. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

    PubMed Central

    Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

  5. Use of 25-hydroxyvitamin D3 and dietary calcium to improve tenderness of beef from the round of beef cows.

    PubMed

    Carnagey, K M; Huff-Lonergan, E J; Lonergan, S M; Trenkle, A; Horst, R L; Beitz, D C

    2008-07-01

    The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH D(3)) supplementation, altering supplemental dietary calcium, or their combination influence postmortem biochemical and tenderness changes in muscles from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3 x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d before slaughter and after a 2-wk limestone withdrawal. Plasma samples were obtained during the feeding period. Upon slaughter, adductor, gracilus, pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P D(3) were administered. Concentrations of 25-OH D(3) in meat and in plasma and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] in plasma were increased when 25-OH D(3) was administered (P D(3) or 1,25-(OH)(2) D(3) in meat or in plasma. Calpastatin activity was affected by treatments only in the gracilus and vastus intermedius muscles (P D(3) has some influence on muscle characteristics known to improve tenderness, but improved tenderness was not observed.

  6. Sequestration and microsomal C-25 hydroxylation of (/sup 3/H)-vitamin D3 by the rat liver

    SciTech Connect

    Gascon-Barre, M.; Elbaz, H.; Therrien-Ferland, D.

    1985-03-01

    A study of the vitamin D3 (D3) 25-hydroxylase was undertaken in an in vivo-in vitro model. (/sup 3/H)-D3 (0.7, 1.0, 10, or 100 nmol/100 g of body weight) was injected into the portal vein and the liver was excised 18 seconds later. The liver homogenate was then submitted to differential centrifugation and the amount of (/sup 3/H)-D3 incorporated in the subcellular fractions was evaluated. The microsomal fraction was also incubated in vitro and the appearance of (/sup 3/H)-25-hydroxyvitamin D3 (25(OH)D3) was determined by high performance liquid chromatography (HPLC). Results showed that the fractional liver (/sup 3/H)-D3 uptake varied between 37 percent and 48 percent of the dose injected. The intracellular distribution of (/sup 3/H)-D3 showed that most of the vitamin was incorporated into the microsomal fraction (45% to 50% of the intracellular (/sup 3/H)-D3) except at the highest dose of (/sup 3/H)-D3 where the cytosolic fraction contained the highest amount (56.4%) of the incorporated vitamin. Mathematical analysis of the intracellular (/sup 3/H)-D3 distribution showed that the microsomal fraction was the only subcellular fraction that was found to incorporate (/sup 3/H)-D3 in relation to the total liver uptake of the vitamin. The apparent Michaelis-Menten kinetics of the (/sup 3/H)-D3-25-hydroxylase showed that with substrate concentration of up to 88.5 nM, the apparent Km and Vmax were 28.2 nM and 25.8 fentomoles (fmol) X min-1 X mg microsomal pro-1, respectively, but the reaction lost considerable efficiency with higher substrate concentrations.

  7. Photoaffinity labeling of serum vitamin D binding protein by 3-deoxy-3-azido-25-hydroxyvitamin D3

    SciTech Connect

    Link, R.P.; Kutner, A.; Schnoes, H.K.; DeLuca, H.F.

    1987-06-30

    3-Deoxy-3-azido-25-hydroxyvitamin D3 was covalently incorporated in the 25-hydroxyvitamin D3 binding site of purified human plasma vitamin D binding protein. Competition experiments showed that 3-deoxy-3-azido-25-hydroxyvitamin D3 and 25-hydroxyvitamin D3 bind at the same site on the protein. Tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was synthesized from tritiated 25-hydroxyvitamin D3, retaining the high specific activity of the parent compound. The tritiated azido label bound reversibly to human vitamin D binding protein in the dark and covalently to human vitamin D binding protein after exposure to ultraviolet light. Reversible binding of tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was compared to tritiated 25-hydroxyvitamin D3 binding to human vitamin D binding protein. Scatchard analysis of the data indicated equivalent maximum density binding sites with a KD,app of 0.21 nM for 25-hydroxyvitamin D3 and a KD,app of 1.3 nM for the azido derivative. Covalent binding was observed only after exposure to ultraviolet irradiation, with an average of 3% of the reversibly bound label becoming covalently bound to vitamin D binding protein. The covalent binding was reduced 70-80% when 25-hydroxyvitamin D3 was present, indicating strong covalent binding at the vitamin D binding site of the protein. When tritiated 3-deoxy-3-azido-25-hydroxyvitamin D3 was incubated with human plasma in the absence and presence of 25-hydroxyvitamin D3, 12% of the azido derivative was reversibly bound to vitamin D binding protein. After ultraviolet irradiation, four plasma proteins covalently bound the azido label, but vitamin D binding protein was the only protein of the four that was unlabeled in the presence of 25-hydroxyvitamin D3.

  8. Relations of Counterface Hardness with Wear Behavior and Tribo-Oxide Layer of AISI H13 Steel

    NASA Astrophysics Data System (ADS)

    Zhang, Q. Y.; Wang, S. Q.; Li, X. X.; Zhou, Y.; Chen, K. M.; Cui, X. H.

    2016-09-01

    Dry sliding wear tests of AISI H13 steel (50 HRC) against AISI D2 steel counterface with three hardness levels (55, 50, and 42 HRC) were performed at 298 K to 873 K (25 °C to 600 °C). The relations of counterface hardness with the wear behavior and tribo-oxide layer of AISI H13 steel were explored. When sliding against the different-hardness counterface, H13 steel presents appreciably changed wear behavior as a function of temperature. For H d/H p (the hardness ratio of disk to pin) > 1, the wear rate increases with the increase of temperature, but the wear rate variation is roughly inversed for H d/H p < 1. For H d/H p = 1, the wear rate first decreases to reach the lowest value at 473 K (200 °C) and then rapidly increases with the increase of temperature. The lowest wear rate appears at 298 K (25 °C) for H d/H p > 1, at 474 K (200 °C) for H d/H p = 1, and at 673 K (400 °C) for H d/H p < 1. As no-oxide tribolayer exists below 473 K (200 °C), the wear behavior roughly complies with Archard's equation; adhesive and abrasive wear prevail, regardless of H d/H p. As tribo-oxide layer exists at 473 K (200 °C) or above, the wear behavior depends on the tribo-oxide layer and thermal strength of the substrate, i.e., the stability of the tribo-oxide layer. Oxidative mild wear prevails at 473 K to 873 K (200 °C to 600 °C) for H d/H p < 1 and merely at 473 K (200 °C) for H d/H p = 1. However, a mild-to-severe transition of oxidative wear occurs at 473 K to 873 K (200 °C to 600 °C) for H d/H p > 1 and at 673 K to 873 K (400 °C to 600 °C) for H d/H p = 1. These findings suggest that the tribo-oxide layers are liable to exist stably for H d/H p ≤ 1 but to readily delaminate for H d/H p > 1.

  9. 2D/3D Program work summary report, [January 1988--December 1992

    SciTech Connect

    Damerell, P. S.; Simons, J. W.

    1993-06-01

    The 2D/3D Program was carried out by Germany, Japan and the United States to investigate the thermal-hydraulics of a PWR large-break LOCA. A contributory approach was utilized in which each country contributed significant effort to the program and all three countries shared the research results. Germany constructed and operated the Upper Plenum Test Facility (UPTF), and Japan constructed and operated the Cylindrical Core Test Facility (CCTF) and the Slab Core Test Facility (SCTF). The US contribution consisted of provision of advanced instrumentation to each of the three test facilities, and assessment of the TRAC computer code against the test results. Evaluations of the test results were carried out in all three countries. This report summarizes the 2D/3D Program in terms of the contributing efforts of the participants.

  10. Supranutritional oral supplementation with vitamin D3 and calcium and the effects on beef tenderness.

    PubMed

    Scanga, J A; Belk, K E; Tatum, J D; Smith, G C

    2001-04-01

    Ultimate meat tenderness can be influenced by numerous preslaughter and postmortem management techniques. Increased levels of intracellular Ca2+, through postmortem injection, infusion, or marination, have been shown to improve the tenderness of cooked meat products. Oral supplementation with vitamin D3 effectively increases serum Ca2+ and has been hypothesized to increase muscle Ca2+ content, the activity of muscle proteases, and thus the tenderness of cooked beef. Individual Charolais x Hereford heifers (n = 191) were assigned to an unsupplemented control group or groups that were supplemented via oral bolus (for dose regulation purposes) with one of seven levels of vitamin D3 (1, 2, 3, 4, or 5 x 10(6) IU D3/d, 2 x 10(6) IU DS/d plus 75 g CaCO3 or 4 x 106 IU D3/d plus 75 g CaCO3) for 2, 4, 6, or 8 d antemortem. Individual feedlot performance, serum Ca2+ levels, and carcass data were collected, and eight longissimus steaks/carcass were used to obtain Warner-Bratzler shear force values measured at 2, 7, 14, and 21 d postmortem for longissimus steaks cooked to 70 degrees or 85 degrees C. Cattle supplemented with 4 x 10(6) IU D3/d plus 75 g of CaCO3 had lower daily feed intake (as-fed) and reduced (P < 0.05) average daily gains compared with controls during the 8-d supplementation period. Additionally, supplemented cattle had numerically higher dressing percentages, possibly due to less fill at the time of slaughter, because carcass weights and USDA yield grades did not differ (P > 0.05) across treatment groups. Supplementation with 1, 2, 3, 4, or 5 x 10(6) IU D3/d, for 2 or more days, increased (P < 0.05) serum Ca2+ concentrations compared with controls. Whereas cattle that received additional dietary Ca2+ in the form of CaCO3 had the lowest blood serum Ca2+ concentration. Although blood serum Ca2+ was increased, supplementation with any level of vitamin D3 for any length of time up to 8 d did not improve (P > 0.05) Warner-Bratzler shear force at 2, 7, 14, or 21 d

  11. Exact solution of the D3 non-Abelian anyon chain

    NASA Astrophysics Data System (ADS)

    Braylovskaya, Natalia; Finch, Peter E.; Frahm, Holger

    2016-08-01

    Commuting transfer matrices for linear chains of interacting non-Abelian anyons from the two-dimensional irreducible representation of the dihedral group D3 [or, equivalently, the integer sector of the s u (2) 4 spin-1 chain] are constructed using the spin-anyon correspondence to a D3-symmetric formulation of the XXZ Heisenberg spin chain. The spectral problem is solved using discrete inversion identities satisfied by these transfer matrices and functional Bethe ansatz methods. The resulting spectrum can be related to that of the XXZ spin-1/2 Heisenberg chain with boundary conditions depending on the topological sector of the anyon chain. The properties of this model in the critical regime are studied by finite size analysis of the spectrum. In particular, points in the phase diagram where the anyon chain realizes some of the rational Z2 orbifold theories are identified.

  12. Supersymmetric D3/D7 for holographic flavors on curved space

    NASA Astrophysics Data System (ADS)

    Karch, Andreas; Robinson, Brandon; Uhlemann, Christoph F.

    2015-11-01

    We derive a new class of supersymmetric D3/D7 brane configurations, which allow to holographically describe N=4 SYM coupled to massive N=2 flavor degrees of freedom on spaces of constant curvature. We systematically solve the κ-symmetry condition for D7-brane embeddings into AdS4-sliced AdS5×S5, and find supersymmetric embeddings in a simple closed form. Up to a critical mass, these embeddings come in surprisingly diverse families, and we present a first study of their (holographic) phenomenology. We carry out the holographic renormalization, compute the one-point functions and attempt a field-theoretic interpretation of the different families. To complete the catalog of supersymmetric D3/D7 configurations, we construct analogous embeddings for flavored N=4 SYM on S4 and dS4.

  13. Advanced 2D-3D registration for endovascular aortic interventions: addressing dissimilarity in images

    NASA Astrophysics Data System (ADS)

    Demirci, Stefanie; Kutter, Oliver; Manstad-Hulaas, Frode; Bauernschmitt, Robert; Navab, Nassir

    2008-03-01

    In the current clinical workflow of minimally invasive aortic procedures navigation tasks are performed under 2D or 3D angiographic imaging. Many solutions for navigation enhancement suggest an integration of the preoperatively acquired computed tomography angiography (CTA) in order to provide the physician with more image information and reduce contrast injection and radiation exposure. This requires exact registration algorithms that align the CTA volume to the intraoperative 2D or 3D images. Additional to the real-time constraint, the registration accuracy should be independent of image dissimilarities due to varying presence of medical instruments and contrast agent. In this paper, we propose efficient solutions for image-based 2D-3D and 3D-3D registration that reduce the dissimilarities by image preprocessing, e.g. implicit detection and segmentation, and adaptive weights introduced into the registration procedure. Experiments and evaluations are conducted on real patient data.

  14. Interface for 15VSM-5 and Elektronika D3-28 minicomputers with digital measuring instruments

    SciTech Connect

    Udovichenko, N.A.; Polikarpov, Yu.I.; Makushkin, B.V.

    1987-07-01

    A device is described for data input (up to 8 decimal digits in 8421 code) into 15VSM-5 and Elektronika D3-28 minicomputers from four measuring instruments: a V7-21 voltmeter and three Ch3-54 frequency counters. Data from the voltmeter are entered by software interrogation and data from the frequency counters are entered by software interrupts. The device is implemented by TTL integrated circuits.

  15. Association of vitamin D3 with alveolar bone regeneration in dogs.

    PubMed

    Hong, Hsiang-Hsi; Yen, Tzung-Hai; Hong, Adrienne; Chou, Ting-An

    2015-06-01

    Designed sockets prepared on the mandibles of nine Beagle dogs were divided into three groups: Calcitriol +Alloplast, Alloplast and Empty. Five of the nine dogs received Vit.D3 and calcium supplement (Vit.D/Ca group), while the other four dogs without supplements were assigned to Non-Vit.D/Ca group. After 4 weeks, the extent of vertical ridge resorption (VRR), bone density (density), new bone formation (NBF) and implant stability quotient (ISQ) were measured. Following systemic Vit.D/Ca administration, the Empty subgroup showed significant differences from the Calcitriol + Alloplast subgroup on variants NBF/Density/VRR and the Alloplast subgroup on items NBF/Density/ISQ/VRR. Alternatively, the Calcitriol + Alloplast subgroup revealed higher values of NBF/Density/ISQ (P < 0.001) and a lower VRR value (P = 0.001) than the Alloplast subgroup. Although there were no significant differences in NBF (P = 0.349), density (P = 0.796), ISQ (P = 0.577) and VRR (0.979) comparisons on alloplast treatment between the Vit.D/Ca and Non-Vit.D/Ca groups, local application with Calcitriol + Alloplast demonstrated better NBF/Density/ISQ (P = 0.02 to <0.001) effects than which of Alloplast subgroups. Consequently, the results showed that both systemic and local vitamin D3 treatment might accelerate bone regeneration in dogs. Within the using dose, systemic vitamin D3 treatment displayed a superior stimulating effect than local vitamin D3 application did.

  16. Fos expression in response to dopamine D3-preferring phenylpiperazine drugs given with and without cocaine

    PubMed Central

    Nolan, Brian C.; Liu, Shinban; Hammerslag, Lindsey R.; Cheung, Timothy H. C.; Lenz, Jeffrey; Mach, Robert H.; Luedtke, Robert R.; Neisewander, Janet L.

    2014-01-01

    WC 44 and WC 10 are phenylpiperazines with low (23 fold) to moderate (42 fold) selectivity for dopamine D3 receptors (D3Rs) over D2Rs, respectively. WC 44 is a full D3R agonist in the forskolin-stimulated adenylyl cyclase (AC) assay, whereas WC 10 has little efficacy. In contrast to their opposite effects in the AC assay, these drugs often produce similar behavioral effects, suggesting that the AC assay does not predict the efficacy of these drugs in vivo. Here we examined whether Fos protein expression induced by these drugs would be more consistent with their behavioral effects in vivo. Rats received either vehicle, WC 10 (5.6 mg/kg, i.p.), WC 44 (10.0 mg/kg, i.p), cocaine (10.0 mg/kg, i.p.), or cocaine with WC 10 (5.6 mg/kg, i.p.) or with WC 44 (10.0 mg/kg, i.p). Locomotion was monitored for 90 min and the brains were harvested for immunohistochemistry. Both WC 10 and WC 44 decreased spontaneous and cocaine-induced locomotion. Both compounds also increased Fos expression relative to saline in the dorsal striatum and nucleus accumbens core and shell, and relative to cocaine alone in the nucleus accumbens shell. The findings suggest that even though these compounds have different efficacy in the AC bioassy, they produce similar brain activation and attenuation of cocaine hyperlocomotion. Together with our previous research demonstrating that these compounds down-shift the cocaine self-administration dose-effect function, the findings support the idea that D3R-selective compounds may be useful for cocaine dependence medications development. PMID:23766142

  17. Functionalized Ergot-alkaloids as potential dopamine D3 receptor agonists for treatment of schizophrenia

    NASA Astrophysics Data System (ADS)

    Ivanova, Bojidarka; Spiteller, Michael

    2012-12-01

    The relationship between the molecular structure and physical properties of functionalized naturally occurred Ergot-alkaloids as potential dopamine D3 receptor agonists is presented. The molecular modeling of the ergoline-skeleton is based on the comprehensive theoretical study of the binding affinity of the isolated chemicals towards the active sites of the D3 sub-type receptor (D3R) loops. The studied proton accepting ability under physiological conditions allows classifying four types of monocationics, characterizing with the different binding modes to D3R involving selected amino acid residues to the active sites. These results marked the pharmaceutical potential and clinical usage of the reported compounds as antipsychotic drugs for Schizophrenia treatment, since they allowed evaluating the highlights of the different hypothesizes of the biochemical causes the illness. The applied complex approach for theoretical and experimental elucidation, including quantum chemistry method, electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometric (MS) methods, nuclear magnetic resonance and vibrational IR and Raman spectroscopy on the isolated fifteen novel derivatives (1)-(15) and their different protonated forms (1a)-(15a) evidenced a strong dependence of molecular conformation, physical properties and binding affinity. Thus, the semi-synthetic functionalization of the naturally occurred products (NPs), provided significant possibilities to further molecular drugs-design and development of novel derivatives with wanted biological function, using the established profile of selected classes/families of NPs. The work described chiefly the non-linear (NL) approach for the interpretation of the mass chromatograms on the performed hybrid high performance liquid chromatography (HPLC) tandem MS/MS and MS/MS/MS experiments, discussing the merits and great diversity of instrumentation flexibility, thus achieving fundamental

  18. PG01037, a novel dopamine D3 receptor antagonist, inhibits the effects of methamphetamine in rats.

    PubMed

    Higley, Amanda E; Spiller, Krista; Grundt, Peter; Newman, Amy Hauck; Kiefer, Stephen W; Xi, Zheng-Xiong; Gardner, Eliot L

    2011-02-01

    Our previous studies have shown that the selective dopamine D(3) receptor antagonists SB-277011A or NGB 2904 significantly attenuate cocaine self-administration under a progressive-ratio reinforcement schedule and cocaine-, methamphetamine- or nicotine-enhanced brain stimulation reward. However, the poor bioavailability of SB-277011A has limited its potential use in humans. In the present study, we investigated the effects of the novel D(3) receptor antagonist PG01037 on methamphetamine self-administration, methamphetamine-associated cue-induced reinstatement of drug seeking and methamphetamine-enhanced brain stimulation reward. Rats were allowed to intravenously self-administer methamphetamine under fixed-ratio 2 and progressive-ratio reinforcement conditions, and then the effects of PG01037 on methamphetamine self-administration and cue-induced reinstatement were assessed. Additional groups of rats were trained for intracranial electrical brain stimulation reward and the effects of PG01037 and methamphetamine on brain stimulation reward were assessed. Acute intraperitoneal administration of PG01037 (3, 10, 30 mg/kg) failed to alter methamphetamine or sucrose self-administration under fixed-ratio 2 reinforcement, but significantly lowered the break-point levels for methamphetamine or sucrose self-administration under progressive-ratio reinforcement. In addition, PG01037 significantly inhibited methamphetamine-associated cue-triggered reinstatement of drug-seeking behavior and methamphetamine-enhanced brain stimulation reward. These data suggest that the novel D(3) antagonist PG01037 significantly attenuates the rewarding effects as assessed by progressive-ratio self-administration and brain stimulation reward, and inhibits methamphetamine-associated cue-induced reinstatement of drug-seeking behavior These findings support the potential use of PG01037 or other selective D(3) antagonists in the treatment of methamphetamine addiction.

  19. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics

    NASA Astrophysics Data System (ADS)

    Sokoloff, Pierre; Giros, Bruno; Martres, Marie-Pascale; Bouthenet, Marie-Louise; Schwartz, Jean-Charles

    1990-09-01

    A dopamine receptor has been characterized which differs in its pharmacology and signalling system from the D1 or D2 receptor and represents both an autoreceptor and a postsynaptic receptor. The D3 receptor is localized to limbic areas of the brain, which are associated with cognitive, emotional and endocrine functions. It seems to mediate some of the effects of antipsychotic drugs and drugs used against Parkinson's disease, that were previously thought to interact only with D2 receptors.

  20. Quantifying the vitamin D3 synthesizing potential of UVB lamps at specific distances over time.

    PubMed

    Schmidt, Debra A; Mulkerin, Diane; Boehm, Daniel R; Ellersieck, Mark R; Lu, Zhiren; Campbell, Matthew; Chen, Tai C; Holick, Michael F

    2010-01-01

    The purpose of this study was to quantify the ultraviolet B (UVB) output and in vitro previtamin D(3) synthesis over time from various artificial light sources. Three incandescent lamps, T-Rex Active UVHeat 160 watt spot, T-Rex Active UVHeat 160 watt flood, and ZooMed PowerSun 160 watt flood, and two 1.2 m fluorescent lamps, Sylvania Blacklight 350 BL and ZooMed Reptisun 5.0, were studied. Total UVB irradiance and concentration of previtamin D synthesized using an in vitro ampoule model were quantified initially and at monthly intervals for 1 year. Incandescent lamps were measured at distances of 0.9 and 1.5 m while fluorescent lamps were measured at distances of 30.5 and 45.7 cm at the lamp's center, using both the radiometer and ampoules. Fluorescent lamp irradiance was also measured at the lamp's ends. Data were analyzed as a repeated measures split-plot in time using SAS with all mean differences determined using Least Squares Means. Incandescent lamp irradiance differences were seen at various distances. The UVHeat lamps had consistently higher previtamin D(3) production and irradiance readings compared with the PowerSun lamp. Reptisun 5.0 was consistently higher in UVB irradiance over Sylvania BL 350 at both 30.5 and 45.7 cm. However, there were no differences when comparing conversion of 7-dehydrocholesterol to previtamin D(3). Irradiance differences were detected between the centers and ends of the fluorescent lamps. Until UVB requirements for vitamin D(3) synthesis in animals are determined, it is impossible to state that one light is superior to another.

  1. What Is Vitamin D3 and Its Potential Use in Dermatology?

    PubMed

    Sánchez-Armendáriz, Karen; García-Gil, Ana; Domínguez-Cherit, Judith

    2016-01-01

    There are many clinical studies that show the importance of vitamin D in multiple skin disorders. Understanding the molecular elements of cathelicidin expression might lead to new treatments and help explain mechanisms of current therapies. Overall, current data are generating many questions and expectations and require larger trials to confirm the therapeutic use of vitamin D3 supplementation. Vitamin D now represents a vast and promising field of research to dermatologists. PMID:27502255

  2. Polymorphism of 14C vitamin D3 binding protein in cattle and water buffalo serum.

    PubMed

    Masina, P; Ramunno, L; Iannelli, D

    1978-01-01

    Cattle and water buffalo sera labelled with vitamin D3[14C] (300 and 480 individual samples respectively) were subjected to starch gel electrophoresis followed by autoradiography in an attempt to identify a possible polymorphism of the proteins capable of binding this vitamin. Three phenotypes controlled by two codominant autosomal alleles were identified in cattle while in water buffalo six phenotypes controlled by three codominant autosomal alleles were observed.

  3. Maturity and storage influence on the apple (Malus domestica) allergen Mal d 3, a nonspecific lipid transfer protein.

    PubMed

    Sancho, Ana I; Foxall, Robert; Rigby, Neil M; Browne, Thomas; Zuidmeer, Laurian; van Ree, Ronald; Waldron, Keith W; Mills, E N Clare

    2006-07-12

    Consumption of apples can provoke severe allergic reactions, in susceptible individuals, due to the presence of the allergen Mal d 3, a nonspecific lipid transfer protein, found largely in the fruit skin. Levels of Mal d 3 were determined in peel as a function of apple cultivar, position of the fruit growing on the tree, apple maturity, and postharvest storage by ELISA. As the apples mature, Mal d 3 levels increased, although the rate was dependent on cultivar and tree position. During storage, levels of Mal d 3 decreased in all cultivars (cvs. Cox, Jonagored, and Gala), the rate of overall decrease being greatest under controlled atmosphere conditions. There was no correlation between Mal d 3 levels and total apple peel protein, indicating specific alterations in Mal d 3 expression. Thus pre- and postharvest treatments (i.e., storage) can modify the allergen load in apple peel, the highest levels being found in overly mature and freshly harvested fruits.

  4. Formulation of Nanoliposomal Vitamin D3 for Potential Application in Beverage Fortification

    PubMed Central

    Mohammadi, Maryam; Ghanbarzadeh, Babak; Hamishehkar, Hamed

    2014-01-01

    Purpose: Vitamin D, a liposoluble vitamin has many benefits on health. Encapsulation of bioactives in lipid-based carrier systems like nanoliposomes preserves their native properties against oxidation over time along with providing its stable aqueous dispersion. Methods: In the current study, vitamin D3 nanoliposomes were prepared using thin-film hydration-sonication method and fully characterized by different instrumental techniques. Results: According to FTIR and DSC results, no interaction was observed between encapsulated nutraceutical and liposome constituents. The particle size and size distribution (Span value) were calculated 82–90 nm and 0.70–0.85, respectively. TEM analysis showed nano sized globular and bilayer vesicles. In all formations, the encapsulation efficiency of vitamin D3 was calculated more than 93%. Addition of cholesterol to lecithin bilayer increased the negative zeta potential from -29 to -43mV. Conclusion: The results of this study concluded that the liposomal nanoparticles may be introduced as a suitable carrier for fortification of beverages with vitamin D3. PMID:25671191

  5. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.

    PubMed

    Newton, Thomas F; Haile, Colin N; Mahoney, James J; Shah, Ravi; Verrico, Christopher D; De La Garza, Richard; Kosten, Thomas R

    2015-11-30

    Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine. PMID:26239766

  6. Association study between schizophrenia and dopamine D3 receptor gene polymorphism

    SciTech Connect

    Tanaka, Toshihisa; Takahashi, Makoto; Maeda, Masaya

    1996-07-26

    Crocq et al. reported the existence of an association between schizophrenia and homozygosity of a BalI polymorphism in the first exon of the dopamine D3 receptor (DRD3) gene. In response to this report, further studies were conducted; however, these studies yielded conflicting results. In the present study, we examined 100 unrelated Japanese schizophrenics and 100 normal controls to determine any association between this polymorphism and schizophrenia. Results suggest that neither allele nor genotype frequencies of the DRD3 gene in the schizophrenics as a whole are significantly different from those of the controls. Further, we found no association between any allele or genotype and any clinical subtype based on family history of schizophrenia and age-at-onset. A significantly high frequency of homozygosity of a dopamine D3 receptor gene allele was not observed in the schizophrenics as a whole, or in clinical subtypes. Our results suggest that an association between the dopamine D3 receptor gene and schizophrenia is unlikely to exist. 26 refs., 1 tab.

  7. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.

    PubMed

    Newton, Thomas F; Haile, Colin N; Mahoney, James J; Shah, Ravi; Verrico, Christopher D; De La Garza, Richard; Kosten, Thomas R

    2015-11-30

    Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine.

  8. Intestinal MUC2 mucin supramolecular topology by packing and release resting on D3 domain assembly.

    PubMed

    Nilsson, Harriet E; Ambort, Daniel; Bäckström, Malin; Thomsson, Elisabeth; Koeck, Philip J B; Hansson, Gunnar C; Hebert, Hans

    2014-07-15

    MUC2 is the major gel-forming mucin of the colon forming a protective gel barrier organized into an inner stratified and an outer loose layer. The MUC2 N-terminus (D1-D2-D'D3 domains) has a dual function in building a net-like structure by disulfide-bonded trimerization and packing the MUC2 polymer into an N-terminal concatenated polygonal platform with the C-termini extending perpendicularly by pH- and calcium-dependent interactions. We studied the N-terminal D'D3 domain by producing three recombinant variants, with or without Myc tag and GFP (green fluorescent protein), and analyzed these by gel filtration, electron microscopy and single particle image processing. The three variants were all trimers when analyzed upon denaturing conditions but eluted as hexamers upon gel filtration under native conditions. Studies by electron microscopy and three-dimensional maps revealed cage-like structures with 2- and 3-fold symmetries. The structure of the MUC2 D3 domain confirms that the MUC2 mucin forms branched net-like structures. This suggests that the MUC2 mucin is stored with two N-terminal concatenated ring platforms turned by 180° against each other, implicating that every second unfolded MUC2 net in mature mucus is turned upside down.

  9. Effect of Cyclosporin A on the Uptake of D3-Selective PET Radiotracers in Rat Brain

    PubMed Central

    Tu, Zhude; Li, Shihong; Xu, Jinbin; Chu, Wenhua; Jones, Lynne A.; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    Introduction Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Methods Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. Results All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters. PMID:21718948

  10. 2.5-D/3-D resistivity modelling in anisotropic media using Gaussian quadrature grids

    NASA Astrophysics Data System (ADS)

    Zhou, Bing; Greenhalgh, Mark; Greenhalgh, S. A.

    2009-01-01

    We present a new numerical scheme for 2.5-D/3-D direct current resistivity modelling in heterogeneous, anisotropic media. This method, named the `Gaussian quadrature grid' (GQG) method, cooperatively combines the solution of the Variational Principle of the partial differential equation, Gaussian quadrature abscissae and local cardinal functions so that it has the main advantages of the spectral element method. The formulation shows that the GQG method is a modification of the spectral element method but does not employ the constant elements or require the mesh generator to match the Earth's surface. This makes it much easier to deal with geological models having a 2-D/3-D complex topography than using traditional numerical methods. The GQG technique can achieve a similar convergence rate to the spectral element method. We show it transforms the 2.5-D/3-D resistivity modelling problem into a sparse and symmetric linear equation system that can be solved by an iterative or matrix inversion method. Comparison with analytic solutions for homogeneous isotropic and anisotropic models shows that the error depends on the Gaussian quadrature order (abscissa number) and the subdomain size. The higher the order or the smaller the subdomain size that is employed, the more accurate are the results obtained. Several other synthetic examples, both homogeneous and inhomogeneous, incorporating sloping, undulating and severe topography, are presented and found to yield results comparable to finite element solutions involving a dense mesh.

  11. Fancy bioisosteres: novel paracyclophane derivatives as super-affinity dopamine D3 receptor antagonists.

    PubMed

    Schlotter, Karin; Boeckler, Frank; Hübner, Harald; Gmeiner, Peter

    2006-06-15

    The exploration of the chemical diversity space depends on the discovery of novel bioisosteric elements. As a continuation of our project on bilayered arene surrogates, we herein report on [2.2]paracyclophane-derived dopamine D3 receptor antagonists of type 4 and 6. For the most promising test compound 6a, bearing a 2-methoxyphenyl substituent, a stereocontrolled preparation was performed when the planar chirality of enantiomers (R)-6a (FAUC 418) and (S)-6a caused a considerable differentiation of D3 binding, which is indicated by K(i) values of 0.19 and 3.0 nM, respectively. Functional experiments showed D3 antagonist properties for the paracyclophane derivatives of type 6. To elucidate putative bioactive low-energy conformations, DFT-based studies including the calculation of diagnostic magnetic shielding properties were performed. An 89% increase in volume for the [2.2]paracyclophane moiety compared to that of the monolayered benzofurane of lead compound 3b indicates higher plasticity of GPCR binding regions than usually expected. PMID:16759104

  12. Prolonged treatment with pramipexole promotes physical interaction of striatal dopamine D3 autoreceptors with dopamine transporters to reduce dopamine uptake.

    PubMed

    Castro-Hernández, Javier; Afonso-Oramas, Domingo; Cruz-Muros, Ignacio; Salas-Hernández, Josmar; Barroso-Chinea, Pedro; Moratalla, Rosario; Millan, Mark J; González-Hernández, Tomás

    2015-02-01

    The dopamine (DA) transporter (DAT), a membrane glycoprotein expressed in dopaminergic neurons, clears DA from extracellular space and is regulated by diverse presynaptic proteins like protein kinases, α-synuclein, D2 and D3 autoreceptors. DAT dysfunction is implicated in Parkinson's disease and depression, which are therapeutically treated by dopaminergic D2/D3 receptor (D2/D3R) agonists. It is, then, important to improve our understanding of interactions between D3R and DAT. We show that prolonged administration of pramipexole (0.1mg/kg/day, 6 to 21 days), a preferential D3R agonist, leads to a decrease in DA uptake in mouse striatum that reflects a reduction in DAT affinity for DA in the absence of any change in DAT density or subcellular distribution. The effect of pramipexole was absent in mice with genetically-deleted D3R (D3R(-/-)), yet unaffected in mice genetically deprived of D2R (D2R(-/-)). Pramipexole treatment induced a physical interaction between D3R and DAT, as assessed by co-immunoprecipitation and in situ proximity ligation assay. Furthermore, it promoted the formation of DAT dimers and DAT association with both D2R and α-synuclein, effects that were abolished in D3R(-/-) mice, yet unaffected in D2R(-/-) mice, indicating dependence upon D3R. Collectively, these data suggest that prolonged treatment with dopaminergic D3 agonists provokes a reduction in DA reuptake by dopaminergic neurons related to a hitherto-unsuspected modification of the DAT interactome. These observations provide novel insights into the long-term antiparkinson, antidepressant and additional clinical actions of pramipexole and other D3R agonists. PMID:25511804

  13. Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor heterotetramer.

    PubMed

    Guitart, Xavier; Navarro, Gemma; Moreno, Estefania; Yano, Hideaki; Cai, Ning-Sheng; Sánchez-Soto, Marta; Kumar-Barodia, Sandeep; Naidu, Yamini T; Mallol, Josefa; Cortés, Antoni; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Ferré, Sergi

    2014-10-01

    The dopamine D1 receptor-D3 receptor (D1R-D3R) heteromer is being considered as a potential therapeutic target for neuropsychiatric disorders. Previous studies suggested that this heteromer could be involved in the ability of D3R agonists to potentiate locomotor activation induced by D1R agonists. It has also been postulated that its overexpression plays a role in L-dopa-induced dyskinesia and in drug addiction. However, little is known about its biochemical properties. By combining bioluminescence resonance energy transfer, bimolecular complementation techniques, and cell-signaling experiments in transfected cells, evidence was obtained for a tetrameric stoichiometry of the D1R-D3R heteromer, constituted by two interacting D1R and D3R homodimers coupled to Gs and Gi proteins, respectively. Coactivation of both receptors led to the canonical negative interaction at the level of adenylyl cyclase signaling, to a strong recruitment of β-arrestin-1, and to a positive cross talk of D1R and D3R agonists at the level of mitogen-activated protein kinase (MAPK) signaling. Furthermore, D1R or D3R antagonists counteracted β-arrestin-1 recruitment and MAPK activation induced by D3R and D1R agonists, respectively (cross-antagonism). Positive cross talk and cross-antagonism at the MAPK level were counteracted by specific synthetic peptides with amino acid sequences corresponding to D1R transmembrane (TM) domains TM5 and TM6, which also selectively modified the quaternary structure of the D1R-D3R heteromer, as demonstrated by complementation of hemiproteins of yellow fluorescence protein fused to D1R and D3R. These results demonstrate functional selectivity of allosteric modulations within the D1R-D3R heteromer, which can be involved with the reported behavioral synergism of D1R and D3R agonists.

  14. 1α,25-dihydroxyvitamin D3 stimulates activin A production to fine-tune osteoblast-induced mineralization.

    PubMed

    Woeckel, V J; van der Eerden, B C J; Schreuders-Koedam, M; Eijken, M; Van Leeuwen, J P T M

    2013-11-01

    In healthy bones, mineralization has to be tightly controlled to avoid pathological phenotypes. In this study, we investigated interactions between 1α,25(OH)2 D3 (1,25D3) and activin A in the regulation of osteoblast induced mineralization. In human osteoblast cultures, we demonstrated that besides stimulation of mineralization, 1,25D3 also induced activin A, a strong inhibitor of mineralization. Simultaneously, follistatin (FST), the natural antagonist of activin A, was down-regulated by1,25D3. This resulted in an increase in activin A activity during 1,25D3 treatment. We also showed that in 1,25D3-treated osteoblasts, mineralization can be further increased when activin A activity was abrogated by adding exogenous FST. This observation implies that, besides stimulation of mineralization, 1,25D3 also controls activin A-mediated inhibition of mineralization. Besides activin A, 1,25D3 also induces osteocalcin (BGLAP), another inhibitor of mineralization. Warfarin, which has been shown to inactivate osteocalcin, increased 1,25D3-induced mineralization. Interaction between these two systems became evident from the synergistic increase in BGLAP expression upon blocking activin activity in 1,25D3-treated cultures. In conclusion, we demonstrate that 1,25D3 stimulation of mineralization by human osteoblasts is suppressed by concomitant induction of inhibitors of mineralization. Mineralization induction by 1,25D3 may actually be controlled via interplay with activin A and osteocalcin. Finally, this complex regulation of mineralization substantiates the significance of tight control of mineralization to prevent excessive mineralization and consequently reduction in bone quality and strength.

  15. Cariprazine for the Treatment of Schizophrenia: A Review of this Dopamine D3-Preferring D3/D2 Receptor Partial Agonist.

    PubMed

    Citrome, Leslie

    2016-01-01

    Cariprazine is an antipsychotic medication and received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in September 2015. Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors. The recommended dose range of cariprazine for the treatment of schizophrenia is 1.5-6 mg/d; the starting dose of 1.5 mg/d is potentially therapeutic. Cariprazine is administered once daily and is primarily metabolized in the liver through the CYP3A4 enzyme system and, to a lesser extent, by CYP2D6. There are two active metabolites of note, desmethyl-cariprazine and didesmethyl-cariprazine; the latter's half-life is substantially longer than that for cariprazine and systemic exposure to didesmethyl-cariprazine is several times higher than that for cariprazine. Three positive, 6-week, Phase 2/3, randomized controlled trials in acute schizophrenia demonstrated superiority of cariprazine over placebo. Pooled responder rates were 31% for cariprazine 1.5-6 mg/d vs. 21% for placebo, resulting in a number needed to treat (NNT) of 10. In a 26-72 week, randomized withdrawal study, significantly fewer patients relapsed in the cariprazine group compared with placebo (24.8% vs. 47.5%), resulting in an NNT of 5. The most commonly encountered adverse events (incidence ≥5% and at least twice the rate of placebo) are extrapyramidal symptoms (number needed to harm [NNH] 15 for cariprazine 1.5-3 mg/d vs. placebo and NNH 10 for 4.5-6 mg/d vs. placebo) and akathisia (NNH 20 for 1.5-3 mg/d vs. placebo and NNH 12 for 4.5-6 mg/d vs. placebo). Short-term weight gain appears small (approximately 8% of patients receiving cariprazine 1.5-6 mg/d gained ≥7% body weight from baseline, compared with 5% for those randomized to placebo, resulting in an NNH of 34). Cariprazine is associated with no clinically

  16. Near surface chemistry and corrosion behavior of excimer laser surface-melted AISI type 304 stainless steel

    SciTech Connect

    Baer, D.R.; Frydrych, D.J.; Jervis, T.R.

    1988-05-01

    The effects of excimer laser surface melting on the near-surface chemistry, and corrosion behavior of AISI 304 stainless steel have been examined as a function of total energy deposited on the specimen. The surface chemistry resulting from the laser treatments has been examined using Auger electron spectroscopy. Electrochemical methods were used to monitor the corrosion behavior of the specimens in deaerated 0.1 M NaCl. Electron microscopy was used to characterize the extent of local corrosion of the specimens. Laser treatment was observed to increase the chromium concentration of the surface oxide and to reduce the number of pits. Two types of pits were observed on untreated material, but only one type of pit occurred after laser treatment. 7 refs., 5 figs.

  17. Fractographic evaluation of creep effects on strain-controlled fatigue-cracking of AISI 304LC and 316 stainless steel

    NASA Technical Reports Server (NTRS)

    Oldrieve, R. E.

    1978-01-01

    Analysis of high temperature low cycle fatigue of AISI 304LC and 316 stainless steels by the method of strainrange partitioning results in four separate strainrange versus life relationships, depending upon the way in which creep-strain and plastic strain are combined within a cycle. Fractography is used in this investigation of the creep-fatigue interaction associated with these cycles. The PP and PC-cycle fractures were transgranular. The PC-cycle resulted in fewer cycles of initiation and shorter total cyclic life for the same applied inelastic strainrange. The CC-cycle had mixed transgranular and intergranular fracture, fewer cycles of initiation and shorter cycle life than PP or PC. The CP-cycle had fully integranular cracking, and failed in fewer cycles than were required for cracks to initate for PP,PC, and CC.

  18. Application of strainrange partitioning to the prediction of creep-fatigue lives of AISI types 304 and 316 stainless steel

    NASA Technical Reports Server (NTRS)

    Saltsman, J. F.; Halford, G. R.

    1976-01-01

    As a demonstration of the predictive capabilities of the method of Strainrange Partitioning, published high-temperature, low cycle, creep-fatigue test results on AISI Types 304 and 316 stainless steel were analyzed and calculated, cyclic lives compared with observed lives. Predicted lives agreed with observed lives within factors of two for 76 percent, factors of three for 93 percent, and factors of four for 98 percent of the laboratory tests analyzed. Agreement between observed and predicted lives is judged satisfactory considering that the data are associated with a number of variables (two alloys, several heats and heat treatments, a range of temperatures, different testing techniques, etc.) that are not directly accounted for in the calculations.

  19. Application of Strainrange Partitioning to the prediction of creep-fatigue lives of AISI Types 304 and 316 stainless steel

    NASA Technical Reports Server (NTRS)

    Saltsman, J. F.; Halford, G. R.

    1977-01-01

    As a demonstration of the predictive capabilities of the method of Strainrange Partitioning, published high-temperature, low cycle, creep-fatigue test results on AISI Types 304 and 316 stainless steel were analyzed and calculated cyclic lives compared with observed lives. Predicted lives agreed with observed lives within factors of two for 76 percent, factors of three for 93 percent, and factors of four for 98 percent of the laboratory tests analyzed. Agreement between observed and predicted lives is judged satisfactory considering that the data are associated with a number of variables (two alloys, several heats and heat treatments, a range of temperatures, different testing techniques, etc.) that are not directly accounted for in the calculations.

  20. Tribo-electrochemical characterization of hafnium multilayer systems deposited on nitride/vanadium nitride AISI 4140 steel

    NASA Astrophysics Data System (ADS)

    Mora, M.; Vera, E.; Aperador, W.

    2016-02-01

    In this work is presented the synergistic behaviour among corrosion/wear (tribocorrosion) of the multilayer coatings hafnium nitride/vanadium nitride [HfN/VN]n. The multilayers were deposited on AISI 4140 steel using the technique of physical vapor deposition PVD magnetron sputtering, the tests were performed using a pin-on-disk tribometer, which has an adapted potentiostat galvanostat with three-electrode electrochemical cell. Tribocorrosive parameters such as: Friction coefficient between the coating and the counter body (100 Cr6 steel ball); Polarization resistance by means of electrochemical impedance spectroscopy technique and corrosion rate by polarization curves were determined. It was observed an increase in the polarization resistance, a decrease in the corrosion rate and a low coefficient of friction in comparison with the substrate, due to an increase on the number of bilayers.

  1. Corrosion-fatigue behavior of an annealed AISI 1045 carbon steel coated with electroless nickel-phosphorus

    SciTech Connect

    Pertuz, A.; Chitty, J.A.; Puchi, E.S. ); Hintermann, H. . Faculty of Sciences)

    1999-08-01

    The influence of an industrial electroless nickel-phosphorus deposit on the corrosion-fatigue properties of an annealed AISI 1045 steel has been investigated. For this purpose, three corrosive media were selected: distilled water and two NaCl solutions of different concentration (3 and 5%) in distilled water. Corrosion-fatigue tests were conducted at alternating stress levels ranging between 219 and 329 MPa at a frequency of 50 Hz. The corrosion-fatigue properties of the coated and uncoated substrates are very similar when testing is conducted in salty water. However, for testing in distilled water the corrosion-fatigue properties of coated substrates were diminished in relation to the uncoated material. The fractographic analysis of the fracture surfaces revealed the presence of fatigue marks within the electroless nickel-phosphorus deposit, which indicate that the fracture mechanism of the coating is associated to the cyclic loading of the material.

  2. Effect of postweld treatment on the fatigue crack growth rate of electron-beam-welded AISI 4130 steel

    NASA Astrophysics Data System (ADS)

    Wang, Chien-Chun; Chang, Yih

    1996-10-01

    This article studies the effect of in-chamber electron beam and ex-chamber furnace postweld treatments on the fatigue crack growth rate of electron-beam-welded AISI 4130 steel. Mechanical properties of the weldment are evaluated by tensile testing, while the fatigue properties are investigated by a fatigue crack propagation method. Microstructural examination shows that both postweld treatments temper the weldment by the appropriate control of beam pattern width, input beam energy, and furnace temperature. In addition, the ductility, strength, and microhardness of the weldment also reflect this tempering effect. The fatigue crack growth rate is decreased after both postweld treatments. This is mainly caused by the existence of a toughened microstructure and relief of the residual stress due to the fact that (1) the residual stress becomes more compressive as more beam energy is delivered into the samples and (2) postweld furnace tempering effectively releases the tensile stress into a compressive stress state.

  3. Influence of PC-GTAW Parameters on the Microstructural and Mechanical Properties of Thin AISI 1008 Steel Joints

    NASA Astrophysics Data System (ADS)

    Kumar, Ravindra; Anant, Ramkishor; Ghosh, P. K.; Kumar, Ankit; Agrawal, B. P.

    2016-09-01

    Butt weld joints are prepared using pulse current gas tungsten arc welding out of thin sheets of AISI 1008 steel using various combinations of pulse parameters. During welding, the welding speed was kept high, but with the increase of welding speed the mean current was also increased to get the required weld joint at the constant heat input. The use of pulse current has led to improvement in mechanical and metallurgical properties of weld joints. It has resulted in less development of humping which is a common problem with high-speed welding. The undercut or dipped weld face is not observed severe. The tensile strength and hardness are enhanced by 12.5 and 12%. The increase of tensile strength and hardness is justified through TEM micrograph showing the presence of dislocation.

  4. Corrosion resistance of multilayer hybrid sol-gel coatings deposited on the AISI 316L austenitic stainless steel

    NASA Astrophysics Data System (ADS)

    Caballero, Y. T.; Rondón, E. A.; Rueda, L.; Hernández Barrios, C. A.; Coy, A.; Viejo, F.

    2016-02-01

    In the present work multilayer hybrid sol-gel coatings were synthesized on the AISI 316L austenitic stainless steel employed in the fabrication of orthopaedic implants. Hybrid sols were obtained from a mixture of inorganic precursor, TEOS, and organic, GPTMS, using ethanol as solvent, and acetic acid as catalyst. The characterization of the sols was performed using pH measurements, rheological tests and infrared spectroscopy (FTIR) for different ageing times. On the other hand, the coatings were characterized by scanning electron microscopy (SEM), while the corrosion resistance was evaluated using anodic potentiodynamic polarization in SBF solution at 37±2°C. The results confirmed that sol-gel synthesis employing TEOS-GPTMS systems produces uniform and homogeneous coatings, which enhanced the corrosion resistance with regard to the parent alloy. Moreover, corrosion performance was retained after applying more than one layer (multilayer coatings).

  5. Application of Deep Cryogenic Treatment to Uncoated Tungsten Carbide Inserts in the Turning of AISI 304 Stainless Steel

    NASA Astrophysics Data System (ADS)

    Özbek, Nursel Altan; Çİçek, Adem; Gülesİn, Mahmut; Özbek, Onur

    2016-09-01

    This study investigated the effects of deep cryogenic treatment (DCT) on the wear performance of uncoated tungsten carbide inserts. AISI 304 austenitic stainless steel, widely used in industry, was selected as the workpiece material. Cutting experiments showed that the amount of wear significantly increased with increasing cutting speed. In addition, it was found that DCT contributed to the wear resistance of the turning inserts. The treated turning inserts were less worn by 48 and 38 pct in terms of crater wear and notch wear, respectively, whereas they exhibited up to 18 pct superior wear performance in terms of flank wear. This was attributed to the precipitation of new and finer η-carbides and their homogeneous distribution in the microstructure of the tungsten carbide material after deep cryogenic treatment. Analyses via image processing, hardness measurements, and SEM observations confirmed these findings.

  6. Microstructural Evolutions During Annealing of Plastically Deformed AISI 304 Austenitic Stainless Steel: Martensite Reversion, Grain Refinement, Recrystallization, and Grain Growth

    NASA Astrophysics Data System (ADS)

    Naghizadeh, Meysam; Mirzadeh, Hamed

    2016-08-01

    Microstructural evolutions during annealing of a plastically deformed AISI 304 stainless steel were investigated. Three distinct stages were identified for the reversion of strain-induced martensite to austenite, which were followed by the recrystallization of the retained austenite phase and overall grain growth. It was shown that the primary recrystallization of the retained austenite postpones the formation of an equiaxed microstructure, which coincides with the coarsening of the very fine reversed grains. The latter can effectively impair the usefulness of this thermomechanical treatment for grain refinement at both high and low annealing temperatures. The final grain growth stage, however, was found to be significant at high annealing temperatures, which makes it difficult to control the reversion annealing process for enhancement of mechanical properties. Conclusively, this work unravels the important microstructural evolution stages during reversion annealing and can shed light on the requirements and limitations of this efficient grain refining approach.

  7. Comparison of Roller Burnishing Method with Other Hole Surface Finishing Processes Applied on AISI 304 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Akkurt, Adnan

    2011-08-01

    Component surface quality and selection of the optimum material are the main factors determining the performance of components used in machine manufacturing. The level of hole surface quality can be evaluated by the measurements regarding surface roughness, micro-hardness, and cylindricity. In this study, data had been obtained for different hole drilling methods. The characteristics of materials obtained after applications were compared for different hole-finishing processes to identify best hole drilling method. AISI 304 austenitic stainless steel material was used. Surface finishing of holes were performed using drilling, turning, reaming, grinding, honing, and roller burnishing methods. The results of the study show that the roller burnishing method gives the best results for mechanical, metallurgical properties, and hole surface quality of the material. On the other hand, the worst characteristics were obtained in the drilling method.

  8. Influence of PC-GTAW Parameters on the Microstructural and Mechanical Properties of Thin AISI 1008 Steel Joints

    NASA Astrophysics Data System (ADS)

    Kumar, Ravindra; Anant, Ramkishor; Ghosh, P. K.; Kumar, Ankit; Agrawal, B. P.

    2016-07-01

    Butt weld joints are prepared using pulse current gas tungsten arc welding out of thin sheets of AISI 1008 steel using various combinations of pulse parameters. During welding, the welding speed was kept high, but with the increase of welding speed the mean current was also increased to get the required weld joint at the constant heat input. The use of pulse current has led to improvement in mechanical and metallurgical properties of weld joints. It has resulted in less development of humping which is a common problem with high-speed welding. The undercut or dipped weld face is not observed severe. The tensile strength and hardness are enhanced by 12.5 and 12%. The increase of tensile strength and hardness is justified through TEM micrograph showing the presence of dislocation.

  9. Effect of polishing treatment and thermal oxidation on the total hemispherical thermal emittance of austenitic stainless steel AISI 321

    SciTech Connect

    Sharma, V.C.

    1982-07-01

    The optimum value of the hemispherical thermal emittance (epsilonh) of austenitic stainless steel (SS AISI 321, polished with ''AB Polishing Alumina'' of particle sizes 0.05, 0.3, and 5.0 /sigma phi/m and abrasives of various grit sizes, is found to be 0.13 + or - 0.01 and is significantly lower than the corresponding value of 0.23 + or - 0.01 for the unpolished samples. Although the epsilonh value at a given firing temperatur is constant, a small but systematic upward trend exists when the temperature is raised from 823 to 1293 K. At a firing temperature of 1293 K and for firing times of 3 to 15 min. epsilonh increases from 0.15 to 0.22 + or - 0.01.

  10. Knock-out mutations of Arabidopsis SmD3-b induce pleotropic phenotypes through altered transcript splicing.

    PubMed

    Swaraz, A M; Park, Young-Doo; Hur, Yoonkang

    2011-05-01

    SmD3 is a core protein of small nuclear ribonucleoprotein (snRNP) essential for splicing of primary transcripts. To elucidate function of SmD3 protein in plants, phenotypes and gene expression of SmD3 knock-out and overexpressing mutants in Arabidopsis have been analyzed. smd3-a knock-out mutant or SmD3-a and SmD3-b overexpressors did not show phenotypic alteration. Knock-out of SmD3-b resulted in the pleotropic phenotypes of delayed flowering time and completion of life cycle, reduced root growth, partially defective leaf venation, abnormal numbers of trichome branches, and changed numbers of floral organs. Microarray data revealed that the smd3-b mutant had altered expression of genes related to the above phenotypes, indirectly suggesting that changed splicing of these genes may cause the observed phenotypes. Splicing of selected genes was either totally blocked or reduced in the smd3-b mutant, indicating the important role of SmD3-b in the process. A double knock-out mutant of smd3-a and smd3-b could not be generated, indicating possible redundant function of these two genes. All data indicate that SmD3-b may be major component of the spliceosomal snRNP in Arabidopsis, but the function of SmD3-a may be redundant.

  11. Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates

    SciTech Connect

    Adams, J.S.; Gacad, M.A.; Baker, A.J.; Kheun, G.; Rude, R.K.

    1985-06-01

    We investigated the occurrence of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM (/sup 3/H)1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell.

  12. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D3 [Δ25(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  13. Availability of 25-hydroxyvitamin D3 to antigen presenting cells controls the balance between regulatory and inflammatory T cell responses

    PubMed Central

    Jeffery, Louisa E.; Wood, Alice M.; Qureshi, Omar S; Hou, Tie Zheng; Gardner, David; Briggs, Zoe; Kaur, Satdip; Raza, Karim; Sansom, David M.

    2012-01-01

    1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, exerts potent effects on several tissues including cells of the immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive form of vitamin D, 25(OH)D3, is generally used as an indication of “vitamin D status”. However, utilization of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D3-1α-hydroxylase (CYP27B1) into active 1,25(OH)2D3. Using human T cells, we now show that addition of inactive 25(OH)D3 is sufficient to alter T cell responses only when dendritic cells (DCs) are present. Mechanistically, CYP27B1 is induced in DCs upon maturation with LPS or upon T cell contact resulting in the generation and release of 1,25(OH)2D3 which subsequently affects T cell responses. In most tissues, vitamin D binding protein (DBP) acts as a carrier to enhance the utilization of vitamin D. However, we show that DBP modulates T cell responses by restricting the availability of inactive 25(OH)D3 to DC. These data indicate that the level of “free” 25(OH)D3 available to DCs determines the inflammatory/regulatory balance of ensuing T cell responses. PMID:23087405

  14. Influence of dissolved hydrogen on the fatigue crack growth behaviour of AISI 4140 steel

    NASA Astrophysics Data System (ADS)

    Ramasagara Nagarajan, Varun

    Many metallic structural components come into contact with hydrogen during manufacturing processes or forming operations such as hot stamping of auto body frames and while in service. This interaction of metallic parts with hydrogen can occur due to various reasons such as water molecule dissociation during plating operations, interaction with atmospheric hydrogen due to the moisture present in air during stamping operations or due to prevailing conditions in service (e.g.: acidic or marine environments). Hydrogen, being much smaller in size compared to other metallic elements such as Iron in steels, can enter the material and become dissolved in the matrix. It can lodge itself in interstitials locations of the metal atoms, at vacancies or dislocations in the metallic matrix or at grain boundaries or inclusions (impurities) in the alloy. This dissolved hydrogen can affect the functional life of these structural components leading to catastrophic failures in mission critical applications resulting in loss of lives and structural component. Therefore, it is very important to understand the influence of the dissolved hydrogen on the failure of these structural materials due to cyclic loading (fatigue). For the next generation of hydrogen based fuel cell vehicles and energy systems, it is very crucial to develop structural materials for hydrogen storage and containment which are highly resistant to hydrogen embrittlement. These materials should also be able to provide good long term life in cyclic loading, without undergoing degradation, even when exposed to hydrogen rich environments for extended periods of time. The primary focus of this investigation was to examine the influence of dissolved hydrogen on the fatigue crack growth behaviour of a commercially available high strength medium carbon low alloy (AISI 4140) steel. The secondary objective was to examine the influence of microstructure on the fatigue crack growth behaviour of this material and to determine the

  15. Conversion electron Mössbauer spectroscopy of plasma immersion ion implanted H13 tool steel

    NASA Astrophysics Data System (ADS)

    Terwagne, G.; Collins, G. A.; Hutchings, R.

    1994-12-01

    Conversion electron Mössbauer spectroscopy (CEMS) has been used to investigate nitride formation in AISI-H13 tool steel after treatment by plasma immersion ion implantation (PI3) at 350 °C. With only slight variation in the plasma conditions, it is possible to influence the kinetics of nitride precipitation so as to obtain nitrogen concentrations that range from those associated with ɛ-Fe2N through ɛ-Fe3N to γ'-Fe4N. The CEMS results enable a more definite identification of the nitrides than that obtained by glancing-angle X-ray diffraction and nuclear reaction analysis alone.

  16. Effects of nitrogen ion implantation time on tungsten films deposited by DC magnetron sputtering on AISI 410 martensitic stainless steel

    NASA Astrophysics Data System (ADS)

    Malau, Viktor; Ilman, Mochammad Noer; Iswanto, Priyo Tri; Jatisukamto, Gaguk

    2016-03-01

    Nitrogen ion implantation time on tungsten thin film deposited on surface of AISI 410 steel has been performed. Tungsten thin film produced by dc magnetron sputtering method was deposited on AISI 410 martensitic stainless steel substrates, and then the nitrogen ions were implanted on tungsten thin film. The objective of this research is to investigate the effects of implantation deposition time on surface roughness, microhardness, specific wear and corrosion rate of nitrogen implanted on tungsten film. Magnetron sputtering process was performed by using plasma gas of argon (Ar) to bombardier tungsten target (W) in a vacuum chamber with a pressure of 7.6 x 10-2 torr, a voltage of 300 V, a sputter current of 80 mA for sputtered time of 10 minutes. Nitrogen implantation on tungsten film was done with an initial pressure of 3x10-6 mbar, a fluence of 2 x 1017 ions/cm2, an energy of 100 keV and implantation deposition times of 0, 20, 30 and 40 minutes. The surface roughness, microhardness, specific wear and corrosion rate of the films were evaluated by surfcorder test, Vickers microhardness test, wear test and potentiostat (galvanostat) test respectively. The results show that the nitrogen ions implanted deposition time on tungsten film can modify the surface roughness, microhardness, specific wear and corrosion rate. The minimum surface roughness, specific wear and corrosion rate can be obtained for implantation time of 20 minutes and the maximum microhardness of the film is 329 VHN (Vickers Hardness Number) for implantation time of 30 minutes. The specific wear and corrosion rate of the film depend directly on the surface roughness.

  17. Electron Backscatter Diffraction Analysis of Joints Between AISI 316L Austenitic/UNS S32750 Dual-Phase Stainless Steel

    NASA Astrophysics Data System (ADS)

    Shamanian, Morteza; Mohammadnezhad, Mahyar; Amini, Mahdi; Zabolian, Azam; Szpunar, Jerzy A.

    2015-08-01

    Stainless steels are among the most economical and highly practicable materials widely used in industrial areas due to their mechanical and corrosion resistances. In this study, a dissimilar weld joint consisting of an AISI 316L austenitic stainless steel (ASS) and a UNS S32750 dual-phase stainless steel was obtained under optimized welding conditions by gas tungsten arc welding technique using AWS A5.4:ER2594 filler metal. The effect of welding on the evolution of the microstructure, crystallographic texture, and micro-hardness distribution was also studied. The weld metal (WM) was found to be dual-phased; the microstructure is obtained by a fully ferritic solidification mode followed by austenite precipitation at both ferrite boundaries and ferrite grains through solid-state transformation. It is found that welding process can affect the ferrite content and grain growth phenomenon. The strong textures were found in the base metals for both steels. The AISI 316L ASS texture is composed of strong cube component. In the UNS S32750 dual-phase stainless steel, an important difference between the two phases can be seen in the texture evolution. Austenite phase is composed of a major cube component, whereas the ferrite texture mainly contains a major rotated cube component. The texture of the ferrite is stronger than that of austenite. In the WM, Kurdjumov-Sachs crystallographic orientation relationship is found in the solidification microstructure. The analysis of the Kernel average misorientation distribution shows that the residual strain is more concentrated in the austenite phase than in the other phase. The welding resulted in a significant hardness increase in the WM compared to initial ASS.

  18. OpenHVSR: imaging the subsurface 2D/3D elastic properties through multiple HVSR modeling and inversion

    NASA Astrophysics Data System (ADS)

    Bignardi, S.; Mantovani, A.; Abu Zeid, N.

    2016-08-01

    OpenHVSR is a computer program developed in the Matlab environment, designed for the simultaneous modeling and inversion of large Horizontal-to-Vertical Spectral Ratio (HVSR or H/V) datasets in order to construct 2D/3D subsurface models (topography included). The program is designed to provide a high level of interactive experience to the user and still to be of intuitive use. It implements several effective and established tools already present in the code ModelHVSR by Herak (2008), and many novel features such as: -confidence evaluation on lateral heterogeneity -evaluation of frequency dependent single parameter impact on the misfit function -relaxation of Vp/Vs bounds to allow for water table inclusion -a new cost function formulation which include a slope dependent term for fast matching of peaks, which greatly enhances convergence in case of low quality HVSR curves inversion -capability for the user of editing the subsurface model at any time during the inversion and capability to test the changes before acceptance. In what follows, we shall present many features of the program and we shall show its capabilities on both simulated and real data. We aim to supply a powerful tool to the scientific and professional community capable of handling large sets of HSVR curves, to retrieve the most from their microtremor data within a reduced amount of time and allowing the experienced scientist the necessary flexibility to integrate into the model their own geological knowledge of the sites under investigation. This is especially desirable now that microtremor testing has become routinely used. After testing the code over different datasets, both simulated and real, we finally decided to make it available in an open source format. The program is available by contacting the authors.

  19. A role for interleukin-1 alpha in the 1,25 dihydroxyvitamin D3 response in mammary epithelial cells.

    PubMed

    Maund, Sophia L; Shi, Lihong; Cramer, Scott D

    2013-01-01

    Breast cancer is the most common non-cutaneous malignancy in American women, and better preventative strategies are needed. Epidemiological and laboratory studies point to vitamin D3 as a promising chemopreventative agent for breast cancer. Vitamin D3 metabolites induce anti-proliferative effects in breast cancer cells in vitro and in vivo, but few studies have investigated their effects in normal mammary epithelial cells. We hypothesized that 1,25(OH)2D3, the metabolically active form of vitamin D3, is growth suppressive in normal mouse mammary epithelial cells. In addition, we have previously established a role for the cytokine interleukin-1 alpha (IL1α) in the anti-proliferative effects of 1,25(OH)2D3 in normal prostate cells, and so we hypothesized that IL1α is involved in the 1,25(OH)2D3 response in mammary cells. Evaluation of cell viability, clonogenicity, senescence, and induction of cell cycle regulators p21 and p27 supported an anti-proliferative role for 1,25(OH)2D3 in mammary epithelial cells. Furthermore, 1,25(OH)2D3 increased the intracellular expression of IL1α, which was necessary for the anti-proliferative effects of 1,25(OH)2D3 in mammary cells. Together, these findings support the chemopreventative potential of vitamin D3 in the mammary gland and present a role for IL1α in regulation of mammary cell proliferation by 1,25(OH)2D3.

  20. A Role for Interleukin-1 Alpha in the 1,25 Dihydroxyvitamin D3 Response in Mammary Epithelial Cells

    PubMed Central

    Maund, Sophia L.; Shi, Lihong; Cramer, Scott D.

    2013-01-01

    Breast cancer is the most common non-cutaneous malignancy in American women, and better preventative strategies are needed. Epidemiological and laboratory studies point to vitamin D3 as a promising chemopreventative agent for breast cancer. Vitamin D3 metabolites induce anti-proliferative effects in breast cancer cells in vitro and in vivo, but few studies have investigated their effects in normal mammary epithelial cells. We hypothesized that 1,25(OH)2D3, the metabolically active form of vitamin D3, is growth suppressive in normal mouse mammary epithelial cells. In addition, we have previously established a role for the cytokine interleukin-1 alpha (IL1α) in the anti-proliferative effects of 1,25(OH)2D3 in normal prostate cells, and so we hypothesized that IL1α is involved in the 1,25(OH)2D3 response in mammary cells. Evaluation of cell viability, clonogenicity, senescence, and induction of cell cycle regulators p21 and p27 supported an anti-proliferative role for 1,25(OH)2D3 in mammary epithelial cells. Furthermore, 1,25(OH)2D3 increased the intracellular expression of IL1α, which was necessary for the anti-proliferative effects of 1,25(OH)2D3 in mammary cells. Together, these findings support the chemopreventative potential of vitamin D3 in the mammary gland and present a role for IL1α in regulation of mammary cell proliferation by 1,25(OH)2D3. PMID:24244740

  1. Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation.

    PubMed

    Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [(11)C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum. PMID:27244237

  2. Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation

    PubMed Central

    Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [11C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum. PMID:27219347

  3. Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.

    PubMed

    Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E

    2016-04-01

    Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established.

  4. Wear testing under high load conditionsThe effect of ``anti-scuff'' additions to AISI 3135, 52100 and 9310 steels introduced by ion implantation and ion beam mixing

    NASA Astrophysics Data System (ADS)

    Hartley, N. E. W.; Hirvonen, J. K.

    1983-05-01

    There is a need to eliminate the sudden onset of severe adhesive wear ("scuffing") in high performance hardened steels (e.g. AISI 9310) under arduous load conditions. We have investigated the friction and wear behavior of three ion implanted and ion beam mixed steels under simulated scuffing conditions using a Falex friction and wear tester. This machine enabled tests to be carried out at a load of 700 lb (318 kg), corresponding to a mean contact pressure of approximately 20 000 psi (i.e., 1×10 8 N/m 2) which was sufficient to induce scuffing. A series of lower load tests at 200 lb (91 kg) load (5.2 × 10 7 N/m 2) enabled the longer term wear performance of various ion/substrate combinations to be measured. The frictional force experienced during wear testing was used to assess the degree of scuffing, and the amount of material worn away was measured on the Falex tester or by subsequent weight loss determinations, depending on the type of test. The following ions were implanted: C +, N +, P +, Ti +, Cr +, Mo +, and Ta +, chosen in order to evaluate the effects of intermetallic additions (C, N, P), alloys elements (Ti, Cr), and anti-scuff elements (Mo, Ta). In addition some thin ( ˜1000 Å) vacuum evaporated layers of Si, V, Ni, Nb, Sn, Mo, Ta and W were prepared, and in some cases intermixed with N + ions at a fluence of typically 2×10 17/cm 2, to compare with the effects of ion implantation. Under the low load conditions the wear rate of AISI 3135 steel (1.5% Ni, 0.65% Cr alloy tool steel) was found to be reduced by a factor 3 as a result of N + implantation under low load, in agreement with previous work reported elsewhere, whereas other ions gave inconclusive results. The 52100 steel (a through-hardened martensitic bearing steel) showed marked improvements after Ti + implantation, revealing a sensitivity to fluence which correlated with known dry sliding behaviour of this steel modified by titanium implantations. Ta + and Mo + implantations into 9310 steel (a

  5. Percussion tool

    DOEpatents

    Reed, Teddy R.

    2006-11-28

    A percussion tool is described and which includes a housing mounting a tool bit; a reciprocally moveable hammer borne by the housing and which is operable to repeatedly strike the tool bit; and a reciprocally moveable piston enclosed within the hammer and which imparts reciprocal movement to the reciprocally moveable hammer.

  6. FORTRAN tools

    NASA Technical Reports Server (NTRS)

    Presser, L.

    1978-01-01

    An integrated set of FORTRAN tools that are commercially available is described. The basic purpose of various tools is summarized and their economic impact highlighted. The areas addressed by these tools include: code auditing, error detection, program portability, program instrumentation, documentation, clerical aids, and quality assurance.

  7. Occupancy of dopamine D2 and D3 and serotonin 5-HT1A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography

    PubMed Central

    Seneca, Nicholas; Finnema, Sjoerd J.; Laszlovszky, István; Kiss, Béla; Horváth, Attila; Pásztor, Gabriella; Kapás, Margó; Gyertyán, István; Farkas, Sándor; Innis, Robert B.; Halldin, Christer

    2011-01-01

    Rationale Cariprazine is a novel antipsychotic drug candidate that exhibits high selectivity and affinity to dopamine D3 and D2 receptors and moderate affinity to serotonin 5-HT1A receptors. Targeting receptors other than D2 may provide a therapeutic benefit for both positive and negative symptoms associated with schizophrenia. Positron emission tomography (PET) can be used as a tool in drug development to assess the in vivo distribution and pharmacological properties of a drug. Objectives The objective of this study was to determine dopamine D2/D3 and serotonin 5-HT1A receptor occupancy in monkey brain after the administration of cariprazine. Methods We examined three monkeys using the following PET radioligands: [11C]MNPA (an agonist at D2 and D3 receptors), [11C]raclopride (an antagonist at D2 and D3 receptors), and [11C]WAY-100635 (an antagonist at 5-HT1A receptors). During each experimental day, the first PET measurement was a baseline study, the second after a low dose of cariprazine, and the third after the administration of a high dose. Results We found that cariprazine occupied D2/D3 receptors in a dose-dependent and saturable manner, with the lowest dose occupying ~5% of receptors and the highest dose showing more than 90% occupancy. 5-HT1A receptor occupancy was considerably lower compared with D2/D3 occupancy at the same doses, with a maximal value of ~30% for the raphe nuclei. Conclusions We conclude that cariprazine binds preferentially to dopamine D2/D3 rather than to serotonin 5-HT1A receptors in monkey brain. These findings can be used to guide the selection of cariprazine dosing in humans. PMID:21625907

  8. [The role of vitamin D3 in the regulation of the mineral metabolism in experimental type 1 diabetes].

    PubMed

    Labudzynskyi, D O; Lisakovska, O A; Shymanskyy, I A; Riasnyi, V M; Veliky, N N

    2014-01-01

    Diabetes was shown to be associated with a considerable lowering of 25(OH)D3 in blood serum of mice. Vitamin D3 deficiency was correlated with impaired mineral metabolism in bone tissue, indicating the development of secondary osteoporosis. A decrease in weight, length and diameter (diaphysis, proximal metaepiphysis) of tibia in diabetic animals was observed as compared with control. Diabetes caused hypocalcemia, hypophosphatemia and increased enzymatic activity of alkaline phosphatase (ALP) and its isoenzymes in serum. This changes were accompanied by the impairments of vitamin D3 25-hydroxylase isoforms (CYP27A1 and CYP2R1) expression, which are the main enzymes of cholecalciferol biotransformation to 25(OH)D3 - precursor of hormonally active form of vitamin D3. A decrease in bone resorption processes was established after vitamin D3 administration as it is evident from normalization of bone morphometrical parameters and mineral metabolism in diabetic mice. Vitamin D3 ability to counter diabetes-induced alterations in bone tissue can be ascribed, at least in part, to its positive effects on the formation of vitamin D3 hormonally active forms.

  9. 17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... sanctions, denials of membership, participation or association, or prohibitions or limitations of access to... disciplinary sanction, denial or conditioning of membership, participation, bar from association,...

  10. 26 CFR 301.6511(d)-3 - Special rules applicable to credit against income tax for foreign taxes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... income tax for foreign taxes. 301.6511(d)-3 Section 301.6511(d)-3 Internal Revenue INTERNAL REVENUE... against income tax for foreign taxes. (a) Period in which claim may be filed. In the case of an overpayment of income tax resulting from a credit, allowed under the provisions of section 901 or under...

  11. The 1,25D3 -MARRS receptor/PDIA3/ERp57 and lifespan.

    PubMed

    Nemere, Ilka; Garbi, Natalio; Winger, Quinton

    2015-03-01

    Using MRI on mice bearing a targeted knockout (KO) of the 1,25D3 -MARRS receptor/PDIA3/ERp57 we found that they had decreased body fat relative to their littermate (LM) controls, a condition associated with increased lifespan. Others have found that lower body fat is correlated with decreased lipid droplets in intestinal cells that may be mediated by a factor secreted by germ cells (possibly estradiol). In a reducing environment estradiol competed for binding to the 1,25D3-MARRS receptor/PDIA3/ERp57. A consequence of this was that estradiol stimulated calcium uptake in enterocytes isolated from LM mice. In time course studies, lipid droplets increased in response to 1 nM estradiol from 1-5 D of culture, relative to corresponding controls, while at 6 and 7 D this steroid decreased lipid droplets. Enterocytes from LM or KOs incubated with estradiol for 1-4 D showed the hormone increased lipid droplets. Using the 4 D culture period, 1 and 10 nM estradiol significantly increased the number of lipid droplets in cells from LM mice by 40-60%, compared to equivalent conditions in KO mice. In assessing signal transduction pathways, the hormone increased phospho-Akt levels, but no differences were observed in phospho-mTORC1, or phospho-S6K (although cells from chicks did exhibit a hormone-mediated difference). Finally, the remaining mice (which had stopped reproducing) were allowed to die naturally and lifespan recorded. LM mice lived 687 ± 77 D (without an outlying value) while KO mice lived 740 D ± 80 D. These data suggest the 25D3 -MARRS receptor/PDIA3/ERp57 may contribute to the length of lifespan in mammals. PMID:25283641

  12. GPU accelerated generation of digitally reconstructed radiographs for 2-D/3-D image registration.

    PubMed

    Dorgham, Osama M; Laycock, Stephen D; Fisher, Mark H

    2012-09-01

    Recent advances in programming languages for graphics processing units (GPUs) provide developers with a convenient way of implementing applications which can be executed on the CPU and GPU interchangeably. GPUs are becoming relatively cheap, powerful, and widely available hardware components, which can be used to perform intensive calculations. The last decade of hardware performance developments shows that GPU-based computation is progressing significantly faster than CPU-based computation, particularly if one considers the execution of highly parallelisable algorithms. Future predictions illustrate that this trend is likely to continue. In this paper, we introduce a way of accelerating 2-D/3-D image registration by developing a hybrid system which executes on the CPU and utilizes the GPU for parallelizing the generation of digitally reconstructed radiographs (DRRs). Based on the advancements of the GPU over the CPU, it is timely to exploit the benefits of many-core GPU technology by developing algorithms for DRR generation. Although some previous work has investigated the rendering of DRRs using the GPU, this paper investigates approximations which reduce the computational overhead while still maintaining a quality consistent with that needed for 2-D/3-D registration with sufficient accuracy to be clinically acceptable in certain applications of radiation oncology. Furthermore, by comparing implementations of 2-D/3-D registration on the CPU and GPU, we investigate current performance and propose an optimal framework for PC implementations addressing the rigid registration problem. Using this framework, we are able to render DRR images from a 256×256×133 CT volume in ~24 ms using an NVidia GeForce 8800 GTX and in ~2 ms using NVidia GeForce GTX 580. In addition to applications requiring fast automatic patient setup, these levels of performance suggest image-guided radiation therapy at video frame rates is technically feasible using relatively low cost PC

  13. Multi-modal 2D-3D non-rigid registration

    NASA Astrophysics Data System (ADS)

    Prümmer, M.; Hornegger, J.; Pfister, M.; Dörfler, A.

    2006-03-01

    In this paper, we propose a multi-modal non-rigid 2D-3D registration technique. This method allows a non-rigid alignment of a patient pre-operatively computed tomography (CT) to few intra operatively acquired fluoroscopic X-ray images obtained with a C-arm system. This multi-modal approach is especially focused on the 3D alignment of high contrast reconstructed volumes with intra-interventional low contrast X-ray images in order to make use of up-to-date information for surgical guidance and other interventions. The key issue of non-rigid 2D-3D registration is how to define the distance measure between high contrast 3D data and low contrast 2D projections. In this work, we use algebraic reconstruction theory to handle this problem. We modify the Euler-Lagrange equation by introducing a new 3D force. This external force term is computed from the residual of the algebraic reconstruction procedures. In the multi-modal case we replace the residual between the digitally reconstructed radiographs (DRR) and observed X-ray images with a statistical based distance measure. We integrate the algebraic reconstruction technique into a variational registration framework, so that the 3D displacement field is driven to minimize the reconstruction distance between the volumetric data and its 2D projections using mutual information (MI). The benefits of this 2D-3D registration approach are its scalability in the number of used X-ray reference images and the proposed distance that can handle low contrast fluoroscopies as well. Experimental results are presented on both artificial phantom and 3D C-arm CT images.

  14. Denoising, deconvolving, and decomposing photon observations. Derivation of the D3PO algorithm

    NASA Astrophysics Data System (ADS)

    Selig, Marco; Enßlin, Torsten A.

    2015-02-01

    The analysis of astronomical images is a non-trivial task. The D3PO algorithm addresses the inference problem of denoising, deconvolving, and decomposing photon observations. Its primary goal is the simultaneous but individual reconstruction of the diffuse and point-like photon flux given a single photon count image, where the fluxes are superimposed. In order to discriminate between these morphologically different signal components, a probabilistic algorithm is derived in the language of information field theory based on a hierarchical Bayesian parameter model. The signal inference exploits prior information on the spatial correlation structure of the diffuse component and the brightness distribution of the spatially uncorrelated point-like sources. A maximum a posteriori solution and a solution minimizing the Gibbs free energy of the inference problem using variational Bayesian methods are discussed. Since the derivation of the solution is not dependent on the underlying position space, the implementation of the D3PO algorithm uses the nifty package to ensure applicability to various spatial grids and at any resolution. The fidelity of the algorithm is validated by the analysis of simulated data, including a realistic high energy photon count image showing a 32 × 32 arcmin2 observation with a spatial resolution of 0.1 arcmin. In all tests the D3PO algorithm successfully denoised, deconvolved, and decomposed the data into a diffuse and a point-like signal estimate for the respective photon flux components. A copy of the code is available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/574/A74

  15. Calcium effects and systemic exposure of vitamin D3 analogues after topical treatment of active vitamin D3-containing ointments in rats.

    PubMed

    Hosomi, Atsushi; Hirabe, Maho; Tokuda, Takuya; Nakamura, Hiroaki; Amano, Toru; Okamoto, Tadao

    2016-10-01

    Topical agents containing vitamin D3 (VD3) analogues such as calcipotriol, maxacalcitol and tacalcitol and the combination of calcipotriol/betamethasone dipropionate (betamethasone) are prescribed for patients with psoriasis. However, they are known to occasionally cause hypercalcemia, and the frequency of hypercalcemia is suggested to vary according to the VD3 analogue used. In this study, to address the reason for these differences, the calcemic effects of maxacalcitol-, calcipotriol- and calcipotriol/betamethasone-containing ointments in rats were evaluated. The serum calcium levels in rats treated with ointments containing maxacalcitol, but not calcipotriol or calcipotriol/betamethasone, were significantly elevated, which is consistent with clinical observations. The serum concentration of VD3 analogue in rats treated with ointments containing calcipotriol and calcipotriol/betamethasone was lower than that in rats treated with maxacalcitol-containing ointment. Thus, the calcemic effects appear to be associated with the systemic exposure of VD3 analogues in rats. To understand the mechanism underlying the different systemic exposures of VD3 analogues, skin permeation and metabolic stability of VD3 analogues were evaluated. The cumulative amount of calcipotriol permeated through rat skin was significantly lower than that of maxacalcitol. On the other hand, the metabolic clearance of calcipotriol in rat hepatocytes was higher than that of maxacalcitol. Similar results were obtained using human skin and human hepatocytes. The current study demonstrates that the lower calcemic effects of calcipotriol- and calcipotriol/betamethasone-containing ointments are caused by the low systemic exposure of calcipotriol according to low skin permeability and rapid hepatic elimination after topical application.

  16. Experimental investigation on geometrical aspects of micro-plasma deposited tool steel for repair applications

    NASA Astrophysics Data System (ADS)

    Jhavar, S.; Paul, C. P.; Jain, N. K.

    2014-08-01

    Recent advancement in direct material deposition processes found wide applications in rapid prototyping, manufacturing and tooling industry. Micro-plasma deposition is one of the recent developments in this domain. This paper reports the deployment of newly integrated micro-plasma deposition system for the deposition of AISI P-20 tool steel on the AISI P20 tool steel substrate. A number of test tracks for single track deposition were deposited at the various combination of processing parameters. The sets of parameters yielding good deposits were selected to deposit overlap tracks. The geometry of single and overlapped tracks was evaluated to understand the parametric dependence. The study indicates that the aspect ratio of track geometry (ratio of width to height of track) is dependent on the processing parameters and the discharge current is identified as the most dominating parameters (contribution = 44%), followed by scan speed (contribution = 26.68%) and wire feed rate (contribution = 26.98%) with almost same e