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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. Acoustic Emission Methodology to Evaluate the Fracture Toughness in Heat Treated AISI D2 Tool Steel

    NASA Astrophysics Data System (ADS)

    Mostafavi, Sajad; Fotouhi, Mohamad; Motasemi, Abed; Ahmadi, Mehdi; Sindi, Cevat Teymuri

    2012-10-01

    In this article, fracture toughness behavior of tool steel was investigated using Acoustic Emission (AE) monitoring. Fracture toughness ( K IC) values of a specific tool steel was determined by applying various approaches based on conventional AE parameters, such as Acoustic Emission Cumulative Count (AECC), Acoustic Emission Energy Rate (AEER), and the combination of mechanical characteristics and AE information called sentry function. The critical fracture toughness values during crack propagation were achieved by means of relationship between the integral of the sentry function and cumulative fracture toughness (KICUM). Specimens were selected from AISI D2 cold-work tool steel and were heat treated at four different tempering conditions (300, 450, 525, and 575 °C). The results achieved through AE approaches were then compared with a methodology proposed by compact specimen testing according to ASTM standard E399. It was concluded that AE information was an efficient method to investigate fracture characteristics.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Assessment of Retained Austenite in AISI D2 Tool Steel Using Magnetic Hysteresis and Barkhausen Noise Parameters

    NASA Astrophysics Data System (ADS)

    Kahrobaee, Saeed; Kashefi, Mehrdad

    2015-03-01

    Inaccurate heat treatment process could result in excessive amount of retained austenite, which degrades the mechanical properties, like strength, wear resistance, and hardness of cold work tool steel parts. Thus, to control the mechanical properties, quantitative measurement of the retained austenite is a critical step in optimizing the heat-treating parameters. X-ray diffraction method is the most frequently used technique for this purpose. This technique is, however, destructive and time consuming. Furthermore, it is not applicable to 100% quality inspection of industrial parts. In the present paper, the influence of austenitizing temperature on the retained austenite content and hardness of AISI D2 tool steel has been studied. Additionally, nondestructive magnetic hysteresis parameters of the samples including coercivity, magnetic saturation, and maximum differential permeability as well as their magnetic Barkhausen noise features (RMS peak voltage and peak position) have been investigated. The results revealed direct relations between magnetic saturation, differential permeability, and MBN peak amplitude with increasing austenitizing temperature due to the retained austenite formation. Besides, both parameters of coercivity and peak position had an inverse correlation with the retained austenite fraction.

  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. Ion-nitriding of the AISI M2 high speed tool steel and comparison of its mechanical properties with nitrided steels

    SciTech Connect

    Cimen, O.; Alnipak, B.

    1995-12-31

    In the past it was shown that plasma diffusion treatment of steels has several advantages over conventional processes such as gas or salt bath nitriding and nitrocarburizing. Plasma diffusion treatment allows close control of the process so that surface layers with defined microstructures and properties can be obtained. The amount of {gamma}{prime} and {epsilon} phase present can be easily controlled. In this paper, variation of surfaces hardness properties of AISI M2 high speed tool speed after ion nitriding treatments were investigated. The mechanical and electro-chemical advantages of the ion nitrided structures were compared with the other methods.

  11. Multi-objective optimization in WEDM of D3 tool steel using integrated approach of Taguchi method & Grey relational analysis

    NASA Astrophysics Data System (ADS)

    Shivade, Anand S.; Shinde, Vasudev D.

    2014-09-01

    In this paper, wire electrical discharge machining of D3 tool steel is studied. Influence of pulse-on time, pulse-off time, peak current and wire speed are investigated for MRR, dimensional deviation, gap current and machining time, during intricate machining of D3 tool steel. Taguchi method is used for single characteristics optimization and to optimize all four process parameters simultaneously, Grey relational analysis (GRA) is employed along with Taguchi method. Through GRA, grey relational grade is used as a performance index to determine the optimal setting of process parameters for multi-objective characteristics. Analysis of variance (ANOVA) shows that the peak current is the most significant parameters affecting on multi-objective characteristics. Confirmatory results, proves the potential of GRA to optimize process parameters successfully for multi-objective characteristics.

  12. Development of flank wear model of cutting tool by using adaptive feedback linear control system on machining AISI D2 steel and AISI 4340 steel

    NASA Astrophysics Data System (ADS)

    Orra, Kashfull; Choudhury, Sounak K.

    2016-12-01

    The purpose of this paper is to build an adaptive feedback linear control system to check the variation of cutting force signal to improve the tool life. The paper discusses the use of transfer function approach in improving the mathematical modelling and adaptively controlling the process dynamics of the turning operation. The experimental results shows to be in agreement with the simulation model and error obtained is less than 3%. The state space approach model used in this paper successfully check the adequacy of the control system through controllability and observability test matrix and can be transferred from one state to another by appropriate input control in a finite time. The proposed system can be implemented to other machining process under varying range of cutting conditions to improve the efficiency and observability of the system.

  13. 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

  14. 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.

  15. DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015

    NASA Astrophysics Data System (ADS)

    Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

    2016-09-01

    Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

  16. DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015.

    PubMed

    Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

    2016-09-01

    Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

  17. Construction of a P450c27 fusion enzyme: a useful tool for analysis of vitamin D3 25-hydroxylase activity.

    PubMed Central

    Dilworth, F J; Black, S M; Guo, Y D; Miller, W L; Jones, G

    1996-01-01

    Liver mitochondrial P450c27, encoded by the CYP27 gene, can catalyse the 25-hydroxylation of vitamin D3 and the 27-hydroxylation of sterols. To facilitate the study of this enzyme in cell culture systems, we engineered a fusion protein consisting of P450c27 coupled to its electron-transport accessory proteins, ferredoxin and ferredoxin reductase, and assessed its enzyme activity by measuring the C-25 and C-27 (side-chain) hydroxylation of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3). When incubated with 1 alpha-OH-D3, COS-1 cells transfected with a vector expressing the fusion protein produced 1 alpha,25-(OH)2D2 and 1 alpha,27-(OH)2D3 about four times more efficiently than did cells transfected with three individual components of the fusion. When incubated with the natural substrate, vitamin D3, the efficiency of hydroxylation was lower than that for 1 alpha-OH-D3 but still 1.7-fold higher for the fusion protein than for its individual components. The fusion protein was also able to reproduce qualitatively and quantitatively the activity shown by P450c27 in liver cells in situ. The P450c27-ferredoxin reductase-ferredoxin fusion construct represents a valuable tool for establishing the substrate specificity of this liver cytochrome and for evaluating its potential for activating pro-drug analogues of vitamin D. PMID:8947497

  18. 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.

  19. Tribological and mechanical properties of Ti/TiAlN/TiAlCN nanoscale multilayer PVD coatings deposited on AISI H11 hot work tool steel

    NASA Astrophysics Data System (ADS)

    AL-Bukhaiti, M. A.; Al-hatab, K. A.; Tillmann, W.; Hoffmann, F.; Sprute, T.

    2014-11-01

    A new [Ti/TiAlN/TiAlCN]5 multilayer coatings were deposited onto polished substrate AISI H11 (DIN 1.2343) steel by an industrial magnetron sputtering device. The tribological performance of the coated system was investigated by a ball-on-disk tribometer against 100Cr6 steel and Al2O3 balls. The friction coefficients and specific wear rates were measured at various normal loads (2, 5, 8, and 10 N) and sliding velocities (0.2, 0.4, and 0.8 m/s) in ambient air and dry conditions. The phase structure, composition, wear tracks morphologies, hardness, and film/substrate adhesion of the coatings were characterized by light-microscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), 3D-surface analyzer, nanoindentation, and scratch tests. Results showed that the deposited coatings showed low wear rates in the scale of 10-15 m3/N m, low friction coefficients against 100Cr6 and Al2O3 balls in the range of 0.25-0.37, and good hardness in the range of 17-20 GPa. Results also revealed that the friction coefficients and disc wear rates decrease and increase, respectively with the increase in normal load and sliding velocity for both coating/Al2O3 and coating/100Cr6 sliding system. Compared with the uncoated-H11 substrate, the deposited coating exhibited superior tribological and mechanical properties. The dominant wear mechanism was abrasive wear for coating/Al2O3 pair, while for coating/100Cr6 pair, a combination of mild adhesive wear, severe adhesive wear, and abrasive wear (extensive plowing) were the dominant wear mechanisms at different applied normal loads.

  20. Liquid chromatography-tandem mass spectrometric method for the determination of salivary 25-hydroxyvitamin D3: a noninvasive tool for the assessment of vitamin D status.

    PubMed

    Higashi, Tatsuya; Shibayama, Yujin; Fuji, Mihoko; Shimada, Kazutake

    2008-05-01

    A sensitive liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-ESI-MS/MS) method for the determination of 25-hydroxyvitamin D(3) [25(OH)D(3)] in human saliva has been developed and validated. The saliva was deproteinized with acetonitrile, purified using a Strata-X cartridge, derivatized with a Cookson-type reagent, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), and subjected to LC-MS/MS. The PTAD derivative was much more easily ionized in positive-ESI-MS and efficiently produced a characteristic product ion during MS/MS, compared to the intact 25(OH)D(3). Methylamine was used as the mobile phase additive, and also effectively enhanced the assay sensitivity. Quantification was based on selected reaction monitoring, and 25-hydroxyvitamin D(4) was used as the internal standard. This method allowed the reproducible and accurate quantification of salivary 25(OH)D(3) using a 1.0-ml sample, and the limit of quantitation for 25(OH)D(3) was 2.0 pg/ml. The applicability of the developed method for clinical studies was then examined. There was a positive linear relationship (r (2) = 0.830) between the serum 25(OH)D(3) level, which is conventionally used as a means of assessing the vitamin D status, and the salivary 25(OH)D(3) level measured using the proposed method. The method also enabled the detection of the increase in the salivary 25(OH)D(3) level after the supplementation of vitamin D(3).

  1. 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.

  2. On-line SPE sample treatment as a tool for method automatization and detection limits reduction: Quantification of 25-hydroxyvitamin D3/D2.

    PubMed

    Palaiogiannis, Dimitrios; Bekou, Evangelia; Pazaitou-Panayiotou, Kalliopi; Samanidou, Victoria; Tsakalof, Andreas

    2017-02-01

    The development and approbation of new, automated UHPLC-DAD method for the quantification of 25-hydroxyvitamin D3/D2 (25OH-D3/D2) metabolites in plasma/serum for the evaluation of patient's vitamin D status are presented. The method was developed on the Ultimate 3000 UHPLC dual gradient system supplied with the on-line SPE-concentration column coupled through six port switching valve to analytical column. This configuration and materials selected enable large volume sample injection (500μL) and on-line sample preconcentration, clean up and subsequent selective metabolites transfer onto the analytical column. The new method abrogates main conventional time consuming and error source off-line steps of analysis and thus simplifies analysis. The large volume injection increases the sensitivity of instrumental analysis by about ten-fold on-line pre-concentration of metabolites. The instrument response is linear (R>0.99) in the investigated concentration range 10-100ngmL(-1) which covers all the possible vitamin D status from serious deficiency (<12ngmL(-1)) to excess. The method detection limits (S/N=3) are LOD (25OH-D3)=0.94ngmL(-1) and LOD (25OH-D2)=2.4ngmL(-1). The method performance was assessed with the use of certified reference samples and perfect agreement between certified and measured values is demonstrated. The method was applied to human samples previously analyzed for total vitamin D by Competitive Protein-binding assay and findings of the two methods are compared.

  3. 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.

  4. Feasibility study of the proton yield from the reaction D(3He,p)4 He as a possible tool for radiotherapy treatment

    NASA Astrophysics Data System (ADS)

    Uzunov, N. M.; Liguori, N.; Fontana, C. L.; Baneva, Y.; Atroshchenko, K.; Bello, M.; Moschini, G.; Rosato, A.; Rigato, V.; Doyle, B.; Rossi, P.

    2012-12-01

    Recent achievements in proton and carbon ions therapy have shown the importance of the hadron therapy methods. Aiming at radiotherapy applications such as dermatological and intra-operative procedures, where a short range treatment is needed, we have studied the use of nuclear reactions induced by low energy ions from small accelerators. A very suitable reaction is D(3He,p)4He, using 3He+ ions with energies of about 800 keV. The resulting protons have energies above 17 MeV and could deliver significant radiation dose depending on the accelerator 3He+ beam current and the irradiation time. The deuterium containing target was prepared by reactive magnetron sputtering of titanium in Ar and Ar + D2 radiofrequency plasma on a substrate of Silicon. The Ti-Dx stoichiometry and deuterium content was determined by Ion Beam Analysis. The accelerated 3He+ beam was provided by the 2.5MV Van de Graaff accelerator at the National Laboratories of Legnaro, INFN, Italy. Proton yield as a function of the beam current at different forward scattering angles has been studied for the energies of the incoming 3He+ in the 700keV - 800keV energy interval. The irradiated volume and the radiation dose in biological tissues as a function of the proton energy and proton yield has been estimated. Possible applications in small animal treatment studies as well as potential clinical radiotherapy applications are discussed.

  5. 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.

  6. Thermal Linear Expansion of Nine Selected AISI Stainless Steels

    DTIC Science & Technology

    1978-04-01

    stainless steels. The nine selected stainless steels are AISI 303, 304, 304L, 316, 317, 321, 347, 410 , and 430. The recoended values Include the...point of the stainless steels. The nine selected stainless steels are AISI 303, 304, 304L, 316, 317, 321, 347, 410 , and 430. The recommended values...Stainless Steel..................................26 8. AISI 410 Stainless Steel..................................29 9. AISI 430 Stainless Steel

  7. Mechanical properties of martensitic alloy AISI 422

    SciTech Connect

    Hamilton, M.L. ); Huang, F.H.; Hu, Wan-Liang )

    1992-06-01

    HT9 is a martensitic stainless steel that has been considered for structural applications in liquid metal reactors (LMRs) as well as in fusion reactors. AISI 422 is a commercially available martensitic stainless steel that closely resembles HT9, and was studied briefly under the auspices of the US LMR program. Previously unpublished tensile, fracture toughness and charpy impact data on AISI 422 were re-examined for potential insights into the consequences of the compositional differences between the two alloys, particularly with respect to current questions concerning the origin of the radiation-induced embrittlement observed in HT9.

  8. Mechanical properties of martensitic alloy AISI 422

    SciTech Connect

    Huang, F.H.; Hu, W.L. ); Hamilton, M.L. )

    1992-09-01

    HT9 is a martensitic stainless steel that has been considered for structural applications in liquid metal reactors (LMRs) as well as in fusion reactors. AISI 422 is a commercially available martensitic stainless steel that closely resembles HT9, and was studied briefly under the auspices of the US LMR program. Previously unpublished tensile, fracture toughness and charpy impact data on AISI 422 were reexamined for potential insights into the consequences of the compositional differences between the two alloys, particularly with respect to current questions concerning the origin of the radiation-induced embrittlement observed in HT9. 8 refs, 8 figs.

  9. Intersecting D 3 -D3 ' -brane system at finite temperature

    NASA Astrophysics Data System (ADS)

    Cottrell, William; Hanson, James; Hashimoto, Akikazu; Loveridge, Andrew; Pettengill, Duncan

    2017-02-01

    We analyze the dynamics of the intersecting D 3 -D3 ' -brane system overlapping in 1 +1 dimensions, in a holographic treatment where N D3 branes are manifested as anti-de Sitter Schwartzschild geometry, and the D3 ' brane is treated as a probe. We extract the thermodynamic equation of state from the set of embedding solutions, and analyze the stability at the perturbative and the nonperturbative level. We review a systematic procedure to resolve local instabilities and multivaluedness in the equations of state based on classic ideas of convexity in the microcanonical ensemble. We then identify a runaway behavior which was not noticed previously for this system.

  10. 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.

  11. 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

  12. Nondestructive evaluation of stresses within AISI stainless steel 304 material -- A magnetometric approach

    SciTech Connect

    Manglik, V.K.; Vaghmare, R.; Modi, H.M.

    1995-12-31

    Stainless steel is widely used industrial material and also used in fabrication of satellite components. The use of optimum section of components calls for Non-Destructive Evaluation of structure to avoid catastrophic failures which are predominantly due to the high stress level. The effect of cold working and/or stress on the magnetic properties of stainless steel was discussed in the past. An attempt is made in present work to correlate the induced magnetic flux density in stainless steel AISI-304 with the stress level. In the present work, various samples of stainless steel were prepared for experiment after confirming the material belongs to AISI-304 by detailed chemical and physical analysis. These samples were also heat treated at 1,066 deg. C. to eliminate presence of initial stresses and obtain austenitic structure. Stresses in identical samples were generated by torsional deformation and induced magnetic flux density were measured in a very well configured test set up which has the resolution of 1 nT (nano-tesla). Finally, a correlation is presented between the induced magnetic flux density and stress level which could be very helpful tool in non-destructive evaluation of stresses in stainless steel AISI-304.

  13. 7 CFR 15d.3 - Compliance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Compliance. 15d.3 Section 15d.3 Agriculture Office of the Secretary of Agriculture NONDISCRIMINATION IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.3 Compliance. The Director of the Office of Civil Rights...

  14. 7 CFR 15d.3 - Compliance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Compliance. 15d.3 Section 15d.3 Agriculture Office of the Secretary of Agriculture NONDISCRIMINATION IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.3 Compliance. The Director of the Office of Civil Rights...

  15. The chemistry of D3-trishomocubane

    NASA Astrophysics Data System (ADS)

    Levandovsky, I. A.; Sharapa, D. I.; Cherenkova, O. A.; Gaidai, A. V.; Shubina, T. E.

    2010-12-01

    Data on the chemistry of D3-trishomocubane and its derivatives are described systematically. Different versions of construction of D3-trishomocubane cage are presented. The methods of synthesis of mono-, di- and poly-substituted D3-trishomocubanes and their heteroanalogues as well as their properties are considered. Data on biological activity of homocubanes are generalized.

  16. 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…

  17. Vitamin D3 in fat tissue

    PubMed Central

    Blum, Miriam; Dolnikowski, Gregory; Seyoum, Elias; Harris, Susan S.; Booth, Sarah L.; Peterson, James; Saltzman, Edward

    2010-01-01

    The literature describing vitamin D content of fat tissue is extremely limited. We conducted a pilot study that measured the concentrations of vitamin D3 in the fat tissue and serum of obese adults. These measurements were performed using a new liquid chromatography mass spectrometry (LC/MS) method. The objectives of this study were: to measure and report the vitamin D3 concentration in serum and subcutaneous fat samples from obese individuals and to examine the association of vitamin D3 in fat with vitamin D3 in serum. This cross-sectional study was conducted in 17 obese men and women who were scheduled to undergo gastric bypass surgery. The mean vitamin D3 concentration in subjects’ subcutaneous fat tissue samples was 102.8 ± 42.0 nmol/kg. The mean vitamin D3 concentration in serum was 7.78 ± 3.99 nmol/l. Vitamin D3 concentrations of fat tissue and serum were positively correlated (r = 0.68, P = 0.003). Consistent with previous findings in obese subjects, subjects in this study had suboptimal vitamin D status as demonstrated by a mean 25-hydroxyvitamin D concentration of 43.3 ± 15.4 nmol/l. In conclusion, fat tissue vitamin D3 can be measured by LC/MS and is detectable in obese subjects with suboptimal vitamin D status. Compatible with the long-standing concept that fat tissue is a storage site for vitamin D, fat tissue and serum vitamin D3 concentrations were positively correlated. PMID:18338271

  18. Dimensional reduction for D3-brane moduli

    NASA Astrophysics Data System (ADS)

    Cownden, Brad; Frey, Andrew R.; Marsh, M. C. David; Underwood, Bret

    2016-12-01

    Warped string compactifications are central to many attempts to stabilize moduli and connect string theory with cosmology and particle phenomenology. We present a first-principles derivation of the low-energy 4D effective theory from dimensional reduction of a D3-brane in a warped Calabi-Yau compactification of type IIB string theory with imaginary self-dual 3-form flux, including effects of D3-brane motion beyond the probe approximation, and find the metric on the moduli space of brane positions, the universal volume modulus, and axions descending from the 4-form potential. As D3-branes may be considered as carrying either electric or magnetic charges for the self-dual 5-form field strength, we present calculations in both duality frames. Our results are consistent with, but extend significantly, earlier results on the low-energy effective theory arising from D3-branes in string compactifications.

  19. Vitamin D3 Mediated Tumor Regression.

    DTIC Science & Technology

    1998-07-01

    1,25(OH)2D3 and its synthetic analog EB 1089 induce characteristic features of apoptosis in MCF-7 cells in vitro. To determine whether vitamin D3...after five weeks. The reduced growth of tumors from EB 1089 treated mice was associated with characteristic apoptotic morphology. After five weeks of...treatment with EB 1089 , MCF-7 tumors exhibited a six-fold increase in DNA fragmentation and a two-fold reduction in proliferation relative to control

  20. Tribological and corrosion behaviors of carburized AISI 4340 steel

    NASA Astrophysics Data System (ADS)

    Thong-on, Atcharawadi; Boonruang, Chatdanai

    2016-01-01

    AISI 4340 steel is widely used in automotive and aircraft industries as gear components. In such applications, surface hardening processes such as carburizing are required in order to improve the life time of the components. There are many studies showing the tribological behavior of the carburized steel, but the corrosion behavior has not yet been clarified. This paper reports on both tribological and corrosion behaviors of the carburized AISI 4340 steel. Factor associated with carburizing, such as the quantities of deposited carbon, dissolved carbon, and formed Cr23C6 and Fe3C, affect the tribological and corrosion behaviors of the steel by improving hardness, friction, lubrication, and wear resistance; but corrosion resistance is reduced. The dissolved carbon affects the formation of the oxide layer of the carburized steel, by obstructing the continuous oxide layer formation and by decreasing the chromium content of the steel, leading to the decrease in the corrosion resistance of the steel.

  1. 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.

  2. D = 3 unification of curious supergravities

    NASA Astrophysics Data System (ADS)

    Duff, M. J.; Ferrara, S.; Marrani, A.

    2017-01-01

    We consider the dimensional reduction to D = 3 of four maximal-rank super-gravities which preserve minimal supersymmetry in D = 11, 7, 5 and 4. Such " curious" theories were investigated some time ago, and the four-dimensional one corresponds to an N=1 supergravity with 7 chiral multiplets spanning the seven-disk manifold. Recently, this latter theory provided cosmological models for α-attractors, which are based on the disk geometry with possible restrictions on the parameter α. A unified picture emerges in D = 3, where the Ehlers group of General Relativity merges with the S-, T- and U-dualities of the D = 4 parent theories.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. 2D/3D switchable displays

    NASA Astrophysics Data System (ADS)

    Dekker, T.; de Zwart, S. T.; Willemsen, O. H.; Hiddink, M. G. H.; IJzerman, W. L.

    2006-02-01

    A prerequisite for a wide market acceptance of 3D displays is the ability to switch between 3D and full resolution 2D. In this paper we present a robust and cost effective concept for an auto-stereoscopic switchable 2D/3D display. The display is based on an LCD panel, equipped with switchable LC-filled lenticular lenses. We will discuss 3D image quality, with the focus on display uniformity. We show that slanting the lenticulars in combination with a good lens design can minimize non-uniformities in our 20" 2D/3D monitors. Furthermore, we introduce fractional viewing systems as a very robust concept to further improve uniformity in the case slanting the lenticulars and optimizing the lens design are not sufficient. We will discuss measurements and numerical simulations of the key optical characteristics of this display. Finally, we discuss 2D image quality, the switching characteristics and the residual lens effect.

  12. The Comstar D/3 gain degradation experiment

    NASA Technical Reports Server (NTRS)

    Lee, T. C.; Hodge, D. B.

    1981-01-01

    The results of gain degradation measurements using the Comstar D/3 19.04 GHz beacon are reported. This experiment utilized 0.6 and 5 m aperture antennas aligned along the same propagation path to examine propagation effects which are related to the antenna aperture size. Sample data for clear air, scintillation in clear air, and precipitation fading are presented. Distributions of the received signal levels and variances for both antennas are also presented.

  13. Wear resistance of quenched and tempered AISI 4137H steel

    NASA Astrophysics Data System (ADS)

    Tumuluru, Murali D.

    1986-02-01

    Abrasive wear resistance of quenched and tempered AISI 4137H steel was studied using the dry sand/rubber wheel test. The variables studied included hardness, tempering temperature, and cleanliness of the steel. The effect of sulfide inclusions on the relative wear performance of the steel was examined. Debris from the wear tests was analyzed using SEM and sieve analysis. The effects of steel cleanliness and sulfide inclusion shape on abrasion resistance are explained in terms of the relative ease for chip formation and its subsequent detachability during the abrasion process.

  14. 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.

  15. Fluorometric assay of 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 in plasma.

    PubMed

    Shimizu, M; Gao, Y; Aso, T; Nakatsu, K; Yamada, S

    1992-08-01

    The first practical fluorometric assay of plasma 25-hydroxyvitamin D3 (25-OH-D3) and 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) is described. The method uses a highly fluorescent dienophile, 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]-1, 2,4- triazoline-3,5-dione (DMEQ-TAD), to fluorescence-label vitamin D. Vitamin D metabolites were roughly purified with a short cartridge column followed by HPLC, labeled with DMEQ-TAD, and the product was analyzed on HPLC. In the assay of 25-OH-D3 the new fluorometric method was compared with the HPLC-uv method and was confirmed to be as accurate and reliable (CV, 4-5%) as the HPLC-uv method. Plasma 24,25-(OH)2D3 was accurately assayed by the HPLC-FL method, where the standard addition method was successfully used to calculate the overall recovery.

  16. Experimental investigations on effects of frequency in ultrasonically-assisted end-milling of AISI 316L: A feasibility study.

    PubMed

    Maurotto, A; Wickramarachchi, C T

    2016-02-01

    The effects of frequency in ultrasonic vibration assisted milling (UVAM) with axial vibration of the cutter is investigated in this paper. A series of face-mill experiment in dry conditions were conducted on AISI 316L, an alloy of widespread use in industry. The finished surfaces roughness were studied along with basic considerations on tool wear for both conventional milling and an array of frequencies for UVAM (20–40–60 kHz) in a wide range of cutting conditions. Surface residual stresses and cross-cut metallographic slides were used to investigate the hidden effects of UVAM. Experimental results showed competitive results for both surface roughness and residual stress in UVAM when compared with conventional milling especially in the low range of frequency with similar trend for tool wear.

  17. 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

  18. 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.

  19. Automated D/3 to Visio Analog Diagrams

    SciTech Connect

    Posey, Stephen B.

    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 diagram 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.

  20. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin D3. 172.380 Section 172.380 Food and Drugs... Dietary and Nutritional Additives § 172.380 Vitamin D3. Vitamin D3 may be used safely in foods as a... prescribed conditions: (a) Vitamin D3, also known as cholecalciferol, is the chemical...

  1. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Vitamin D3. 172.380 Section 172.380 Food and Drugs... Dietary and Nutritional Additives § 172.380 Vitamin D3. Vitamin D3 may be used safely in foods as a... prescribed conditions: (a) Vitamin D3, also known as cholecalciferol, is the chemical...

  2. 21 CFR 172.380 - Vitamin D 3;.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D 3;. 172.380 Section 172.380 Food and... Dietary and Nutritional Additives § 172.380 Vitamin D 3;. Vitamin D3 may be used safely in foods as a... prescribed conditions: (a) Vitamin D3, also known as cholecalciferol, is the chemical...

  3. 21 CFR 172.380 - Vitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D3. 172.380 Section 172.380 Food and Drugs... Dietary and Nutritional Additives § 172.380 Vitamin D3. Vitamin D3 may be used safely in foods as a... prescribed conditions: (a) Vitamin D3, also known as cholecalciferol, is the chemical...

  4. Brain Regional and Cortical Laminar Effects of Selective D3 Agonists and Antagonists

    PubMed Central

    Choi, Ji-Kyung; Mandeville, Joseph B.; Chen, Y. Iris; Grundt, Peter; Sarkar, Susanta; Newman, Amy Hauck; Jenkins, Bruce G.

    2013-01-01

    Dopamine receptors are divided into two families: D1 including D1 and D5 receptors and D2 including D2, D3 and D4 receptors. The role of dopamine D3 receptors in the brain remains controversial. We found that highly selective D3 antagonists induced positive cerebral blood volume (CBV) changes whereas D3 agonism using 7-OH-DPAT induced negative CBV changes in brain regions including nucleus accumbens, antero-medial striatum, cingulate cortex, thalamus, interpeduncular region and hypothalamus. There was pronounced activation in the hippocampus restricted to the subiculum – the output from the infralimbic cortex and dentate gyrus. At higher doses of D3 agonist, functional changes were differentiated across cortical lamina, with layer V–VI yielding positive CBV changes and layer IV yielding negative CBV changes. These results are consistent with differential D1 and D3 innervation in these layers respectively and provide evidence of D1–D3 receptor interactions. Further, the use of MRI provides a new tool for testing the in vivo selectivity of novel dopaminergic ligands where radiolabels are not available - as in the case of D3 receptors. PMID:20628733

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings.

    PubMed

    Le Foll, Bernard; Collo, Ginetta; Rabiner, Eugenii A; Boileau, Isabelle; Merlo Pich, Emilio; Sokoloff, Pierre

    2014-01-01

    The dopamine D3 receptor is located in the limbic area and apparently mediates selective effects on motivation to take drugs and drug-seeking behaviors, so that there has been considerable interest on the possible use of D3 receptor ligands to treat drug addiction. However, only recently selective tools allowing studying this receptor have been developed. This chapter presents an overview of findings that were presented at a symposium on the conference Dopamine 2013 in Sardinia in May 2013. Novel neurobiological findings indicate that drugs of abuse can lead to significant structural plasticity in rodent brain and that this is dependent on the availability of functional dopamine D3 autoreceptor, whose activation increased phosphorylation in the ERK pathway and in the Akt/mTORC1 pathway indicating the parallel engagement of a series of intracellular signaling pathways all involved in cell growth and survival. Preclinical findings using animal models of drug-seeking behaviors confirm that D3 antagonists have a promising profile to treat drug addiction across drugs of abuse type. Imaging the D3 is now feasible in human subjects. Notably, the development of (+)-4-propyl-9-hydroxynaphthoxazine ligand used in positron emission tomography (PET) studies in humans allows to measure D3 and D2 receptors based on the area of the brain under study. This PET ligand has been used to confirm up-regulation of D3 sites in psychostimulant users and to reveal that tobacco smoking produces elevation of dopamine at the level of D3 sites. There are now novel antagonists being developed, but also old drugs such as buspirone, that are available to test the D3 hypothesis in humans. The first results of clinical investigations are now being provided. Overall, those recent findings support further exploration of D3 ligands to treat drug addiction.

  10. The vitamin D3 transcriptomic response in skin cells derived from the Atlantic bottlenose dolphin

    PubMed Central

    Ellis, Blake C.; Gattoni-Celli, Sebastiano; Mancia, Annalaura; Kindy, Mark S.

    2012-01-01

    The Atlantic bottlenose dolphin has attracted attention due to the evident impact that environmental stressors have taken on its health. In order to better understand the mechanisms linking environmental health with dolphin health, we have established cell cultures from dolphin skin as in vitro tools for molecular evaluations. The vitamin D3 pathway is one mechanism of interest because of its well established chemopreventative and immunomodulatory properties in terrestrial mammals. On the other hand, little is known of the physiological role of this molecule in aquatic animals. 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive and hormonal form of vitamin D3, exerts its biological function by binding to the vitamin D receptor (VDR), a ligand-activated regulator of gene transcription. Therefore, we investigated the transcriptomic changes induced by 1,25D3 administration in dolphin skin cells. Identification of specific genes activated by 1,25D3 has provided clues to the physiological function of the vitamin D3 pathway in the dolphin. We found that exposure of the cells to 1,25D3 upregulated transactivation of a vitamin D-sensitive promoter. cDNA microarray analysis, using a novel dolphin array, identified specific gene targets within this pathway, and real-time PCR (qPCR) confirmed the enhanced expression of select genes of interest. These transcriptional changes correlated with an increase in VDR levels. This is the first report of the presence and activation of the vitamin D3 pathway in a marine mammal, and our experimental results demonstrate a number of similarities to terrestrial animals. Conservation of this pathway in the Atlantic bottlenose dolphin is consistent with the importance of nonclassic functions of vitamin D3, such as its role in innate immunity, similar to what has been demonstrated in other mammals. PMID:19454332

  11. 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.

  12. Residual Stress Analysis of Boronized AISI 1018 Steel

    SciTech Connect

    Payne,J.; Petrova, R.; White, H.; Chauhan, A.; Bai, J.

    2008-01-01

    AISI 1018 steel substrates were powder-pack, diffusion boronized at 850 C for 4 h, followed by air quenching. Optical microscopy in conjunction with color etching was used to obtain the average penetration depth of the iron monoboride layer (9 {mu}m) and the iron diboride layer (57 {mu}m). X-ray diffraction by synchrotron radiation, conducted at the National Synchrotron Light Source in Brookhaven National Laboratory, confirmed the presence of iron monoboride and iron diboride in the boronized plain steel substrates. The sin2 {psi} technique was employed to calculate the residual stress found in the iron monoboride layer (-237 MPa) and in the substrate layer (-150 MPa) that is intertwined with the needle-like, iron diboride penetration.

  13. Chemical composition of passive films on AISI 304 stainless steel

    SciTech Connect

    Lorang, G.; Da Cunha Belo, M. ); Simoes, A.M.P.; Ferreira, M.G.S. . Dept. de Engenharia Quimica)

    1994-12-01

    Chemical characterization of passive films formed on AISI 304 austenitic stainless steel, in a borate/boric acid solution at pH 9.2, under various conditions of potential, temperature, and polarizations time, was made by Auger electron spectroscopy combined with ion sputtering, and x-ray photoelectron spectroscopy (XPS). The depth chemical composition, thickness, and duplex character of the passive layers were determined after processing AES sputter profiles by their quantitative approach based on the sequential layer sputtering model. Moreover, separated contributions of elements in their oxidized and unoxidized state could be disclosed from part to part of the oxide-alloy interface. The XPS study specified the chemical bondings which take placed inside the film, between Fe and oxygen (and water).

  14. Embrittlement of an AISI 8640 lower bainite steel

    SciTech Connect

    Rinnovatore, J.V. . Development and Engineering Center); Lukens, K.F.; Reinhold, J.; Mahon, W. . Development and Engineering Center)

    1993-09-01

    A study was performed to determine the cause of an abnormally low fracture toughness of an AISI 8640 resulfurized steel. The embrittlement effects of phosphorus and arsenic on this steel heat-treated to a lower bainitic structure were studied by employing fracture toughness tests, Charpy impact tests, X-ray fluorescent spectroscopy, and scanning electron microscopy (SEM). The results showed that the steel was embrittled by phosphorus at prior austenite grain boundaries in a manner similar to the tempered martensite embrittlement (TME) phenomenon. Arsenic is also believed to be involved in the embrittlement effect, specifically as related to producing a reduction in the upper shelf Charpy impact energy. Embrittlement was manifested by a reduced fracture toughness, an increase in the Charpy transition temperature, and intergranular fracture.

  15. 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.

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

    DTIC Science & Technology

    2013-05-01

    of the commercially available metallic materials, in particular, steels (including stainless steels ), super alloys, aluminum alloys, etc.; (b) welding...REPORT Computational Modeling of Microstructural-Evolution in AISI 1005 Steel During Gas Metal Arc Butt Welding 14. ABSTRACT 16. SECURITY...Computational Modeling of Microstructural-Evolution in AISI 1005 Steel During Gas Metal Arc Butt Welding Report Title ABSTRACT A fully coupled (two-way

  17. 20-Hydroxyvitamin D3, a Product of Vitamin D3 Hydroxylation by Cytochrome P450scc, Stimulates Keratinocyte Differentiation

    PubMed Central

    Zbytek, Blazej; Janjetovic, Zorica; Tuckey, Robert C.; Zmijewski, Michal A.; Sweatman, Trevor W.; Jones, Emily; Nguyen, Minh N.; Slominski, Andrzej T.

    2008-01-01

    It has been shown that mammalian cytochrome P450scc can metabolize vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,22(OH)2D3. To define the biological significance of this pathway, we tested the effects of 20(OH)D3 on the differentiation program of keratinocytes and on the expression of enzymes engaged in vitamin D3 metabolism. Immortalized HaCaT and adult human epidermal keratinocytes were used as a model and the effects of 20(OH)D3 were compared with those of 25(OH)D3 and 1,25(OH)2D3. 20(OH)D3 inhibited proliferation and caused G2/M arrest. 20(OH)D3 stimulated involucrin and inhibited cytokeratin 14 expression. The potency of 20(OH)D3 was comparable to that of 1,25(OH)2D3. 20(OH)D3 decreased the expression of cytochrome P450 enzyme (CYP)27A1 and CYP27B1, however, having only slight effect on CYP24. The effect of 20(OH)D3 was dependent on the vitamin D receptor (VDR). As shown by electrophoretic mobility shift assay, 20(OH)D3 stimulated the binding of nuclear proteins to the VDRE. Transfection of cells with VDR-specific siRNA decreased 20(OH)D3-stimulated transcriptional activity of the VDRE promoter and the expression of involucrin and CYP24 mRNA. Therefore, the above studies identify 20(OH)D3 as a biologically active secosteroid that induces keratinocyte differentiation. These data imply that the previously unreported pathway of vitamin D3 metabolism by P450scc may have wider biological implications depending, for example, on the extent of adrenal gland or cutaneous metabolism. PMID:18368131

  18. Validity and Reliability of the Attachment Insecurity Screening Inventory (AISI) 2-5 Years.

    PubMed

    Wissink, I B; Colonnesi, C; Stams, G J J M; Hoeve, M; Asscher, J J; Noom, M J; Polderman, N; Kellaert-Knol, M G

    The Attachment Insecurity Screening Inventory (AISI) 2-5 years is a parent-report questionnaire for assessing attachment insecurity in preschoolers. Validity and reliability of the AISI 2-5 years were examined in a general sample (n = 429) and in a clinical sample (n = 71). Confirmatory factor analysis (CFA) confirmed a three-factor model of avoidant, ambivalent/resistant and disorganized attachment, and one higher-order factor of total attachment insecurity. Multi-group CFA indicated measurement invariance across mothers and fathers, and across the general and clinical population sample. Reliability coefficients were generally found to be good. We found partial support for convergent validity in associations between AISI-scores and observed attachment (AQS). Concurrent validity was supported by associations between AISI-scores and observed parental sensitivity (MBQS) and parent-reported psychopathology (SDQ). Finally, the AISI discriminated well between children from the general and from the clinical sample. We argue that both research and practice could benefit from the AISI as there is now a prospect of quickly, reliably and validly screening for attachment insecurity in pre-school aged children. Based on this information, help can be offered timely and, subsequently, the prevention of attachment related problems of children can be strengthened.

  19. 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.

  20. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders.

    PubMed

    Sokoloff, P; Diaz, J; Le Foll, B; Guillin, O; Leriche, L; Bezard, E; Gross, C

    2006-02-01

    The role of the D(3) receptor has remained largely elusive before the development of selective research tools, such as selective radioligands, antibodies, various highly specific pharmacological agents and knock-out mice. The data collected so far with these tools have removed some of the uncertainties regarding the functions mediated by the D(3) receptor. The D(3) receptor is an autoreceptor that controls the phasic, but not tonic activity of dopamine neurons. The D(3) receptor, via regulation of its expression by the brain-derived neurotrophic factor (BDNF), mediates sensitization to dopamine indirect agonists. This process seems responsible for side-effects of levodopa (dyskinesia) in the treatment of Parkinson's disease (PD), as well as for some aspects of conditioning to drugs of abuse. The D(3) receptor mediates behavioral abnormalities elicited by glutamate/NMDA receptor blockade, which suggests D(3) receptor-selective antagonists as novel antipsychotic drugs. These data allow us to propose novel treatment options in PD, schizophrenia and drug addiction, which are awaiting evaluation in clinical trials.

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

    PubMed

    Keck, Thomas M; John, William S; Czoty, Paul W; Nader, Michael A; Newman, Amy Hauck

    2015-07-23

    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.

  2. 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

  3. 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.

  4. 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.

  5. 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. PMID:27873912

  6. 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

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

    PubMed

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

    2016-06-01

    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.

  8. Surface Fatigue Life of M50NiL and AISI 9310 Spur Gears and R C Bars

    DTIC Science & Technology

    1991-11-26

    AD-A241 470 NASA AVSCOM Technical Memorandum 104496 Technical Report 91- C- 034 Surface Fatigue Life of M50NiL and AISI 9310 Spur Gears and R C Bars...AISI 9310 and M50NIL In rolUng-contact ilof AISI 9310 and MSON fatigue tester. Maximum Hertz stress, 4.83 GPaFigure 4.- Typical fatigue spail (70fkA

  9. Comparative study of pulsed Nd:YAG laser welding of AISI 304 and AISI 316 stainless steels

    NASA Astrophysics Data System (ADS)

    Kumar, Nikhil; Mukherjee, Manidipto; Bandyopadhyay, Asish

    2017-02-01

    Laser welding is a potentially useful technique for joining two pieces of similar or dissimilar materials with high precision. In the present work, comparative studies on laser welding of similar metal of AISI 304SS and AISI 316SS have been conducted forming butt joints. A robotic control 600 W pulsed Nd:YAG laser source has been used for welding purpose. The effects of laser power, scanning speed and pulse width on the ultimate tensile strength and weld width have been investigated using the empirical models developed by RSM. The results of ANOVA indicate that the developed models predict the responses adequately within the limits of input parameters. 3-D response surface and contour plots have been developed to find out the combined effects of input parameters on responses. Furthermore, microstructural analysis as well as hardness and tensile behavior of the selected weld of 304SS and 316SS have been carried out to understand the metallurgical and mechanical behavior of the weld. The selection criteria are based on the maximum and minimum strength achieved by the respective weld. It has been observed that the current pulsation, base metal composition and variation in heat input have significant influence on controlling the microstructural constituents (i.e. phase fraction, grain size etc.). The result suggests that the low energy input pulsation generally produce fine grain structure and improved mechanical properties than the high energy input pulsation irrespective of base material composition. However, among the base materials, 304SS depict better microstructural and mechanical properties than the 316SS for a given parametric condition. Finally, desirability function analysis has been applied for multi-objective optimization for maximization of ultimate tensile strength and minimization of weld width simultaneously. Confirmatory tests have been conducted at optimum parametric conditions to validate the optimization techniques.

  10. 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

  11. 21 CFR 172.380 - Vitamin D 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D 3. 172.380 Section 172.380 Food and....380 Vitamin D 3. Vitamin D3 may be used safely in foods as a nutrient supplement defined under § 170.3(o)(20) of this chapter in accordance with the following prescribed conditions: (a) Vitamin D3,...

  12. The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure.

    PubMed

    Holmes, Ian P; Blunt, Richard J; Lorthioir, Olivier E; Blowers, Stephen M; Gribble, Andy; Payne, Andrew H; Stansfield, Ian G; Wood, Martyn; Woollard, Patrick M; Reavill, Charlie; Howes, Claire M; Micheli, Fabrizio; Di Fabio, Romano; Donati, Daniele; Terreni, Silvia; Hamprecht, Dieter; Arista, Luca; Worby, Angela; Watson, Steve P

    2010-03-15

    The identification of a highly selective D(2) partial agonist, D(3) antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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.

  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. 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.

  1. Evaluation of the tool life and fracture toughness of cutting tools boronized by the paste boriding process

    NASA Astrophysics Data System (ADS)

    Campos, I.; Farah, M.; López, N.; Bermúdez, G.; Rodríguez, G.; VillaVelázquez, C.

    2008-03-01

    The present study evaluates the tool life and the fracture toughness of AISI M2 steel cutting tools boronized by the paste boriding process. The treatment was done in selective form on the tool tips of the steels. The temperatures were set at 1173 and 1273 K with 4 h of exposure time and modifying the boron carbide paste thicknesses in 3 and 4 mm. Microindentation fracture toughness method was used on the borided tool at the temperature of 1273 K and a 4 mm paste thickness, with a 100 g load at different distances from the surface. Also, the borided cutting tools were worn by the turning process that implied the machining of AISI 1018 steel increasing the nominal cutting speed, of 55 m/min, in 10 and 25% and maintaining the feed and the depth cut constants. The tool life was evaluated by the Taylor's equation that shows the dependence of the experimental parameters of the boriding process.

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

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Dependence on displacement rate of radiation-induced changes in microstructure and tensile properties of AISI 304 and 316

    SciTech Connect

    Brager, H.R.; Blackburn, L.D.; Greenslade, D.L.

    1983-08-01

    Annealed specimens of AISI 304 and 316 were irradiated in the EBR-II fast reactor at approx. 400/sup 0/C over a range of neutron fluxes and energy spectra. Tensile tests show that the hardening of the AISI 304 is sensitive to the displacement rate while the hardening of AISI 316 is not. However, the microstructures of both AISI 304 and 316 are influenced by displacement rate. The increase in yield strength of the specimens is correlated with the contribution of the various microstructural components produced during irradiation. The insensitivity in the hardening of AISI 316 to displacement rate arises because the strengthening contribution from precipitates increases with displacement rate, whereas the strengthening contribution from voids decreases.

  8. Surface textural features and its formation process of AISI 304 stainless steel subjected to massive LSP impacts

    NASA Astrophysics Data System (ADS)

    Luo, K. Y.; Yao, H. X.; Dai, F. Z.; Lu, J. Z.

    2014-04-01

    The effects of massive laser shock peening (LSP) impacts on surface textural feature of AISI 304 stainless steel (AISI 304 SS), including surface waviness, surface roughness, and machining texture and direction, have been investigated by using WKYO-NT1100 surface profiler and TR300 stylus roughness shape measuring instrument. Experimental results show that massive LSP impacts have an important influence on the surface waviness of the AISI 304 SS sample, but do not have a measurable impact on the surface roughness. Moreover, massive LSP impacts with constraint and ablation mode generate a novel compound texture on the surface of the AISI 304 SS sample. In addition, the formation process of surface compound texture in AISI 304 SS by massive LSP impacts is also entirely revealed.

  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. 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.

  11. Kinetics and Tribological Characterization of Pack-Borided AISI 1025 Steel

    NASA Astrophysics Data System (ADS)

    Gómez-Vargas, O. A.; Keddam, M.; Ortiz-Domínguez, M.

    2017-03-01

    In this present study, the AISI 1025 steel was pack-borided in the temperature range of 1,123-1,273 K for different treatment times ranging from 2 to 8 h. A diffusion model was suggested to estimate the boron diffusion coefficients in the Fe2B layers. As a result, the boron activation energy for the AISI 1025 steel was estimated as 174.36 kJ/mol. This value of energy was compared with the literature data. To extend the validity of the present model, other additional boriding conditions were considered. The boride layers formed on the AISI 1025 steel were characterized by the following experimental techniques: scanning electron microscopy, X-ray diffraction analysis and the Daimler-Benz Rockwell-C indentation technique. Finally, the scratch and pin-on-disc tests for wear resistance were achieved using an LG Motion Ltd and a CSM tribometer, respectively, under dry sliding conditions.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Characterization of Tungsten Carbide coatings deposited on AISI 1020 steel

    NASA Astrophysics Data System (ADS)

    Santos, A.; Gonzalez, C.; Ramirez, Z. Y.

    2017-01-01

    In order to determine the variation in the mechanical properties of AISI 1020 standardized steel, heat treated by a quenching and tempering process and with a Tungsten Carbide coating, was performed a microstructural and chemical characterization of the coating material through electron microscopy scanning and X-ray energy dispersive spectroscopy. The steel received a heat treatment of quenching performed by heating to 850°C, followed by cooling in water and tempering at a temperature of 450°C with air cooling. Tests of a) microhardness with a Wilson-Wolpert Tukon 2100B micro durometer and b) resistance to adhesive and abrasive wear following the ASTM G99-05 “Standard test method for wear testing with a pin-on-disk machine” and ASTM G65-04 “standard test method for measuring abrasion using dry sand and rubber Wheel” standards respectively. The results show that the microhardness of the steel do not vary with the load used to perform the test; in addition, the heat treatment of quenching and tempering improves by 5.5% the property while the coating increase it by 124.2%. Regarding the abrasive wear resistance, it is observed that the amount of material lost increases linearly with the distance covered. It was determined that the heat treatment decreased on average by 17.5% the volume of released material during the tests while the coating recued it by 66.7%. The amount volume of material lost during the adhesive wear tests increases linearly with the distance covered while the heat treatment decreased on average by 10.5% the volume of released material during the trial and the coating reduced it by 66.5%.

  17. Continuous-flow synthesis of vitamin D3.

    PubMed

    Fuse, Shinichiro; Tanabe, Nobutake; Yoshida, Masahito; Yoshida, Hayato; Doi, Takayuki; Takahashi, Takashi

    2010-12-14

    A highly efficient, two-stage, continuous-flow synthesis of vitamin D(3) from provitamin D(3) was achieved. The developed method afforded the desired product in high yield (HPLC-UV: 60%, isolated: 32%) and required neither intermediate purification nor high-dilution conditions.

  18. Current drug treatments targeting dopamine D3 receptor.

    PubMed

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

    2016-09-01

    Dopamine receptors (DR) have been extensively studied, but only in recent years they became object of investigation to elucidate the specific role of different subtypes (D1R, D2R, D3R, D4R, D5R) in neural transmission and circuitry. D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D2R and D4R) differ in signal transduction, binding profile, localization in the central nervous system and physiological effects. D3R is involved in a number of pathological conditions, including schizophrenia, Parkinson's disease, addiction, anxiety, depression and glaucoma. Development of selective D3R ligands has been so far challenging, due to the high sequence identity and homology shared by D2R and D3R. As a consequence, despite a rational design of selective DR ligands has been carried out, none of currently available medicines selectively target a given D2-like receptor subtype. The availability of the D3R ligand [(11)C]-(+)-PHNO for positron emission tomography studies in animal models as well as in humans, allows researchers to estimate the expression of D3R in vivo; displacement of [(11)C]-(+)-PHNO binding by concurrent drug treatments is used to estimate the in vivo occupancy of D3R. Here we provide an overview of studies indicating D3R as a target for pharmacological therapy, and a review of market approved drugs endowed with significant affinity at D3R that are used to treat disorders where D3R plays a relevant role.

  19. 1,25-Vitamin D3 Deficiency Induces Albuminuria.

    PubMed

    Sonneveld, Ramon; Hoenderop, Joost G J; Stavenuiter, Andrea W D; Ferrantelli, Evelina; Baltissen, Marijke P A; Dijkman, Henry B; Florquin, Sandrine; Rops, Angelique L; Wetzels, Jack F M; Berden, Jo H M; van der Vlag, Johan; Nijenhuis, Tom

    2016-04-01

    Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

  20. Long-term evaluation of solid oxide fuel cell candidate materials in a 3-cell generic stack test fixture, part III: Stability and microstructure of Ce-(Mn,Co)-spinel coating, AISI441 interconnect, alumina coating, cathode and anode

    NASA Astrophysics Data System (ADS)

    Chou, Yeong-Shyung; Stevenson, Jeffry W.; Choi, Jung-Pyung

    2014-07-01

    A generic solid oxide fuel cell stack test fixture was developed to evaluate candidate materials and processing under realistic conditions. Part III of the work investigated the stability of Ce-(Mn,Co) spinel coating, AISI441 metallic interconnect, alumina coating, and cell's degradation. After 6000 h test, the spinel coating showed densification with some diffusion of Cr. At the metal interface, segregation of Si and Ti was observed, however, no continuous layer formed. The alumina coating for perimeter sealing areas appeared more dense and thick at the air side than the fuel side. Both the spinel and alumina coatings remained bonded. EDS analysis of Cr within the metal showed small decrease in concentration near the coating interface and would expect to cause no issue of Cr depletion. Inter-diffusion of Ni, Fe, and Cr between spot-welded Ni wire and AISI441 interconnect was observed and Cr-oxide scale formed along the circumference of the weld. The microstructure of the anode and cathode was discussed relating to degradation of the top and middle cells. Overall, the Ce-(Mn,Co) spinel coating, alumina coating, and AISI441 steel showed the desired long-term stability and the developed generic stack fixture proved to be a useful tool to validate candidate materials for SOFC.

  1. 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.

  2. Vitamin D3 analogs stimulate hair growth in nude mice.

    PubMed

    Vegesna, Vijaya; O'Kelly, James; Uskokovic, Milan; Said, Jonathan; Lemp, Nathan; Saitoh, Takayuki; Ikezoe, Takayuki; Binderup, Lise; Koeffler, H Phillip

    2002-11-01

    The active form of vitamin D3 can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D3 pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D3 analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D3 analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D3 analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

  3. 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.

  4. Alberta Initiative for School Improvement: AISI Handbook for Cycle 3, 2006-2009

    ERIC Educational Resources Information Center

    Online Submission, 2006

    2006-01-01

    The purpose of the AISI (Alberta Initiative for School Improvement) Handbook for Cycle 3, 2006-2009 is to provide school authorities with the provincial and local requirements and processes for planning, funding, implementing, managing, evaluating, reporting and sharing school improvement projects. The handbook provides a framework for the…

  5. Novel water-air circulation quenching process for AISI 4140 steel

    NASA Astrophysics Data System (ADS)

    Zheng, Liyun; Zheng, Dawei; Zhao, Lixin; Wang, Lihui; Zhang, Kai

    2013-11-01

    AISI 4140 steel is usually used after quenching and tempering. During the heat treatment process in industry production, there are some problems, such as quenching cracks, related to water-cooling and low hardness due to oil quenching. A water-air circulation quenching process can solve the problems of quenching cracks with water and the high cost quenching with oil, which is flammable, unsafe and not enough to obtain the required hardness. The control of the water-cooling and air-cooling time is a key factor in the process. This paper focuses on the quenching temperature, water-air cycle time and cycle index to prevent cracking for AISI 4140 steel. The optimum heat treatment parameters to achieve a good match of the strength and toughness of AISI 4140 steel were obtained by repeated adjustment of the water-air circulation quenching process parameters. The tensile strength, Charpy impact energy at -10 °C and hardness of the heat treated AISI 4140 steel after quenching and tempering were approximately 1098 MPa, 67.5 J and 316 HB, respectively.

  6. Field Operational and Environmental Evaluation of the Automated Integrated Surveying Instrument (AISI). Volume 1

    DTIC Science & Technology

    1988-04-01

    DO NOT REPRODUCE LEGIBLY, ADDENDUM (FINAL REPORT VOL. I OF I) FIELD OPERATIONAL & ENVIRONMENTAL EVALUATION OF THE AUTOMATED INTEGRATED SURVEYING...close a traverse Construction Same as topographic L2 r II I AUOAE7NEGAINSREIGIShMN AUOAE NEGAINSREIGISRMN (AISI) TABLE OF CONT-ENTS Tot i c Volume I P...18 Environmental Tests. .. .. .... .... .... ..... ..... 29 Electromagnetic interference Tests .. .. ..... .... .... .... 34

  7. 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.

  8. Modeling and Investigation of the Wear Resistance of Salt Bath Nitrided Aisi 4140 via ANN

    NASA Astrophysics Data System (ADS)

    Ekinci, Şerafettin; Akdemir, Ahmet; Kahramanli, Humar

    2013-05-01

    Nitriding is usually used to improve the surface properties of steel materials. In this way, the wear resistance of steels is improved. We conducted a series of studies in order to investigate the microstructural, mechanical and tribological properties of salt bath nitrided AISI 4140 steel. The present study has two parts. For the first phase, the tribological behavior of the AISI 4140 steel which was nitrided in sulfinuz salt bath (SBN) was compared to the behavior of the same steel which was untreated. After surface characterization using metallography, microhardness and sliding wear tests were performed on a block-on-cylinder machine in which carbonized AISI 52100 steel discs were used as the counter face. For the examined AISI 4140 steel samples with and without surface treatment, the evolution of both the friction coefficient and of the wear behavior were determined under various loads, at different sliding velocities and a total sliding distance of 1000 m. The test results showed that wear resistance increased with the nitriding process, friction coefficient decreased due to the sulfur in salt bath and friction coefficient depended systematically on surface hardness. For the second part of this study, four artificial neural network (ANN) models were designed to predict the weight loss and friction coefficient of the nitrided and unnitrided AISI 4140 steel. Load, velocity and sliding distance were used as input. Back-propagation algorithm was chosen for training the ANN. Statistical measurements of R2, MAE and RMSE were employed to evaluate the success of the systems. The results showed that all the systems produced successful results.

  9. Mechanochemical synthesis and crystal structure of alpha'-AlD3 and alpha-AlD3.

    PubMed

    Brinks, Hendrik W; Istad-Lem, Andreas; Hauback, Bjørn C

    2006-12-28

    AlD3 AlD3 was synthesized by ball milling of 3LiAlD4 + AlCl3. Planetary ball milling at room temperature resulted in a mixture of AlD3 (alpha and alpha') and Al in addition to LiCl, whereas cryomilling at 77 K resulted in only AlD3 and LiCl. The AlD3 obtained was a mixture of about 2/3alpha and 1/3alpha'. Alpha' was determined by powder neutron diffraction to take the beta-AlF3 structure with space group Cmcm and a = 6.470(3), b = 11.117(5), and c = 6.562(2) A. It is built up of corner-sharing AlD6 octahedra in an open structure with hexagonal holes of radius 3.9 A. Alpha' slowly decomposes during storage at 40 degrees C. Alpha-AlD3 is also described by a corner-sharing AlD6 network but in a more dense ReO3-type arrangement. Both AlD3 modifications have slightly shorter Al-D distances compared to Na3AlD6, Na2LiAlD6, and K2NaAlH6.

  10. Phagocytic cells metabolize 25-hydroxyvitamin D3 in vitro.

    PubMed Central

    Cohen, M S; Gray, T K

    1984-01-01

    Phagocytic cells are widely distributed in tissues known to be important in the metabolism of vitamin D. Incubation of human polymorphonuclear leukocytes and monocytes and resident rat peritoneal macrophages with 3H-labeled 25-hydroxyvitamin D3 leads to the formation of three radioactive peaks. Peak I is most consistent with a lactone derivative of 25-hydroxyvitamin D3, and peak II has been identified as putative 24,25-dihydroxyvitamin D3. Peak III is a novel metabolite of 25-hydroxyvitamin D3 unlike any of the synthetic standards available in our laboratories. Human neutrophils converted more substrate than did the other phagocytes examined. The stimulation of neutrophils by opsonized zymosan or phorbol myristate acetate led to a 4-fold increase in synthesis of the metabolites. These results suggest that vitamin D metabolism by phagocytic cells may play a role in the microenvironmental events that surround bony metabolism and calcium homeostasis. PMID:6322179

  11. He I D3 OBSERVATIONS OF THE 1984 MAY 22 M6.3 SOLAR FLARE

    SciTech Connect

    Liu Chang; Xu Yan; Deng Na; Lee, Jeongwoo; Zhang Jifeng; Wang Haimin; Prasad Choudhary, Debi

    2013-09-01

    The He I D3 line has a unique response to a flare impact on the low solar atmosphere and can be a powerful diagnostic tool for energy transport processes. Using images obtained from the recently digitized films of the Big Bear Solar Observatory, we report D3 observations of the M6.3 flare on 1984 May 22, which occurred in an active region with a circular magnetic polarity inversion line (PIL). The impulsive phase of the flare starts with a main elongated source that darkens in D3, inside of which bright emission kernels appear at the time of the initial small peak in hard X-rays (HXRs). These flare cores subsequently evolve into a sharp emission strand lying within the dark halo; this evolution occurs at the same time as the main peak in HXRs, reversing the overall source contrast from -5% to 5%. The radiated energy in D3 during the main peak is estimated to be about 10{sup 30} erg, which is comparable to that carried by nonthermal electrons above 20 keV. Afterward, the flare proceeds along the circular PIL in the counterclockwise direction to form a dark circular ribbon in D3, which apparently mirrors the bright ribbons in H{alpha} and He I 10830 A. All of these ribbons last for over one hour in the late gradual phase. We suggest that the present event resembles the so-called black-light flare that was proposed based on continuum images, and that D3 darkening and brightening features herein may be due to thermal conduction heating and the direct precipitation of high-energy electrons, respectively.

  12. Analysis of Human Dopamine D3 Receptor Quaternary Structure*

    PubMed Central

    Marsango, Sara; Caltabiano, Gianluigi; Pou, Chantevy; Varela Liste, María José; Milligan, Graeme

    2015-01-01

    The dopamine D3 receptor is a class A, rhodopsin-like G protein-coupled receptor that can form dimers and/or higher order oligomers. However, the molecular basis for production of these complexes is not well defined. Using combinations of molecular modeling, site-directed mutagenesis, and homogenous time-resolved FRET, the interfaces that allow dopamine D3 receptor monomers to interact were defined and used to describe likely quaternary arrangements of the receptor. These were then compared with published crystal structures of dimeric β1-adrenoreceptor, μ-opioid, and CXCR4 receptors. The data indicate important contributions of residues from within each of transmembrane domains I, II, IV, V, VI, and VII as well as the intracellular helix VIII in the formation of D3-D3 receptor interfaces within homo-oligomers and are consistent with the D3 receptor adopting a β1-adrenoreceptor-like quaternary arrangement. Specifically, results suggest that D3 protomers can interact with each other via at least two distinct interfaces: the first one comprising residues from transmembrane domains I and II along with those from helix VIII and a second one involving transmembrane domains IV and V. Moreover, rather than existing only as distinct dimeric species, the results are consistent with the D3 receptor also assuming a quaternary structure in which two transmembrane domain I-II-helix VIII dimers interact to form a ”rhombic” tetramer via an interface involving residues from transmembrane domains VI and VII. In addition, the results also provide insights into the potential contribution of molecules of cholesterol to the overall organization and potential stability of the D3 receptor and possibly other GPCR quaternary structures. PMID:25931118

  13. 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

  14. 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

  15. Experimental investigation and modelling of surface roughness and resultant cutting force in hard turning of AISI H13 Steel

    NASA Astrophysics Data System (ADS)

    Boy, M.; Yaşar, N.; Çiftçi, İ.

    2016-11-01

    In recent years, turning of hardened steels has replaced grinding for finishing operations. This process is compared to grinding operations; hard turning has higher material removal rates, the possibility of greater process flexibility, lower equipment costs, and shorter setup time. CBN or ceramic cutting tools are widely used hard part machining. For successful application of hard turning, selection of suitable cutting parameters for a given cutting tool is an important step. For this purpose, an experimental investigation was conducted to determine the effects of cutting tool edge geometry, feed rate and cutting speed on surface roughness and resultant cutting force in hard turning of AISI H13 steel with ceramic cutting tools. Machining experiments were conducted in a CNC lathe based on Taguchi experimental design (L16) in different levels of cutting parameters. In the experiments, a Kistler 9257 B, three cutting force components (Fc, Ff and Fr) piezoelectric dynamometer was used to measure cutting forces. Surface roughness measurements were performed by using a Mahrsurf PS1 device. For statistical analysis, analysis of variance has been performed and mathematical model have been developed for surface roughness and resultant cutting forces. The analysis of variance results showed that the cutting edge geometry, cutting speed and feed rate were the most significant factors on resultant cutting force while the cutting edge geometry and feed rate were the most significant factor for the surface roughness. The regression analysis was applied to predict the outcomes of the experiment. The predicted values and measured values were very close to each other. Afterwards a confirmation tests were performed to make a comparison between the predicted results and the measured results. According to the confirmation test results, measured values are within the 95% confidence interval.

  16. 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.

  17. 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

  18. A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues

    PubMed Central

    2011-01-01

    Background Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening methods that allow a comparative evaluation of drug properties. As a new tool in functional screening of vitamin D3 analogues, we describe a genomically integratable sensor for sensitive drug detection. This system facilitates assessment of the pharmacokinetic and pharmadynamic properties of vitamin D3 analogues. The tri-cistronic genetic sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a resistance marker. Results The three expression cassettes, inserted in a head-to-tail orientation in a Sleeping Beauty DNA transposon vector, are efficiently inserted as a single genetic entity into the genome of cells of interest in a reaction catalyzed by the hyperactive SB100X transposase. The applicability of the sensor for screening purposes is demonstrated by the functional comparison of potent synthetic analogues of vitamin D3 designed for the treatment of psoriasis and cancer. In clones of human keratinocytes carrying from a single to numerous insertions of the vitamin D3 sensor, a sensitive sensor read-out is detected upon exposure to even low concentrations of vitamin D3 analogues. In comparative studies, the sensor unveils superior potency of new candidate drugs in comparison with analogues that are currently in clinical use. Conclusions Our findings demonstrate the use of the genetic sensor as a tool in first-line evaluation of new vitamin D3 analogues and pave the way for new types of drug delivery studies in sensor-transgenic animals. PMID:21473770

  19. Rolling Contact Fatigue Life and Spall Propagation Characteristics of AISI M50, M50 NiL, and AISI 52100. Part 1. Experimental Results (Preprint)

    DTIC Science & Technology

    2009-10-01

    factors to the L-P life model are currently used as standard practice to account for improvements in bearing material cleanliness and processing...eleven 12.7 mm diameter ABMA Grade 10 silicon nitride (Si3N4) balls, Ra finish of 6.4 nm and one piece machined silver plated AISI 4340 steel cages...piloted on both sides of the outer ring. The outer ring cage- land shoulders of the M50NiL bearings were titanium nitride (TiN) coated per aerospace

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

    PubMed

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

    2016-04-08

    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.

  1. Ghost-free, finite, fourth-order D = 3 gravity.

    PubMed

    Deser, S

    2009-09-04

    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.

  2. 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.

  3. 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

  4. Finite Element Simulation and Experimental Verification of Internal Stress of Quenched AISI 4140 Cylinders

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Qin, Shengwei; Hao, Qingguo; Chen, Nailu; Zuo, Xunwei; Rong, Yonghua

    2017-03-01

    The study of internal stress in quenched AISI 4140 medium carbon steel is of importance in engineering. In this work, the finite element simulation (FES) was employed to predict the distribution of internal stress in quenched AISI 4140 cylinders with two sizes of diameter based on exponent-modified (Ex-Modified) normalized function. The results indicate that the FES based on Ex-Modified normalized function proposed is better consistent with X-ray diffraction measurements of the stress distribution than FES based on normalized function proposed by Abrassart, Desalos and Leblond, respectively, which is attributed that Ex-Modified normalized function better describes transformation plasticity. Effect of temperature distribution on the phase formation, the origin of residual stress distribution and effect of transformation plasticity function on the residual stress distribution were further discussed.

  5. 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.

  6. 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.

  7. 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.

  8. Finite Element Simulation and Experimental Verification of Internal Stress of Quenched AISI 4140 Cylinders

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Qin, Shengwei; Hao, Qingguo; Chen, Nailu; Zuo, Xunwei; Rong, Yonghua

    2017-01-01

    The study of internal stress in quenched AISI 4140 medium carbon steel is of importance in engineering. In this work, the finite element simulation (FES) was employed to predict the distribution of internal stress in quenched AISI 4140 cylinders with two sizes of diameter based on exponent-modified (Ex-Modified) normalized function. The results indicate that the FES based on Ex-Modified normalized function proposed is better consistent with X-ray diffraction measurements of the stress distribution than FES based on normalized function proposed by Abrassart, Desalos and Leblond, respectively, which is attributed that Ex-Modified normalized function better describes transformation plasticity. Effect of temperature distribution on the phase formation, the origin of residual stress distribution and effect of transformation plasticity function on the residual stress distribution were further discussed.

  9. Effect of Thermomechanical Treatment on the Microstructure and Mechanical Properties of AISI 52100 Steel.

    DTIC Science & Technology

    1981-06-01

    Thermomechanical Process- in& and Heat Treatment on the Fatigue Resistance and Fractographic Characteristics of a High-Carbon Bearing Steel, M.S. Thesis...SUPPLEMENTARY NOTCS to. 14 IV WORDS (Cominu. -s bree coer It arneemp aE~ndt bay .4*l ONber) 52100 Steel, thermomechanical processing; heat treatment...properties of AISI 52100 steel, in particular the alloys resistance to fatigue failure. Much of this research has concentrated on improving heat treating

  10. Mechanical properties of cold-rolled AISI 304LN steel at low temperatures

    SciTech Connect

    Ilola, R.J.; Haenninen, H.E.; Heinaekari, M.J.

    1996-12-01

    Mechanical properties of 0--70% cold-rolled AISI 304LN steel (0, 16 wt.% N) were investigated by means of tensile and Charpy V-notch impact tests between room temperature and {minus}196 C. Fracture surfaces of the tested specimens were investigated using SEM (scanning electron microscope). Austenite stability against {alpha}{prime}-martensite formation during cooling and during deformation in cold-rolling and mechanical testing was determined using magnetic measurements.

  11. Experimental study on the stress corrosion cracking behavior of AISI347 in acid chloride ion solution

    NASA Astrophysics Data System (ADS)

    Qu, Yanpeng; Wang, Runkun; Wang, Chao; Chen, Songying

    The stress corrosion cracking (SCC) behavior of AISI347 austenitic stainless steel exposed to acid solution containing chloride ion at different temperature and pressure is studied through slow strain rate testing (SSRT) at different test condition. The result of SSRT shows, with the pressure increasing, the SCC resistance is getting worse and the trend of brittle fracture presented by the fracture surface is more obvious. With the temperature rising, the mechanical properties of AISI347 getting worse first and then getting better, it gets to be the worst when the temperature is 260 °C. The result of significance effect analysis of temperature and pressure on SCC shows that the temperature has a greater effect on the resistance to SCC of AISI347 austenitic stainless steel than the pressure. The main component of passive film is analyzed and the mechanism of SCC is discussed. Chromium oxides soluble in the acidic chloride solution results in the forming of corrosion pits and the cracking of the passive film under stress.

  12. Effects of gaseous nitriding AISI4140 alloy steel on corrosion and hardness properties

    NASA Astrophysics Data System (ADS)

    Tamil Moli, L.; Wahab, N.; Gopinathan, M.; Karmegam, K.; Maniyarasi, M.

    2016-10-01

    Corrosion is one of the major problems in the industry especially on machinery since it weakens the structure of the machinery part and causes the mechanical failure. This will stop the production and increase the maintenance cost. In this study, the corrosion behaviour of gas nitriding on a screw press machine shaft made from AISI 4140 steel was investigated. Pitting corrosion was identified as a major cause of the shaft failure and this study was conducted to improve the corrosion resistance on the AISI 4140 alloy steel shaft by gas nitriding as a surface hardening treatment. Gas nitriding was performed with composition of 15% ammonia and 85% nitrogen at temperatures of 525 °C, 550 °C and 575 °C and with the soaking time of 30, 45 and 60 minutes, respectively. The samples were prepared as rectangular sized of 30mm x 12mm x 3mm for immersion testing. The results showed that corrosion rate of untreated samples was 77% higher compared to the nitrided samples. It was also found that hardness of the nitrided samples was higher than untreated sample. All in all, it can be concluded that gaseous nitriding can significantly improve the surface hardness and the corrosion resistance of the shaft made of AISI 4140 alloy steel, hence reduces the pitting that is the root cause of failure.

  13. Low Temperature Salt Bath Hardening of AISI 201 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Luo, H. S.; Zhao, C.

    Salt bath hardening at low temperature was applied in order to enhance the surface hardness of AISI 201 stainless steel. The structure and properties of the hardened layer were investigated, such as microstructure, hardness, wear resistance and corrosion resistance. The experiment results show that the treatment temperature plays an importance role in the microstructure and properties of the hardened layer. If the treatment temperature is below 460°C, the hardened layer was a face centre tetragonal (fct) structure without chromium nitride precipitation. The corrosion resistance of hardened layer is better than the matrix and as good as AISI 316 austenitic stainless steel. If the temperature rises above 460 °C the precipitation show up and the corrosion resistance gets worse. The hardness and thickness of the layer increase as the raising of treatment temperature. The test of wear resistance shows that the amount of wear reduces rapidly after hardening treatment and the worn morphology of the surface behaves abrasive wear while that of AISI 201 stainless steel behaves adhesive wear.

  14. 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.

  15. 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.

  16. Converting Basic D3 Charts into Reusable Style Templates.

    PubMed

    Harper, Jonathan; Agrawala, Maneesh

    2017-02-07

    We present a technique for converting a basic D3 chart into a reusable style template. Then, given a new data source we can apply the style template to generate a chart that depicts the new data, but in the style of the template. To construct the style template we first deconstruct the input D3 chart to recover its underlying structure: the data, the marks and the mappings that describe how the marks encode the data. We then rank the perceptual effectiveness of the deconstructed mappings. To apply the resulting style template to a new data source we first obtain importance ranks for each new data field. We then adjust the template mappings to depict the source data by matching the most important data fields to the most perceptually effective mappings. We show how the style templates can be applied to source data in the form of either a data table or another D3 chart. While our implementation focuses on generating templates for basic chart types (e.g. variants of bar charts, line charts, dot plots, scatterplots, etc.), these are the most commonly used chart types today. Users can easily find such basic D3 charts on the Web, turn them into templates, and immediately see how their own data would look in the visual style (e.g. colors, shapes, fonts, etc.) of the templates. We demonstrate the effectiveness of our approach by applying a diverse set of style templates to a variety of source datasets.

  17. 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.

  18. 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 section. (c) Limitations. (1) Not to exceed 69 parts per billion (ppb) in feed or 34.5 ppb in...

  19. 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 section. (c) Limitations. (1) Not to exceed 69 parts per billion (ppb) in feed or 34.5 ppb in...

  20. 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 section. (c) Limitations. (1) Not to exceed 69 parts per billion (ppb) in feed or 34.5 ppb in...

  1. 21 CFR 584.725 - 25-Hydroxyvitamin D3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 section. (c) Limitations. (1) Not to exceed 69 parts per billion (ppb) in feed or 34.5 ppb in...

  2. 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 section. (c) Limitations. (1) Not to exceed 69 parts per billion (ppb) in feed or 34.5 ppb in...

  3. A study on the control of melting ratio to increase mechanical properties of laser welded joints between AISI 440C and AISI 430F

    NASA Astrophysics Data System (ADS)

    Romoli, L.; Rashed, C. A. A.; Lovicu, G.; Ishak, R.

    2015-05-01

    Laser beam welding of dissimilar AISI 440C and AISI 430F stainless steels was investigated in a circular constrained configuration. The beam incidence angle and the offset of the focusing position respect to the contact point between the two materials were used as main control parameters to vary the melting ratio inside the seam. The objective of the study is twofold: to avoid surface microcracks related to the high percentage of carbon of the martensitic steel and to enhance the shear strength of the weld by making it less brittle. To reach this scope the effects of incidence angle and offset on weld bead geometry and melting ratio were studied by means of metallographic analyses, microstructure and microhardness characterization. As last step, the weld mechanical strength was tested by tensile-shear stress test on the whole seam. Experiments demonstrated that varying incidence angle and offsetting the focal position is a reliable method to modify the melting ratio and maintaining the expected resistance length at the material interface, as well. It was found that increasing the percentage of ferritic steel into the joint has beneficial effects on the weld quality and on the shear resistance. The critical carbon content determining the mechanical properties in the fusion zone can be calculated by taking into account the melting ratio.

  4. Genetic diversity of genotype D3 in acute hepatitis B.

    PubMed

    Alestig, Erik; Söderström, Ann; Norkrans, Gunnar; Lindh, Magnus

    2013-07-01

    Acute hepatitis B related to injection drug use is often caused by HBV-D3, a subgenotype that probably was introduced in Western Europe in the 1960s. The aim of this study was to describe genetic change over time in injection drug use-related HBV-D3 in one geographic area. Fourteen complete genomes and partial genomic regions of 17 HBV strains of subgenotype D3 causing acute (n = 30) or chronic (n = 1) hepatitis B at different time points between 1975 and 2009 were investigated. The 14 complete genomes clustered in phylogenetic trees on a sub-branch of HBV-D3 along with a few published sequences with high bootstrap values. In contrast, the phylogenetic tree topology based on nucleotides coding for surface antigen or core was uncertain with bootstrap values below 70% or lower. Variation of nucleotides coding for amino acids 125, 136, and 143 in the a determinant of HBsAg was however linked to complete genome phylogeny, indicating that these codons might be useful as markers for clades. The results show that knowledge about circulating strains is critical for the interpretation of molecular epidemiology investigations. The low degree of genetic change over time of HBV-D3 in the studied groups suggests that outbreaks of acute hepatitis B in injection drug users might originate from a limited number of individuals with chronic infection. Classification based on core or S region phylogeny obtained poor support from bootstrap values, but the presence of clade-specific amino acid substitutions suggests that the S region may be useful for subgenomic molecular epidemiology of HBV.

  5. On the origin of mRNA encoding the truncated dopamine D3-type receptor D3nf and detection of D3nf-like immunoreactivity in human brain.

    PubMed

    Liu, K; Bergson, C; Levenson, R; Schmauss, C

    1994-11-18

    A truncated dopamine D3-receptor-like mRNA, named D3nf, predicts a protein that differs from the D3-receptor only in the carboxyl terminus. However, such a protein has lost the predicted membrane topology typically found for G protein-coupled receptors. Results presented here show that D3nf mRNA arises from the D3-encoded primary transcript via alternative splicing. This splicing, however, appears to involve cleavage of an unusual 3' splice site. Therefore, we tested the possibility that D3nf mRNA results from a splicing error. If this were the case, D3nf mRNA would be expected to be present in the cytoplasm only at very low amounts, and it would not be expected to be translated into protein. However, the relative abundance of cytoplasmic D3/D3nf mRNA in human cortical tissues was found to be similar. Furthermore, we raised polyclonal antisera against the predicted carboxyl-terminal peptide sequence of D3nf that reacts specifically with a protein expressed in stably D3nf mRNA-expressing COS 7 cells. The use of this antiserum also revealed the presence of a approximately 68 kDa D3nf-like immunoreactive protein in human brain, suggesting that the atypically processed D3nf mRNA is translated.

  6. 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.

  7. 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.

  8. Fast wave current drive antenna performance on D3-D

    NASA Astrophysics Data System (ADS)

    Mayberry, M. J.; Pinsker, R. I.; Petty, C. C.; Chiu, S. C.; Jackson, G. L.; Lippmann, S. I.; Prater, R.; Porkolab, M.

    1991-10-01

    Fast wave current drive (FWCD) experiments at 60 MHz are being performed on the D3-D tokamak for the first time in high electron temperature, high (beta) target plasmas. A four-element phased-array antenna is used to launch a directional wave spectrum with the peak n(sub parallel) value (approximately = 7) optimized for strong single-pass electron absorption due to electron Landau damping. For this experiment, high power FW injection (2 MW) must be accomplished without voltage breakdown in the transmission lines or antenna, and without significant impurity influx. In addition, there is the technological challenge of impedance matching a four-element antenna while maintaining equal currents and the correct phasing (90 degrees) in each of the straps for a directional spectrum. We describe the performance of the D3-D FWCD antenna during initial FW electron heating and current drive experiments in terms of these requirements.

  9. 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.

  10. Rotation invariance principles in 2D/3D registration

    NASA Astrophysics Data System (ADS)

    Birkfellner, Wolfgang; Wirth, Joachim; Burgstaller, Wolfgang; Baumann, Bernard; Staedele, Harald; Hammer, Beat; Gellrich, Niels C.; Jacob, Augustinus L.; Regazzoni, Pietro; Messmer, Peter

    2003-05-01

    2D/3D patient-to-computed tomography (CT) registration is a method to determine a transformation that maps two coordinate systems by comparing a projection image rendered from CT to a real projection image. Applications include exact patient positioning in radiation therapy, calibration of surgical robots, and pose estimation in computer-aided surgery. One of the problems associated with 2D/3D registration is the fast that finding a registration includes sovling a minimization problem in six degrees-of-freedom in motion. This results in considerable time expenses since for each iteration step at least one volume rendering has to be computed. We show that by choosing an appropriate world coordinate system and by applying a 2D/2D registration method in each iteration step, the number of iterations can be grossly reduced from n6 to n5. Here, n is the number of discrete variations aroudn a given coordinate. Depending on the configuration of the optimization algorithm, this reduces the total number of iterations necessary to at least 1/3 of its original value. The method was implemented and extensively tested on simulated x-ray images of a pelvis. We conclude that this hardware-indepenent optimization of 2D/3D registration is a step towards increasing the acceptance of this promising method for a wide number of clinical applications.

  11. Multiple D3-Instantons and Mock Modular Forms I

    NASA Astrophysics Data System (ADS)

    Alexandrov, Sergei; Banerjee, Sibasish; Manschot, Jan; Pioline, Boris

    2016-11-01

    We study D3-instanton corrections to the hypermultiplet moduli space in type IIB string theory compactified on a Calabi-Yau threefold. In a previous work, consistency of D3-instantons with S-duality was established at first order in the instanton expansion, using the modular properties of the M5-brane elliptic genus. We extend this analysis to the two-instanton level, where wall-crossing phenomena start playing a role. We focus on the contact potential, an analogue of the Kähler potential which must transform as a modular form under S-duality. We show that it can be expressed in terms of a suitable modification of the partition function of D4-D2-D0 BPS black holes, constructed out of the generating function of MSW invariants (the latter coincide with Donaldson-Thomas invariants in a particular chamber). Modular invariance of the contact potential then requires that, in the case where the D3-brane wraps a reducible divisor, the generating function of MSW invariants must transform as a vector-valued mock modular form, with a specific modular completion built from the MSW invariants of the constituents. Physically, this gives a powerful constraint on the degeneracies of BPS black holes. Mathematically, our result gives a universal prediction for the modular properties of Donaldson-Thomas invariants of pure two-dimensional sheaves.

  12. How 3-D, 3-C seismic characterized a carbonate reservoir

    SciTech Connect

    Arestad, J.F.; Mattocks, B.W.; Davis, T.L.; Benson, R.D.

    1995-04-01

    The Reservoir Characterization Project (RCP) at the Colorado School of Mines has pioneered research into 3-D, 3-C (multicomponent) reflection seismology for nearly a decade utilizing both P-wave and S-wave sources. Multicomponent-seismic surveys provide significantly more information about petroleum reservoirs than compressional-wave surveys. Initial 3-D, 3-C surveys acquired by RCP were targeted at characterizing naturally fractured reservoirs. The current phase of the project is oriented towards utilizing shear waves to discriminate lithologic and diagenetic changes within stratigraphic reservoirs where compressional-seismic data has not be effective. The Joffre field, Nisku reservoir, is the site of RCP`s ongoing multidisciplinary research effort in Western Canada. The research team is directed by Colorado School of Mines faculty with graduate team members from geology, geophysics and petroleum engineering departments. While this study is still in progress, some key findings and directions of this research are reported here. The following topics will be discussed: Joffre field 3-D, 3-C survey; compressional wave 3-D technique; shear-wave 3-D technique; converted-wave 3-D technique; reservoir characterization, and future directions.

  13. 25(OH)D status: Effect of D3 supplement

    PubMed Central

    Luebbers, P. E.

    2017-01-01

    Summary Background Excess adipose tissue may lead to sequestrating of vitamin D, making it less available for use in the body. Objective This study determined if overweight or obese individuals (BMI > 25 kg m−2) had insufficient (<30 ng mL−1) levels of 25‐hydroxyvitamin D [25(OH)D] and, if so, would serum levels respond to exogenous supplementation. Methods Sixty‐three women who were overweight/obese (BMI = 31.07 ± 5.00 kg m−2) were randomly assigned in a double‐blind manner to receive 5,000 IU of vitamin D3 (D3) (n = 31) or a placebo (PL) (n = 32) daily. Serum 25(OH)D concentrations were measured by finger‐stick analyses at baseline and after 8 weeks of supplementation. Data were analyzed by using a 2 × 2 (group × time) repeated measure multivariate analysis of variance to determine group differences for pre‐values and post‐values (p < 0.05). Results On day one of the study, both D3 and PL groups had insufficient levels of vitamin D (mean ± SD) 24.03 ± 9.78 ng mL−1 and 23.62 ± 9.77 ng mL−1, respectively. After 8 weeks of supplementation, the D3 group 25(OH)D level rose to a mean of 43.57 ± 10.87 ng mL−1 (p < 0.001) versus the PL group whose 25(OH)D level remained statistically unchanged 24.31 ± 8.84 ng mL−1. Women who were overweight/obese had insufficient vitamin D levels prior to supplementation. Conclusions Following supplementation with 5,000 IU of vitamin D3, all subjects' 25(OH)D levels rose to a sufficient level (≥30 ng mL−1). The findings of this study concur with the Institute of Medicine and Endocrine Society recommendations in that two to three times the daily requirement of vitamin D is required to improve serum vitamin D levels in individuals who are overweight or obese. PMID:28392936

  14. 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.

  15. 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

    2016-10-01

    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.

  16. Correlating tool wear, tool life, surface roughness and tool vibration in finish turning with coated carbide tools

    NASA Astrophysics Data System (ADS)

    Bonifacio, M. E. R.; Diniz, A. E.

    1994-04-01

    Experiments have been carried out in an attempt to monitor the change of workpiece surface roughness caused by the increase of tool wear, through the variation of the vibration in finish turning, under different cutting conditions. The vibration was measured by two accelerometers attached to the tool and the parameter used to make the correlation with surface roughness was the r.m.s. of the signal. The tool of one experiment was photographed at different stages of the cut in order to explain the wear formation and the behaviour of surface roughness as the cutting time elapsed. The material machined was AISI 4340 steel and the tool was coated carbide inserts. The results show that vibration of the tool can be a good way to monitor on-line the growth of surface roughness in finish turning and, therefore, it can be useful for establishing the end of tool life in these operations. Another conclusion is that, when coated tools are used, the behaviour of surface roughness as cutting time elapses is very different from that when uncoated tools are used.

  17. Attenuation of UVR-induced vitamin D3 synthesis in a mouse model deleted for keratinocyte lathosterol 5-desaturase.

    PubMed

    Makarova, Anastasia M; Pasta, Saloni; Watson, Gordon; Shackleton, Cedric; Epstein, Ervin H

    2017-03-19

    The lower risk of some internal cancers at lower latitudes has been linked to greater sun exposure and consequent higher levels of ultraviolet radiation (UVR)-produced vitamin D3 (D3). To separate the experimental effects of sunlight and of all forms of D3, a mouse in which UVR does not produce D3 would be useful. To this end we have generated mice carrying a modified allele of sterol C5-desaturase (Sc5d), the gene encoding the enzyme that converts lathosterol to 7-dehydrocholesterol (7-DHC), such that Sc5d expression can be inactivated using the Cre/lox site-specific recombination system. By crossing to mice with tissue-specific expression of Cre or CreER(2) (Cre/estrogen receptor), we generated two lines of transgenic mice. One line has constitutive keratinocyte-specific inactivation of Sc5d (Sc5d(k14KO)). The other line (Sc5d(k14KOi)) has tamoxifen-inducible keratinocyte-specific inactivation of Sc5d. Mice deleted for keratinocyte Sc5d lose the ability to increase circulating D3 following UVR exposure of the skin. Thus, unlike in control mice, acute UVR exposure did not affect circulating D3 level in inducible Sc5d(k14KOi) mice. Keratinocyte-specific inactivation of Sc5d was proven by sterol measurement in hair - in control animals lathosterol and cholesta-7,24-dien-3β-ol, the target molecules of SC5D in the sterol biosynthetic pathways, together constituted a mean of 10% of total sterols; in the conditional knockout mice these sterols constituted a mean of 56% of total sterols. The constitutive knockout mice had an even greater increase, with lathosterol and cholesta-7,24-dien-3β-ol accounting for 80% of total sterols. In conclusion, the dominant presence of the 7-DHC precursors in hair of conditional animals and the lack of increased circulating D3 following exposure to UVR reflect attenuated production of the D3 photochemical precursor 7-DHC and, consequently, of D3 itself. These animals provide a useful new tool for investigating the role of D3 in UVR

  18. 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.

  19. D3-D5 theories with unquenched flavors

    NASA Astrophysics Data System (ADS)

    Conde, Eduardo; Lin, Hai; Penín, José Manuel; Ramallo, Alfonso V.; Zoakos, Dimitrios

    2017-01-01

    We construct the string duals of the defect theories generated when Nf flavor D5-branes intersect Nc color D3-branes along a 2 + 1 dimensional subspace. We work in the Veneziano limit in which Nc and Nf are large and Nf /Nc is fixed. By smearing the D5-branes, we find supergravity solutions that take into account the backreaction of the flavor branes and preserve two supercharges. When the flavors are massless the resulting metric displays an anisotropic Lifshitz-like scale invariance. The case of massive quarks is also considered.

  20. Electrochemical and pitting corrosion resistance of AISI 4145 steel subjected to massive laser shock peening treatment with different coverage layers

    NASA Astrophysics Data System (ADS)

    Lu, J. Z.; Han, B.; Cui, C. Y.; Li, C. J.; Luo, K. Y.

    2017-02-01

    The effects of massive laser shock peening (LSP) treatment with different coverage layers on residual stress, pitting morphologies in a standard corrosive solution and electrochemical corrosion resistance of AISI 4145 steel were investigated by pitting corrosion test, potentiodynamic polarisation test, and SEM observations. Results showed massive LSP treatment can effectively cause an obvious improvement of pitting corrosion resistance of AISI 4145 steel, and increased coverage layer can also gradually improve its corrosion resistance. Massive LSP treatment with multiple layers was shown to influence pitting corrosion behaviour in a standard corrosive solution.

  1. Effects of vitamin D3 supplementation and UVb exposure on the growth and plasma concentration of vitamin D3 metabolites in juvenile bearded dragons (Pogona vitticeps).

    PubMed

    Oonincx, D G A B; Stevens, Y; van den Borne, J J G C; van Leeuwen, J P T M; Hendriks, W H

    2010-06-01

    The effectiveness of dietary vitamin D3 and UVb exposure on plasma vitamin D metabolites in growing bearded dragons (Pogona vitticeps) was studied. A total of 84 (40 males and 44 females) newly hatched bearded dragons were allocated to six levels of oral vitamin D3 supplementation (0 to 400%) or six UVb exposure times (2 to 12 h). At 3 and 6 months of age, blood samples were obtained from each animal and analysed for 25(OH)D3 and 1,25(OH)2D3. At 3 months of age, plasma concentrations of 25(OH)D3 did not increase with increasing vitamin D3 supplementation unlike the 1,25(OH)2D3. At 6 months of age, plasma concentrations of both 25(OH)D(3) and 1,25(OH)2D3 increased with increasing vitamin D(3) supplementation. Plasma concentrations in UVb-exposed animals were 18 times higher for 25(OH)D3 (178.4+/-9.0 vs. 9.9+/-1.3 nmol/L) and 5.3 times higher for 1,25(OH)2D3 (1.205+/-0.100 vs. 0.229+/-0.025 nmol/L) than in vitamin D(3) supplemented animals at 6 months of age. This study shows that 2h of UVb exposure enables adequate physiological concentrations of plasma vitamin D metabolites to be maintained in growing bearded dragons. Oral supplementation of vitamin D(3) is ineffective in raising plasma concentrations of 25(OH)D3 and 1,25(OH)2D3 to concentrations observed in UVb-exposed animals.

  2. 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.

  3. Experimental and Analytical Load-Life Relation for AISI 9310 Steel Spur Gears

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

    Life tests were conducted at three different loads with three groups of 8.9 cm pitch diameter spur gears made of vacuum arc remelted VAR AISI 9310 steel. Life was found to vary inversely with load to the 4.3 and 5.1 power at the L10 sub and L50 sub life levels, respectively. The Weibull slope varied linearly with maximum Hertz contact stress, having an average value of 2.5. The test data when compared to AGMA standards showed a steeper slope for the load-life diagram.

  4. 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

  5. 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.

  6. Influence of microstructure on micromagnetic Barkhausen emissions in AISI 4140 steel

    SciTech Connect

    Mitra, A.; Govindaraju, M.R.; Jiles, D.C.

    1995-11-01

    The effects of microstructure on the micromagnetic Barkhausen signal emissions in AISI 4140 steel are reported. The Barkhausen signal amplitude is known to be highly sensitive to the type and distribution of microstructural inhomogeneities, such as grain boundaries, precipitates and dislocations. The Barkhausen measurements were taken on samples having pearlitic, spheroidized and bainitic microstructures. The Barkhausen emissions were measured in terms of rms voltage, peak-to-peak voltage and number of events per cycle. It is shown that Barkhausen signals can be used to distinguish between pearlitic and bainitic microstructures.

  7. 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.

  8. AdS spacetimes from wrapped D3-branes

    NASA Astrophysics Data System (ADS)

    Gauntlett, Jerome P.; MacConamhna, Oisín A. P.

    2007-12-01

    We derive a geometrical characterization of a large class of AdS3 and AdS2 supersymmetric spacetimes in type IIB supergravity with non-vanishing five-form flux using G-structures. These are obtained as special cases of a class of supersymmetric spacetimes with an {{\\bb R}}^{1,1} or {{\\bb R}} (time) factor that are associated with D3 branes wrapping calibrated two or three cycles, respectively, in manifolds with SU(2), SU(3), SU(4) and G2 holonomy. We show how two explicit AdS solutions, previously constructed in gauged supergravity, satisfy our more general G-structure conditions. For each explicit solution, we also derive a special holonomy metric which, although singular, has an appropriate calibrated cycle. After analytic continuation, some of the classes of AdS spacetimes give rise to known classes of BPS bubble solutions with {{\\bb R}}\\times {\\it SO}(4)\\times {\\it SO}(4), {{\\bb R}}\\times {\\it SO}(4)\\times U(1) and {{\\bb R}}\\times {\\it SO}(4) symmetry. These have 1/2, 1/4 and 1/8 supersymmetry, respectively. We present a new class of 1/8 BPS geometries with {{\\bb R}}\\times {\\it SU}(2) symmetry, obtained by analytic continuation of the class of AdS spacetimes associated with D3-brane wrapped on associative three cycles.

  9. A fast scanning probe for D3-D

    NASA Astrophysics Data System (ADS)

    Watkins, J. G.; Salmonson, J.; Doerner, R.; Lehmer, R.; Moyer, R.; Schmitz, L.; Hill, D. N.

    A fast reciprocating probe was developed for D3-D which can penetrate the separatrix during H - mode with up to 5MW of NBI heating. The probe was designed to carry various sensor tips into the scrape-off layer at a velocity of 3 m/sec and dwell motionless for a programmed period of time. The driving force is provided by a pneumatic cylinder charged with helium to facilitate greater mass flow. The first series of experiments were done using a Langmuir probe head with 5 graphite tips to measure radial profiles of n(sub e), T(sub e), phi(sub f), (n tilde)(sub e), and (phi tilde)(sub f). The amplitude and phase of the fluctuating quantities are measured by using specially constructed vacuum compatible 5 kV coaxial transmission lines which allow us to extend the measurements into the MHz range. TTZ ceramic bearings and fast stroke bellows were also specially designed for the D3-D probe. Initial measurements will be presented.

  10. Simultaneous measurement of plasma vitamin D3 metabolites including 4β,25-dihydroxyvitamin D3 using liquid chromatography-tandem mass spectrometry

    PubMed Central

    Wang, Zhican; Senn, Tauri; Kalhorn, Tom; Zheng, Xi Emily; Zheng, Songmao; Davis, Connie L.; Hebert, Mary F.; Lin, Yvonne S.; Thummel, Kenneth E.

    2011-01-01

    Simultaneous and accurate measurement of circulating vitamin D metabolites is critical to studies of the metabolic regulation of vitamin D and its impact on health and disease. To that end, we developed a specific LC-MS/MS method that permits the quantification of major circulating vitamin D3 metabolites in human plasma. Plasma samples were subjected to a protein precipitation, liquid-liquid extraction and Diels-Alder derivatization procedure prior to LC-MS/MS analysis. Importantly, in all human plasma samples tested, we identified a significant dihydroxyvitamin D3 peak that could potentially interfere with the determination of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] concentrations. This interfering metabolite has been identified as 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] and was found at concentrations comparable to 1α,25(OH)2D3. Quantification of 1α,25(OH)2D3 in plasma required complete chromatographic separation of 1α,25(OH)2D3 from 4β,25(OH)2D3. An assay incorporating this feature was used to simultaneously determine the plasma concentrations of 25OHD3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 in healthy individuals. The LC-MS/MS method developed and described here, could result in considerable improvement in the quantification of 1α,25(OH)2D3, as well as monitoring the newly identified circulating metabolite, 4β,25(OH)2D3. PMID:21784054

  11. Structural and Microhardness Changes After Turning of the AISI 1045 Steel for Minimum Quantity Cooling Lubrication

    NASA Astrophysics Data System (ADS)

    Maruda, Radoslaw W.; Krolczyk, Grzegorz M.; Michalski, Mariusz; Nieslony, Piotr; Wojciechowski, Szymon

    2016-11-01

    This work presents the cooling effect under minimum quantity cooling lubrication and dry cutting on structural changes and microhardness of the ferritic-pearlitic AISI 1045 steel after turning. Due to the fact that the AISI 1045 steel has a two-phase structure, microhardness tests using the Vickers method were conducted with a load of 0.05 HV separately for ferrite and pearlite grains. The tests showed that cooling of the cutting zone under minimum quantity cooling lubrication (MQCL) condition decreased the depth of the hardened layer compared to dry cutting by approximately 40% for both pearlite and ferrite. Scanning electron microscopy analysis revealed that applying MQCL limits the formation of plastic deformations, among others, by reducing the surface crumple zone by approximately 50% compared to dry cutting. As a result of cooling being applied to the cutting zone using the MQCL method, the average diameter of ferrite grains has been decreased in the entire surface area compared to dry cutting. When using dry cutting, clear structural changes of the surface layer were also observed. This may be the result of sulfide inclusions which have formed, causing microcracks on the edge of the hardened layer and surface deformation visible as notches.

  12. Structural and Microhardness Changes After Turning of the AISI 1045 Steel for Minimum Quantity Cooling Lubrication

    NASA Astrophysics Data System (ADS)

    Maruda, Radoslaw W.; Krolczyk, Grzegorz M.; Michalski, Mariusz; Nieslony, Piotr; Wojciechowski, Szymon

    2017-01-01

    This work presents the cooling effect under minimum quantity cooling lubrication and dry cutting on structural changes and microhardness of the ferritic-pearlitic AISI 1045 steel after turning. Due to the fact that the AISI 1045 steel has a two-phase structure, microhardness tests using the Vickers method were conducted with a load of 0.05 HV separately for ferrite and pearlite grains. The tests showed that cooling of the cutting zone under minimum quantity cooling lubrication (MQCL) condition decreased the depth of the hardened layer compared to dry cutting by approximately 40% for both pearlite and ferrite. Scanning electron microscopy analysis revealed that applying MQCL limits the formation of plastic deformations, among others, by reducing the surface crumple zone by approximately 50% compared to dry cutting. As a result of cooling being applied to the cutting zone using the MQCL method, the average diameter of ferrite grains has been decreased in the entire surface area compared to dry cutting. When using dry cutting, clear structural changes of the surface layer were also observed. This may be the result of sulfide inclusions which have formed, causing microcracks on the edge of the hardened layer and surface deformation visible as notches.

  13. Improvement in cavitation erosion resistance of AISI 316L stainless steel by friction stir processing

    NASA Astrophysics Data System (ADS)

    Hajian, M.; Abdollah-zadeh, A.; Rezaei-Nejad, S. S.; Assadi, H.; Hadavi, S. M. M.; Chung, K.; Shokouhimehr, M.

    2014-07-01

    Commercial AISI 316L plates with the initial grain size of 14.8 μm were friction stir processed (FSP) with different processing parameters, resulting in two fine-grained microstructures with the grain sizes of 4.6 and 1.7 μm. The cavitation erosion behavior, before and after FSP, was evaluated in terms of incubation time, cumulative mass loss and mean depth of erosion. A separate cavitation erosion test was performed on the transverse cross section of a FSP sample to reveal the effect of grain structure. It was observed that FSP samples, depending on their grain size, are at least 3-6 times more resistant than the base material against cavitation erosion. The improvement in cavitation erosion resistance is attributed to smaller grain structure, lower fraction of twin boundaries, and favorable crystallographic orientation of grains in FSP samples. The finer the grain size, the more cavitation erosion resistance was achieved. Moreover, the microstructures of eroded surfaces were studied using a scanning electron microscope equipped with EBSD, and an atomic force microscope. The mechanisms controlling the cavitation erosion damage in friction stir processed AISI 316L are also discussed.

  14. 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.

  15. 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}.

  16. Improving by postoxidation of corrosion resistance of plasma nitrocarburized AISI 316 stainless steels

    NASA Astrophysics Data System (ADS)

    Yenilmez, A.; Karakan, M.; Çelik, İ.

    2017-01-01

    Austenitic stainless steels are widely used in several industries such as chemistry, food, health and space due to their perfect corrosion resistance. However, in addition to corrosion resistance, the mechanic and tribological features such as wear resistance and friction are required to be good in the production and engineering of this type of machines, equipment and mechanic parts. In this study, ferritic (FNC) and austenitic (ANC) nitrocarburizing were applied on AISI 316 stainless steel specimens with perfect corrosion resistance in the plasma environment at the definite time (4 h) and constant gas mixture atmosphere. In order to recover corrosion resistance which was deteriorated after nitrocarburizing again, plasma postoxidation process (45 min) was applied. After the duplex treatment, the specimens' structural analyses with XRD and SEM methods, corrosion analysis with polarization method and surface hardness with microhardness method were examined. At the end of the studies, AISI 316 surface hardness of stainless steel increased with nitrocarburizing process, but the corrosion resistance was deteriorated with FNC (570 °C) and ANC (670 °C) nitrocarburizing. With the following of the postoxidation treatment, it was detected that the corrosion resistance became better and it approached its value before the process.

  17. 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.

  18. Effect of mechanical activation on jell boronizing treatment of the AISI 4140

    NASA Astrophysics Data System (ADS)

    Yılmaz, S. O.; Karataş, S.

    2013-06-01

    The article presents the effect of mechanical activation on the growth kinetics of boride layer of boronized AISI 4140 steel. The samples were boronized by ferroboron + (SiO2-Na2O) powders for 873-1173 K temperature and 2, 4, 6 and 8 h times, respectively. The morphology and types of borides formed on the surface of AISI 4140 steel substrate were analyzed. Layer growth kinetics were analyzed by measuring the extent of penetration of FeB and Fe2B sublayers as function of treatment time and temperature in the range of 873-1173 K. High diffusivity was obtained by creating a large number of defects through mechanical activation in the form of nanometer sized crystalline particles through the repeated fracturing and cold-welding of the powder particles, and a depth of 100 μm was found in the specimen borided by the 2 h MA powders, for 4 h and 1073 K, where 2000-2350 HV were measured. Consequently, the application conditions of boronizing were improved by usage of mechanical activation. The preferred Fe2B boride without FeB could be formed in the boride layer under 973 K boronizing temperature by mechanically activated by ferroboron + sodium silicate powder mixture due to the decrease of the activation energy.

  19. Microstructure and Properties of Plasma Source Nitrided AISI 316 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Li, G. Y.; Lei, M. K.

    2017-01-01

    Plasma source nitriding is a relatively new nitriding technology which can overcome those inherent shortcomings associated with conventional direct current plasma nitriding technology such as the arcing surface damage, the edging effect and the hollow cathode effect. There is considerable study on the properties of nitrided samples for laboratorial scale plasma source nitriding system; however, little information has been reported on the industrial-scale plasma source nitriding system. In this work, AISI 316 austenitic stainless steel samples were nitrided by an industrial-scale plasma source nitriding system at various nitriding temperatures (350, 400, 450 and 500 °C) with a floating potential. A high-nitrogen face-centered-cubic phase (γN) formed on the surface of nitrided sample surface. As the nitriding temperature was increased, the γN phase layer thickness increased, varying from 1.5 μm for the lowest nitriding temperature of 350 °C, to 30 μm for the highest nitriding temperature of 500 °C. The maximum Vickers microhardness of the γN phase layer with a peak nitrogen concentration of 20 at.% is about HV 0.1 N 15.1 GPa at the nitriding temperature of 450 °C. The wear and corrosion experimental results demonstrated that the γN phase was formed on the surface of AISI 316 austenitic stainless steel by plasma source nitriding, which exhibits not only high wear resistance, but also good pitting corrosion resistance.

  20. Hall Petch Behavior in Ultra-Fine-Grained AISI 301LN Stainless Steel

    NASA Astrophysics Data System (ADS)

    Rajasekhara, S.; Ferreira, P. J.; Karjalainen, L. P.; Kyröläinen, A.

    2007-06-01

    An ultra-fine-grained AISI 301LN austenitic stainless steel has been achieved by heavy cold rolling, to induce the formation of martensite, and subsequent annealing at 800 °C, 900 °C, and 1000 °C, from 1 to 100 seconds. The microstructural evolution was analyzed using transmission electron microscopy and the yield strength determined by tension testing. Ultra-fine austenite grains, as small as ˜0.54 μm, were obtained in samples annealed at 800 °C for 1 second. For these samples, tensile tests revealed a very high yield strength of ˜700 MPa, which is twice the typical yield strength of conventional fully annealed AISI 301LN stainless steels. An analysis of the relationship between yield strength and grain size in these submicron-grained stainless steels indicates a classical Hall Petch behavior. Furthermore, when the yield dependence on annealing temperature is considered, the results show that the Hall Petch relation is due to an interplay between fine-grained austenite, solid solution strengthening, precipitate hardening, and strain hardening.

  1. Microstructure and Properties of Plasma Source Nitrided AISI 316 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Li, G. Y.; Lei, M. K.

    2016-11-01

    Plasma source nitriding is a relatively new nitriding technology which can overcome those inherent shortcomings associated with conventional direct current plasma nitriding technology such as the arcing surface damage, the edging effect and the hollow cathode effect. There is considerable study on the properties of nitrided samples for laboratorial scale plasma source nitriding system; however, little information has been reported on the industrial-scale plasma source nitriding system. In this work, AISI 316 austenitic stainless steel samples were nitrided by an industrial-scale plasma source nitriding system at various nitriding temperatures (350, 400, 450 and 500 °C) with a floating potential. A high-nitrogen face-centered-cubic phase (γN) formed on the surface of nitrided sample surface. As the nitriding temperature was increased, the γN phase layer thickness increased, varying from 1.5 μm for the lowest nitriding temperature of 350 °C, to 30 μm for the highest nitriding temperature of 500 °C. The maximum Vickers microhardness of the γN phase layer with a peak nitrogen concentration of 20 at.% is about HV 0.1 N 15.1 GPa at the nitriding temperature of 450 °C. The wear and corrosion experimental results demonstrated that the γN phase was formed on the surface of AISI 316 austenitic stainless steel by plasma source nitriding, which exhibits not only high wear resistance, but also good pitting corrosion resistance.

  2. Microstructure, Texture, and Mechanical Property Analysis of Gas Metal Arc Welded AISI 304 Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Saha, Saptarshi; Mukherjee, Manidipto; Pal, Tapan Kumar

    2015-03-01

    The present study elaborately explains the effect of welding parameters on the microstructure, texture, and mechanical properties of gas metal arc welded AISI 304 austenitic stainless steel sheet (as received) of 4 mm thickness. The welded joints were prepared by varying welding speed (WS) and current simultaneously at a fixed heat input level using a 1.2-mm-diameter austenitic filler metal (AISI 316L). The overall purpose of this study is to investigate the effect of the variation of welding conditions on: (i) Microstructural constituents using optical microscope and transmission electron microscope; (ii) Micro-texture evolution, misorientation distributions, and grain boundaries at welded regions by measuring the orientation data from electron back scattered diffraction; and (iii) Mechanical properties such as hardness and tensile strength, and their correlation with the microstructure and texture. It has been observed that the higher WS along with the higher welding current (weld metal W1) can enhance weld metal mechanical properties through alternation in microstructure and texture of the weld metal. Higher δ-ferrite formation and high-angle boundaries along with the <101> + <001> grain growth direction of the weld metal W1 were responsible for dislocation pile-ups, SFs, deformation twinning, and the induced martensite with consequent strain hardening during tensile deformation. Also, fusion boundary being the weakest link in the welded structure, failure took place mainly at this region.

  3. 25-Hydroxyvitamin D3 induces osteogenic differentiation of human mesenchymal stem cells

    PubMed Central

    Lou, Yan-Ru; Toh, Tai Chong; Tee, Yee Han; Yu, Hanry

    2017-01-01

    25-Hydroxyvitamin D3 [25(OH)D3] has recently been found to be an active hormone. Its biological actions are demonstrated in various cell types. 25(OH)D3 deficiency results in failure in bone formation and skeletal deformation. Here, we investigated the effect of 25(OH)D3 on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We also studied the effect of 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2D3], a metabolite of 25(OH)D3. One of the vitamin D responsive genes, 25(OH)D3-24-hydroxylase (cytochrome P450 family 24 subfamily A member 1) mRNA expression is up-regulated by 25(OH)D3 at 250–500 nM and by 1α,25-(OH)2D3 at 1–10 nM. 25(OH)D3 and 1α,25-(OH)2D3 at a time-dependent manner alter cell morphology towards osteoblast-associated characteristics. The osteogenic markers, alkaline phosphatase, secreted phosphoprotein 1 (osteopontin), and bone gamma-carboxyglutamate protein (osteocalcin) are increased by 25(OH)D3 and 1α,25-(OH)2D3 in a dose-dependent manner. Finally, mineralisation is significantly increased by 25(OH)D3 but not by 1α,25-(OH)2D3. Moreover, we found that hMSCs express very low level of 25(OH)D3-1α-hydroxylase (cytochrome P450 family 27 subfamily B member 1), and there is no detectable 1α,25-(OH)2D3 product. Taken together, our findings provide evidence that 25(OH)D3 at 250–500 nM can induce osteogenic differentiation and that 25(OH)D3 has great potential for cell-based bone tissue engineering. PMID:28211493

  4. 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] controls growth plate development by inhibiting apoptosis in the reserve zone and stimulating response to 1alpha,25(OH)2D3 in hypertrophic cells.

    PubMed

    Boyan, B D; Hurst-Kennedy, J; Denison, T A; Schwartz, Z

    2010-07-01

    Previously we showed that costochondral growth plate resting zone (RC) chondrocytes response primarily to 24R,25(OH)2D3 whereas prehypertrophic and hypertrophic (GC) cells respond to 1alpha,25(OH)2D3. 24R,25(OH)2D3 increases RC cell proliferation and inhibits activity of matrix processing enzymes, suggesting it stabilizes cells in the reserve zone, possibly by inhibiting the matrix degradation characteristic of apoptotic hypertrophic GC cells. To test this, apoptosis was induced in rat RC cells by treatment with exogenous inorganic phosphate (Pi). 24R,25(OH)2D3 blocked apoptotic effects in a dose-dependent manner. Similarly, apoptosis was induced in ATDC5 cell cultures and 24R,25(OH)2D3 blocked this effect. Further studies indicated that 24R,25(OH)2D3 acts via at least two independent pathways. 24R,25(OH)2D3 increases LPA receptor-1 (LPA R1) expression and production of lysophosphatidic acid (LPA), and subsequent LPA R1/3-dependent signaling, thereby decreasing p53 abundance. LPA also increases the Bcl-2/Bax ratio. In addition, 24R,25(OH)2D3 acts by increasing PKC activity. 24R,25(OH)2D3 stimulates 1-hydroxylase activity, resulting in increased levels of 1,25(OH)2D3, and it increases levels of phospholipase A2 activating protein, which is required for rapid 1alpha,25(OH)2D3-dependent activation of PKC in GC cells. These results suggest that 24R,25(OH)2D3 modulates growth plate development by controlling the rate and extent of RC chondrocyte transition to a GC chondrocyte phenotype.

  5. Direct energy conversion system for D(3)-He fusion

    NASA Astrophysics Data System (ADS)

    Tomita, Y.; Shu, L. Y.; Momota, H.

    1993-11-01

    A novel and highly efficient direct energy conversion system is proposed for utilizing D(3)-He fueled fusion. In order to convert kinetic energy of ions, we applied a pair of direct energy conversion systems each of which has a cusp-type DEC and a traveling wave DEC (TWDEC). In a cusp-type DEC, electrons are separated from the escaping ions at the first line-cusp and the energy of thermal ion components is converted at the second cusp DEC. The fusion protons go through the cusp-type DEC and arrive at the TWDEC, which principle is similar to 'LINAC'. The energy of fusion protons is recovered to electricity with an efficiency of more than 70%. These DEC's bring about the high efficient fusion plant.

  6. 2D-3D transition of gold cluster anions resolved

    NASA Astrophysics Data System (ADS)

    Johansson, Mikael P.; Lechtken, Anne; Schooss, Detlef; Kappes, Manfred M.; Furche, Filipp

    2008-05-01

    Small gold cluster anions Aun- are known for their unusual two-dimensional (2D) structures, giving rise to properties very different from those of bulk gold. Previous experiments and calculations disagree about the number of gold atoms nc where the transition to 3D structures occurs. We combine trapped ion electron diffraction and state of the art electronic structure calculations to resolve this puzzle and establish nc=12 . It is shown that theoretical studies using traditional generalized gradient functionals are heavily biased towards 2D structures. For a correct prediction of the 2D-3D crossover point it is crucial to use density functionals yielding accurate jellium surface energies, such as the Tao-Perdew-Staroverov-Scuseria (TPSS) functional or the Perdew-Burke-Ernzerhof functional modified for solids (PBEsol). Further, spin-orbit effects have to be included, and large, flexible basis sets employed. This combined theoretical-experimental approach is promising for larger gold and other metal clusters.

  7. The d 3Π state of LiRb

    NASA Astrophysics Data System (ADS)

    Stevenson, I. C.; Blasing, D. B.; Altaf, A.; Chen, Y. P.; Elliott, D. S.

    2016-12-01

    We report our spectroscopic studies of the d 3Π state of ultra-cold 7Li85Rb using resonantly enhanced multi-photon ionization and depletion spectroscopy with bound-to-bound transitions originating from the metastable a 3Σ+ state. We evaluate the potential of this state for use as the intermediate state in a stimulated-Raman-adiabatic-passage transfer scheme from triplet Feshbach LiRb molecules to the X 1Σ+ ground state and find that the lowest several vibrational levels possess the requisite overlap with initial and final states, as well as convenient energies. Using depletion measurements, we measured the well depth and spin-orbit splitting. We suggest possible pathways for short-range photoassociation using deeply bound vibrational levels of this electronic state.

  8. Fully automated 2D-3D registration and verification.

    PubMed

    Varnavas, Andreas; Carrell, Tom; Penney, Graeme

    2015-12-01

    Clinical application of 2D-3D registration technology often requires a significant amount of human interaction during initialisation and result verification. This is one of the main barriers to more widespread clinical use of this technology. We propose novel techniques for automated initial pose estimation of the 3D data and verification of the registration result, and show how these techniques can be combined to enable fully automated 2D-3D registration, particularly in the case of a vertebra based system. The initialisation method is based on preoperative computation of 2D templates over a wide range of 3D poses. These templates are used to apply the Generalised Hough Transform to the intraoperative 2D image and the sought 3D pose is selected with the combined use of the generated accumulator arrays and a Gradient Difference Similarity Measure. On the verification side, two algorithms are proposed: one using normalised features based on the similarity value and the other based on the pose agreement between multiple vertebra based registrations. The proposed methods are employed here for CT to fluoroscopy registration and are trained and tested with data from 31 clinical procedures with 417 low dose, i.e. low quality, high noise interventional fluoroscopy images. When similarity value based verification is used, the fully automated system achieves a 95.73% correct registration rate, whereas a no registration result is produced for the remaining 4.27% of cases (i.e. incorrect registration rate is 0%). The system also automatically detects input images outside its operating range.

  9. 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.

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

    PubMed Central

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

    2016-01-01

    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)2D by 1α‐hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2D3 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)2D3. We show that myoblasts not only responded to 1,25(OH)2D3, 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)2D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2D3 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)2D3 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)2D3 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)2D3. J. Cell. Physiol. 231: 2517–2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27018098

  11. Total synthesis of biologically active 20S-hydroxyvitamin D3

    PubMed Central

    Wang, Qinghui; Lin, Zongtao; Kim, Tae-Kang; Slominski, Andrzej T.; Miller, Duane D.; Li, Wei

    2015-01-01

    A total synthetic strategy of 20S-hydroxyvitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoseletively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4 %. The synthetic 20S-(OH)D3 activated vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells. PMID:26433048

  12. Projection-slice theorem based 2D-3D registration

    NASA Astrophysics Data System (ADS)

    van der Bom, M. J.; Pluim, J. P. W.; Homan, R.; Timmer, J.; Bartels, L. W.

    2007-03-01

    In X-ray guided procedures, the surgeon or interventionalist is dependent on his or her knowledge of the patient's specific anatomy and the projection images acquired during the procedure by a rotational X-ray source. Unfortunately, these X-ray projections fail to give information on the patient's anatomy in the dimension along the projection axis. It would be very profitable to provide the surgeon or interventionalist with a 3D insight of the patient's anatomy that is directly linked to the X-ray images acquired during the procedure. In this paper we present a new robust 2D-3D registration method based on the Projection-Slice Theorem. This theorem gives us a relation between the pre-operative 3D data set and the interventional projection images. Registration is performed by minimizing a translation invariant similarity measure that is applied to the Fourier transforms of the images. The method was tested by performing multiple exhaustive searches on phantom data of the Circle of Willis and on a post-mortem human skull. Validation was performed visually by comparing the test projections to the ones that corresponded to the minimal value of the similarity measure. The Projection-Slice Theorem Based method was shown to be very effective and robust, and provides capture ranges up to 62 degrees. Experiments have shown that the method is capable of retrieving similar results when translations are applied to the projection images.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  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. Kinetics Analysis of Higher Temperature Salt Bath Nitriding for Aisi 1045 Steel

    NASA Astrophysics Data System (ADS)

    Dai, Mingyang; Chen, Yao; Chai, Yating; Hu, Jing

    2016-05-01

    Rapid salt bath nitriding was conducted at higher temperature above 600∘C instead of normally used 560∘C for AISI 1045 steel. Optical microscopy (OM), X-ray diffraction (XRD) and micro-hardness tester were employed to characterize the microstructure, phase constituents and micro-hardness of the treated specimens. The results showed that salt bath nitriding at higher temperature could significantly increase the compound layer thickness and higher cross-sectional hardness can be obtained. Kinetics analysis illustrated that the nitrogen atoms diffusion coefficient was obviously increased with temperature, and the activation energy of nitrogen atom diffusion was decreased from 220kJṡmol-1 to 142kJṡmol-1.

  20. 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.

  1. 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.

  2. Residual Stress Analysis of Boronized AISI 1018 Steel by Synchrotron Radiation

    SciTech Connect

    Payne, J A; Petrova, R S; White, H J; Chauhan, A; Bai, Jianming

    2008-01-01

    AISI 1018 steel substrates were powder-pack, diffusion boronized at 850 C for 4 h, followed by air quenching. Optical microscopy in conjunction with color etching was used to obtain the average penetration depth of the iron monoboride layer (9 {micro}m) and the iron diboride layer (57 {micro}m). X-ray diffraction by synchrotron radiation, conducted at the National Synchrotron Light Source in Brookhaven National Laboratory, confirmed the presence of iron monoboride and iron diboride in the boronized plain steel substrates. The sin{sup 2} {Psi} technique was employed to calculate the residual stress found in the iron monoboride layer (-237 MPa) and in the substrate layer (-150 MPa) that is intertwined with the needle-like, iron diboride penetration.

  3. Stress-Corrosion Cracking of AISI 4340 Steel in Aqueous Environments

    NASA Astrophysics Data System (ADS)

    Kalnaus, Sergiy; Zhang, Jixi; Jiang, Yanyao

    2011-02-01

    Stress corrosion cracking of the high-strength martensitic steel AISI 4340 (yield stress = 1503 MPa) in NaCl aqueous solutions of different concentrations was studied experimentally using compact tension specimens in free corroding conditions. The experiments were conducted under the controls of constant load, constant crack opening displacement (COD), constant loading rate, and constant COD rate. Despite the differences in controlling conditions, the experiments yielded similar results for the threshold stress intensity factor and the plateau velocity in the 3.5 wt pct NaCl solution. Dependence of the plateau velocity on the NaCl concentration was observed, whereas the values of the threshold stress intensity factors seem to be independent of the NaCl concentration in distilled water.

  4. 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.

  5. Long-range effect in nitrogen ion-implanted AISI 316L stainless steel

    NASA Astrophysics Data System (ADS)

    Budzynski, P.

    2015-01-01

    The effect of nitrogen ion implantation on AISI 316L stainless steel was investigated. The microstructure and composition of an N implanted layer were studied by RBS, GIXRD, SEM, and EDX measurements. Friction and wear tests were also performed. The discrepancy between the measured and calculated stopped ion maximum range does not exceed 0.03 μm. After nitrogen implantation with a fluence of 5 × 1017 ion/cm2, additional phases of expanded austenite were detected. At a 5-fold larger depth than the maximum ion range, improvement in the coefficient of friction and wear was detected. We have shown, for the first time, the long-range effect in tribological investigations. The long-range effect is caused by movement of not only defects along the depth of the sample, as assumed so far, but also nitrogen atoms.

  6. 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.

  7. 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.

  8. An investigation of the aseptic loosening of an AISI 316L stainless steel hip prosthesis.

    PubMed

    Godec, Matjaz; Kocijan, Aleksandra; Dolinar, Drago; Mandrino, Djordje; Jenko, Monika; Antolic, Vane

    2010-08-01

    The total replacement of joints by the implantation of permanently indwelling prosthetic components has been one of the major successes of modern surgery in terms of relieving pain and correcting deformity. However, the aseptic loosening of a prosthetic-joint component is the most common reason for joint-revision surgery. Furthermore, it is thought that wear particles are one of the major contributors to the development and perpetuation of aseptic loosening. The aim of the present study was to identify the factors related to the aseptic loosening of an AISI 316L stainless steel total hip prosthesis. The stem was evaluated by x-ray photoelectron spectroscopy, with polished and rough regions being analyzed in order to establish the differences in the chemical compositions of both regions. Specific areas were examined using scanning electron microscopy with energy dispersive x-ray spectroscopy and light microscopy.

  9. 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.

  10. Influence of nitrogen alloying on hydrogen embrittlement in AISI 304-type stainless steels

    NASA Astrophysics Data System (ADS)

    Hannula, Simo-Pekka; Hänninen, Hannu; Tähtinen, Seppo

    1984-12-01

    Hydrogen embrittlement of AISI 304-type austenitic stainless steels has been studied with special emphasis on the effects of the nitrogen content of the steels. Hydrogen charging was found to degrade the mechanical properties of all the steels studied, as measured by a tensile test. The fracture surfaces of hydrogen charged specimens were brittle cleavage-like whereas the uncharged specimens showed ductile, dimpled fracture. In sensitized materials transgranular cleavage mode of fracture was replaced by an intergranular mode of fracture and the losses of mechanical properties were higher. Nitrogen alloying decreased the hydrogen-induced losses of mechanical properties by increasing the stability of austenite. In sensitized steels the stability of austenite and nitrogen content were found to have only a minor effect on hydrogen embrittlement, except when sensitization had caused α'-martensite transformation at the grain boundaries.

  11. 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.

  12. Study on surface finish of AISI 2080 steel based on the Taguchi method

    NASA Astrophysics Data System (ADS)

    Yalcinkaya, S.; Şahin, Y.

    2017-02-01

    Surface finish and dimensional accuracy play a vital role in manufacturing engineering applications. Grinding is one of the most important methods for producing a better surface quality. This paper describes a study of the influences of cutting parameters such as table speed, depth of cut and feed rate on surface finish of AISI 2080 steels, based on the Taguchi (L27) method. The experimental results showed that the table speed was the machining parameter, which had a greater effect on the surface finish, followed by depth of cut, whereas feed rate showed no significant effect. Analysis of variance indicated that a better surface finish was obtained at 190 m/min speed, 0.003 mm depth of cut and 0.08 mm/rev feed rate.

  13. Serum Concentrations of 1,25-Dihydroxyvitamin D2 and 1,25-Dihydroxyvitamin D3 in Response to Vitamin D2 and Vitamin D3 Supplementation

    PubMed Central

    Biancuzzo, Rachael M.; Clarke, Nigel; Reitz, Richard E.; Travison, Thomas G.

    2013-01-01

    Objective: The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Subjects and Design: Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography–tandem mass spectroscopy. Results: Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4–10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (−15.8 to −4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Conclusion: Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum

  14. 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.

  15. Effect of vitamin D3 on self-perceived fatigue

    PubMed Central

    Nowak, Albina; Boesch, Lukas; Andres, Erik; Battegay, Edouard; Hornemann, Thorsten; Schmid, Christoph; Bischoff-Ferrari, Heike A.; Suter, Paolo M.; Krayenbuehl, Pierre-Alexandre

    2016-01-01

    Abstract Background: Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. Methods: This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. Result: The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (−3.3 ± 5.3; 95% confidence interval [CI] for change −14.1 to 4.1) compared with placebo (−0.8 ± 5.3; 95% CI for change −9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23–5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = −0.22, P = 0.02). Conclusion: Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency. This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475. PMID:28033244

  16. Green Tea Polyphenols and Vitamin D3 Protect Bone Microarchitecture in Female Rats with Chronic Inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our recent study showed that green tea polyphenols (GTP) in conjunction with 1-a-OH¬vit-D3 (vitD3) treatment mitigates lipopolysaccharide (LPS)-induced bone mineral density loss in female rats. This study was undertaken to further explore the mechanism and bone microarchitecture of GTP plus vitD3 in...

  17. 22 CFR 40.301 - Waiver for ineligible nonimmigrants under INA 212(d)(3)(A).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 212(d)(3)(A). 40.301 Section 40.301 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING... Ground of Ineligibility § 40.301 Waiver for ineligible nonimmigrants under INA 212(d)(3)(A). (a) Report... Homeland Security pursuant to the provisions of INA 212(d)(3)(A) in the case of an alien who...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

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

    MedlinePlus

    ... lower airway diseases have found an association between vitamin D3 deficiency and more severe inflammation. Furthermore, several reports have ... D3 activation and is associated with more severe vitamin D3 deficiency both in healthy patients and patients with chronic ...

  4. Prospective evaluation of shape similarity based pose prediction method in D3R Grand Challenge 2015

    NASA Astrophysics Data System (ADS)

    Kumar, Ashutosh; Zhang, Kam Y. J.

    2016-09-01

    Evaluation of ligand three-dimensional (3D) shape similarity is one of the commonly used approaches to identify ligands similar to one or more known active compounds from a library of small molecules. Apart from using ligand shape similarity as a virtual screening tool, its role in pose prediction and pose scoring has also been reported. We have recently developed a method that utilizes ligand 3D shape similarity with known crystallographic ligands to predict binding poses of query ligands. Here, we report the prospective evaluation of our pose prediction method through the participation in drug design data resource (D3R) Grand Challenge 2015. Our pose prediction method was used to predict binding poses of heat shock protein 90 (HSP90) and mitogen activated protein kinase kinase kinase kinase (MAP4K4) ligands and it was able to predict the pose within 2 Å root mean square deviation (RMSD) either as the top pose or among the best of five poses in a majority of cases. Specifically for HSP90 protein, a median RMSD of 0.73 and 0.68 Å was obtained for the top and the best of five predictions respectively. For MAP4K4 target, although the median RMSD for our top prediction was only 2.87 Å but the median RMSD of 1.67 Å for the best of five predictions was well within the limit for successful prediction. Furthermore, the performance of our pose prediction method for HSP90 and MAP4K4 ligands was always among the top five groups. Particularly, for MAP4K4 protein our pose prediction method was ranked number one both in terms of mean and median RMSD when the best of five predictions were considered. Overall, our D3R Grand Challenge 2015 results demonstrated that ligand 3D shape similarity with the crystal ligand is sufficient to predict binding poses of new ligands with acceptable accuracy.

  5. Evaluation of a novel case-based training program (d3web.Train) in hematology.

    PubMed

    Kraemer, Doris; Reimer, Stanislaus; Hörnlein, Alexander; Betz, Christian; Puppe, Frank; Kneitz, Christian

    2005-11-01

    The new media such as the internet and digital imaging offer new opportunities in medical education. In addition to conventional lectures, we developed a case-based simulation training program of 17 hematology cases using the novel training system d3web.Train. We evaluated the assessment of this internet course by medical students, as well as their results in the hematology exam. From a group of 150 students, 47 worked through at least one case and solved 435 cases in total; in average, these students solved 9.5 cases. Eighteen different students filled in a questionnaire about the training system and 68 questionnaires about individual cases. The main results were the students found the cases very helpful (1.5+/-0.6 on a scale from 1=very helpful to 5=not at all), the training system very good (1.4+/-0.5 on a scale from 1 to 6), and want to work with it further (1.2+/-0.4 on a scale from 1 to 5). During the final examination, those 16 students who answered that they had solved more than 5 from the 17 cases scored significantly better (two-sided t test, p<0.01) in the hematological part of the exam than those 34 students solving 0 to 5 cases. To our knowledge, this is the first student evaluation of a case-based training program in general hematology. The d3web.Train system offers a new and great tool for creating a training program in a reasonable amount of time, because it is able to process available patient records.

  6. Influence of grain refinement on the electrochemical behavior of AISI 430 ferritic stainless steel in an alkaline solution

    NASA Astrophysics Data System (ADS)

    Fattah-alhosseini, A.; Vafaeian, S.

    2016-01-01

    In this paper, the effect of grain refinement on the electrochemical behavior of AISI 430 ferritic stainless steel in 0.1 M NaOH solution was investigated. Potentiodynamic polarization curves showed that fine-grained samples have less corrosion potential, higher corrosion current density, and less protective passive film in comparison to coarse-grained samples. Electrochemical impedance spectroscopy (EIS) analysis revealed that implementing the thermomechanical operation led to lower polarization resistance. Also, Mott-Schottky analysis revealed that the passive films on both fine-grained and coarse-grained samples behave as n-type and p-type semiconductors and the semiconductor character of the passive films did not change by grain refinement. Moreover, it was found that the calculated donor and acceptor densities increased with grain refinement. Thus, the presented results indicated that grain refinement weakens the corrosion and passivation behavior of AISI 430 stainless steel in this alkaline solution.

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

    PubMed

    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 [3H]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.

  8. Effect of quenching method on the wear and corrosion resistance of stainless steel AISI 420 (TYPE 30Kh13)

    NASA Astrophysics Data System (ADS)

    Sola, R.; Giovanardi, R.; Veronesi, P.; Poli, G.

    2013-03-01

    The effect of different kinds of quenching, i.e., laser, vacuum, and induction ones, on the mechanical properties and wear and corrosion resistances of stainless steel AISI 420 is studied. It is shown that all the three kinds of heat treatment raise considerably the wear resistance of the steel due to growth in the hardness. Laser and vacuum quenching also increases the corrosion resistance. After induction quenching the resistance to corrosion is lower than in untreated steel.

  9. 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.

  10. Comparative effects of 1,25-dihydroxyvitamin D3 and EB 1089 on mouse renal and intestinal 25-hydroxyvitamin D3-24-hydroxylase.

    PubMed

    Roy, S; Martel, J; Tenenhouse, H S

    1995-12-01

    EB 1089 is a vitamin D analog that is less potent than 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in its calcemic action but more potent in its antiproliferative action. We characterized the interaction of 1,25(OH)2D3 and EB 1089 with renal 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway, and compared the effects of 1,25(OH)2D3 and EB 1089 on induction of 24-hydroxylase mRNA in mouse kidney and intestine. 1,25(OH)2D3 and EB 1089 were competitive inhibitors of 24-hydroxylase activity. However, the Ki for 1,25(OH)2D3 (5.2 +/- 2.5 nM) was significantly lower than that for EB 1089 (286 +/- 59 nM). In the kidney, the time course and extent of 24-hydroxylase mRNA induction, relative to 18S rRNA, was similar for 1,25(OH)2D3 and EB 1089 with a peak response at approximately equal to 6 h that was sustained for at least 16 h. In the intestine, however, induction of 24-hydroxylase mRNA, relative to 18S rRNA, was approximately 50% lower for EB 1089 than for 1,25(OH)2D3 at 3 h (p < 0.05) and 6 h (p < 0.05) while at 16 h 24-hydroxylase mRNA was no longer detectable. Moreover, while both 1,25(OH)2D3 and EB 10898 elicited a similar dose-dependent induction of 24-hydroxylase mRNA in the kidney (EC50 = 0.4 +/- 0.13 and 0.3 +/- 0.08 ng/g for EB 1089 and 1,25(OH)2D3, respectively), the EC50 for EB 1089 (6.6 +/- 1.7 ng/g) was significantly higher than that for 1,25(OH)2D3 (0.9 +/- 0.32 ng/g) in the intestine (p < 0.01). EB 1089 was also less effective than 1,25(OH)2D3 in the induction of intestinal but not renal calbindin-D9k mRNA. To determine the mechanism for tissue-specific differences in potency, we determined the binding affinity of 1,25(OH)2D3 and EB 1089 for the vitamin D receptor. In the kidney, Kd values for 1,25(OH)2D3 (0.40 +/- 0.95 nM) and EB 1089 (0.48 +/- 0.04 nM) were not different. However, in the intestine, the Kd for EB 1089 (1.43 +/- 0.19 nM) was significantly higher than that for 1,25(OH)2D3 (0.85 +/- 0.06 nM; p < 0

  11. 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.

  12. Selective Overexpression of Dopamine D3 Receptors in the Striatum Disrupts Motivation but not Cognition

    PubMed Central

    Simpson, Eleanor H.; Winiger, Vanessa; Biezonski, Dominik K.; Haq, Iram; Kandel, Eric R.; Kellendonk, Christoph

    2014-01-01

    Background Evidence indicating an increase in dopamine D2 receptor (D2R) density and occupancy in patients with schizophrenia comes from positron emission tomography studies using ligands that bind both D2Rs and dopamine D3 receptors (D3Rs), questioning the role of D3Rs in the pathophysiology of the disease. Dopamine D3 receptor positron emission tomography ligands have recently been developed and antagonists with preferential affinity for D3R versus D2R are undergoing clinical evaluation. To determine if an increase in D3Rs in the striatum could produce phenotypes relevant to schizophrenia, we generated a transgenic model of striatal D3R overexpression. Methods A bi-transgenic system was used to generate mice with increased D3Rs selectively in the striatum. Mice with overexpression of D3R were subjected to an extensive battery of behavioral tests, including several relevant to schizophrenia. Ligand binding and quantitative reverse transcription polymerase chain reaction methods were used to quantify the effect of D3R overexpression on dopamine D1 receptors (D1Rs) in the striatum. Results Mice with overexpression of D3R show no abnormalities in basic behavioral functions or cognitive tests but do display a deficit in incentive motivation. This was associated with a reduction in striatal D1R ligand binding, driven by a downregulation at the level of transcription. Both motivation and D1R expression were rescued by switching off the transgene in adulthood. Conclusions Overexpression of D3Rs in the striatum of mice does not elicit cognitive deficits but disrupts motivation, suggesting that changes in D3Rs may be involved in the negative symptoms of schizophrenia. These data imply that it will be important to evaluate the effects of D3R antagonists on motivational symptoms, which are not improved by currently available antipsychotic medications. PMID:24387821

  13. Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

    PubMed Central

    Chen, Pei-zhan; Li, Mian; Duan, Xiao-hua; Jia, Jing-ying; Li, Jing-quan; Chu, Rui-ai; Yu, Chen; Han, Jun-hua; Wang, Hui

    2016-01-01

    Aim: To examine the biological consequences and demographic factors that might affect the pharmacokinetics of vitamin D3 after a single high dose intervention in a young Chinese population with vitamin D insufficiency status. Methods: A total of 28 young subjects (25 to 35 years old) with vitamin D insufficiency status [serum 25(OH)D <30 ng/mL] was recruited in Shanghai, China. The subjects were orally administered a single high dose of vitamin D3 (300 000 IU). Baseline characteristics and blood samples were collected at d 0, 1, 2, 3, 7, 28, 56, 84 and 112 after the intervention. The blood biomarker levels were determined with standardized methods. Results: The intervention markedly increased the blood 25(OH)D3 levels within the first five days (mean Tmax=5.1±2.1 d) and sustained an optimal circulating level of 25(OH)D3 (≥30 ng/mL) for 56 d. After the intervention, body weight and baseline 25(OH)D3 levels were significantly correlated with circulating 25(OH)D3 levels. No adverse events and no consistently significant changes in serum calcium, creatinine, glucose, parathyroid hormone, vitamin D binding protein, or the urinary calcium/reatinine ratio were observed. However, there was a significant increase in phosphorus after the vitamin D3 intervention. Total cholesterol and triglyceride levels were decreased at the end of the trial. Conclusion: The pharmacokinetics of vitamin D after intervention were influenced by baseline 25(OH)D3 levels and the body weight of the subjects. The results suggest that a single high oral vitamin D3 intervention is safe and efficient for improving the vitamin D status of young Chinese people with vitamin D insufficiency. PMID:27569392

  14. 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.

  15. 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.

  16. Zr/ZrC modified layer formed on AISI 440B stainless steel by plasma Zr-alloying

    NASA Astrophysics Data System (ADS)

    Shen, H. H.; Liu, L.; Liu, X. Z.; Guo, Q.; Meng, T. X.; Wang, Z. X.; Yang, H. J.; Liu, X. P.

    2016-12-01

    The surface Zr/ZrC gradient alloying layer was prepared by double glow plasma surface alloying technique to increase the surface hardness and wear resistance of AISI 440B stainless steel. The microstructure of the Zr/ZrC alloying layer formed at different alloying temperatures and times as well as its formation mechanism were discussed by using scanning electron microscopy, glow discharge optical emission spectrum, X-ray diffraction and X-ray photoelectron spectroscopy. The adhesive strength, hardness and tribological property of the Zr/ZrC alloying layer were also evaluated in the paper. The alloying surface consists of the Zr-top layer and ZrC-subsurface layer which adheres strongly to the AISI 440B steel substrate. The thickness of the Zr/ZrC alloying layer increases gradually from 16 μm to 23 μm with alloying temperature elevated from 900 °C to 1000 °C. With alloying time from 0.5 h to 4 h, the alloyed depth increases from 3 μm to 30 μm, and the ZrC-rich alloyed thickness vs time is basically parabola at temperature of 1000 °C. Both the hardness and wear resistance of the Zr/ZrC alloying layer obviously increase compared with untreated AISI 440B steel.

  17. 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.

  18. 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

  19. 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.

  20. Degradation of vitamin D3 in a stressed formulation: the identification of esters of vitamin D3 formed by a transesterification with triglycerides.

    PubMed

    Ballard, John M; Zhu, Limin; Nelson, Eric D; Seburg, Randal A

    2007-01-04

    Four unknown degradants in the LC-UV profile of a stressed experimental tablet formulation that contains vitamin D3 have been identified by a combination of Ag+-cationization electrospray ionization (ESI) LC/MS and atmospheric pressure chemical ionization (APCI) LC/MS/MS. The peaks elute in the method chromatography in two pairs of two peaks. The first pair of peaks has m/z 511 while the second pair has m/z 539. The major, first peak of each set of peaks corresponds to the octanoate and decanoate ester of vitamin D3, respectively. These are formed by a transesterification with the two major fatty acid components (octanoate and decanoate) of the triglycerides present in the formulation. The formation of two degradation products with each fatty acid is due to the presence of both vitamin D3 (major component) and the isomeric pre-vitamin D3 (minor component) in the stressed formulation.

  1. Biocompatibility evaluation of surface-treated AISI 316L austenitic stainless steel in human cell cultures.

    PubMed

    Martinesi, M; Bruni, S; Stio, M; Treves, C; Bacci, T; Borgioli, F

    2007-01-01

    The effects of AISI 316L austenitic stainless steel, tested in untreated state or subjected to glow-discharge nitriding (at 10 or 20 hPa) and nitriding + post-oxidizing treatments, on human umbilical vein endothelial cells (HUVEC) and on peripheral blood mononuclear cells (PBMC) were evaluated. All the treated samples showed a better corrosion resistance in PBS and higher surface hardness in comparison with the untreated alloy. In HUVEC put in contact for 72 h with the sample types, proliferation and apoptosis decreased and increased, respectively, in the presence of the nitrided + post-oxidized samples, while only slight differences in cytokine (TNF-alpha, IL-6, and TGF-beta1) release were registered. Intercellular adhesion molecule-1 (ICAM-1) increased in HUVEC incubated with all the treated samples, while vascular cell adhesion molecule-1 (VCAM-1) and E-selectin increased in the presence of all the sample types. PBMC incubated for 48 h with the samples showed a decrease in proliferation and an increase in apoptosis in the presence of the untreated samples and the nitrided + post-oxidized ones. All the sample types induced a remarkable increase in TNF-alpha and IL-6 release in PBMC culture medium, while only the untreated sample and the nitrided at 10 hPa induced an increase in ICAM-1 expression. In HUVEC cocultured with PBMC, previously put in contact with the treated AISI 316L samples, increased levels of ICAM-1 were detected. In HUVEC coincubated with the culture medium of PBMC, previously put in contact with the samples under study, a noteworthy increase in ICAM-1, VCAM-1, and E-selectin levels was always registered, with the exception of VCAM-1, which was not affected by the untreated sample. In conclusion, even if the treated samples do not show a marked increase in biocompatibility in comparison with the untreated alloy, their higher corrosion resistance may suggest a better performance as the contact with physiological environment becomes longer.

  2. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells

    PubMed Central

    Nemere, I.; Farach-Carson, M. C.; Rohe, B.; Sterling, T. M.; Norman, A. W.; Boyan, B. D.; Safford, S. E.

    2004-01-01

    We used a ribozyme loss-of-function approach to demonstrate that the protein product of a cDNA encoding a multifunctional membrane-associated protein binds the seco-steroid 1,25(OH)2D3 and transduces its stimulatory effects on phosphate uptake. These results are paralleled by studies in which the ability of the hormone to stimulate phosphate uptake in isolated chick intestinal epithelial cells is abolished by preincubation with Ab099 directed against the amino terminus of the protein. We now report the complete sequence of the cloned chicken cDNA for the 1,25D3-MARRS (membrane-associated, rapid-response steroid-binding) protein and reveal it to be identical to the multifunctional protein ERp57. Functional studies showed that active ribozyme, but not a scrambled control, decreased specific membrane-associated 1,25(OH)2D3 binding, but did not affect binding to the nuclear receptor for 1,25(OH)2D3. Seco-steroid-dependent stimulation of protein kinase C activity was diminished as 1,25D3-MARRS protein levels were reduced in the presence of the ribozyme, as judged by Western blot analyses. Phosphate uptake in isolated cells is an index of intestinal phosphate transport that occurs during growth and maturation. Whereas cells and perfused duodena robustly responded to 1,25(OH)2D3 in preparations from young birds, older animals no longer responded with stimulated phosphate uptake or transport. The age-related decline was accompanied by a decrease in 1,25D3-MARRS mRNA that was apparent up to 1 year of age. Together, these studies functionally link phosphate transport in the chick duodenum with the 1,25D3-MARRS protein and point to a previously uncharacterized role for this multifunctional protein class. PMID:15123837

  3. 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.

  4. Vitamin D(3) synthesis in the entire skin surface of dairy cows despite hair coverage.

    PubMed

    Hymøller, L; Jensen, S K

    2010-05-01

    How hair-coated animals such as dairy cows synthesize endogenous vitamin D(3) during exposure to summer sunlight has been unclear since vitamin D(3) and its relation to sunlight was discovered. The fur of fur-bearing animals is thought to be comparable to clothing in humans, which prevents vitamin D(3) synthesis in the skin during exposure to sunlight. Different scenarios have been suggested but never tested in cows; for example, that vitamin D(3) is synthesized from sebum on the hair and ingested by cows during grooming or that body areas such as the udder and muzzle that have scant hair exclusively produce the vitamin. To test different scenarios, 16 Danish Holstein dairy cows were subjected to 4 degrees of coverage of their bodies with fabric that prevented vitamin D(3) synthesis in the covered skin areas. The treatments were horse blanket (cows fitted with horse blankets), udder cover (cows fitted with udder covers, horse blanket+udder cover (cows fitted with both horse blankets and udder covers), and natural (cows without any coverage fitted). The cows were let out to pasture daily between 1000 and 1500h for 4 wk in July and August 2009. Blood samples were collected 15 times during the study and analyzed for content of 25-hydroxyvitamin D(3) [25(OH)D(3)] indicative of the animals' vitamin D(3) status. Results showed that uncovered cows had a higher 25(OH)D(3) concentration in plasma after 28 d of access to sunlight compared with covered cows and that the plasma concentration of 25(OH)D(3) was strongly inversely correlated to the body surface area covered. These results are consistent with findings in humans, wherein the vitamin D(3) status of different individuals was inversely proportional to the amount of clothing worn during exposure to artificial sunlight. Hence, it appears that human clothing and cow hair are not comparable with respect to prevention of vitamin D(3) synthesis and that cows, like humans, synthesize vitamin D(3) evenly over their body

  5. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin.

    PubMed

    Yuk, Jae-Min; Shin, Dong-Min; Lee, Hye-Mi; Yang, Chul-Su; Jin, Hyo Sun; Kim, Kwang-Kyu; Lee, Zee-Won; Lee, Sang-Hee; Kim, Jin-Man; Jo, Eun-Kyeong

    2009-09-17

    Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.

  6. Vitamin D3 for the Treatment of Epilepsy: Basic Mechanisms, Animal Models, and Clinical Trials

    PubMed Central

    Pendo, Kevin; DeGiorgio, Christopher M.

    2016-01-01

    There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D3 is actively under investigation as a potential intervention for epilepsy. Vitamin D3 is fat-soluble steroid, which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D3 may reduce seizures, and animal data support the efficacy of Vitamin D3 in rat and mouse models of epilepsy. Very little clinical data exist to support the treatment of human epilepsy with Vitamin D3, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D3 as a treatment for human epilepsy. PMID:28008324

  7. 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

    2011-12-09

    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.

  8. Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury.

    PubMed

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

    2015-08-01

    Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.

  9. 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.

  10. The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

    PubMed Central

    Heidbreder, Christian A.; Gardner, Eliot L.; Xi, Zheng-Xiong; Thanos, Panayotis K.; Mugnaini, Manolo; Hagan, Jim J.; Ashby, Charles R.

    2013-01-01

    The cDNA for the dopamine D3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D3 receptors, as well as D3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D3 receptors. The interpretation of results from studies using mixed D2/D3 agonists and/or antagonists is problematic because these agents have low selectivity for D3 over D2 receptors and it is likely that their actions are primarily related to D2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stress-induced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction. PMID:15960988

  11. 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.

  12. Subapical localization of the dopamine D3 receptor in proximal tubules of the rat kidney.

    PubMed

    Nürnberger, Asja; Räbiger, Marcus; Mack, Andreas; Diaz, Jorge; Sokoloff, Pierre; Mühlbauer, Bernd; Luippold, Gerd

    2004-12-01

    The dopamine D3 receptor (D3R), intensively studied in neuroscience, also plays an important role in the regulation of renal and cardiovascular function. In contrast to functional findings, less information is available on its localization in the kidney. Neither RT-PCR studies nor radioligand binding assays are suitable to selectively determine the distribution of renal D3R at the level of cellular or even subcellular structures. We studied the renal D3R distribution in Sprague-Dawley rats by a polyclonal antiserum directed against an epitope in the third intracytoplasmic loop. D3R immunoreactivity was detected by indirect immunofluorescence and confocal laser scanning microscopy. D3R staining was confined to the renal cortex and occurred in proximal convoluted tubules near or in direct connection with the urinary pole of the glomeruli. The fluorescent spots were restricted to the subapical portion of the proximal tubular cells. Double staining with the F-actin marker phalloidin revealed a localization of the D3R below the brush border region. However, staining by anti-beta1/beta2-adaptins, recognizing clathrin-coated compartments, did not correspond to the distribution of the D3R signal. This is the first description of a D3R accumulation in a cytoplasmic pool in the kidney, probably corresponding to a recycling mechanism or storage compartment.

  13. Evaluation of DFT-D3 dispersion corrections for various structural benchmark sets

    NASA Astrophysics Data System (ADS)

    Schröder, Heiner; Hühnert, Jens; Schwabe, Tobias

    2017-01-01

    We present an evaluation of our newly developed density functional theory (DFT)-D3 dispersion correction D3(CSO) in comparison to its predecessor D3(BJ) for geometry optimizations. Therefore, various benchmark sets covering bond lengths, rotational constants, and center of mass distances of supramolecular complexes have been chosen. Overall both corrections give accurate structures and show no systematic differences. Additionally, we present an optimized algorithm for the computation of the DFT-D3 gradient, which reduces the formal scaling of the gradient calculation from O (N3) to O (N2) .

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Influence of tempering temperature on both the microstructural evolution and elemental distribution in AISI 4340 steels

    NASA Astrophysics Data System (ADS)

    Lim, Nam Suk; Bang, Chan Woo; Das, Sanjeev; Jin, Hyun Woo; Ayer, Raghavan; Park, Chan Gyung

    2012-02-01

    In the present study, the influence of tempering temperature on the microstructural evolution and prior austenite grain boundary segregation of AISI 4340 steels was investigated by transmission electron microscope and atom probe. The transmission electron microscopy results showed a variation in the microstructure and the morphology of carbides with a change in tempering temperature. Additionally, the chemical compositions of the prior austenite grain boundaries and carbides were quantified by atom probe tomography. An increase in the tempering temperature led to a decrease in the amount of carbon segregated at the prior austenite grain boundary from 7.9 to 1.3 at.%. It was found that a higher tempering temperature can accelerate the diffusion of carbon from the prior austenite grain boundary into carbide. However, phosphorus atoms were segregated mainly at the prior austenite grain boundary in steel tempered at 400°C (up to 0.18 at.%). It was found that formation of film-like carbide and phosphorus segregation along the prior austenite grain boundary is the main cause of embrittlement in steel tempered at 400°C.

  20. Solidification Microstructure of AISI M2 High Speed Steel Manufactured by the Horizontal Continuous Casting Process

    NASA Astrophysics Data System (ADS)

    Zhou, X. F.; Fang, F.; Jiang, J. Q.

    2011-01-01

    In the present work, AISI M2 high speed steel is produced by the horizontal continuous casting process. The difference of solidification microstructure in ingots by mould casting and continuous casting has been examined by means of scanning electron microscope (SEM), electron back-scatter diffraction (EBSD), transmission electron microscope (TEM) and high resolution electron microscope (HREM). The results show that the as-cast structure consists of iron matrix and networks of M2C eutectic carbides, which are greatly refined in the continuous casting ingot compared to the case of ingot by mould casting. Meanwhile, the morphology of M2C eutectic carbides changes from the plate-like shape into the fibrous one. Micro-twining and stacking faults are observed in the plate-like M2C, whereas they are rarely identified in the fibrous M2C. Based on the characteristic of morphology and microstructure, it is expected that the plate-like M2C is a faceted phase while the fibrous M2C is a non-faceted phase.

  1. 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.

  2. 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.

  3. Niobized AISI 304 stainless steel bipolar plate for proton exchange membrane fuel cell

    NASA Astrophysics Data System (ADS)

    Wang, Lixia; Sun, Juncai; Li, Pengbin; Jing, Bo; Li, Song; Wen, Zhongsheng; Ji, Shijun

    2012-06-01

    AISI 304 stainless steel (SS) has been niobized by a plasma surface diffusion alloying method. A 3 μm niobized layer with dominant niobium elements has been formed on the 304 SS surface and the performances of the niobized 304 SS has been examined and evaluated as bipolar plate for proton exchange membrane fuel cell (PEMFC). Results show that the average contact angle with water for the niobized 304 SS is about 90.4°, demonstrating better hydrophobicity as compared with the untreated 304 SS (68.1°). The corrosion resistance of the 304 SS is considerably improved by the niobized layer with the corrosion current densities decreased at 0.2 and 0.4 μA cm-2 in simulated PEMFC anode purged with hydrogen and the cathode purged with air condition (0.05 M H2SO4 + 2 ppm F- solution at 70 °C), respectively. The interfacial contact resistance (ICR) for the as-prepared niobized 304 SS is 10.53 mΩ cm2 at the compaction of 140 N cm-2. Furthermore, after 4 h potentiostatic tests, the niobizied specimens exhibit much lower ICR than that for the untreated ones. Thus, the niobized layer can act as a conductively protective layer of the 304 SS bipolar plate for PEMFC.

  4. DCEMS Study of Thin Stainless Steel Films Deposited by RF Sputtering of AISI316L

    SciTech Connect

    Nomura, K.; Iio, S.; Ujihira, Y.; Terai, T.

    2005-04-26

    Thin stainless steel films were prepared on SiO2/Si plate heated at 100 deg. C and 400 deg. C using AISI316L as target, by a RF magnetron Ar sputtering method. RF sputtered-deposited films and the oxidized surface layers by post heating were characterized by depth selective conversion electron Moessbauer spectroscopy (DCEMS) using a He+5%CH4 gas proportional counter. The as-deposited films consisted of magnetic phases, the magnetic orientation of which had a tendency to be perpendicular to the surface of the film. In the case of the deposited films at substrate temperature of 100 deg. C, a small amount of Fe2O3 and ferritic stainless steel formed by post-heating in air. A magnetic subcomponent and a austenite phase were formed in the films deposited at substrate temperature of 400 deg. C. {alpha}-Fe2O3 and magnetite formed easily on the top and middle layers of the films by post-heating in air. The oxide states of the films deposited at different temperatures of substrate were clearly distinguished by post-heating. Thus it was found by DCEMS that the structures of the deposited films were strongly affected by the preparation method and the temperature of the substrate.

  5. Rapid Tempering of Martensitic Stainless Steel AISI420: Microstructure, Mechanical and Corrosion Properties

    NASA Astrophysics Data System (ADS)

    Abbasi-Khazaei, Bijan; Mollaahmadi, Akbar

    2017-03-01

    In this research, the effect of rapid tempering on the microstructure, mechanical properties and corrosion resistance of AISI 420 martensitic stainless steel has been investigated. At first, all test specimens were austenitized at 1050 °C for 1 h and tempered at 200 °C for 1 h. Then, the samples were rapidly reheated by a salt bath furnace in a temperature range from 300 to 1050 °C for 2 min and cooled in air. The tensile tests, impact, hardness and electrochemical corrosion were carried out on the reheated samples. Scanning electron microscopy was used to study the microstructure and fracture surface. To investigate carbides, transmission electron microscopy and also scanning electron microscopy were used. X-ray diffraction was used for determination of the retained austenite. The results showed that the minimum properties such as the tensile strength, impact energy, hardness and corrosion resistance were obtained at reheating temperature of 700 °C. Semi-continuous carbides in the grain boundaries were seen in this temperature. Secondary hardening phenomenon was occurred at reheating temperature of 500 °C.

  6. Effect of Beam Oscillation on Microstructure and Mechanical Properties of AISI 316L Electron Beam Welds

    NASA Astrophysics Data System (ADS)

    Kar, Jyotirmaya; Roy, Sanat Kumar; Roy, Gour Gopal

    2017-04-01

    The properties of electron beam-welded AISI 316L stainless steel butt joints prepared with and without beam oscillation were evaluated by microstructural analysis, mechanical testing like microhardness measurements, tensile tests at room and elevated temperature 973 K (700 °C), three-point bend, and Charpy impact tests. All joints, irrespective of being prepared with or without beam oscillation, were found to be defect free. Welds produced by beam oscillation exhibited narrower fusion zone (FZ) with lathy ferrite morphology, while the weld without beam oscillation was characterized by wider FZ and skeletal ferrite morphology. During tensile tests at room and elevated temperature 973 K (700 °C), all samples fractured in the base metal (BM) and showed almost the same tensile properties as that of the BM. However, the notch tensile tests at room temperature demonstrated higher strength for joints prepared with the oscillating beam. Besides, face and root bend tests, as well as Charpy impact tests, showed higher bending strength and notch toughness, respectively, for joints prepared with beam oscillation.

  7. Aluminum-silicon co-deposition by FB-CVD on austenitic stainless steel AISI 316

    NASA Astrophysics Data System (ADS)

    Marulanda, J. L.; Perez, F. J.; Remolina-Millán, A.

    2013-11-01

    Aluminum-silicon coatings were deposited on stainless steel AISI 316 in the temperature range of 540 to 560°C by CVD-FBR. It was used a fluidized bed with 2.5% silicon and 7.5% aluminum powder and 90% inert (alumina). This bed was fluidized with Ar and as an activator a mixture of HCl/H2 in ratios of 1/10 to 1/16. Furthermore, the deposition time of the coatings was varied between 45 minutes to 1.5 hours, with a 50% active gas, neutral gases 50%. Thermodynamic simulation was conducted with the Thermocalc software to get the possible compositions and amount of material deposited for the chosen conditions. The coatings presented the follow compounds FeAl2Si, FeAl2 and Fe2Al5. Aluminum-silicon coatings were heat treated to improve its mechanical properties and its behavior against oxidation for the inter diffusion of the alloying elements. The heat treatment causes the aluminum diffuse into the substrate and the iron diffuse into coating surface. This leads to the transformation of the above compounds in FeAl, Al2FeSi, Cr3Si, AlFeNi and AlCrFe.

  8. Effect of Beam Oscillation on Microstructure and Mechanical Properties of AISI 316L Electron Beam Welds

    NASA Astrophysics Data System (ADS)

    Kar, Jyotirmaya; Roy, Sanat Kumar; Roy, Gour Gopal

    2017-02-01

    The properties of electron beam-welded AISI 316L stainless steel butt joints prepared with and without beam oscillation were evaluated by microstructural analysis, mechanical testing like microhardness measurements, tensile tests at room and elevated temperature 973 K (700 °C), three-point bend, and Charpy impact tests. All joints, irrespective of being prepared with or without beam oscillation, were found to be defect free. Welds produced by beam oscillation exhibited narrower fusion zone (FZ) with lathy ferrite morphology, while the weld without beam oscillation was characterized by wider FZ and skeletal ferrite morphology. During tensile tests at room and elevated temperature 973 K (700 °C), all samples fractured in the base metal (BM) and showed almost the same tensile properties as that of the BM. However, the notch tensile tests at room temperature demonstrated higher strength for joints prepared with the oscillating beam. Besides, face and root bend tests, as well as Charpy impact tests, showed higher bending strength and notch toughness, respectively, for joints prepared with beam oscillation.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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 aspects of thermomechanical fatigue of AISI 304L stainless steel: Part I. creep- fatigue damage

    NASA Astrophysics Data System (ADS)

    Zauter, R.; Christ, H. J.; Mughrabi, H.

    1994-02-01

    Thermomechanical fatigue (TMF) tests on the austenitic stainless steel AISI 304L have been conducted under “true≓ plastic-strain control in vacuum. This report considers the damage oc-curring during TMF loading. It is shown how the temperature interval and the phasing (in-phase, out-of-phase) determine the mechanical response and the lifetime of the specimens. If creep-fatigue interaction takes place during in-phase cycling, the damage occurs inside the ma-terial, leading to intergranular cracks which reduce the lifetime considerably. Out-of-phase cy-cling inhibits creep-induced damage, and no lifetime reduction occurs, even if the material is exposed periodically to temperatures in the creep regime. A formula is proposed which allows prediction of the failure mode, depending on whether creep-fatigue damage occurs or not. At a given strain rate, the formula is able to estimate the temperature of transition between pure fatigue and creep-fatigue damage.

  17. Formation of titanium aluminum nitride layers on AISI D2 steel by nitro-titanizing treatment

    NASA Astrophysics Data System (ADS)

    Cegil, Ozkan; Sen, Saduman

    2012-09-01

    In this study, titanium aluminum nitride coating was realized on AISI D2 steels by nitro-titanizing treatment. Steel samples were nitrided at 575 °C for 8 h in the first step of the coating process, and then titanized by thermo-reactive diffusion method in the powder mixture consisting of ferro-titanium, aluminum, ammonium chloride and alumina at 1000 °C for 2 h. The effects of the aluminum content to the coating bath were investigated. The thickness of the titanium aluminum nitride layer formed on the steel samples ranged from 6.30±0.5 to 7.89±0.34μm, depending on the aluminum content. The average micro-hardness value of the layer was 1468 ± 96 HV0.005 and 2630± 83 HV0.005. The phases formed on the coating layers are TiN, AlTi3N and Ti3Al2N2 which are characterized by XRD. EDS analysis results showed that coating layer includes titanium, aluminum and nitrogen.

  18. Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

    PubMed Central

    Czoty, Paul W.; Gage, H. Donald; Garg, Pradeep K.; Garg, Sudha; Nader, Michael A.

    2013-01-01

    Rationale Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. Objective We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n=5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n=9). Methods Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and four days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. Results ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. Conclusions The results indicate that repeated treatment with a low efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity. PMID:24077804

  19. 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.

  20. 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

  1. 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

    2015-12-22

    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.

  2. 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

  3. 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

  4. Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

    PubMed

    Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

    2016-09-26

    Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc.

  5. 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

  6. 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression

    PubMed Central

    Hassan-Smith, Zaki K.; Jenkinson, Carl; Smith, David J.; Hernandez, Ivan; Morgan, Stuart A.; Crabtree, Nicola J.; Gittoes, Neil J.; Keevil, Brian G.; Stewart, Paul M.

    2017-01-01

    Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)2D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)2D3 has limited effects on muscle gene expression

  7. 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

  8. Induction of CFTR gene expression by 1,25(OH)2 vitamin D3, 25OH vitamin D3, and vitamin D3 in cultured human airway epithelial cells and in mouse airways.

    PubMed

    DiFranco, Kristina M; Mulligan, Jennifer K; Sumal, Aman S; Diamond, Gill

    2017-01-24

    Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which often leads to protein misfolding and no CFTR surface localization. This then leads to chronic airway infections, inflammation, and tissue damage. Although vitamin D has been explored as a therapy to treat CF due to its antimicrobial-inducing and anti-inflammatory properties, the effect of 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3) on CFTR directly has not been studied. We treated cultured healthy and diseased bronchial epithelial cells (BEC) with 10nM 1α,25(OH)2D3 for 6 and 24h and found that 1α,25(OH)2D3 increases both mRNA and protein CFTR levels using RT-qPCR, flow cytometry and fluorescence immunohistochemistry. Treatment of CF cells with 10nM 1α,25(OH)2D3 led to an increase in both total and surface CFTR expression, suggesting 1α,25(OH)2D3 could be used to increase properly localized CFTR in airway cells. To determine if BEC could convert the more clinically relevant cholecalciferol to 25OHD3, cultured non-CF and CF BECs were treated with a range of cholecalciferol concentrations, and 25OHD3 levels were quantified by ELISA. We found that 25OHD3 levels increased in a concentration-dependent manner. Treatment of BEC with 10μM cholecalciferol led to increases in both CYP24A1 and CFTR mRNA levels, even when added to the apical surface of cells grown in an air-liquid interface, suggesting that topical administration of vitamin D could be used therapeutically. To demonstrate this in vivo, we intranasally delivered 1μM 1α,25(OH)2D3 into mice. After 6h, we observed induction of both Cyp24A1 and CFTR expression in the tracheas of treated mice. The major findings of this study are that vitamin D can be converted to the active form when topically administered to the airway, and this could be used to increase CFTR levels in patients with CF. This could potentially be useful as an adjunctive therapy, together with

  9. 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.

  10. 22 CFR 40.301 - Waiver for ineligible nonimmigrants under INA 212(d)(3)(A).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...)(ii), (3)(A)(iii), (3)(C), (3)(E)(i), or (3)(E)(ii). (b) Recommendation to designated DHS officer... 212(d)(3)(A). 40.301 Section 40.301 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING... Ground of Ineligibility § 40.301 Waiver for ineligible nonimmigrants under INA 212(d)(3)(A). (a)...

  11. 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.

  12. 26 CFR 31.3406(d)-3 - Special 30-day rules for certain reportable payments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Special 30-day rules for certain reportable payments. 31.3406(d)-3 Section 31.3406(d)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... account. (b) Sale of an instrument for a customer by electronic transmission or by mail. The special...

  13. 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...

  14. 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 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...

  15. 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...

  16. 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... 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...

  17. 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...

  18. Extended evaluation on the ES-D3 cell differentiation assay combined with the BeWo transport model, to predict relative developmental toxicity of triazole compounds.

    PubMed

    Li, Hequn; Flick, Burkhard; Rietjens, Ivonne M C M; Louisse, Jochem; Schneider, Steffen; van Ravenzwaay, Bennard

    2016-05-01

    The mouse embryonic stem D3 (ES-D3) cell differentiation assay is based on the morphometric measurement of cardiomyocyte differentiation and is a promising tool to detect developmental toxicity of compounds. The BeWo transport model, consisting of BeWo b30 cells grown on transwell inserts and mimicking the placental barrier, is useful to determine relative placental transport velocities of compounds. We have previously demonstrated the usefulness of the ES-D3 cell differentiation assay in combination with the in vitro BeWo transport model to predict the relative in vivo developmental toxicity potencies of a set of reference azole compounds. To further evaluate this combined in vitro toxicokinetic and toxicodynamic approach, we combined ES-D3 cell differentiation data of six novel triazoles with relative transport rates obtained from the BeWo model and compared the obtained ranking to the developmental toxicity ranking as derived from in vivo data. The data show that the combined in vitro approach provided a correct prediction for in vivo developmental toxicity, whereas the ES-D3 cell differentiation assay as stand-alone did not. In conclusion, we have validated the combined in vitro approach for developmental toxicity, which we have previously developed with a set of reference azoles, for a set of six novel triazoles. We suggest that this combined model, which takes both toxicodynamic and toxicokinetic aspects into account, should be further validated for other chemical classes of developmental toxicants.

  19. 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

  20. Pramipexole Derivatives as Potent and Selective Dopamine D3 Receptor Agonists with Improved Human Microsomal Stability

    PubMed Central

    Jiang, Cheng; Levant, Beth; Li, Xiaoqin; Zhao, Ting; Wen, Bo; Luo, Ruijuan; Sun, Duxin

    2014-01-01

    We report herein the synthesis and evaluation of a series of new pramipexole derivatives as highly potent and selective dopamine-3 (D3) receptor agonists. A number of these new compounds bind to the D3 receptor with subnanomolar affinities and show excellent selectivity (>10,000) for the D3 receptor over the D1 and D2 receptors. Compound 23 for example, binds to the D3 receptor with a Ki value of 0.53 nM and shows a selectivity of >20,000 over the D2 receptor and the D1 receptor in the binding assays using a rat brain preparation. It has excellent stability in human liver microsomes and in vitro functional assays showed it to be a full agonist for the human D3 receptor. PMID:25338762

  1. 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.

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

    PubMed

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

    2005-08-01

    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.

  3. 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

  4. Effects of friction and high torque on fatigue crack propagation in mode III. [AISI 4140 and 4340

    SciTech Connect

    Nayeb-Hashemi, H.; McClintock, F.A.; Ritchie, R.O.

    1982-12-01

    Turbo-generator and automotive shafts are often subjected to complex histories of high torques. To provide a basis for fatigue life estimation in such components, a study of fatigue crack propagation in Mode III (anti-plane shear) for a mill-annealed AISI 4140 steel (R /SUB B/ 88, 590 MN/m/sup 2/ tensile strength) has been undertaken, using torsionally-loaded, circumferentially-notched cylindrical specimens. As demonstrated previously for higher strength AISI 4340 steel, Mode III cyclic crack growth rates (dc/dN) /SUB III/ can be related to the alternating stress intensity factor ..delta..K /SUB III/ for conditions of small-scale yielding. However, to describe crack propagation behavior over an extended range of crack growth rates (about 10/sup -6/ to 10/sup -2/ mm per cycle), where crack growth proceeds under elastic-plastic and full plastic conditions, no correlation between (dc/dN) /SUB III/ and ..delta..K /SUB III/ is possible. Accordingly, a new parameter for torsional crack growth, termed the plastic strain intensity GAMMA /SUB III/, is introduced and is shown to provide a unique description of Mode III crack growth behavior for a wide range of testing conditions, provided a mean load reduces friction, abrasion, and interlocking between mating fracture surfaces A micro-mechanical model for the main radial Mode III growth is extended to high nominal stress levels, and predicts that Mode III fatigue crack propagation rates should be proportional to the range of plastic strain intensity (..delta..GAMMA /SUB III/) if local Mode II growth rates are proportional to the displacements. Such predictions are shown to be in agreement with measured growth rates in AISI 4140 steel from 10/sup -6/ to 10/sup -2/ mm per cycle.

  5. 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.

  6. 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.

  7. Influence of pulsating magnetic field on softening behavior of cold rolled AISI 4340 steel at room temperature

    SciTech Connect

    Prasad, S.N.; Singh, P.N.; Singh, V.

    1996-06-15

    The mechanical behavior of a ferromagnetic material is influenced by presence of magnetic field. The rate of stress relaxation in nickel increases by a.c. magnetic field of 11 Oersted (Oe) and 60 Hz. The application of 800 Oe steady magnetic field accelerates the process of creeping in high purity iron. The purpose of the present investigation was to examine the influence of pulsating magnetic field of 942 Oe, produced by a.c. current (50Hz), on the softening behavior of AISI 4340 steel, cold rolled to 20, 60, and 80%.

  8. Rutherford backscattering spectrometry (RBS) characterization of oxide scale formed on (AISI-304) steel after surface deposition of lanthanum

    SciTech Connect

    Ager, F.J.; Respaldiza, M.A.; Benitez, J.J.; Odriozola, J.A.; Botella, J.; Soares, J.C.; Silva, M.F. da

    1996-02-01

    Oxidized AISI-304 steel samples coated with lanthanum have been investigated by Rutherford backscattering spectrometry (RBS) in order to determine the composition profile of the oxide scale. In this sense, RBS technique has been revealed as a very reliable and nondestructive method for depth profile analysis. Lanthanum deposition, specially over preoxidized specimens, has proven to improve their resistance to high temperature oxidation. The formation of a LaCrO{sub 3} perovskite-like phase uniformly distributed along the oxide scale is proposed as being responsible for this behavior.

  9. Decreased Conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 Following Cholecalciferol Therapy in Patients with CKD

    PubMed Central

    Zhang, Shiqin; Friedman, Peter A.; Nolin, Thomas D.

    2014-01-01

    Background and objectives Elevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking. Design, setting, participants, & measurements An open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D–insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters. Results Vitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9–25.6 ng/ml] for controls versus 12.6 ng/ml [6.9–41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9–47.2 ng/ml] for controls versus 39.9 ng/ml [31.5–44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3–141.6 pg/ml] for controls versus 101.1 pg/ml [74.2–123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3–3.5 ng/ml] for controls versus 1.2 ng/ml [0.6–1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis. Conclusions Patients with CKD exhibit an altered

  10. 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).

  11. 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.

  12. 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.

  13. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs.

    PubMed

    Lin, Zongtao; Marepally, Srinivasa R; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen Sw; Postlethwaite, Arnold E; Myers, Linda K; Tuckey, Robert C; Slominski, Andrzej T; Miller, Duane D; Li, Wei

    2016-03-01

    Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR.

  14. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs

    PubMed Central

    LIN, ZONGTAO; MAREPALLY, SRINIVASA R.; KIM, TAE-KANG; JANJETOVIC, ZORICA; OAK, ALLEN SW.; POSTLETHWAITE, ARNOLD E.; MYERS, LINDA K.; TUCKEY, ROBERT C.; SLOMINSKI, ANDRZEJ T.; MILLER, DUANE D.; LI, WEI

    2017-01-01

    Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR. PMID:26976974

  15. 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.

  16. Short- and long-range corrected hybrid density functionals with the D3 dispersion corrections

    NASA Astrophysics Data System (ADS)

    Wang, Chih-Wei; Hui, Kerwin; Chai, Jeng-Da

    2016-11-01

    We propose a short- and long-range corrected (SLC) hybrid scheme employing 100% Hartree-Fock exchange at both zero and infinite interelectronic distances, wherein three SLC hybrid density functionals with the D3 dispersion corrections (SLC-LDA-D3, SLC-PBE-D3, and SLC-B97-D3) are developed. SLC-PBE-D3 and SLC-B97-D3 are shown to be accurate for a very diverse range of applications, such as core ionization and excitation energies, thermochemistry, kinetics, noncovalent interactions, dissociation of symmetric radical cations, vertical ionization potentials, vertical electron affinities, fundamental gaps, and valence, Rydberg, and long-range charge-transfer excitation energies. Relative to ωB97X-D, SLC-B97-D3 provides significant improvement for core ionization and excitation energies and noticeable improvement for the self-interaction, asymptote, energy-gap, and charge-transfer problems, while performing similarly for thermochemistry, kinetics, and noncovalent interactions.

  17. Evaluation of N-Phenyl Homopiperazine Analogs as Potential Dopamine D3 Receptor Selective Ligands

    PubMed Central

    Li, Aixiao; Mishra, Yogesh; Malik, Maninder; Wang, Qi; Li, Shihong; Taylor, Michelle; Reichert, David E.; Luedtke, Robert R.; Mach, Robert H.

    2013-01-01

    A series of N-(2-methoxyphenyl)homopiperazine analogs was prepared and their affinities for dopamine D2, D3, and D4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D3 dopamine receptor compared to the D2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7–3.9 nM for the D3 receptor with 30- to 170-fold selectivity for the D3 vs. D2 receptor. Calculated log P values (log P = 2.6–3.6) are within the desired range for passive transport across the blood brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that a) affinity at D2 and D3 dopamine receptors generally decreased, b) the D3 receptor binding selectivity (D2:D3 Ki value ratio) decreased and, c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. PMID:23618707

  18. Molecular Determinants of Selectivity and Efficacy at the Dopamine D3 Receptor

    PubMed Central

    Newman, Amy Hauck; Beuming, Thijs; Banala, Ashwini K.; Donthamsetti, Prashant; Pongetti, Katherine; LaBounty, Alex; Levy, Benjamin; Cao, Jianjing; Michino, Mayako; Luedtke, Robert R.; Javitch, Jonathan A.; Shi, Lei

    2012-01-01

    The dopamine D3 receptor (D3R) has been implicated in substance abuse and other neuropsychiatric disorders. The high sequence homology between the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has made the development of D3R-selective compounds challenging. Here, we deconstruct into pharmacophoric elements a series of D3R-selective substituted-4-phenylpiperazine compounds, and use computational simulations and binding and activation studies to dissect the structural bases for D3R selectivity and efficacy. We find that selectivity arises from divergent interactions within a second binding pocket (SBP) separate from the OBS, whereas efficacy depends on the binding mode in the OBS. Our findings reveal structural features of the receptor that are critical to selectivity and efficacy that can be used to design highly D3R-selective ligands with targeted efficacies. These findings are generalizable to other GPCRs in which the SBP can be targeted by bitopic or allosteric ligands. PMID:22632094

  19. Biphasic effect of 1,25-dihydroxyvitamin D3 on primary mouse epidermal keratinocyte proliferation.

    PubMed

    Bollag, W B; Ducote, J; Harmon, C S

    1995-05-01

    1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been proposed as a physiologic regulator of keratinocyte growth and differentiation. Utilizing a proliferative serum-free culture system, we have found that a physiologic (picomolar) concentrations this hormone stimulated proliferation of primary mouse epidermal keratinocytes; at higher (nanomolar to micromolar) doses, growth was inhibited by 1,25(OH)2D3. We investigated the nature of the signal transduction mechanism underlying the response to 1,25(OH)2D3 and observed little or no effect of either low or high concentrations of the hormone on cytosolic calcium levels or Fos expression. Furthermore, the protein kinase C inhibitor, Ro 31-7549, had very little effect on the growth inhibition induced by a high dose (1 microM) of 1,25(OH)2D3. This lack of rapid signal transduction events was consistent with the inability of a short (4-hour) exposure to 1,25(OH)2D3 to initiate a complete growth-inhibitory response as measured using [3H]thymidine incorporation. Our results indicate that physiologic concentrations of 1,25(OH)2D3 are required for optimal keratinocyte growth. Furthermore, we found no evidence of rapid effects of 1,25(OH)2D3 and suggest that in mouse epidermal keratinocytes, the response to this hormone is mediated by a slow transduction pathway, such as that activated by the intracellular 1,25(OH)2D3 receptor (VDR).

  20. 25(OH)D3 and Cardiovascular Risk Factors in Female Nonhuman Primates

    PubMed Central

    Jorgensen, Matthew J.; Rudel, Lawrence L.; Nudy, Matthew; Kaplan, Jay R.; Clarkson, Thomas B.; Pajewski, Nicholas M.

    2012-01-01

    Abstract Objective To determine if interindividual differences in plasma concentrations of 25-hydroxyvitamin D3 (25(OH)D3) have pathophysiologic significance, we evaluated a cohort of female monkeys, seeking to identify associations with clinically relevant cardiovascular risk factors, including age, abdominal obesity (waist circumference), and high-density lipoprotein cholesterol (HDL-C). Methods One hundred fifty-five female vervet monkeys (Chlorocebus aethiops sabaeus) aged 3–25 years consumed a typical western diet for 7–8 weeks that provided a woman's equivalent of approximately 1000 IU/day of vitamin D3. Measurements of vitamin D3 and HDL-C concentrations, as well as waist circumference, were obtained. Results Among young monkeys (aged 3–5 years), compared to older monkeys (aged 16–25 years), the mean plasma 25(OH)D3 concentrations were 82.3±3.2 ng/mL and 58.6±2.9 ng/mL (p<0.0001), respectively. Plasma 25(OH)D3 concentrations had a range of 19.6–142.0 ng/mL (mean±standard error [SE] 66.4±1.7 ng/mL). 25(OH)D3 concentrations were inversely associated with age (p<0.0001) and waist circumference (p=0.016) and were positively correlated with HDL-C (p=0.01). However, when statistically controlling for age, none of these relationships remained significant. Conclusions Higher plasma concentrations of 25(OH)D3 were associated with more favorable cardiovascular risk factors, with inverse associations observed between 25(OH)D3 and abdominal obesity, HDL-C, and age. These associations were no longer significant when controlling for age. PMID:22876774

  1. Differential regulation of cyclins D1 and D3 in hepatocyte proliferation.

    PubMed

    Rickheim, David G; Nelsen, Christopher J; Fassett, John T; Timchenko, Nikolai A; Hansen, Linda K; Albrecht, Jeffrey H

    2002-07-01

    Substantial evidence suggests that cyclin D1 plays a pivotal role in the control of the hepatocyte cell cycle in response to mitogenic stimuli, whereas the closely related protein cyclin D3 has not been extensively evaluated. In the current study, we examined the regulation of cyclins D1 and D3 during hepatocyte proliferation in vivo after 70% partial hepatectomy (PH) and in culture. In contrast to cyclin D1, which was nearly undetectable in quiescent liver and substantially up-regulated after PH, cyclin D3 was constitutively expressed and induced only modestly. In the regenerating liver, the concentration of cyclin D3 was only about 10% of that of cyclin D1. Cyclin D1 formed complexes primarily with cyclin-dependent kinase 4 (cdk4), which were markedly activated in the regenerating liver and readily sequestered the cell cycle inhibitory proteins, p21 and p27. Cyclin D3 bound to both cdk4 and cdk6. Cyclin D3/cdk6 activity was readily detectable in quiescent liver and changed little after PH, and this complex appeared to play a minor role in sequestering p21 and p27. In cultured hepatocytes, epidermal growth factor or insulin had little effect, but the combination of these agents substantially induced cyclin D1 and cell cycle progression. Inhibition of Mek1 or phosphoinositide 3-kinase markedly inhibited cyclin D1 expression and replication. In contrast, cyclin D3 was expressed in the absence of mitogens and was only modestly affected by these manipulations. In addition, growth-inhibitory extracellular matrix conditions inhibited cyclin D1 but not cyclin D3 expression. In conclusion, these results support the concept that cyclin D1 is critically regulated by extracellular stimuli that control proliferation, whereas cyclin D3 is regulated through different pathways and plays a distinct role in the liver.

  2. Dopamine D3 receptor specifically modulates motor and sensory symptoms in iron-deficient mice.

    PubMed

    Dowling, Pascal; Klinker, Florian; Stadelmann, Christine; Hasan, Kenan; Paulus, Walter; Liebetanz, David

    2011-01-05

    Restless legs syndrome (RLS) is a common neurological disorder whose exact pathophysiological mechanism remains unclear despite the successful use of dopaminergic treatment and recent discovery of predisposing genetic factors. As iron deficiency has been associated with RLS for some patients and there is evidence for decreased spinal dopamine D(3)-receptor (D3R) signaling in RLS, we aimed at establishing whether D3R activity and iron deficiency share common pathways within the pathophysiology of RLS sensory and motor symptoms. Using a combined mouse model of iron deficiency and dopamine D(3)-receptor deficiency (D3R-/-), circadian motor symptoms were evaluated by continuous recording of spontaneous wheel running activity. Testing the acute and persistent pain responses with the hot-plate test and formalin test, respectively, assessed sensory symptoms. A 15 week iron-deficient (ID) diet alone increased acute and persistent pain responses as compared to control diet. As compared to C57BL/6 (WT), homozygous D3R-/- mice already exhibited elevated responses to acute and persistent pain stimuli, where the latter was further elevated by concurrent iron deficiency. ID changed the circadian activity pattern toward an increased running wheel usage before the resting period, which resembled the RLS symptom of restlessness before sleep. Interestingly, D3R-/- shifted this effect of iron deficiency to a time point 3-4 h earlier. The results confirm the ability of iron deficiency and D3R-/- to evoke sensory and motor symptoms in mice resembling those observed in RLS patients. Furthermore this study suggests an increase of ID-related sensory symptoms and modification of ID-related motor symptoms by D3R-/-.

  3. [The quantitative determination of vitamin D3 and its metabolites in plasma].

    PubMed

    Kaune, R; Harmeyer, J

    1986-11-01

    A method is described which enables determination of vitamin D3 and its physiologically most important metabolites, i.e. 25-OHD3, 24,25-(OH)2D3, 25,26-(OH)2D3 and 1,25-(OH)2D3 in a plasma sample of about 2 to 4 ml. The whole procedure involves two preparative and one analytical steps: Extraction with methanol/methylene chloride (2:1), chromatographic separation on Lipidex 5000 using a stepwise gradient of n-hexane and chloroform and finally HPLC separation on Zorbax-Sil columns with n-hexane isopropanol mixtures and subsequently reversed phase separation on RP 18-columns and mixtures of methanol and water. Except for 1,25-(OH)2D3 all D compounds were quantified by UV-detection with 1.4 ng of substance being the lowest detectable amount. 1,25-(OH)2D3 was measured by radioimmunoassay. Prior to HPLC analysis the extract was separated into three fractions on Lipidex 5000 which contained 1) vitamin D3, 2) 25-OHD3 and 3) the dihydroxy metabolites. The three fractions were separated by HPLC using different mixtures of isopropanol/n-hexane and methanol/water, respectively. Retention times of the individual D-components longer than 10 min appeared to be essential to separate these compounds from accompanying material. Overall recoveries of the individual metabolites were for vitamin D3 48.9%, for 25-OHD3 54.2%, for 24,25-(OH)2D3 50.9% and for 1,25-(OH)2D3 52.5%. Application of the methods to plasma samples from pigs with pseudovitamin D deficiency rickets, typ I, revealed a reduced concentration of 1,25-(OH)2D3 and 24,25-(OH)2D3 and an elevated level of 25-OHD3 in these animals. The results obtained by this method contributed substantially to a better understanding of the aetiological factors associated with this disease.

  4. 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.

  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. 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.

  8. Quantitative analysis of vitamin D3 in a feed using normal phase high pressure liquid chromatography.

    PubMed

    Cohen, H; Lapointe, M

    1979-09-01

    A procedure is described for the separation and quantification of Vitamin D3 from different feeds and premixes. The study was conducted, first using a liquid partition step as a preliminary clean-up after extraction, then chromatography on activated Silica gel 60 before final analysis on a high pressure liquid chromatograph (HPLC) using a LiChrosorb NH2 (10 mu) column and a variable wavelength UV detector set at 264 nm. Total analysis on the HPLC was achieved in fifteen minutes. The detector response curve for an authentic D3 standard was linear using peak areas with a minimum detectable amount being 5 ng. The overall percent recovery of D3 in feeds was 94.4 +/- 2.4%. The minimum detectable amount of D3 in animal feeds was found to be in the region of 2,000 I.U./kg.

  9. 8 CFR 287.7 - Detainer provisions under section 287(d)(3) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS FIELD OFFICERS; POWERS AND DUTIES § 287.7 Detainer provisions under section 287(d)(3) of the Act... designated individually or as a class, by the Commissioner of CBP, the Assistant Secretary for ICE, or...

  10. Tranylcypromine Substituted cis-Hydroxycyclobutylnaphthamides as Potent and Selective Dopamine D3 Receptor Antagonists

    PubMed Central

    2015-01-01

    We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor. PMID:24848155

  11. Tolerance to 1,25 dihydroxyvitamin D3 glycosides from Solanum glaucophyllum by the growing pig.

    PubMed

    Schlegel, P; Guggisberg, D; Gutzwiller, A

    2017-02-16

    Solanum glaucophyllum leaves contain high levels of glycosidically bound 1,25 dihydroxyvitamin D3, the most important vitamin D metabolite. The tolerance to this source was evaluated during six weeks with fifty weaned pigs fed increasing levels (0, 2.5, 5, 10 and 20μg 1,25(OH)2D3/kg diet). The diet contained, per kg, 9.7g Ca, 3.5g digestible P and 2000IU cholecalciferol. Ten additional pigs were fed a diet containing 1000IU cholecalciferol/kg, without 1,25(OH)2D3. Weekly plasma and final kidney, bone and urinary mineral contents, bone density and breaking strength served as indicators for possible adverse effects of the supplement. All animals grew well and remained clinically healthy. The measured parameters remained unchanged when 1000 replaced 2000IU cholecalciferol/kg and when 1,25(OH)2D3 was fed up to 10μg/kg. Twenty μg 1,25(OH)2D3 increased plasma Ca and decreased plasma P from the 2(nd) and the 4(th) experimental week onwards, respectively. Twenty μg 1,25(OH)2D3 increased final plasma Ca and 1,25(OH)2D3 and reduced final plasma P by respectively 19, 56 and 13%. Twenty μg 1,25(OH)2D3 also increased kidney Ca and urinary Ca by 43 and 69%, respectively, reduced bone breaking strength by 12% and tended to decrease bone ash by 3%. To conclude, 2000IU D3 was not beneficial compared to 1000IU cholecalciferol; up to 10μg 1,25(OH)2D3 per kg diet did not lead to observed adverse effects; 20μg 1,25(OH)2D3 altered the homeostatic regulation of Ca and P thus, may lead to first signs of possible adverse effects, such as soft tissue calcification.

  12. Vitamin D3 attenuates oxidative stress and cognitive deficits in a model of toxic demyelination

    PubMed Central

    Tarbali, Sepideh; Khezri, Shiva

    2016-01-01

    Objective(s): Multiple sclerosis (MS) is a demyelinating disease. The prevalence of MS is highest where environmental supplies of vitamin D are low. Cognitive deficits have been observed in patients with MS. Oxidative damage may contribute to the formation of MS lesions. Considering the involvement of hippocampus in MS, an attempt is made in this study to investigate the effects of vitamin D3 on behavioral process and the oxidative status in the dorsal hippocampus (CA1 area) following the induction of experimental demyelination in rats. Materials and Methods: Animals were divided into six groups. Control group: animals received no surgery and treatment; saline group: animals received normal saline; sham group: animals received 150 μl sesame oil IP; vitamin D3 group: animals received 5 μg/kg vitamin D3 IP; lysophosphatidyl choline (LPC) group (toxic demyelination’s model): animals received LPC by stereotaxic intra-hippocampal injection of 2 μl LPC in CA1 area; Vitamin D3- treated group: animals were treated with vitamin D3 at doses of 5 μg/kg IP for 7 and 21 days post lesion. The spatial memory, biochemical parameters including catalase (CAT) activities and lipid peroxidation levels were investigated. Results: Animals in LPC group had more deficits in spatial memory than the control group in radial arm maze. Vitamin D3 significantly improved spatial memory compared to LPC group. Also, results indicated that vitamin D3 caused a decrease in lipid peroxidation levels and an increase in CAT activities. Conclusion: Current findings suggest that vitamin D3 may have a protective effect on cognitive deficits and oxidative stress in toxic demyelination’s model. PMID:27096068

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

    DOE PAGES

    Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

    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

  14. Randomized, Blinded Trial of Vitamin D3 for Treating Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS)

    PubMed Central

    Shapiro, Alice C.; Adlis, Susan A.; Robien, Kim; Kirstein, Mark N.; Liang, Shuang; Richter, Sara A.; Lerner, Rachel E.

    2017-01-01

    Purpose To evaluate the efficacy and safety of vitamin D3 at 4,000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. Methods 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 stage I-IIIA breast cancer, taking AI and experiencing AIMSS (Breast Cancer Prevention Trial Symptom Scale-Musculoskeletal Subscale ≥1.5 (BCPT-MS)) 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 4,000 IU D3 (n=57) daily for 6 months. The primary endpoint was change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general musculoskeletal pain; joint pain; muscle stiffness; range for each question: 0=not at all to 4=extremely). Results 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. Conclusions 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

  15. 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

  16. 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.

  17. Draft Genome Sequence of the Pediocin-Encoding Biopreservative and Biocontrol Strain Pediococcus acidilactici D3

    PubMed Central

    Rajendran, Mahitha; Altermann, Eric

    2013-01-01

    We describe a draft genome sequence for Pediococcus acidilactici strain D3, a component of multistrain commercial cultures with biopreservative and biocontrol properties in food-based applications. Strain D3 encodes at least one antimicrobial peptide, pediocin AMPd3. The AMPd3-encoding operon exhibits high sequence similarity to the archetype pediocin, PA-1, encoded by P. acidilactici PAC 1.0. PMID:23788534

  18. Overexpression of the dopamine D3 receptor in the rat dorsal striatum induces dyskinetic behaviors.

    PubMed

    Cote, Samantha R; Chitravanshi, Vineet C; Bleickardt, Carina; Sapru, Hreday N; Kuzhikandathil, Eldo V

    2014-04-15

    L-DOPA-induced dyskinesias (LID) are motor side effects associated with treatment of Parkinson's disease (PD). The etiology of LID is not clear; however, studies have shown that the dopamine D3 receptor is upregulated in the basal ganglia of mice, rats and non-human primate models of LID. It is not known if the upregulation of D3 receptor is a cause or result of LID. In this paper we tested the hypothesis that overexpression of the dopamine D3 receptor in dorsal striatum, in the absence of dopamine depletion, will elicit LID. Replication-deficient recombinant adeno-associated virus-2 expressing the D3 receptor or enhanced green fluorescent protein (EGFP) were stereotaxically injected, unilaterally, into the dorsal striatum of adult rats. Post-hoc immunohistochemical analysis revealed that ectopic expression of the D3 receptor was limited to neurons near the injection sites in the dorsal striatum. Following a 3-week recovery period, rats were administered saline, 6 mg/kg L-DOPA, 0.1 mg/kg PD128907 or 10 mg/kg ES609, i.p., and motor behaviors scored. Rats overexpressing the D3 receptor specifically exhibited contralateral axial abnormal involuntary movements (AIMs) following administration of L-DOPA and PD128907 but not saline or the novel agonist ES609. Daily injection of 6 mg/kg L-DOPA to the rats overexpressing the D3 receptor also caused increased vacuous chewing behavior. These results suggest that overexpression of the D3 receptor in the dorsal striatum results in the acute expression of agonist-induced axial AIMs and chronic L-DOPA-induced vacuous chewing behavior. Agonists such as ES609 might provide a novel therapeutic approach to treat dyskinesia.

  19. 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

  20. Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands.

    PubMed

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

    2015-02-01

    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.

  1. The Effects of Uric Acid, Serum Vitamin D3, and Their Interaction on Parkinson's Disease Severity

    PubMed Central

    Meamar, Rokhsareh; Shaabani, Pooria; Tabibian, Seyed Reza; Aghaye Ghazvini, Mohammad Reza

    2015-01-01

    Objectives. In current study, the relationships between serum vitamin D3 levels and serum UA concentrations as well as their interaction with severity of PD were evaluated in a sample of Iranian PD patients. Method. In a cross sectional study at the one of the main referral hospitals in central region of Iran, during September to November 2011, 112 patients were recruited. Severity of PD was evaluated sing H&R stages and UPDRS. Results. The Spearman rank correlation coefficient suggests the negative significant association between serum vitamin D3 and UPDRS in patients aged >62 (r = −0.34, P < 0.05). No statistically significant association was observed between the UA levels and severity of PD (represented by H&Y categories) in different levels of serum vitamin D3 not only in total sample but also in separate age and sex groups. The linear regression coefficients suggested positive association between UA and serum vitamin D3 with UPDRSIII scores while negative relationship between UA and serum vitamin D3 interaction with UPDRSIII; however it was only statistically significant in age group ≤62 (P < 0.05). Conclusion. Our study revealed a negative correlation between interaction of serum vitamin D3 and UA with severity of PD; other studies are required to confirm our findings. PMID:25802799

  2. 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.

  3. Parkinson's disease treatment may cause impulse-control disorder via dopamine D3 receptors.

    PubMed

    Seeman, Philip

    2015-04-01

    In treating Parkinson's disease with dopaminergic agonists, such as pramipexole, ropinirole, pergolide, rotigotine, apomorphine, or bromocriptine, it has been observed that a significant number of patients develop impulse-control disorders, such as compulsive shopping, pathological gambling, or hypersexuality. Because the dopamine agonists have high affinities for the dopamine D2 and D3 receptors, the drug dissociation constants of these drugs at the functional high-affinity states of these receptors, namely D2High and D3High, were compared. The data show that, compared to the other dopamine agonist drugs, pramipexole has a relatively high selectivity for the dopamine D3 receptor, as compared to D2, suggesting that the D3 receptor may be a primary target for pramipexole. There is a trend showing that the proportion of impulse-control disorders is related to the selectivity for D3 receptors over D2 receptors, with pramipexole having the highest association with, or frequency of, impulse-control disorders. While the number of studies are limited, the proportion of patients with impulse-control disorder in Parkinson patients treated with an add-on agonist were 32% for pramipexole, 25% for ropinirole, 16% for pergolide, 22% for rotigotine, 10% for apomorphine, and 6.8% for bromocriptine. Clinically, temporary replacement of pramipexole by bromocriptine may provide relief or reversal of the impulsive behavior associated with selective D3 stimulation by either pramipexole or ropinirole, while maintaining D2 stimulation needed for the anti-Parkinson action.

  4. A role for cyclin D3 in the endomitotic cell cycle.

    PubMed Central

    Zimmet, J M; Ladd, D; Jackson, C W; Stenberg, P E; Ravid, K

    1997-01-01

    Platelets, essential for thrombosis and hemostasis, develop from polyploid megakaryocytes which undergo endomitosis. During this cell cycle, cells experience abrogated mitosis and reenter a phase of DNA synthesis, thus leading to endomitosis. In the search for regulators of the endomitotic cell cycle, we have identified cyclin D3 as an important regulatory factor. Of the D-type cyclins, cyclin D3 is present at high levels in megakaryocytes undergoing endomitosis and is markedly upregulated following exposure to the proliferation-, maturation-, and ploidy-promoting factor, Mpl ligand. Transgenic mice in which cyclin D3 is overexpressed in the platelet lineage display a striking increase in endomitosis, similar to changes seen following Mpl ligand administration to normal mice. Electron microscopy analysis revealed that unlike such treated mice, however, D3 transgenic mice show a poor development of demarcation membranes, from which platelets are believed to fragment, and no increase in platelets. Thus, while our model supports a key role for cyclin D3 in the endomitotic cell cycle, it also points to the unique role of Mpl ligand in priming megakaryocytes towards platelet fragmentation. The role of cyclin D3 in promoting endomitosis in other lineages programmed to abrogate mitosis will need further exploration. PMID:9372957

  5. In vitro performance of prefilled CO₂ absorbers with the Aisys®.

    PubMed

    Hendrickx, Jan F A; De Ridder, Simon P A J; Dehouwer, Alexander; Carette, Rik; De Cooman, Sofie; De Wolf, Andre M

    2016-04-01

    Low flow anesthesia increases the use of CO2 absorbents, but independent data that compare canister life of the newest CO2 absorbents are scarce. Seven different pre-packed CO2 canisters were tested in vitro: Amsorb Plus, Spherasorb, LoFloSorb, Medisorb, Medisorb EF, LithoLyme, and SpiraLith. CO2 (160 mL min(-1)) flowed into the tip of a 2 L breathing bag that was ventilated with a tidal volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the controlled mechanical ventilation mode of the Aisys (®) (GE, Madison, WI, USA). In part I, canister life of each brand (all of the same lot) was tested with 12 different fresh gas flows (FGF) ranging from 0.25 to 4 L min(-1). In part II, canister life of six canisters each of two different lots of each brand were tested with a 350 mL min(-1) FGF. Canister life is presented as "FCU", fractional canister usage, the fraction of a canister used per hour, and is defined for the inspired CO2 concentration (FICO2) that denotes exhaustion. In part III, canister life per 100 g fresh granule content was calculated. FCU decreased linearly with increasing FGF. The relative position of the FCU-FGF curves of the different brands depends on the FICO2 threshold because the exhaustion rate (the rate of rise once FICO2 starts to increase) differs among the brands. Intra-lot variability was 18 % or less. The different prepacks can be ranked according their efficiency (least to most efficient) as follows: Amsorb Plus = Medisorb EF < LoFloSorb < Medisorb = Spherasorb = LithoLyme < SpiraLith (all for an FICO2 threshold = 0.5 %). Canister life per 100 g fresh granule content is almost twice as long when LiOH is used as the primary absorbent. The most important factors that determine canister life of prepacks in a circle breathing system are the chemical composition of the canister, the absolute amount of absorbent present in the canister, and the FICO2 replacement threshold. The use of the fractional canister usage allows

  6. 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.

  7. Dopamine receptor D3 regulates endocytic sorting by a Prazosin-sensitive interaction with the coatomer COPI.

    PubMed

    Zhang, Xin; Wang, Wenchao; Bedigian, Anne V; Coughlin, Margaret L; Mitchison, Timothy J; Eggert, Ulrike S

    2012-07-31

    Macromolecules enter cells by endocytosis and are sorted to different cellular destinations in early/sorting endosomes. The mechanism and regulation of sorting are poorly understood, although transitions between vesicular and tubular endosomes are important. We found that the antihypertensive drug Prazosin inhibits endocytic sorting by an off-target perturbation of the G protein-coupled receptor dopamine receptor D(3) (DRD3). Prazosin is also a potent cytokinesis inhibitor, likely as a consequence of its effects on endosomes. Prazosin stabilizes a normally transient interaction between DRD3 and the coatomer COPI, a complex involved in membrane transport, and shifts endosomal morphology entirely to tubules, disrupting cargo sorting. RNAi depletion of DRD3 alone also inhibits endocytic sorting, indicating a noncanonical role for a G protein-coupled receptor. Prazosin is a powerful tool for rapid and reversible perturbation of endocytic dynamics.

  8. 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

    2016-06-03

    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.

  9. 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.

  10. 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.

  11. Dopamine D3 Receptor Availability Is Associated with Inflexible Decision Making

    PubMed Central

    Groman, Stephanie M.; Smith, Nathaniel J.; Petrullli, J. Ryan; Massi, Bart; Chen, Lihui; Ropchan, Jim; Huang, Yiyun; Lee, Daeyeol; Morris, Evan D.

    2016-01-01

    Dopamine D2/3 receptor signaling is critical for flexible adaptive behavior; however, it is unclear whether D2, D3, or both receptor subtypes modulate precise signals of feedback and reward history that underlie optimal decision making. Here, PET with the radioligand [11C]-(+)-PHNO was used to quantify individual differences in putative D3 receptor availability in rodents trained on a novel three-choice spatial acquisition and reversal-learning task with probabilistic reinforcement. Binding of [11C]-(+)-PHNO in the midbrain was negatively related to the ability of rats to adapt to changes in rewarded locations, but not to the initial learning. Computational modeling of choice behavior in the reversal phase indicated that [11C]-(+)-PHNO binding in the midbrain was related to the learning rate and sensitivity to positive, but not negative, feedback. Administration of a D3-preferring agonist likewise impaired reversal performance by reducing the learning rate and sensitivity to positive feedback. These results demonstrate a previously unrecognized role for D3 receptors in select aspects of reinforcement learning and suggest that individual variation in midbrain D3 receptors influences flexible behavior. Our combined neuroimaging, behavioral, pharmacological, and computational approach implicates the dopamine D3 receptor in decision-making processes that are altered in psychiatric disorders. SIGNIFICANCE STATEMENT Flexible decision-making behavior is dependent upon dopamine D2/3 signaling in corticostriatal brain regions. However, the role of D3 receptors in adaptive, goal-directed behavior has not been thoroughly investigated. By combining PET imaging with the D3-preferring radioligand [11C]-(+)-PHNO, pharmacology, a novel three-choice probabilistic discrimination and reversal task and computational modeling of behavior in rats, we report that naturally occurring variation in [11C]-(+)-PHNO receptor availability relates to specific aspects of flexible decision making

  12. 1,25-Dihydroxyvitamin D(3) Inhibits Podocyte uPAR Expression and Reduces Proteinuria

    PubMed Central

    Liu, Shuangxin; Xie, Shaoting; Yang, Yun; Ma, Juan; Deng, Yujun; Wang, Wenjian; Xu, Lixia; Li, Ruizhao; Zhang, Li; Yu, Chunping; Shi, Wei

    2013-01-01

    Background Accumulating studies have demonstrated that 1,25-Dihydroxyvitamin D(3) (1,25(OH)2D3) reduces proteinuria and protects podocytes from injury. Recently, urokinase receptor (uPAR) and its soluble form have been shown to cause podocyte injury and focal segmental glomerulosclerosis (FSGS). Here, our findings showed that 1,25(OH)2D3 did inhibit podocyte uPAR expression and attenuate proteinuria and podocyte injury. Methodology/Principal Findings In this study, the antiproteinuric effect of 1,25(OH)2D3 was examined in the lipopolysaccharide mice model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model(NTX rats). uPAR protein expression were tested by flow cytometry, immune cytochemistry and western blot analysis, and uPAR mRNA expression by real-time quantitative PCR in cultured podocytes and kidney glomeruli isolated from mice and rats. Podocyte motility was observed by transwell migration assay and wound healing assay. Podocyte foot processes effacement was identified by transmission electron microscopy. We found that 1,25(OH)2D3 inhibited podocyte uPAR mRNA and protein synthesis in LPS-treated podocytes, LPS mice and NTX rats, along with 1,25(OH)2D3 reducing proteinuria in NTX rats and LPS mice.1,25(OH)2D3 reduced glomerulosclerosis in NTX rats and alleviated podocyte foot processes effacement in LPS mice. Transwell migration assay and wound healing assay showed that LPS-induced podocyte motility, irrespective of random or directed motility, were substantially reduced by 1,25(OH)2D3. Conclusions/Significance Our results demonstrated that 1,25(OH)2D3 inhibited podocyte uPAR expression in vitro and in vivo, which may be an unanticipated off target effect of 1,25(OH)2D3 and explain its antiproteinuric effect in the 5/6 nephrectomy rat FSGS model and the LPS mouse model of transient proteinuria. PMID:23741418

  13. 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.

  14. 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

  15. Identification of Human UDP-glucuronosyltransferases Catalyzing Hepatic 1α,25-Dihydroxyvitamin D3 Conjugation

    PubMed Central

    Hashizume, Takanori; Xu, Yang; Mohutsky, Michael A.; Alberts, Jeffrey; Hadden, Chad; Kalhorn, Thomas F.; Isoherranen, Nina; Shuhart, Margaret C.; Thummel, Kenneth E.

    2009-01-01

    The biological effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) are terminated primarily by P450-dependent hydroxylation reactions. However, the hormone is also conjugated in the liver and a metabolite, presumably a glucuronide, undergoes enterohepatic cycling. In this study, the identity of human enzymes capable of catalyzing the 1,25(OH)2D3 glucuronidation reaction was investigated in order to better understand environmental and endogenous factors affecting the disposition and biological effects of vitamin D3. Among twelve different UGT isozymes tested, only UGT1A4 ≫ 2B4 and 2B7 supported the reaction. Two different 1,25(OH)2D3 monoglucuronide metabolites were generated by recombinant UGT1A4 and human liver microsomes. The most abundant product was identified by mass spectral and NMR analyses as the 25-O-glucuronide isomer. The formation of 25-O-glucuronide by UGT1A4 Supersomes and human liver microsomes followed simple hyperbolic kinetics, yielding respective Km and Vmax values of 7.3 and 11.2 μM, and 33.7 ± 1.4 and 32.9 ± 1.9 pmol/min/mg protein. The calculated intrinsic 25-O-glucuronide M1 formation clearance for UGT1A4 was 14-fold higher than the next best isozyme, UGT2B7. There was only limited (4-fold) inter-liver variability in the 25-O-glucuronidation rate, but it was highly correlated with the relative rate of formation of the second, minor metabolite. In addition, formation of both metabolites was inhibited > 80% by the selective UGT1A4 inhibitor, hecogenin. If enterohepatic recycling of 1,25(OH)2D3 represents a significant component of intestinal and systemic 1,25(OH)2D3 disposition, formation of monoglucuronides by hepatic UGT1A4 constitutes an important initial step. PMID:18177842

  16. Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

    PubMed Central

    Fan, Ying; Mok, Chris Ka-Pun; Chan, Michael Chi Wai; Zhang, Yang; Nal, Béatrice; Kien, François; Bruzzone, Roberto; Sanyal, Sumana

    2017-01-01

    To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection. PMID:28130444

  17. Cell Cycle Independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection.

    PubMed

    Fan, Ying; Mok, Chris Ka-Pun; Chan, Michael Chi Wai; Zhang, Yang; Nal-Rogier, Béatrice; Kien, François; Bruzzone, Roberto; Sanyal, Sumana

    2017-01-27

    To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se, and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into the S phase, failed to normalize virus production. Infection by IAV triggered redistribution of cyclin D3 from the nucleus to the cytoplasm followed by its proteasomal degradation. When over-expressed in HEK 293T cells cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection.

  18. Quantitative Evaluation of Aged AISI 316L Stainless Steel Sensitization to Intergranular Corrosion: Comparison Between Microstructural Electrochemical and Analytical Methods

    NASA Astrophysics Data System (ADS)

    Sidhom, H.; Amadou, T.; Sahlaoui, H.; Braham, C.

    2007-06-01

    The evaluation of the degree of sensitization (DOS) to intergranular corrosion (IGC) of a commercial AISI 316L austenitic stainless steel aged at temperatures ranging from 550 °C to 800 °C during 100 to 80,000 hours was carried out using three different assessment methods. (1) The microstructural method coupled with the Strauss standard test (ASTM A262). This method establishes the kinetics of the precipitation phenomenon under different aging conditions, by transmission electronic microscope (TEM) examination of thin foils and electron diffraction. The subsequent chromium-depleted zones are characterized by X-ray microanalysis using scanning transmission electronic microscope (STEM). The superimposition of microstructural time-temperature-precipitation (TTP) and ASTM A262 time-temperature-sensitization (TTS) diagrams provides the relationship between aged microstructure and IGC. Moreover, by considering the chromium-depleted zone characteristics, sensitization and desensitization criteria could be established. (2) The electrochemical method involving the double loop-electrochemical potentiokinetic reactivation (DL-EPR) test. The operating conditions of this test were initially optimized using the experimental design method on the bases of the reliability, the selectivity, and the reproducibility of test responses for both annealed and sensitized steels. The TTS diagram of the AISI 316L stainless steel was established using this method. This diagram offers a quantitative assessment of the DOS and a possibility to appreciate the time-temperature equivalence of the IGC sensitization and desensitization. (3) The analytical method based on the chromium diffusion models. Using the IGC sensitization and desensitization criteria established by the microstructural method, numerical solving of the chromium diffusion equations leads to a calculated AISI 316L TTS diagram. Comparison of these three methods gives a clear advantage to the nondestructive DL-EPR test when it is

  19. 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.

    2016-12-01

    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.

  20. Unfolding of the RAP-D3 helical bundle facilitates dissociation of RAP-receptor complexes.

    PubMed

    Estrada, Kristine; Fisher, Carl; Blacklow, Stephen C

    2008-02-12

    The receptor-associated protein (RAP) functions as an escort protein for receptors of the low-density lipoprotein receptor (LDLR) family by preventing premature intracellular binding of ligands and assisting with delivery of mature receptors to the cell surface. The modulation of affinity by pH is believed to play an important role in the escort function of RAP, because RAP binds tightly to proteins of the LDLR family at near-neutral pH early in the secretory pathway where its high affinity precludes premature binding of ligands but then dissociates from bound receptors at the lower pH of the Golgi compartment. The third domain of RAP (RAP-D3), which forms a three-helix bundle, is sufficient to reconstitute the escort activity. Here, we test the hypothesis that low-pH induced unfolding of the RAP-D3 helical bundle facilitates dissociation of RAP-receptor complexes. First, variants of RAP-D3 resistant to low pH-induced unfolding were constructed by replacing interior histidine residues with phenylalanines. In contrast to native RAP-D3, which exhibits an unfolding pKa of 6.3 and a Tm of 42 degrees C, the most hyperstable variant of RAP-D3, in which four histidine residues are replaced with phenylalanine, has an unfolding pKa of 4.8, and a Tm of 58 degrees C. The phenylalanine substitutions in RAP-D3 confer increased stability to pH-induced dissociation of complexes formed between RAP-D3 and a two-repeat fragment of the LDLR (LA3-4). When introduced into full-length RAP, the four mutations that confer hyperstability on RAP-D3 interfere with transport of endogenous LRP-1 to the cell surface in a dominant negative fashion under conditions where expression of normal RAP has no effect on LRP-1 transport. Our studies support a model in which low pH-dependent unfolding of RAP-D3 facilitates dissociation of RAP from the LA repeats of LDLR family proteins in the mildly acidic pH of the Golgi.

  1. The action spectrum for vitamin D3: initial skin reaction and prolonged exposure.

    PubMed

    van Dijk, Arjan; den Outer, Peter; van Kranen, Henk; Slaper, Harry

    2016-07-06

    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

  2. Tolerance evaluation of overdosed dietary levels of 25-hydroxyvitamin D3 in growing piglets.

    PubMed

    von Rosenberg, S J; Weber, G M; Erhardt, A; Höller, U; Wehr, U A; Rambeck, W A

    2016-04-01

    Forty-eight, cross-bred (GL × LW × P) piglets were used in a 42-day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25-hydroxyvitamin D3 (25-OH-D3 ). Six-week-old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D3 /kg feed. The experimental groups received 25-OH-D3 at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25-OH-D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25-OH-D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25-OH-D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25-OH-D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25-OH-D3 can be regarded as a supplement with a very high safety margin when used at the recommended level.

  3. Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation

    PubMed Central

    Arnardottir, Hildur H.; Dalli, Jesmond; Norling, Lucy V.; Colas, Romain A.; Perretti, Mauro; Serhan, Charles N.

    2016-01-01

    Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rv) are a new family from the endogenous specialized pro-resolving lipid mediators (SPM) that actively stimulate resolution of inflammation. Herein, using lipid mediator (LM) metabololipidomics with murine joints we found a temporal regulation of endogenous SPM during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series resolvins, e.g. Resolvin (Rv) D1, RvD2, RvD3 and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared to self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis (RA) patients compared to healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores and edema. 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. 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.

  5. Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280).

    PubMed

    Li, Ming; Li, Chuanyu; Weingarten, Paul; Bunzow, James R; Grandy, David K; Zhou, Qun Yong

    2002-03-01

    Proteins that bind to G protein-coupled receptors have been identified as regulators of receptor localization and signaling. In our previous studies, a cytoskeletal protein, actin-binding protein 280 (ABP-280), was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D(3) receptors, but not with D(4) receptors. Similar to the dopamine D(2) receptor, the D(3)/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280, D(3) receptors were unable to inhibit forskolin-stimulated cyclic AMP (cAMP) production significantly. D(4) receptors, however, exhibited a similar degree of inhibition of forskolin-stimulated cAMP production in ABP-280-deficient M2 cells and ABP-280-replent M2 subclones (A7 cells). Further experiments revealed that the D(3)/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D(3) receptor third loop, which is conserved in the D(2) receptor but not in the D(4) receptor. Our results demonstrate a subtype-specific regulation of dopamine D(2)-family receptor signaling by the cytoskeletal protein ABP-280.

  6. 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.

  7. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter.

    PubMed

    Kitazawa, Sohei; Kajimoto, Kazuyoshi; Kondo, Takeshi; Kitazawa, Riko

    2003-07-01

    Receptor activator of NF-kappaB ligand (RANKL) has been identified as requisite for osteoclastogenesis. To elucidate the molecular mechanism that conducts its catabolic action on bone, the effect of 1alpha,25 dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) on osteoclastogenesis and RANKL mRNA expression was examined by coculture, RT-PCR and nuclear run-on studies. By accelerating the transcription rate of the RANKL gene in SaOS2 osteoblastic cells, 1alpha,25(OH)(2)D(3) enhanced in vitro osteoclast formation from peripheral monocytes. Cloning and characterization of the 5'-flanking region of the human RANKL gene revealed that the basic promoter comprises inverted TATA- and CAAT-boxes flanked by RUNX2 binding sites. Both electrophoresis mobility shift assay (EMSA) and transfection studies demonstrated that 1alpha,25(OH)(2)D(3) activated human RANKL promoter through vitamin D responsive elements (VDRE) located at -1584/-1570 by binding VDR and RXRalpha heterodimers in a ligand-dependent manner. The results provide direct evidence that 1alpha,25(OH)(2)D(3) augments osteoclastogenesis by transactivating the human RANKL gene in osteoblastic cells through VDRE.

  8. 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.

  9. 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.

  10. Controllable liquid crystal gratings for an adaptive 2D/3D auto-stereoscopic display

    NASA Astrophysics Data System (ADS)

    Zhang, Y. A.; Jin, T.; He, L. C.; Chu, Z. H.; Guo, T. L.; Zhou, X. T.; Lin, Z. X.

    2017-02-01

    2D/3D switchable, viewpoint controllable and 2D/3D localizable auto-stereoscopic displays based on controllable liquid crystal gratings are proposed in this work. Using the dual-layer staggered structure on the top substrate and bottom substrate as driven electrodes within a liquid crystal cell, the ratio between transmitting region and shielding region can be selectively controlled by the corresponding driving circuit, which indicates that 2D/3D switch and 3D video sources with different disparity images can reveal in the same auto-stereoscopic display system. Furthermore, the controlled region in the liquid crystal gratings presents 3D model while other regions maintain 2D model in the same auto-stereoscopic display by the corresponding driving circuit. This work demonstrates that the controllable liquid crystal gratings have potential applications in the field of auto-stereoscopic display.

  11. 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.

  12. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

    PubMed

    Nykjaer, A; Fyfe, J C; Kozyraki, R; Leheste, J R; Jacobsen, C; Nielsen, M S; Verroust, P J; Aminoff, M; de la Chapelle, A; Moestrup, S K; Ray, R; Gliemann, J; Willnow, T E; Christensen, E I

    2001-11-20

    Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

  13. 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.

  14. A study of corrosion inhibition of steel AISI-SAE 1020 in CO2-brine using surfactant Tween 80

    NASA Astrophysics Data System (ADS)

    Cedeño, M. L.; L, E. Vera; Pineda T, Y.

    2017-01-01

    Surfactant inhibitors also called active surface agents are molecules composed of a polar hydrophilic group and a non-polar hydrophobic group, with characteristics of adsorption on metal surfaces, high efficiency of inhibiting, low price, low toxicity and easy production. In this work, the corrosion inhibition was study by CO2 steel AISI-SAE 1020 with the addition of 0.01M Tween 80 surfactant to a brine solution (3% NaCl). Electrochemical Impedance Spectroscopy and potentiodynamic polarization testing investigated the phenomenon. The results revealed that the surfactant studied acts as an excellent corrosion inhibitor and inhibition efficiency (E%) increases with increasing fluid velocity. The morphology of the steel surface after exposure to the solution of 3% NaCl with and without surfactant indicates the inhibition phenomenon is due to the adsorption of the surfactant molecules, which insulate the surface of the corrosive medium and reduces the attack surficial.

  15. Weldability, machinability and surfacing of commercial duplex stainless steel AISI2205 for marine applications - A recent review.

    PubMed

    Vinoth Jebaraj, A; Ajaykumar, L; Deepak, C R; Aditya, K V V

    2017-05-01

    In the present review, attempts have been made to analyze the metallurgical, mechanical, and corrosion properties of commercial marine alloy duplex stainless steel AISI 2205 with special reference to its weldability, machinability, and surfacing. In the first part, effects of various fusion and solid-state welding processes on joining DSS 2205 with similar and dissimilar metals are addressed. Microstructural changes during the weld cooling cycle such as austenite reformation, partitioning of alloying elements, HAZ transformations, and the intermetallic precipitations are analyzed and compared with the different welding techniques. In the second part, machinability of DSS 2205 is compared with the commercial ASS grades in order to justify the quality of machining. In the third part, the importance of surface quality in a marine exposure is emphasized and the enhancement of surface properties through peening techniques is highlighted. The research gaps and inferences highlighted in this review will be more useful for the fabrications involved in the marine applications.

  16. 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).

  17. 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.

  18. Characteristics and Modification of Non-metallic Inclusions in Titanium-Stabilized AISI 409 Ferritic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Kruger, Dirk; Garbers-Craig, Andrie

    2017-02-01

    This study describes an investigation into the improvement of castability, final surface quality and formability of titanium-stabilized AISI 409 ferritic stainless steel on an industrial scale. Non-metallic inclusions found in this industrially produced stainless steel were first characterized using SEM-EDS analyses through the INCA-Steel software platform. Inclusions were found to consist of a MgO·Al2O3 spinel core, which acted as heterogeneous nucleation site for titanium solubility products. Plant-scale experiments were conducted to either prevent the formation of spinel, or to modify it by calcium treatment. Modification to spherical dual-phase spinel-liquid matrix inclusions was achieved with calcium addition, which eliminated submerged entry nozzle clogging for this grade. Complete modification to homogeneous liquid calcium aluminates was achieved at high levels of dissolved aluminum. A mechanism was suggested to explain the extent of modification achieved.

  19. HVEM studies of the effects of hydrogen on the deformation and fracture of AISI type 316 austenitic stainless steel

    SciTech Connect

    Rozenak, P.; Robertson, I.M.; Birnbaum, H.K. )

    1990-01-01

    The mechanisms of hydrogen embrittlement in AISI type 316 austenitic stainless steel have been investigated by in situ straining in a high-voltage electron microscope (HVEM) equipped with an environmental cell. Hydrogen effects on strain-induced phase transformations, the generation rate and velocity of dislocations, and crack propagation rates were studied. The salient features of the fracture were similar for cracks propagating in vacuum and in hydrogen gas. In each case, [epsilon] and [alpha][prime] martensite formed at the crack; the [epsilon] phase extended ahead of the crack while the [alpha][prime] phase was restricted to high stress regions near the crack tip. The principal effect of hydrogen was to decrease the stress required for dislocation motion, for phase transformation of the austenite, and for crack propagation.

  20. TEM and AES investigations of the natural surface nano-oxide layer of an AISI 316L stainless steel microfibre.

    PubMed

    Ramachandran, Dhanya; Egoavil, Ricardo; Crabbe, Amandine; Hauffman, Tom; Abakumov, Artem; Verbeeck, Johan; Vandendael, Isabelle; Terryn, Herman; Schryvers, Dominique

    2016-11-01

    The chemical composition, nanostructure and electronic structure of nanosized oxide scales naturally formed on the surface of AISI 316L stainless steel microfibres used for strengthening of composite materials have been characterised using a combination of scanning and transmission electron microscopy with energy-dispersive X-ray, electron energy loss and Auger spectroscopy. The analysis reveals the presence of three sublayers within the total surface oxide scale of 5.0-6.7 nm thick: an outer oxide layer rich in a mixture of FeO.Fe2 O3 , an intermediate layer rich in Cr2 O3 with a mixture of FeO.Fe2 O3 and an inner oxide layer rich in nickel.

  1. 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

    2016-12-01

    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.

  2. 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.

  3. Some aspects of thermomechanical fatigue of AISI 304L stainless steel; Part 1: Creep-fatigue damage

    SciTech Connect

    Zauter, R. ); Christ, H.J. . Inst. of Materials Technology); Mughrabi, H. . Inst. for Materials Science)

    1994-02-01

    Thermomechanical fatigue (TMF) tests on the austenitic stainless steel AISI 304L have been conducted under true' plastic-strain control in vacuum. This report considers the damage occurring during TMF loading. It is shown how the temperature interval and the phasing (in phase, out-of-phase) determine the mechanical response and the lifetime of the specimens. If creep-fatigue interaction takes place during in-phase cycling, the damage occurs inside the material, leading creep-induced damage, and no lifetime reduction occurs, even if the material is exposed periodically to temperature in the creep regime. A formula is proposed which allows prediction of the failure mode, depending on whether creep-fatigue damage occurs or not. At a given strain rate, the formula is able to estimate the temperature of transition between pure fatigue and creep-fatigue damage.

  4. 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

  5. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    PubMed

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  6. RUNX2 Mutation Impairs 1α,25-Dihydroxyvitamin D3 mediated Osteoclastogenesis in Dental Follicle Cells

    PubMed Central

    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.

  8. Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells.

    PubMed

    Marchionatti, Ana M; Picotto, Gabriela; Narvaez, Carmen J; Welsh, Joellen; Tolosa de Talamoni, Nori G

    2009-02-01

    Calcitriol or 1,25(OH)(2)D(3) is a negative growth regulator of MCF-7 breast cancer cells. The growth arrest is due to apoptosis activation, which involves mitochondrial disruption. This effect is blunted in vitamin D resistant cells (MCF-7(DRes) cells). Menadione (MEN), a glutathione (GSH)-depleting compound, may potentiate antitumoral effects of anticancer drugs. The aim of this study was to investigate whether MEN enhances cellular responsiveness of MCF-7 cells to 1,25(OH)(2)D(3). Cells were cultured and treated with different concentrations of 1,25(OH)(2)D(3)+/-MEN or vehicle for 96 h. GSH levels and the activity of antioxidant enzymes were determined by spectrophotometry and ROS production by flow cytometry. Both drugs decreased growth and enhanced ROS in MCF-7 cells, obtaining the maximal effects when 1,25(OH)(2)D(3) was combined with MEN (P<0.01 vs. Control and vs. each compound alone). MCF-7(DRes) cells were not responsive to 1,25(OH)(2)D(3), but the cell proliferation was slightly inhibited by the combined treatment. Calcitriol and MEN separately enhanced antioxidant enzyme activities, but when they were used in combination, the effect was more pronounced (P<0.05 vs. Control and vs. each compound alone). MEN, calcitriol and the combined treatment decreased GSH levels (P<0.05 vs. Control). The data indicate that MEN potentiates the effect of 1,25(OH)(2)D(3) on growth arrest in MCF-7 cells by oxidative stress and increases the activities of antioxidant enzymes, probably as a compensatory mechanism.

  9. 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

  10. 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

  11. 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

  12. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.

    PubMed

    Trinko, Joseph R; Land, Benjamin B; Solecki, Wojciech B; Wickham, Robert J; Tellez, Luis A; Maldonado-Aviles, Jaime; de Araujo, Ivan E; Addy, Nii A; DiLeone, Ralph J

    2016-01-01

    The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.

  13. CYP24 inhibition preserves 1α,25-dihydroxyvitamin D3 anti-proliferative signaling in lung cancer cells

    PubMed Central

    Zhang, Qiuhong; Kanterewicz, Beatriz; Buch, Shama; Petkovich, Martin; Parise, Robert; Beumer, Jan; Lin, Yan; Diergaarde, Brenda; Hershberger, Pamela A.

    2012-01-01

    Human lung tumors aberrantly express the 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3)-catabolizing enzyme, CYP24. We hypothesized that CYP24 reduces 1,25(OH)2D3-mediated transcription and allows lung cancer cells to escape its growth-inhibitory action. To test this, H292 lung cancer cells and the CYP24-selective inhibitor CTA091 were utilized. In H292 cells, CTA091 reduces 1,25(OH)2D3 catabolism, significantly increases 1,25(OH)2D3-mediated growth inhibition, and increases 1,25(OH)2D3 effects on induced and repressed genesin gene expression profiling studies. Pathway mapping of repressed genes uncovered cell cycle as a predominant 1,25(OH)2D3 target. In H292 cells, 1,25(OH)2D3 significantly decreases cyclin E2 levels and induces G0/G1 arrest. A broader set of cyclins is down-regulated when 1,25(OH)2D3 is combined with CTA091, and cell cycle arrest further increases. Effects of CTA091 on 1,25(OH)2D3 signaling are vitamin D receptor-dependent. These data provide evidence that CYP24 limits 1,25(OH)2D3 anti-proliferative signaling in cancer cells, and suggest that CTA091 may be beneficial in preserving 1,25(OH)2D3 action in lung cancer. PMID:22386975

  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. Effect of Vitamin D3 on Monocyte Chemoattractant Protein 1 Production in Monocytes and Macrophages

    PubMed Central

    Wang, Yi-Chen; Hsieh, Chong-Chao; Kuo, Hsuan-Fu; Tsai, Ming-Kai; Yang, San-Nan; Kuo, Chang-Hung; Lee, Min-Sheng; Hung, Chih-Hsing

    2014-01-01

    Background Chemokine is important in the initiation and progression of atherosclerosis, the clinically manifest stages of atherosclerosis and acute coronary syndrome. Vitamin D deficiency has been reportedly linked with hypertension and myocardial infarction, as well as other cardiovascular-related diseases, such as congestive heart failure, peripheral vascular disease and atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1) mediates atherosclerosis and other cardiovascular diseases. However, there have been few studies conducted about the role of 1α,25-(OH)2D3 on MCP-1 expression in human monocytes. Methods We investigated the effects of vitamin A, C and 1α,25-(OH)2D3, three common vitamins, to better ascertain MCP-1 expression in human monocyte and also the associated intracellular mechanism. Human monocyte cell line (THP-1 cell) and THP-1 cell-induced macrophage were treated with varying doses of vitamin A, C and 1α,25-(OH)2D3 for 2 hours before LPS stimulation. Supernatants were harvested to measure MCP-1 levels by the enzyme-linked immunosorbent assay (ELISA). The intracellular mechanism about the effects of vitamin A, C and 1α,25-(OH)2D3 on the expression of MCP-1 expression in human monocytes was assessed by western blot. Results We found that Lipopolysaccharides (LPS)-induced MCP-1 production was suppressed by 1α,25-(OH)2D3 in THP-1 cells and THP-1-induced macrophage. Only high concentration of vitamin A and C could reduce LPS-induced MCP-1 production in THP-1-induced macrophage, but not in THP-1 cells. LPS-induced p38 expression in THP-1 cells was suppressed by 1α,25-(OH)2D3. A selective p38 pathway inhibitor SB203580 could also suppress LPS-induced MCP-1 production. However, vitamin D receptor blocking antibody could reverse the suppressive effect of 1α,25-(OH)2D3 on MCP-1 expression. Conclusions These data demonstrate that 1α,25-(OH)2D3 is effective in down-regulating LPS-induced MCP-1. The suppressive effect on MCP-1 may, at least in part

  16. Determination of some physiological factors affecting xylanase production from Trichoderma harzianum 1073 D3.

    PubMed

    Seyis, I; Aksoz, N

    2003-01-01

    In this study, different Trichoderma strains were tested and Trichoderma harzianum 1073 D3 was found to be the most potent xylanase producer. Then some cultural parameters, namely, incubation time, substrate concentration, initial culture pH and temperature were optimized in order to increase xylanase production from Trichoderma harzianum 1073 D3. The optimum incubation time was found to be 13 days. It was concluded that 1% xylan concentration is suitable for high xylanase production rate. The optimum temperature and pH were found to be 30 degrees C and 7, respectively. Also, it was determined that agitation during growth was suitable for efficient production.

  17. Dissecting high from low responders in a vitamin D3 intervention study.

    PubMed

    Saksa, Noora; Neme, Antonio; Ryynänen, Jussi; Uusitupa, Matti; de Mello, Vanessa D F; Voutilainen, Sari; Nurmi, Tarja; Virtanen, Jyrki K; Tuomainen, Tomi-Pekka; Carlberg, Carsten

    2015-04-01

    Vitamin D3 is a pleiotropic signaling molecule that has via activation of the transcription factor vitamin D receptor (VDR) a direct effect on the expression of more than 100 genes. The aim of this study was to find transcriptomic and clinical biomarkers that are most suited to identify vitamin D3 responders within 71 pre-diabetic subjects during a 5-month intervention study (VitDmet). In hematopoietic cells, the genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are known as primary vitamin D targets. We demonstrate that each of these 12 genes carries a conserved VDR binding site within its genomic region and is expressed in human peripheral blood mononuclear cells (PBMCs). The changes in the expression of these genes in human PBMCs at the start and the end of the vitamin D-intervention were systematically correlated with the alteration in the circulating form of vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3). Only 39-44 (55-62%) of the study subjects showed a highly significant response to vitamin D3, i.e., we considered them as "responders". In comparison, we found for 37-53 (52-75%) of the participants that only 12 biochemical and clinical parameters, such as concentrations of parathyroid hormone (PTH) and insulin, or computed values, such as homeostatic model assessment and insulin sensitivity index, show a correlation with serum 25(OH)D3 levels that is as high as that of the selected VDR target genes. All 24 parameters together described the pleiotropic vitamin D response of the VitDmet study subjects. Interestingly, they demonstrated a number of additional correlations that define a network, in which PTH plays the central role. In conclusion, vitamin D3-induced changes in human PBMCs can be described by transcriptomic and serum biomarkers and allow a segregation into high and low responders. This article is part of a Special Issue entitled '17th Vitamin D Workshop' .

  18. 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.

  19. Role of megalin and cubilin in the metabolism of vitamin D(3).

    PubMed

    Kaseda, Ryohei; Hosojima, Michihiro; Sato, Hiroyoshi; Saito, Akihiko

    2011-06-01

    Vitamin D deficiency is associated with various medical conditions including musculoskeletal disorders, infection, metabolic diseases, and cardiovascular disease. Megalin and cubilin, endocytic receptors in proximal tubule cells, are involved in the reabsorption of vitamin D binding protein from glomerular filtrates and the subsequent intracellular conversion of 25-hydroxyvitamin D(3) to biologically active 1α,25-dihydroxyvitamin D(3). Dysfunction of these receptors, which is commonly found in patients with diabetic nephropathy, even at early stages, may explain why vitamin D deficiency is often complicated in these patients. Therapeutic strategies to protect the functions of these receptors from injury could be used to prevent vitamin D deficiency and its related disorders.

  20. Modulation of mouse RANKL gene expression by Runx2 and vitamin D3.

    PubMed

    Kitazawa, Riko; Mori, Kiyoshi; Yamaguchi, Akira; Kondo, Takeshi; Kitazawa, Sohei

    2008-12-01

    The expression of receptor activator of nuclear factor-kappaB ligand (RANKL) is regulated by bone-seeking hormones such as PTH and 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). Runx2, a master gene for osteoblastic differentiation, also modulates osteoclastogenesis by regulating the RANKL gene. To elucidate the mechanism whereby runx2 and 1,25(OH)2D3 regulate RANKL expression, we studied the function of runx2 on the chromatin structure and on the proximal binding sites using osteoblastic cell lines derived from normal (ST2) and runx2-deficient mice (RD-C6). Although the expression of RANKL in the steady-state was higher in RD-C6 than in ST2, 1,25(OH)2D3-treatment of the cells increased it 20-fold in ST2 but only 1.8-fold in RD-C6. Transient transfection studies with proximal RANKL 2kb promoter, runx2 knock-down in ST2, and forced expression of runx2 in RD-C6 all confirmed that runx2 set the steady-state expression of the RANKL gene at a low level, but exerted a positive effect on enhanced transcriptional activity in response to 1,25(OH)2D3. Also, assessment of the acetylation status of the area spanning 40 kb upstream of the basic promoter in ST2 and RD-C6 by ChIP assay revealed that whereas H3 and H4 histone acetylation was detected even in the steady-state in RD-C6, it was detected only with 1,25(OH)2D3 in ST2. In the steady-state, runx2 may suppress RANKL gene by condensing the chromatin structure; however, it exerts a positive effect on 1,25(OH)2D3-induced RANKL transcription when the proximal runx2 sites are accessible. Thus, RANKL expression in stromal/osteoblastic cells is keenly regulated by 1,25(OH)2D3 which transactivates the gene at two different levels

  1. A Map Between d = 3 and d = 4 Spacetime Dimensional k-strings Using Holography

    NASA Astrophysics Data System (ADS)

    Liu, Xiaolong; Stiffler, Kory

    2009-11-01

    We investigate k-string in d=3 and d=4 spacetime dimensions using holography. Exploiting the similarities between two supergravity backgrounds,Maldacena-Nunez background and Maldacena-Nastase background, we map calculations for k-strings between d = 3 and d = 4 spacetime dimensions. The specific calculations investigated are the usual lowest order tension term for the energy of k-strings and the first order, one loop corrections, the Luscher term. The tension term is proportional to L, the length between quark antiquark pairs and the Luscher term is the typical 1/L Coulombic correction.

  2. 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.

  3. 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.

  4. 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

  5. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose

    PubMed Central

    Nazarian, Shaban; Peter, John V St; Boston, Raymond C; Jones, Sidney A; Mariash, Cary N

    2011-01-01

    Vitamin D has in vitro and in vivo effects on β-cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and pre-diabetes with the modified frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennnium to obtain estimates of Acute Insulin Response to Glucose (AIRg), Insulin Sensitivity (SI), and Disposition Index (DI). We found that AIRg decreased (p = 0.011) and insulin sensitivity, expressed as SI, increased (p = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind, sudy the results indicate that orally administered high dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes. PMID:22005267

  6. 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.

  7. Serum calcium level of freshwater snake, Natrix piscator, in response to vitamin D3 administration.

    PubMed

    Srivastav, A K; Srivastav, S P; Srivastav, S K; Swarup, K

    1986-01-01

    The effect of i.m. injection of vitamin D3 (25 IU/100 g b.wt) on serum calcium level was investigated in Natrix piscator. This treatment evokes hypercalcemia at day 3 which progresses up to day 5. Thereafter, a decline was observed in the serum calcium level at day 10 and day 15.

  8. 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

  9. Specific features of provitamin D 3 photoisomerization in a cholesteric liquid crystal

    NASA Astrophysics Data System (ADS)

    Orlova, T. N.; Terenetskaya, I. P.

    2010-04-01

    The method of UV absorption spectroscopy is used to study the influence of the cholesteric pitch on the efficiency of previtamin D (photoisomer of provitamin D 3) cis-trans isomerization in a cholesteric liquid crystal (nematic + optically active dopant + provitamin D 3). It is found that a change in pitch from 14 to 0.364 μm due to an increase in the concentration of an optically active dopant in a wide range (1.6-61 wt %) only slightly reduces the efficiency of the cis-trans isomerization. However, small changes in pitch (0.364-0.368 μm) due to an increase in the provitamin D 3 concentration within the range of 0.07-2.2 wt % significantly increase the efficiency. Reducing in the influence of provitamin D 3 concentration on the cis-trans isomerization efficiency with an increase in mesophase temperature was found in both nematic and cholesteric liquid crystals up to the disappearing of the concentration dependence in the isotropic phase. Altogether, the obtained results indicate the collective character of cis-trans isomerization in liquid crystals due to the ordering of the medium.

  10. The effect of microgravity on 1,25-dihydroxyvitamin d3 signalling in osteoblasts

    NASA Astrophysics Data System (ADS)

    Coenegrachts, Lieve; Stockmans, Ingrid; Segers, Ilse; Bouillon, Roger; Carmeliet, Geert

    2007-09-01

    Microgravity encountered during space flight induces bone loss, as seen in both humans and rats. This type of bone loss is mainly caused by decreased bone formation due to reduced osteoblast proliferation and differentiation. Yet, the molecular alterations induced by microgravity during osteoblast differentiation are still enigmatic. Therefore, the effect of microgravity on the intracellular signalling pathway of 1,25-dihydroxyvita-min D3 was investigated during the Odissea Mission. The ligand 1,25-dihydroxyvitamin D3 interacts with the vitamin D receptor (VDR) and this complex binds to vitamin D response elements (VDRE) in the promoter region of target genes to stimulate or suppress gene transcription. To investigate the interaction of liganded VDR with VDRE, the mouse osteoblastic cell line, MC3T3, was stable transfected with a construct containing multiple VDREs of the rat osteocalcin promoter fused to growth hormone as reporter gene. Treatment of these transfectants with 1,25-dihydroxyvitamin D3 resulted in a time- and dose-dependent release of growth hormone in the culture medium. Space flight cultures responded to 1,25-dihydroxyvitamin D3 treatment with increased growth hormone production that was comparable with the induction observed in ground cultures. No 1g centrifuge was available during the space flight. These data indicate that microgravity for 5 days did not alter the interaction of VDR with the osteocalcin VDRE or the subsequent gene transcription.

  11. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.

    PubMed

    Deevi, Ravi K; McClements, Jane; McCloskey, Karen D; Fatehullah, Aliya; Tkocz, Dorota; Javadi, Arman; Higginson, Robyn; Marsh Durban, Victoria; Jansen, Marnix; Clarke, Alan; Loughrey, Maurice B; Campbell, Frederick C

    2016-08-02

    Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3,theactive form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta). Suppression of AP genes initiated a spatiotemporal cascade of mitotic spindle misorientation, apical membrane misalignment and aberrant epithelial configuration. Collectively, these events promoted "Swiss cheese-like" cribriform morphology (CM) comprising multiple abnormal "back to back" lumens surrounded by atypical stratified epithelium, in 3D colorectal gland models. Intestinal cancer driven purely by PTEN-deficiency in transgenic mice developed CM and in human CRC, CM associated with PTEN and PRKCZ readouts. Treatment of PTEN-deficient 3D cultures with 1,25(OH)2D3 upregulated PTEN, rapidly activated CDC42 and PRKCZ, corrected mitotic spindle alignment and suppressed CM development. Conversely, mutationally-activated KRAS blocked1,25(OH)2D3 rescue of glandular architecture. We conclude that 1,25(OH)2D3 upregulates AP signalling to reverse CM in a KRAS wild type (wt), clinically predictive CRC model system. Vitamin D could be developed as therapy to suppress inception or progression of a subset of colorectal tumors.

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

    PubMed

    Byrdwell, William C

    2009-03-25

    A method for analysis of vitamin D(3) in commonly fortified foods and in fish, which contains endogenous vitamin D(3), 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 separation and use of an internal standard (vitamin D(2)) from AOAC 2002.05 to produce a method that was applicable to a variety of food samples. Results for skim milk, orange juice, breakfast cereal, salmon, a diluted USP reference standard (vitamin D(3) in peanut oil), and processed cheese are presented. Results indicated that UV detection was adequate in most cases, but the absence of interfering species must be determined in each food by mass spectrometry. Selected ion monitoring (SIM) atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) was shown to produce statistically indistinguishable results compared to UV detection for the skim milk, orange juice, multigrain cereal, and salmon samples. The processed cheese exhibited interferences that precluded quantification of vitamin D(3) by UV detection, and therefore, only SIM APCI-MS data for that sample were valid.

  13. 25(OH)D3 Levels Relative to Muscle Strength and Maximum Oxygen Uptake in Athletes

    PubMed Central

    Zagrodna, Aleksandra; Dziubek, Wioletta; Pietraszewski, Bogdan; Ochmann, Bartosz; Słowińska – Lisowska, Małgorzata

    2016-01-01

    Abstract Vitamin D is mainly known for its effects on the bone and calcium metabolism. The discovery of Vitamin D receptors in many extraskeletal cells suggests that it may also play a significant role in other organs and systems. The aim of our study was to assess the relationship between 25(OH)D3 levels, lower limb isokinetic strength and maximum oxygen uptake in well-trained professional football players. We enrolled 43 Polish premier league soccer players. The mean age was 22.7±5.3 years. Our study showed decreased serum 25(OH)D3 levels in 74.4% of the professional players. The results also demonstrated a lack of statistically significant correlation between 25(OH)D3 levels and lower limb muscle strength with the exception of peak torque of the left knee extensors at an angular velocity of 150°/s (r=0.41). No significant correlations were found between hand grip strength and maximum oxygen uptake. Based on our study we concluded that in well-trained professional soccer players, there was no correlation between serum levels of 25(OH)D3 and muscle strength or maximum oxygen uptake. PMID:28149343

  14. Vitamin E induces regular structure and stability of human insulin, more intense than vitamin D3.

    PubMed

    Soleymani, Hossein; Saboury, Ali A; Moosavi-Movahedi, Ali A; Rahmani, Fatemeh; Maleki, Javad; Yousefinejad, Saeid; Maghami, Parvaneh

    2016-12-01

    Changes in human environment and lifestyle over the last century have caused a dramatic increase in the occurrence of diabetes. Research of past decades illustrated that vitamin D and E have a key role in the improvement of diabetes by reducing oxidative stress, protein glycosylation, insulin resistance and also improving beta cell function. Binding properties and conformational changes of human insulin upon interaction with vitamins D3 and E (α-tocopherol) were investigated by spectroscopy, differential scanning calorimetry (DSC) and molecular dynamic simulation. Tyrosine fluorescence quenching studies indicates changes in the human insulin conformation in the presence of vitamins. Binding constants of vitamins D3 and E for human insulin were determined to be 2.7 and 1.5 (×10(-5)M(-1)) and the corresponding average numbers of binding sites were determined to be 1.3 and 1.2, respectively. Far- and near-UV circular dichroism studies showed that vitamin E can significantly change the secondary and tertiary structures of human insulin via an increase in the content of α-helix structure. Results of DSC showed that both vitamins D3 and E stabilize the structure of human insulin. Molecular dynamic simulation results indicated that vitamin D3 decreases the helical and strand structural contents of human insulin, but vitamin E stabilizes more regular secondary structures such as helical and strand structural contents as shown by experimental results.

  15. Effect of mixed micellar lipid on the absorption of cholesterol and vitamin D3 into lymph

    PubMed Central

    Thompson, Gilbert R.; Ockner, Robert K.; Isselbacher, Kurt J.

    1969-01-01

    The absorption of endogenous cholesterol, labeled with tracer doses of cholesterol 14C or cholesterol-3H and of near physiological doses of vitamin D3-3H was studied in rats with cannulated intestinal lymphatics. The effects of administering mixed micellar solutions of fatty acid, monoglyceride, and bile salt on the absorption of these labeled sterols was determined. It was observed that the specific activity of free cholesterol and the amounts of vitamin D3 appearing in lymph were significantly increased during the intraduodenal administration of mixed micellar solutions of either linoleic or palmitic acid, in contrast to control rats receiving a micellar solution of taurocholate. These increases were related linearly to the lymph triglyceride level. In addition it was observed that when the linoleic acid solution was administered there was a more marked increase in the ratio of the specific activities of free and esterified cholesterol in lymph than with either the palmitic acid or taurocholate solutions. Additional studies in rats with intact lymphatics showed that the uptake of labeled cholesterol and vitamin D3 from the intestinal lumen into the wall was similar whether the sterols were administered in taurocholate or in mixed micellar solution. These findings suggest that mixed micellar lipid increased the rate of appearance of labeled free cholesterol and vitamin D3 in lymph by enhancing their transport out of the intestinal mucosa, rather than by an effect on uptake. PMID:4303790

  16. 26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Section 411(d)(6) protected benefits. 1.411(d)-3... has at least 5 consecutive 1-year breaks in service and whose number of consecutive 1-year breaks in... section 411(d)(6) protected benefits, as of January 1, 2008, for participants who have fewer than 5...

  17. 26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Section 411(d)(6) protected benefits. 1.411(d)-3... has at least 5 consecutive 1-year breaks in service and whose number of consecutive 1-year breaks in... section 411(d)(6) protected benefits, as of January 1, 2008, for participants who have fewer than 5...

  18. 26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Section 411(d)(6) protected benefits. 1.411(d)-3... has at least 5 consecutive 1-year breaks in service and whose number of consecutive 1-year breaks in... section 411(d)(6) protected benefits, as of January 1, 2008, for participants who have fewer than 5...

  19. 26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Section 411(d)(6) protected benefits. 1.411(d)-3... has at least 5 consecutive 1-year breaks in service and whose number of consecutive 1-year breaks in... section 411(d)(6) protected benefits, as of January 1, 2008, for participants who have fewer than 5...

  20. 26 CFR 31.3406(d)-3 - Special 30-day rules for certain reportable payments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Special 30-day rules for certain reportable... COLLECTION OF INCOME TAX AT SOURCE Collection of Income Tax at Source § 31.3406(d)-3 Special 30-day rules for... certification of notified payee underreporting) within 30 days after the establishment or acquisition...

  1. 26 CFR 31.3406(d)-3 - Special 30-day rules for certain reportable payments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Special 30-day rules for certain reportable... COLLECTION OF INCOME TAX AT SOURCE Collection of Income Tax at Source § 31.3406(d)-3 Special 30-day rules for... certification of notified payee underreporting) within 30 days after the establishment or acquisition...

  2. 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

  3. 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...

  4. HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.

    PubMed

    Tan, Yi; Li, Meiling; Cox, Sandra; Davis, Marilyn K; Tawfik, Ossama; Paria, Bibhash C; Das, Sanjoy K

    2004-01-01

    Stromal cell polyploidy is a unique phenomenon that occurs during uterine decidualization following embryo implantation, although the developmental mechanism still remains elusive. The general consensus is that the aberrant expression and altered functional activity of cell cycle regulatory molecules at two particular checkpoints G1 to S and G2 to M in the cell cycle play an important role in the development of cellular polyploidy. Despite the compelling evidence of intrinsic cell cycle alteration, it has been implicated that the development of cellular polyploidy may be controlled by specific actions of extracellular growth regulators. Here we show a novel role for heparin-binding EGF-like growth factor (HB-EGF) in the developmental process of stromal cell polyploidy in mice. HB-EGF, which is one of the earliest known molecular mediators of implantation in mice and humans, promotes stromal cell polyploidy via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3 attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell polyploidy in vitro and in vivo. Collectively, the results demonstrate that the regulation of stromal cell polyploidy and decidualization induced by HB-EGF depend on cyclin D3 induction.

  5. Transgenic tobacco plants overexpressing the Nicta; CycD3; 4 gene demonstrate accelerated growth rates.

    PubMed

    Guo, Jia; Wang, Myeong Hyeon

    2008-07-31

    D-type cyclins control the onset of cell division and the response to extracellular signals during the G1 phase. In this study, we transformed a D-type cyclin gene, Nicta;CycD3;4, from Nicotiana tabacum using an Agrobacterium-mediated method. A predicted 1.1 kb cyclin gene was present in all of the transgenic plants, but not in wild-type. Northern analyses showed that the expression level of the Nicta;CycD3;4 gene in all of the transgenic plants was strong when compared to the wild-type plants, suggesting that Nicta;CycD3;4 gene driven by the CaMV 35S promoter was being overexpressed. Our results revealed that transgenic plants overexpressing Nicta;CycD3;4 had an accelerated growth rate when compared to wild-type plants, and that the transgenic plants exhibited a smaller cell size and a decreased cell population in young leaves when compared to wild-type plants.

  6. Dynamical D4-D8 and D3-D7 branes in supergravity

    SciTech Connect

    Binetruy, Pierre; Sasaki, Misao; Uzawa, Kunihito

    2009-07-15

    We present a class of dynamical solutions for intersecting D4-D8 and D3-D7 brane systems in ten-dimensional type IIA and IIB supergravity. We discuss if these solutions can be recovered in lower-dimensional effective theories for the warped compactification of a general p-brane system. It is found that an effective p+1-dimensional description is not possible in general due to the entanglement of the transverse coordinates and the p+1-dimensional coordinates in the metric components. For the D4-D8 brane system, the dynamical solutions reduces to a static warped AdS{sub 6}xS{sup 4} geometry in a certain spacetime region. For the D3-D7 brane system, we find a dynamical solution whose metric form is similar to that of a D3-brane solution. The main difference is the existence of a nontrivial dilaton configuration in the D3-D7 solution. Then we discuss cosmology of these solutions. We find that they behave like a Kasner-type cosmological solution at {tau}{yields}{infinity}, while it reduces to a warped static solution at {tau}{yields}0, where {tau} is the cosmic time.

  7. 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.

  8. Jetting tool

    SciTech Connect

    Szarka, D.D.; Schwegman, S.L.

    1991-07-09

    This patent describes an apparatus for hydraulically jetting a well tool disposed in a well, the well tool having a sliding member. It comprises positioner means for operably engaging the sliding member of the well tool; and a jetting means, connected at a rotatable connection to the positioner means so that the jetting means is rotatable relative to the positioner means and the well tool, for hydraulically jetting the well tool as the jetting means is rotated relative thereto.

  9. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets.

    PubMed

    Thacher, Tom D; Fischer, Philip R; Obadofin, Michael O; Levine, Michael A; Singh, Ravinder J; Pettifor, John M

    2010-09-01

    Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D(2) and vitamin D(3). Our objective was to compare the metabolism of vitamins D(2) and D(3) in rachitic and control children. We administered an oral single dose of vitamin D(2) or D(3) of 1.25 mg to 49 Nigerian children--28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25-dihydroxyvitamin D [1,25(OH)(2)D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25-dihydroxyvitamin D [24,25(OH)(2)D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D(2) and D(3) in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)(2)D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D(2) and D(3) administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)(2)D (19 ± 28 and 16 ± 38 pg/mL after vitamin D(2) and D(3) administration, respectively). We conclude that in the short term, vitamins D(2) and D(3) similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)(2)D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral

  10. 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

  11. 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

  12. 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

  13. Molecular characterization and phylogenetic analysis of full-genome HBV subgenotype D3 sequences from Serbia.

    PubMed

    Stanojević, Boban; Osiowy, Carla; Schaefer, Stephan; Bojović, Ksenija; Blagojević, Jelena; Nešić, Milica; Yamashita, Shunichi; Stamenković, Gorana

    2011-08-01

    Hepatitis B virus (HBV) is classified into 8 genotypes with distinct geographical distribution. Genotype D (HBV/D) has the widest distribution area and is comprised of 7 subgenotypes. Subgenotypes D1, D2 and D3 appear worldwide, while D4-D7 have a more restricted distribution. Within the Mediterranean area, HBV/D and subgenotype D3 are the most prevalent. The purpose of this study was to characterize the full genome of Serbian HBV/D3 isolates by comparison and phylogenetic analysis with HBV/D3 sequences (66 samples) found in GeneBank/DDBJ databases from different parts of the world. Isolates were obtained from three patients diagnosed with chronic hepatitis B (HBsAg+). All three isolates have two very rare nucleotide substitutions, A929T and T150A, which indicate the same ancestor. Phylogenetic analysis of HBV/D3 genome sequences throughout the world follows an ethno-geographical origin of isolates with rare exceptions, which could be explained by human travelling and migration. The geographically close but ethnically different Serbian and Italian isolates clustered in the same subnode, and on a common branch with strains from Northern Canada. To test the apparently close HBV phylogenetic relationship between completely separated patients from Serbia and Northern Canada we analyzed in depth a 440 bp region of the HBsAg from Canadian (n=73) and Serbian (n=70) isolates. The constructed parsimony tree revealed that strains from Serbia and Northern Canada fell along the same branch which indicates independent evolution within regions of each country. Considering that HBsAg sequence has limited variability for phylogenetic analyses, our hypothesis needs further confirmation with more HBV complete genome sequences.

  14. Effects of supplemental vitamin D3 on feed intake, carcass characteristics, tenderness, and muscle properties of beef steers.

    PubMed

    Karges, K; Brooks, J C; Gill, D R; Breazile, J E; Owens, F N; Morgan, J B

    2001-11-01

    Research was conducted to determine the effects of supplemental dietary vitamin D3 on DMI, carcass traits, Warner Bratzler shear (WBS) force, calpastatin activity, plasma minerals, pH (0, 3, 12, and 24 h after slaughter), water-holding capacity (WHC), and sensory characteristics of three muscles. Pre-slaughter vitamin D3 treatments included no supplemental vitamin D3, 6 x 106 IU (MIU) of vitamin D3 for 4 d, or 6 MIU of vitamin D3 for 6 d. Cattle were slaughtered and carcasses were chilled for 48 h before removal of steaks from the longissimus, gluteus medius, and biceps femoris muscles. Steaks were aged at 2 degrees C for 7, 14, or 21 d before cooking to a final internal temperature of 70 degrees C for WBS and sensory panel analysis. Dry matter intake was lower for steers supplemented with vitamin D3 for 4 or 6 d. Live and carcass weights were lower (P < 0.05) in steers supplemented with vitamin D3. Supplementing 6 MIU/6 d of vitamin D3 decreased (P < 0.05) WBS values of gluteus steaks (pooled over aging times). Longissimus steaks from steers supplemented with vitamin D3 for 6 d had lower (P < 0.05) WBS force values than these steaks from control steers or steers fed vitamin D3 for 4 d at 7 d postmortem. Biceps femoris steaks from steers receiving vitamin D3 for 4 d had higher WBS values than steaks from control steers at 14 and 21 d postmortem. Feeding vitamin D3 at 6 MIU for 6 d decreased (P < 0.05) the percentage of steaks that had WBS values > or = 3.86 kg for all steaks. Feeding vitamin D3 had no effect on palatability traits evaluated by trained panelists. Blood Ca concentrations were greater (P < 0.05) when vitamin D3 was fed and with increased vitamin D3 feeding time. Feeding vitamin D3 for 6 d (vs 4 d) delayed pH decline for all muscle types after 0, 3, and 12 h postmortem. Water-holding capacity was increased (P > 0.02) after 0 h, 24 h, and 21 d postmortem when vitamin D3 was fed and was greater at 0 and 24 h if vitamin D3 was fed for 6 d rather than 4 d

  15. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells*

    PubMed Central

    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

    2016-01-01

    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

  16. 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

  17. Activated vitamin D3 and pro-activated vitamin D3 attenuate induction of permanent changes caused by neonatal estrogen exposure in the mouse vagina.

    PubMed

    Matsuda, Manabu; Kurosaki, Keiko; Okamura, Naomichi

    2014-01-01

    Exposure of mice to a high dose of estrogens including diethylstilbestrol (DES) during the neonatal period modifies the developmental plan of the genital tract, which leads to various permanent changes in physiology, morphology and gene expression. These changes include development of an abnormal vaginal epithelium lined with hyperplastic mucinous cells accompanied by Tff1 gene expression in mice. Here, the influence of vitamin D on the direct effect of estrogen on the developing mouse vagina was examined. The mid-vagina of neonatal mice was cultured in a serum-free medium containing estradiol-17β (E2) and various concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) ex vivo and then was transplanted under the renal capsule of ovariectomized host mice for 35 days. Exposure to E2 alone caused the vaginal tissue to develop estrogen-independent epithelial hyperplasia and to express TFF1 mRNA, while addition of a low nanomolar amount of 1,25(OH)2D added at the same time as E2 to the culture medium attenuated the effects of estrogen. Expression of vitamin D receptor was also evident in the neonatal mouse vagina. Interestingly, addition of 25-hydroxyvitamin D3, a pro-activated form of vitamin D, at the micromolar level was found to be potent in disrupting the developmental effects of E2, while cholecalciferol was not at least at the dose examined. Correspondingly, expression of Cyp27B1, a kidney-specific 25-hydroxyvitamin D hydroxylase, was evident in the neonatal mouse vagina when examined by RT-PCR. In addition, simultaneous administration of 1,25(OH)2D successfully attenuated DES-induced ovary-independent hyperplasia in the vagina in neonatal mice in vivo. Thus, manipulation of vitamin D influenced the harmful effects of estrogens on mouse vaginal development.

  18. 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 effect. The microscopic study of the deposits indicates that the material deposited at the optimum processing parameters is free from surface and bulk defects. The estimated material properties are found to be at par with conventional processed material. This feasibility study proved that the micro-plasma deposition can be used for the generation of surfaces and multi-featured material deposition. It paved a way for the application of the process in die/mold repairs.

  19. In vitro response of human peripheral blood mononuclear cells to AISI 316L austenitic stainless steel subjected to nitriding and collagen coating treatments.

    PubMed

    Stio, Maria; Martinesi, Maria; Treves, Cristina; Borgioli, Francesca

    2015-02-01

    Surface modification treatments can be used to improve the biocompatibility of austenitic stainless steels. In the present research two different modifications of AISI 316L stainless steel were considered, low temperature nitriding and collagen-I coating, applied as single treatment or in conjunction. Low temperature nitriding produced modified surface layers consisting mainly of S phase, which enhanced corrosion resistance in PBS solution. Biocompatibility was assessed using human peripheral blood mononuclear cells (PBMC) in culture. Proliferation, lactate dehydrogenase (LDH) levels, release of cytokines (TNF-α, IL-1β, IL-12, IL-10), secretion of metalloproteinase (MMP)-9 and its inhibitor TIMP-1, and the gelatinolytic activity of MMP-9 were determined. While the 48-h incubation of PBMC with all the sample types did not negatively influence cell proliferation, LDH and MMP-9 levels, suggesting therefore a good biocompatibility, the release of the pro-inflammatory cytokines was always remarkable when compared to that of control cells. However, in the presence of the nitrided and collagen coated samples, the release of the pro-inflammatory cytokine IL-1β decreased, while that of the anti-inflammatory cytokine IL-10 increased, in comparison with the untreated AISI 316L samples. Our results suggest that some biological parameters were ameliorated by these surface treatments of AISI 316L.

  20. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    PubMed

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  1. Vitamin D3 and its metabolites have no role in calcium and phosphorus metabolism in Tilapia mossambica.

    PubMed

    Rao, D S; Raghuramulu, N

    1999-01-01

    The physiological function of vitamin D in fishes still remains uncertain. Earlier we observed no relationship between vitamin D3 content of several freshwater fishes and their calcemic/phosphatemic status and bone mineral content. In the present study the effects of vitamin D3 and its metabolites, 25-hydroxy vitamin D3 (25-OH-D3) and 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3], administration on serum calcium-phosphorus levels, intestinal calcium absorption, whole-body calcium-phosphorus uptake, and gill calcium binding protein (CaBP) activity in the freshwater fish, Tilapia mossambica (Tilapia) was examined. It was observed that vitamin D3 and its metabolites could alter neither serum calcium-phosphorus levels nor intestinal calcium absorption and gill CaBP activity in fish at various doses. Further, the whole-body uptake of labelled calcium and phosphorus was also unaffected by vitamin D3/1,25-(OH)2D3 at different levels and/or at various lengths of time. Thus these studies indicate that unlike in terrestrial vertebrates, vitamin D3 or its metabolites are not needed for calcium-phosphorus homeostasis in fish.

  2. 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.

  3. 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.

  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. Peripubertal Vitamin D3 Deficiency Delays Puberty and Disrupts the Estrous Cycle in Adult Female Mice1

    PubMed Central

    Dicken, Cary L.; Israel, Davelene D.; Davis, Joe B.; Sun, Yan; Shu, Jun; Hardin, John; Neal-Perry, Genevieve

    2012-01-01

    ABSTRACT The mechanism(s) by which vitamin D3 regulates female reproduction is minimally understood. We tested the hypothesis that peripubertal vitamin D3 deficiency disrupts hypothalamic-pituitary-ovarian physiology. To test this hypothesis, we used wild-type mice and Cyp27b1 (the rate-limiting enzyme in the synthesis of 1,25-dihydroxyvitamin D3) null mice to study the effect of vitamin D3 deficiency on puberty and reproductive physiology. At the time of weaning, mice were randomized to a vitamin D3-replete or -deficient diet supplemented with calcium. We assessed the age of vaginal opening and first estrus (puberty markers), gonadotropin levels, ovarian histology, ovarian responsiveness to exogenous gonadotropins, and estrous cyclicity. Peripubertal vitamin D3 deficiency significantly delayed vaginal opening without affecting the number of GnRH-immunopositive neurons or estradiol-negative feedback on gonadotropin levels during diestrus. Young adult females maintained on a vitamin D3-deficient diet after puberty had arrested follicular development and prolonged estrous cycles characterized by extended periods of diestrus. Ovaries of vitamin D3-deficient Cyp27b1 null mice responded to exogenous gonadotropins and deposited significantly more oocytes into the oviducts than mice maintained on a vitamin D3-replete diet. Estrous cycles were restored when vitamin D3-deficient Cyp27b1 null young adult females were transferred to a vitamin D3-replete diet. This study is the first to demonstrate that peripubertal vitamin D3 sufficiency is important for an appropriately timed pubertal transition and maintenance of normal female reproductive physiology. These data suggest vitamin D3 is a key regulator of neuroendocrine and ovarian physiology. PMID:22572998

  6. Comparative therapeutic effects of orally administered 1,25-dihydroxyvitamin D3 and 1alpha-hydroxyvitamin D3 on type-1 diabetes in non-obese diabetic mice fed a normal-calcaemic diet

    PubMed Central

    Driver, J P; Foreman, O; Mathieu, C; van Etten, E; Serreze, D V

    2008-01-01

    Frequent injections of the hormonal form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D3 (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+ forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca. PMID:17983444

  7. Tool Carrier

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Tool organizer accommodates a selection of hand tools on a waist or thigh belt or alternately on wall, work bench, or car trunk mountings. Tool caddy is widely used by industrial maintenance personnel, TV technicians, mechanics, artists, draftsmen, hobbyists and homeowners. Its innovative feature is rows of flexible vinyl "fingers" like the bristles of a hairbrush which mesh together to hold the tool securely in place yet allow easy insertion or withdrawal. Product is no longer commercially available.

  8. Melting temperature of water: DFT-based molecular dynamics simulations with D3 dispersion correction

    NASA Astrophysics Data System (ADS)

    Seitsonen, Ari P.; Bryk, Taras

    2016-11-01

    Extensive ab initio simulations of ice-water basal interface at seven temperatures in the range 250-400 K were performed in NVT and NPT ensembles with a collection of 389 water molecules in order to estimate the melting point of ice from direct liquid-solid two-phase coexistence. Density functional theory with the BLYP (Becke-Lee-Yang-Parr) exchange-correlation functional and the D3 dispersion correction were used in the expression of total energy. Analysis of density profiles and the evolution of the total potential, or Kohn-Sham plus D3, energy in the simulations at different temperatures resulted in an estimate for melting temperature of ice of 325 K.

  9. High-resistance liquid-crystal lens array for rotatable 2D/3D autostereoscopic display.

    PubMed

    Chang, Yu-Cheng; Jen, Tai-Hsiang; Ting, Chih-Hung; Huang, Yi-Pai

    2014-02-10

    A 2D/3D switchable and rotatable autostereoscopic display using a high-resistance liquid-crystal (Hi-R LC) lens array is investigated in this paper. Using high-resistance layers in an LC cell, a gradient electric-field distribution can be formed, which can provide a better lens-like shape of the refractive-index distribution. The advantages of the Hi-R LC lens array are its 2D/3D switchability, rotatability (in the horizontal and vertical directions), low driving voltage (~2 volts) and fast response (~0.6 second). In addition, the Hi-R LC lens array requires only a very simple fabrication process.

  10. Recent advances in the development of dopamine D3 receptor antagonists: a medicinal chemistry perspective.

    PubMed

    Micheli, Fabrizio

    2011-07-04

    Dopamine (DA) D(3) receptor antagonism might play a significant role in different therapeutic areas. A high number of preclinical studies on DA D(3) receptor antagonists have shown efficacy in animal models of Parkinson's disease, schizophrenia and drug dependence. This Review covers the activities of medicinal chemists in this field over the last ten years towards the identification of truly selective compounds. Both primary and patent literature is reviewed here. Since the original discoveries, a clear trend towards the optimization of the developability properties of the new scaffold has clearly emerged with time, from both academic and industrial researchers. Examples of advanced leads from academia and industry are described. The latest potential therapeutic applications are reported too.

  11. 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.

  12. A specific LC/ESI-MS/MS method for determination of 25-hydroxyvitamin D3 in neonatal dried blood spots containing a potential interfering metabolite, 3-epi-25-hydroxyvitamin D3.

    PubMed

    Higashi, Tatsuya; Suzuki, Masahiro; Hanai, Junji; Inagaki, Shinsuke; Min, Jun Zhe; Shimada, Kazutake; Toyo'oka, Toshimasa

    2011-04-01

    Vitamin D deficiency in an infant is associated with a wide range of adverse health outcomes in later life. A method for the quantification of 25-hydroxyvitamin D(3) [25(OH)D(3), the best-established indicator of vitamin D status] in neonatal dried blood spots (DBSs) using LC/ESI-MS/MS has been developed and validated. The method employed two steps of derivatization, a Diels-Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione followed by acetylation, to enhance the detectability of 25(OH)D(3) in ESI-MS/MS and to separate 25(OH)D(3) from 3-epi-25-hydroxyvitamin D(3) [3-epi-25(OH)D(3)], a potent interfering metabolite. 25(OH)D(3) was extracted from two DBS punches (3  mm in diameter, equivalent to 5.3  μL of whole blood), purified using an Oasis HLB(®) cartridge, and subjected to derivatization prior to analysis with LC/ESI-MS/MS. 25-Hydroxyvitamin D(4) was used as the internal standard. This method was reproducible (intra- and inter-assay RSDs, <6.9%) and accurate (analytical recovery, 95.2-102.7%), and the LOQ was 3.0  ng/mL. The developed method enabled specific quantification of 25(OH)D(3) in neonatal DBSs and detection of vitamin D deficiency without interference from 3-epi-25(OH)D(3).

  13. Regulation of expression of 1,25D3-MARRS/ERp57/PDIA3 in rat IEC-6 cells by TGF beta and 1,25(OH)2D3.

    PubMed

    Rohe, Benjamin; Safford, Susan E; Nemere, Ilka; Farach-Carson, Mary C

    2007-02-01

    We examined the transcriptional regulation of expression of the redox-sensitive Membrane-Associated-Rapid Response, Steroid-binding (1,25D(3)-MARRS) protein specific for 1,25(OH)(2)D(3) in a rat small intestinal cell line, IEC-6, that demonstrates rapid responses to 1,25(OH)(2)D(3). 1,25D(3)-MARRS binds and is activated by 1,25(OH)(2)D(3), but is not itself up-regulated by treatment with 1,25(OH)(2)D(3), nor is there a Vitamin D response element (VDRE) in its proximal promoter. We previously reported that transforming growth factor beta (TGFbeta) increased steady state levels of 1,25D(3)-MARRS transcript and protein approximately two-fold [Rohe B, Safford SE, Nemere I, Farach-Carson, MC. Identification and characterization of 1,25D(3)-membrane-associated rapid response, steroid (1,25D(3)-MARRS)-binding protein in rat IEC-6 cells. Steroids 2005;70:458-63]. To determine if this up-regulation could be attributed to the function of a highly conserved consensus smad 3 binding element present in the proximal promoter of the 1,25D(3)-MARRS gene, we created a promoter-reporter [SEAP] construct that was responsive to TGFbeta (200 pM). Deletion or mutation of the smad 3 element greatly reduced the response of the 1,25D(3)-MARRS promoter to TGFbeta. Subsequent studies found that the smad 3 response element is bound by a protein found in the IEC-6 nuclear extract, most likely smad 3. Interestingly, although 1,25(OH)(2)D(3) alone did not increase expression of the 1,25D(3)-MARRS promoter-reporter, co-treatment of transfected IEC-6 cells with 1,25(OH)(2)D(3) and TGFbeta shifted the dose-response curve to a lower effective concentration (100 pM peptide). We conclude that TGFbeta is a transcriptional regulator of 1,25D(3)-MARRS expression via a functional smad 3 element and that cross-talk with non-classical 1,25(OH)(2)D(3)-stimulated pathways occurs. The findings have broad implications for redox-sensitive signaling phenomena including those that regulate phosphate transport in

  14. 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.

  15. 25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

    PubMed Central

    Peng, Xinjian; Hawthorne, Michael; Vaishnav, Avani; St-Arnaud, René

    2009-01-01

    Despite the role of vitamin D3 endocrine system in prevention of mammary gland transformation in animal models, use of 1,25(OH)2D3 in clinical settings is precluded due to its toxicity in vivo. Therefore much effort has been placed in developing relatively non-toxic vitamin D analogs. Recently, with the discovery of the expression of 25-hydroxy vitamin D3 1α-hydroxylase (CYP27B1) in multiple extrarenal organs, the functional role of prohormone, 25-hydroxyvitamin D3 [25(OH)D3], has been redefined. Since 25(OH)D3 does not cause hypercalcemia and maintains relative high concentration in serum, it is possible that the prohormone can be converted to active hormone in mammary epithelial cells to provide chemopreventive effects. In the present study, we evaluated its functional significance using mouse mammary organ culture (MMOC) system. We first showed that 25(OH)D3 1α-hydroxylase is extensively expressed in mammary ductal epithelial cells at both protein and mRNA levels, which is a prerequisite for 25(OH)D3 to function in an autocrine/paracrine manner. However, we also observed that clotrimazol (1α-hydroxylase inhibitor) enhanced 25(OH)D3 -induced CYP24 expression in breast cancer cells. In mammary glands derived from 1α-hydroxylase knockout mice, 25(OH)D3 treatment in organ culture significantly induced CYP24 expression, indicating a potential direct effect of 25(OH)D3. In MMOC, 100–250 nM 25(OH)D3 suppressed both ovarian hormone-dependent and -independent mammary precancerous lesions (induced by DMBA) by more than 50%, while the active hormone 1,25(OH)2D3 (positive control) at 100 nM suppressed alveolar lesions by more than 80%. The inactive vitamin D3 (negative control) at 100 nM suppressed alveolar lesions by only 20% (P > 0.05). We found that 25(OH)D3 inhibits DMBA-induced mammary alveolar lesions (MAL) in a stage-specific manner: 25(OH)D3 mainly inhibits the promotion stage of lesion formation. We conclude that 25(OH)D3 could serve as a non-toxic natural

  16. 25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture.

    PubMed

    Peng, Xinjian; Hawthorne, Michael; Vaishnav, Avani; St-Arnaud, René; Mehta, Rajendra G

    2009-01-01

    Despite the role of vitamin D(3) endocrine system in prevention of mammary gland transformation in animal models, use of 1,25(OH)(2)D(3 )in clinical settings is precluded due to its toxicity in vivo. Therefore much effort has been placed in developing relatively non-toxic vitamin D analogs. Recently, with the discovery of the expression of 25-hydroxy vitamin D(3) 1alpha-hydroxylase (CYP27B1) in multiple extrarenal organs, the functional role of prohormone, 25-hydroxyvitamin D(3) [25(OH)D(3)], has been redefined. Since 25(OH)D(3) does not cause hypercalcemia and maintains relative high concentration in serum, it is possible that the prohormone can be converted to active hormone in mammary epithelial cells to provide chemopreventive effects. In the present study, we evaluated its functional significance using mouse mammary organ culture (MMOC) system. We first showed that 25(OH)D(3) 1alpha-hydroxylase is extensively expressed in mammary ductal epithelial cells at both protein and mRNA levels, which is a prerequisite for 25(OH)D(3) to function in an autocrine/paracrine manner. However, we also observed that clotrimazol (1alpha-hydroxylase inhibitor) enhanced 25(OH)D(3) -induced CYP24 expression in breast cancer cells. In mammary glands derived from 1alpha-hydroxylase knockout mice, 25(OH)D(3) treatment in organ culture significantly induced CYP24 expression, indicating a potential direct effect of 25(OH)D(3). In MMOC, 100-250 nM 25(OH)D(3) suppressed both ovarian hormone-dependent and -independent mammary precancerous lesions (induced by DMBA) by more than 50%, while the active hormone 1,25(OH)(2)D(3) (positive control) at 100 nM suppressed alveolar lesions by more than 80%. The inactive vitamin D(3) (negative control) at 100 nM suppressed alveolar lesions by only 20% (P>0.05). We found that 25(OH)D(3) inhibits DMBA-induced mammary alveolar lesions (MAL) in a stage-specific manner: 25(OH)D(3) mainly inhibits the promotion stage of lesion formation. We conclude that 25

  17. Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment.

    PubMed

    Yanagihara, Makoto; Takeda, Kiminobu; Tanabe, Hiroshi; Abe, Shinya; Ishizaki, Hiroshi

    2007-01-01

    In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect.

  18. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype

    PubMed Central

    Deevi, Ravi K.; McClements, Jane; McCloskey, Karen D.; Fatehullah, Aliya; Tkocz, Dorota; Javadi, Arman; Higginson, Robyn; Durban, Victoria Marsh; Jansen, Marnix; Loughrey, Maurice B.; Campbell, Frederick C.

    2016-01-01

    Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3, the active form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta). Suppression of AP genes initiated a spatiotemporal cascade of mitotic spindle misorientation, apical membrane misalignment and aberrant epithelial configuration. Collectively, these events promoted “Swiss cheese-like” cribriform morphology (CM) comprising multiple abnormal “back to back” lumens surrounded by atypical stratified epithelium, in 3D colorectal gland models. Intestinal cancer driven purely by PTEN-deficiency in transgenic mice developed CM and in human CRC, CM associated with PTEN and PRKCZ readouts. Treatment of PTEN-deficient 3D cultures with 1,25(OH)2D3 upregulated PTEN, rapidly activated CDC42 and PRKCZ, corrected mitotic spindle alignment and suppressed CM development. Conversely, mutationally-activated KRAS blocked 1,25(OH)2D3 rescue of glandular architecture. We conclude that 1,25(OH)2D3 upregulates AP signalling to reverse CM in a KRAS wild type (wt), clinically predictive CRC model system. Vitamin D could be developed as therapy to suppress inception or progression of a subset of colorectal tumors. PMID:27119498

  19. 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

  20. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    PubMed

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3-not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D3. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D3 provide equal efficacy and safety profiles.

  1. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose.

    PubMed

    Nazarian, Shaban; St Peter, John V; Boston, Raymond C; Jones, Sidney A; Mariash, Cary N

    2011-11-01

    Vitamin D has in vitro and in vivo effects on β cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with the onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high-dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and prediabetes with the modified, frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennium (purchased from Dr. Richard Bergman, Keck School of Medicine of USC, Los Angeles, Calif) to obtain estimates of acute insulin response to glucose (AIRg), insulin sensitivity (SI), and disposition index (DI). We found that AIRg decreased (P = 0.011) and SI increased (P = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind study, the results indicate that orally administered high-dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high-dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes.

  2. 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.

  3. Polymeric-lens-embedded 2D/3D switchable display with dramatically reduced crosstalk.

    PubMed

    Zhu, Ruidong; Xu, Su; Hong, Qi; Wu, Shin-Tson; Lee, Chiayu; Yang, Chih-Ming; Lo, Chang-Cheng; Lien, Alan

    2014-03-01

    A two-dimensional/three-dimensional (2D/3D) display system is presented based on a twisted-nematic cell integrated polymeric microlens array. This device structure has the advantages of fast response time and low operation voltage. The crosstalk of the system is analyzed in detail and two approaches are proposed to reduce the crosstalk: a double lens system and the prism approach. Illuminance distribution analysis proves these two approaches can dramatically reduce crosstalk, thus improving image quality.

  4. Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3

    SciTech Connect

    Sun Maoyun; Wei Yuanyan; Yao Luyang; Xie Jianhui; Chen Xiaoning; Wang Hanzhou; Jiang Jianhai; Gu Jianxin . E-mail: jxgu@shmu.edu.cn

    2006-02-03

    Cyclin D3, like cyclin D1 and D2 isoforms, is a crucial component of the core cell cycle machinery in mammalian cells. It also exhibits its unique properties in many other physiological processes. In the present study, using yeast two-hybrid screening, we identified ERK3, an atypical mitogen-activated protein kinase (MAPK), as a cyclin D3 binding partner. GST pull-down assays showed that cyclin D3 interacts directly and specifically with ERK3 in vitro. The binding of cyclin D3 and ERK3 was further confirmed in vivo by co-immunoprecipitation assay and confocal microscopic analysis. Moreover, carboxy-terminal extension of ERK3 was responsible for its association with intact cyclin D3. These findings further expand distinct roles of cyclin D3 and suggest the potential activity of ERK3 in cell proliferation.

  5. 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.

  6. Examination of structurally selective derivatization of vitamin D(3) analogues by electrospray mass spectrometry.

    PubMed

    Weiskopf, A S; Vouros, P; Cunniff, J; Binderup, E; Björkling, F; Binderup, L; White, M C; Posner, G H

    2001-01-01

    The structural specificity of vitamin D derivatization by PTAD (4-phenyl-1,2,4-triazoline-3,5-dione) was probed using synthetic analogues and ion trap mass spectrometry. EB 1089, a vitamin D(3) analogue which contains a second site for Diels--Alder cycloaddition on its side-chain, allowed the examination of derivatization modes and comparisons of ion fragment structures. The origins of a PTAD-vitamin D(3) ion fragment, commonly used in metabolite characterization and quantitation of vitamin D(3) analogues (m/z 314), were established; ion trap mass spectrometry revealed that the PTAD comprises a portion of this diagnostic fragment, and is not lost by a retro-Diels--Alder step. Furthermore, the unique structure of the EB 1089 side-chain also permits facile determination of its side-chain metabolism. Use of PTAD derivatization and detection of metabolite-specific ion fragments identify hydroxylation at the end of the EB 1089 sidechain. It is believed that the results from these studies provide a clearer understanding of the mass spectrometry of triazolinedione derivatives, not only in the specific case of EB