SRC Residual fuel oils

DOEpatents

Tewari, Krishna C.; Foster, Edward P.

1985-01-01

Coal solids (SRC) and distillate oils are combined to afford single-phase blends of residual oils which have utility as fuel oils substitutes. The components are combined on the basis of their respective polarities, that is, on the basis of their heteroatom content, to assure complete solubilization of SRC. The resulting composition is a fuel oil blend which retains its stability and homogeneity over the long term.

SRC-I demonstration plant analytical laboratory methods manual. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klusaritz, M.L.; Tewari, K.C.; Tiedge, W.F.

1983-03-01

This manual is a compilation of analytical procedures required for operation of a Solvent-Refined Coal (SRC-I) demonstration or commercial plant. Each method reproduced in full includes a detailed procedure, a list of equipment and reagents, safety precautions, and, where possible, a precision statement. Procedures for the laboratory's environmental and industrial hygiene modules are not included. Required American Society for Testing and Materials (ASTM) methods are cited, and ICRC's suggested modifications to these methods for handling coal-derived products are provided.

Aging of SRC liquids

NASA Astrophysics Data System (ADS)

Hara, T.; Jones, L.; Tewari, K. C.; Li, N. C.

1981-02-01

The viscosity of SRC-LL liquid increases when subjected to accelerated aging by bubbling oxygen in the presence of copper strip at 62°C. Precipitates are formed and can be separated from the aged liquid by Soxhlet extraction with pentane. A 30-70 blend of SRC-I with SRC-LL was subjected to oxygen aging in the absence of copper, and the viscosity increased dramatically after 6 days at 62°. The content of preasphaltene and its molecular size increase with time of aging, accompanied by decrease of asphaltene and pentane-soluble contents. For the preasphaltene fraction on aging, gel permeation chromatography shows formation of larger particles. ESR experiments show that with oxygen aging, spin concentration in the preasphaltene fraction decreases. Perhaps some semiquinone, together with di- and tri-substituted phenoxy radicals, generated by oxygen aging of the coal liquid, interact with the free radicals already present in coal to yield larger particles and reduce free radical concentration. We are currently using the very high-field (600-MHz) NMR spectrometer at Mellon Institute to determine changes in structural parameters before and after aging of SRC-II and its chromatographically separated fractions.

Filtration of micron-sized particles for coal liquids: carbonaceous precoats. [5 refs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodgers, B.R.

Carbonaceous precoats, such as bituminous coal and char from hydrocarbonization, are shown to be effective, inexpensive substitutes for traditional diatomaceous earth materials, both at laboratory-scale and bench-scale. Model equations are developed for filtration of Solvent Refined Coal-Unfiltered Oil (SRC-UFO).

AIR EMISSIONS FROM COMBUSTION OF SOLVENT REFINED COAL

EPA Science Inventory

The report gives details of a Solvent Refined Coal (SRC) combustion test at Georgia Power Company's Plant Mitchell, March, May, and June 1977. Flue gas samples were collected for modified EPA Level 1 analysis; analytical results are reported. Air emissions from the combustion of ...

Solvent refined coal reactor quench system

DOEpatents

Thorogood, Robert M.

1983-01-01

There is described an improved SRC reactor quench system using a condensed product which is recycled to the reactor and provides cooling by evaporation. In the process, the second and subsequent reactors of a series of reactors are cooled by the addition of a light oil fraction which provides cooling by evaporation in the reactor. The vaporized quench liquid is recondensed from the reactor outlet vapor stream.

Solvent refined coal reactor quench system

DOEpatents

Thorogood, R.M.

1983-11-08

There is described an improved SRC reactor quench system using a condensed product which is recycled to the reactor and provides cooling by evaporation. In the process, the second and subsequent reactors of a series of reactors are cooled by the addition of a light oil fraction which provides cooling by evaporation in the reactor. The vaporized quench liquid is recondensed from the reactor outlet vapor stream. 1 fig.

Integrated report on the toxicological mitigation of coal liquids by hydrotreatment and other processes. [Petroleum and coal-derived products

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerin, M.R.; Griest, W.H.; Ho, C.H.

1986-06-01

Research here on the toxicological properties of coal-derived liquids focuses on characterizing the refining process and refined products. Principle attention is given to the potential tumorigenicity of coal-derived fuels and to the identification of means to further reduce tumorigenicity should this be found necessary. Hydrotreatment is studied most extensively because it will be almost certainly required to produce commercial products and because it is likely to also greatly reduce tumorigenic activity relative to that of crude coal-liquid feedstocks. This report presents the results of a lifetime C3H mouse skin tumorigenicity assay of an H-Coal series of oils and considers themore » relationships between tumorigenicity, chemistry, and processing. Lifetime assay results are reported for an H-Coal syncrude mode light oil/heavy oil blend, a low severity hydrotreatment product, a high severity hydrotreatment product, a naphtha reformate, a heating oil, a petroleum-derived reformate, and a petroleum derived heating oil. Data are compared with those for an earlier study of an SRC-II blend and products of its hydrotreatment. Adequate data are presented to allow an independent qualitative assessment of the conclusions while statistical evaluation of the data is being completed. The report also documents the physical and chemical properties of the oils tested. 33 refs., 14 figs., 53 tabs.« less

Evaluation of electrostatic precipitator during SRC combustion tests. Final task report Apr--Aug 1977

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, G.B.; Barrett, W.J.

1978-07-01

The report deals with the evaluation of an electrostatic precipitator (ESP) and associated environmental factors during the burning of solvent refined coal (SRC) in a boiler at Plant Mitchell of the Georgia Power Company. The effort was part of an overall study of the use of SRC in a full-scale electric power plant. Results of a performance evaluation of the ESP are reported and interpreted. Samples of stack emissions were collected with a Source Assessment Sampling System (SASS) train for chemical analysis: results of the analysis are to be reported later.

Modules for estimating solid waste from fossil-fuel technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crowther, M.A.; Thode, H.C. Jr.; Morris, S.C.

1980-10-01

Solid waste has become a subject of increasing concern to energy industries for several reasons. Increasingly stringent air and water pollution regulations result in a larger fraction of residuals in the form of solid wastes. Control technologies, particularly flue gas desulfurization, can multiply the amount of waste. With the renewed emphasis on coal utilization and the likelihood of oil shale development, increased amounts of solid waste will be produced. In the past, solid waste residuals used for environmental assessment have tended only to include total quantities generated. To look at environmental impacts, however, data on the composition of the solidmore » wastes are required. Computer modules for calculating the quantities and composition of solid waste from major fossil fuel technologies were therefore developed and are described in this report. Six modules have been produced covering physical coal cleaning, conventional coal combustion with flue gas desulfurization, atmospheric fluidized-bed combustion, coal gasification using the Lurgi process, coal liquefaction using the SRC-II process, and oil shale retorting. Total quantities of each solid waste stream are computed together with the major components and a number of trace elements and radionuclides.« less

Chemical analysis and biological testing of materials from the EDS coal liquefaction process: a status report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Later, D.W.; Pelroy, R.A.; Wilson, B.W.

1984-05-01

Representative process materials were obtained from the EDS pilot plant for chemical and biological analyses. These materials were characterized for biological activity and chemical composition using a microbial mutagenicity assay and chromatographic and mass spectrometric analytical techniques. The two highest boiling distillation cuts, as well as process solvent (PS) obtained from the bottoms recycle mode operation, were tested for initiation of mouse skin tumorigenicity. All three materials were active; the crude 800/sup 0 +/F cut was substantially more potent than the crude bottoms recycle PS or 750 to 800/sup 0/F distillate cut. Results from chemical analyses showed the EDS materials,more » in general, to be more highly alkylated and have higher hydroaromatic content than analogous SRC II process materials (no in-line process hydrogenation) used for comparison. In the microbial mutagenicity assays the N-PAC fractions showed greater activity than did the aliphatic hydrocarbon, hydroxy-PAH, or PAH fractions, although mutagenicity was detected in certain PAH fractions by a modified version of the standard microbial mutagenicity assay. Mutagenic activities for the EDS materials were lower, overall, than those for the corresponding materials from the SRC II process. The EDS materials produced under different operational modes had distinguishable differences in both their chemical constituency and biological activity. The primary differences between the EDS materials studied here and their SRC II counterparts used for comparison are most likely attributable to the incorporation of catalytic hydrogenation in the EDS process. 27 references, 28 figures, 27 tables.« less

Coal Technology Program progress report, March 1976

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

Shakedown tests of the bench-scale hydrocarbonization system were successfully completed. Wyodak coal was fed to the reactor at a rate of 9.9 lb/hr where it was hydrocarbonized at 1050/sup 0/F under 20-atm hydrogen pressure. Laboratory results including settling tests, bench-scale settling tests, and sample ageing tests were continued. Two of ten compounds tested with the laboratory-scale apparatus were effective in increasing settling rates of solids in Solvent Refined Coal unfiltered oil, but bench-scale tests failed to show any improvements in the settling rate over the untreated SRC-UFO. Analytical chemistry efforts involved the removal and concentration of organic components in by-productmore » waters from fossil fuel conversion processes. A sephadex gel is being used to achieve hydrophilic-lipophilic separations in organic mixtures as a step in the analysis of fossil fuel related materials. Engineering Evaluations of the Synthiol and Hydrocarbonization Processes continued with the Synthiol process flow diagrams, heat and material balances, and utilities requirements being completed. Inspection techniques were developed for wear- and process-resistant coatings. Orders were placed for the Incoloy 800 tubing and a smaller quantity of Inconel 600 tubing for the tube matrix in the coal-fueled MIUS fluidized bed. An engineering feasibility review of General Atomic's proposal to ERDA for a bench-scale test program on thermochemical water splitting for hydrogen production was completed. (auth)« less

40 CFR 60.43Da - Standards for sulfur dioxide (SO2).

Code of Federal Regulations, 2014 CFR

2014-07-01

... into the atmosphere from any affected facility which combusts solid solvent refined coal (SRC-I) any... (1.2 lb/MWh) net energy output; or (iii) 3 percent of the potential combustion concentration (97...

40 CFR 60.43Da - Standards for sulfur dioxide (SO2).

Code of Federal Regulations, 2013 CFR

2013-07-01

... into the atmosphere from any affected facility which combusts solid solvent refined coal (SRC-I) any... (1.2 lb/MWh) net energy output; or (iii) 3 percent of the potential combustion concentration (97...

Chemistry and structure of coal-derived asphaltenes, Phase III. Quarterly progress report, January--March 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yen, T. F.

1978-01-01

The solubility limits of Synthoil and PAMCO asphaltenes have been measured as a function of Hildebrand solubility parameters and hydrogen bonding. Solvents with moderate hydrogen bonding capacity such as dioxane, ethyl benzoate and dibutyl phthalate were found to be most effective in dissolving asphaltenes over the widest range of solubility parameters. VPO molecular weight studies of coal liquid derived carbenes, as a function of concentration in the solvent THF, indicate that these fractions are more strongly self-associated than the corresponding asphaltenes, and generally afford high infinite dilution number average molecular weights: Synthoil, 861; HRI H-Coal, 1156; Cat. Inc. SRC, 1228;more » PAMCO SRC, 1054. The variable ESR temperature dependence of the spin intensity for a Synthoil asphaltene-I/sub 2/ charge transfer followed a 1/T (Curie--Weiss) dependence over the temperature range from 25/sup 0/ to -114/sup 0/C suggesting that independent, non-interacting donor and acceptor doublets were formed. Weight percent OH values, determined from 'H NMR analysis of silylated asphaltenes, were found to provide a reasonably linear correlation with the absorbance of the monomeric OH infrared stretching bands of the asphaltenes.« less

Effects of inhalation exposure to SRC-II heavy and middle distillates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Springer, D.L.; Miller, R.A.; Weimer, W.C.

1984-11-01

To expand the data base on potential health effects of coal liquefaction materials, we have performed studies with both solvent refined coal (SRC)-II heavy distillate (HD) and middle distillate (MD). Weight gain for exposed animals was less than that of controls and was dose-related, ranging from no significant difference for animals in the low-exposure group to failure to gain in the high-dose animals. Liver weights increased significantly over controls, and thymus weights decreased for animals sacrificed at 5 and 13 weeks. After both exposure periods, there were significant treatment-related decreases in erythrocyte parameters and in certain types of white bloodmore » cells (WBC). Bone marrow cellularity, and numbers of megakaryocytes consistently decreased, suggesting that bone marrow is a target tissue for high-boiling coal liquids. Microscopic evaluation of tissue indicated exposure-related changes is listed. In contrast to the reported mutagenic and carcinogenic effects observed for the high-boiling coal liquids, middle-boiling-range materials lacked such activity in these assays. These data demonstrate a great deal of similarity in the kinds of effects observed following exposure to middle- and high-boiling-range coal liquids. However, the significance of changes in organ weights and peripheral blood parameters are not always readily apparent following a subchronic study. Because of this, we exposed animals to HD in a manner similar to that for the subchronic experiment and have followed these animals throughout their lives for the development of adverse effects such as reduced longevity and the appearance of tumors. Results from this study will be available for mice in FY 1985 and for rats in FY 1986.« less

Catalytic combustion of coal-derived liquids

NASA Technical Reports Server (NTRS)

Bulzan, D. L.; Tacina, R. R.

1981-01-01

A noble metal catalytic reactor was tested with three grades of SRC 2 coal derived liquids, naphtha, middle distillate, and a blend of three parts middle distillate to one part heavy distillate. A petroleum derived number 2 diesel fuel was also tested to provide a direct comparison. The catalytic reactor was tested at inlet temperatures from 600 to 800 K, reference velocities from 10 to 20 m/s, lean fuel air ratios, and a pressure of 3 x 10 to the 5th power Pa. Compared to the diesel, the naphtha gave slightly better combustion efficiency, the middle distillate was almost identical, and the middle heavy blend was slightly poorer. The coal derived liquid fuels contained from 0.58 to 0.95 percent nitrogen by weight. Conversion of fuel nitrogen to NOx was approximately 75 percent for all three grades of the coal derived liquids.

Plan for radionuclide tracer studies of the residence time distribution in the Wilsonville dissolver and preheater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jolley, R.L.; Begovich, J.M.; Brashear, H.R.

1983-12-01

Stimulus-response measurements using radiotracers to measure residence time distribution (RTD) and hydrodynamic parameters for the preheaters and dissolvers at the Ft. Lewis Solvent Refined Coal (SRC) and the Exxon Donor Solvent (EDS) coal conversion pilot plants are reviewed. A plan is also presented for a series of radioactive tracer studies proposed for the Advanced Coal Liquefaction Facility at Wilsonville, Alabama, to measure the RTD for the preheater and dissolvers in the SRC-I mode. The tracer for the gas phase will be /sup 133/Xe, and /sup 198/Au (on carbonized resin or as an aqueous colloidal suspension) will be used as themore » slurry tracer. Four experimental phases are recommended for the RTD tracer studies: (1) preheater; (2) dissolver with 100% takeoff; (3) dissolver with 100% takeoff and solids withdrawal; and (4) dissolver with 50% takeoff. Eighteen gas-tracer and 22 liquid-tracer injections are projected to accomplish the four experimental phases. Two to four tracer injections are projected for preliminary tests to ensure the capability of safe injection of the radiotracers and the collection of statistically significant data. A complete projected cost and time schedule is provided, including procurement of necessary components, preparation of the radiotracers, assembly and testing of tracer injection apparatus and detection systems, onsite work and tracer injections, laboratory experimentation, data analysis, and report writing.« less

Enthalpy measurement of coal-derived liquids. Combined quarterly technical progress reports, April-June 1979 and July-September 1979. [Effect of association

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kidnay, A.J.; Yesavage, V.F.

1979-01-01

Enthalpy measurements on a coal-derived naphtha and middle distillate, both produced by the SRC-II process, were made using flow calorimetry. The accuracy of the measurements, as reported by Omid, was within +- 1% of the measured enthalpy differences, ..delta..H. Experimental data for the naphtha were obtained over a pressure range of 100-300 psia and temperatures from 148/sup 0/ to 456/sup 0/F. The middle distillate enthalpy measurements were made in the pressure and temperature ranges of 130 to 1000 psia, and 157/sup 0/ to 675/sup 0/F, respectively. The methods of prediction of enthalpy developed for petroleum fractions were unsatisfactory when appliedmore » to the above data. A negative bias was observed in the predicted enthalpy values for several of the coal-liquids. Based on these results, it was theorized that the high experimental enthalpy values for coal-liquids were due to an energy of association attributed, primarily, to hydrogen-bonding effects. The petroleum-fraction enthalpy correlations were then tested on the experimental data for pure compounds, both associating and non-associating. The predicted values compared very well with the experimental results for non-associating model compounds. However, for associating model compounds the predicted enthalpy values were considerably lower than their experimental data. This served to confirm the basic premise that the high experimental enthalpy values, for model compounds and coal liquids, were a direct consequence of an energy of association attributed, primarily, to hydrogen-bonding effects.« less

Low NOx heavy fuel combustor concept program, phase 1

NASA Technical Reports Server (NTRS)

Cutrone, M. B.

1981-01-01

Combustion tests were completed with seven concepts, including three rich/lean concepts, three lean/lean concepts, and one catalytic combustor concept. Testing was conducted with ERBS petroleum distillate, petroleum residual, and SRC-II coal-derived liquid fuels over a range of operating conditions for the 12:1 pressure ratio General Electric MS7001E heavy-duty turbine. Blends of ERBS and SRC-II fuels were used to vary fuel properties over a wide range. In addition, pyridine was added to the ERBS and residual fuels to vary nitrogen level while holding other fuel properties constant. Test results indicate that low levels of NOx and fuel-bound nitrogen conversion can be achieved with the rich/lean combustor concepts for fuels with nitrogen contents up to 1.0% by weight. Multinozzle rich/lean Concept 2 demonstrated dry low Nox emissions within 10-15% of the EPA New Source Performance Standards goals for SRC-II fuel, with yields of approximately 15%, while meeting program goals for combustion efficiency, pressure drop, and exhaust gas temperature profile. Similar, if not superior, potential was demonstrated by Concept 3, which is a promising rich/lean combustor design.

Summary of synfuel characterization and combustion studies

NASA Technical Reports Server (NTRS)

Schultz, D. F.

1983-01-01

Combustion component research studies aimed at evolving environmentally acceptable approaches for burning coal derived fuels for ground power applications were performed at the NASA Lewis Research Center under a program titled the ""Critical Research and Support Technology Program'' (CRT). The work was funded by the Department of Energy and was performed in four tasks. This report summarizes these tasks which have all been previously reported. In addition some previously unreported data from Task 4 is also presented. The first, Task 1 consisted of a literature survey aimed at determining the properties of synthetic fuels. This was followed by a computer modeling effort, Task 2, to predict the exhaust emissions resulting from burning coal liquids by various combustion techniques such as lean and rich-lean combustion. The computer predictions were then compared to the results of a flame tube rig, Task 3, in which the fuel properties were varied to simulate coal liquids. Two actual SRC 2 coal liquids were tested in this flame tube task.

4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B

PubMed Central

Zhang, Hongqiao; Forman, Henry Jay

2015-01-01

Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src. In the canonical pathway Src activation is initiated by dephosphorylation of pTyr530 followed by conformational change that causes Src auto-phosphorylation at Tyr419 and its activation. HNE increased Src activation in both dose- and time-dependent manner, while it also increased Src phosphorylation at Tyr530 (pTyr530 Src), suggesting that HNE activated Src via a non-canonical mechanism. Protein tyrosine phosphatase 1B inhibitor (539741), at concentrations that increased basal pTyr530 Src, also increased basal Src activity and significantly reduced HNE-mediated Src activation. The EGFR inhibitor, AG1478, and EGFR silencing, abrogated HNE-mediated EGFR activation and inhibited basal and HNE-induced Src activity. In addition, AG1478 also eliminated the increase of basal Src activation by a PTP1B inhibitor. Taken together these data suggest that HNE can activate Src partly through a non-canonical pathway involving activation of EGFR and inhibition of PTP1B. PMID:26453921

Src- and Fyn-dependent apical membrane trafficking events control endothelial lumen formation during vascular tube morphogenesis.

PubMed

Kim, Dae Joong; Norden, Pieter R; Salvador, Jocelynda; Barry, David M; Bowers, Stephanie L K; Cleaver, Ondine; Davis, George E

2017-01-01

Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases. Functional blockade of Src kinases completely blocks EC lumen and tube formation, whether this occurs during vasculogenic tube assembly or angiogenic sprouting events. Multiple Src kinases participate in this apical membrane formation process and siRNA suppression of Src, Fyn and Yes, but not Lyn, blocks EC lumen formation. We also demonstrate strong apical targeting of Src-GFP and Fyn-GFP fusion proteins and increasing their expression enhances lumen formation. Finally, we show that Src- and Fyn-associated vacuoles track and fuse along a subapically polarized microtubule cytoskeleton, which is highly acetylated. These vacuoles generate the apical luminal membrane in a stereotypically polarized, perinuclear position. Overall, our study identifies a critical role for Src kinases in creating and decorating the EC apical membrane surface during early and late stages of lumen and tube formation, a central event in the molecular control of vascular morphogenesis.

Stimulus-response correspondence effect as a function of temporal overlap between relevant and irrelevant information processing.

PubMed

Wang, Dong-Yuan Debbie; Richard, F Dan; Ray, Brittany

2016-01-01

The stimulus-response correspondence (SRC) effect refers to advantages in performance when stimulus and response correspond in dimensions or features, even if the common features are irrelevant to the task. Previous research indicated that the SRC effect depends on the temporal course of stimulus information processing. The current study investigated how the temporal overlap between relevant and irrelevant stimulus processing influences the SRC effect. In this experiment, the irrelevant stimulus (a previously associated tone) preceded the relevant stimulus (a coloured rectangle). The irrelevant and relevant stimuli onset asynchrony was varied to manipulate the temporal overlap between the irrelevant and relevant stimuli processing. Results indicated that the SRC effect size varied as a quadratic function of the temporal overlap between the relevant stimulus and irrelevant stimulus. This finding extends previous experimental observations that the SRC effect size varies in an increasing or decreasing function with reaction time. The current study demonstrated a quadratic function between effect size and the temporal overlap.

Effect of addition of semi refined carrageenan on mechanical characteristics of gum arabic edible film

NASA Astrophysics Data System (ADS)

Setyorini, D.; Nurcahyani, P. R.

2016-04-01

Currently the seaweed is processed flour and Semi Refined Carraagenan (SRC). However, total production is small, but both of these products have a high value and are used in a wide variety of products such as cosmetics, processed foods, medicines, and edible film. The aim of this study were (1) to determine the effect of SRC on mechanical characteristics of edible film, (2) to determine the best edible film which added by SRC with different concentration. The edible film added by SRC flour which divided into three concentrations of SRC. There are 1.5%; 3%; and 4.5% of SRC, then added 3% glycerol and 0.6% arabic gum. The mechanical properties of the film measured by a universal testing machine Orientec Co. Ltd., while the water vapor permeability measured by the gravimetric method dessicant modified. The experimental design used was completely randomized design with a further test of Duncan. The result show SRC concentration differences affect the elongation breaking point and tensile strength. But not significant effect on the thickness, yield strength and the modulus of elasticity. The best edible film is edible film with the addition of SRC 4.5%.

Attentional Modulation of Emotional Conflict Processing with Flanker Tasks

PubMed Central

Zhou, Pingyan; Liu, Xun

2013-01-01

Emotion processing has been shown to acquire priority by biasing allocation of attentional resources. Aversive images or fearful expressions are processed quickly and automatically. Many existing findings suggested that processing of emotional information was pre-attentive, largely immune from attentional control. Other studies argued that attention gated the processing of emotion. To tackle this controversy, the current study examined whether and to what degrees attention modulated processing of emotion using a stimulus-response-compatibility (SRC) paradigm. We conducted two flanker experiments using color scale faces in neutral expressions or gray scale faces in emotional expressions. We found SRC effects for all three dimensions (color, gender, and emotion) and SRC effects were larger when the conflicts were task relevant than when they were task irrelevant, suggesting that conflict processing of emotion was modulated by attention, similar to those of color and face identity (gender). However, task modulation on color SRC effect was significantly greater than that on gender or emotion SRC effect, indicating that processing of salient information was modulated by attention to a lesser degree than processing of non-emotional stimuli. We proposed that emotion processing can be influenced by attentional control, but at the same time salience of emotional information may bias toward bottom-up processing, rendering less top-down modulation than that on non-emotional stimuli. PMID:23544155

Attentional modulation of emotional conflict processing with flanker tasks.

PubMed

Zhou, Pingyan; Liu, Xun

2013-01-01

Emotion processing has been shown to acquire priority by biasing allocation of attentional resources. Aversive images or fearful expressions are processed quickly and automatically. Many existing findings suggested that processing of emotional information was pre-attentive, largely immune from attentional control. Other studies argued that attention gated the processing of emotion. To tackle this controversy, the current study examined whether and to what degrees attention modulated processing of emotion using a stimulus-response-compatibility (SRC) paradigm. We conducted two flanker experiments using color scale faces in neutral expressions or gray scale faces in emotional expressions. We found SRC effects for all three dimensions (color, gender, and emotion) and SRC effects were larger when the conflicts were task relevant than when they were task irrelevant, suggesting that conflict processing of emotion was modulated by attention, similar to those of color and face identity (gender). However, task modulation on color SRC effect was significantly greater than that on gender or emotion SRC effect, indicating that processing of salient information was modulated by attention to a lesser degree than processing of non-emotional stimuli. We proposed that emotion processing can be influenced by attentional control, but at the same time salience of emotional information may bias toward bottom-up processing, rendering less top-down modulation than that on non-emotional stimuli.

Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced Oncogenesis.

PubMed

Nakayama, Yuji; Soeda, Shuhei; Ikeuchi, Masayoshi; Kakae, Keiko; Yamaguchi, Naoto

2017-04-12

v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src-expressing cells showed that cytokinesis failure is caused by cleavage furrow regression. Microscopic analysis revealed that v-Src induces delocalization of cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is one of the causes of chromosome instability; however, tetraploid cells can be eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription coactivator YAP, which is downstream of the Hippo pathway and its nuclear exclusion is critical in the tetraploidy checkpoint. We also discuss the relationship between v-Src-induced chromosome instability and growth suppression in v-Src-induced oncogenesis.

Deposition and material response from Mach 0.3 burner rig combustion of SRC 2 fuels

NASA Technical Reports Server (NTRS)

Santoro, G. J.; Kohl, F. J.; Stearns, C. A.; Fryburg, G. C.; Johnson, J. R.

1980-01-01

Collectors at 1173K (900 C) were exposed to the combustion products of a Mach 0.3 burner rig fueled with various industrial turbine liquid fuels from solvent refined coals. Four fuels were employed: a naphtha, a light oil, a wash solvent and a mid-heavy distillate blend. The response of four superalloys (IN-100, U 700, IN 792 and M-509) to exposure to the combustion gases from the SRC-2 naphtha and resultant deposits was also determined. The SRC-2 fuel analysis and insights obtained during the combustion experience are discussed. Particular problems encountered were fuel instability and reactions of the fuel with hardware components. The major metallic elements which contributed to the deposits were copper, iron, chromium, calcium, aluminum, nickel, silicon, titanium, zinc, and sodium. The deposits were found to be mainly metal oxides. An equilibrium thermodynamic analysis was employed to predict the chemical composition of the deposits. The agreement between the predicted and observed compounds was excellent. No hot corrosion was observed. This was expected because the deposits contained very little sodium or potassium and consisted mainly of the unreactive oxides. However, the amounts of deposits formed indicated that fouling is a potential problem with the use of these fuels.

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

PubMed

Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

2017-09-19

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Low NO sub x heavy fuel combustor concept program. Phase 1A: Combustion technology generation coal gas fuels

NASA Technical Reports Server (NTRS)

Sherlock, T. P.

1982-01-01

Combustion tests of two scaled burners using actual coal gas from a 25 ton/day fluidized bed coal gasifier are described. The two combustor configurations studied were a ceramic lined, staged rich/lean burner and an integral, all metal multiannual swirl burner (MASB). The tests were conducted over a range of temperature and pressures representative of current industrial combustion turbine inlet conditions. Tests on the rich lean burner were conducted at three levels of product gas heating values: 104, 197 and 254 btu/scf. Corresponding levels of NOx emissions were 5, 20 and 70 ppmv. Nitrogen was added to the fuel in the form of ammonia, and conversion efficiencies of fuel nitrogen to NOx were on the order of 4 percent to 12 percent, which is somewhat lower than the 14 percent to 18 percent conversion efficiency when src-2 liquid fuel was used. The MASB was tested only on medium btu gas (220 to 270 btu/scf), and produced approximately 80 ppmv NOx at rated engine conditions. Both burners operated similarly on actual coal gas and erbs fuel, and all heating values tested can be successfully burned in current machines.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soeda, Shuhei; Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp; Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414

Src-family tyrosine kinases are aberrantly activated in cancers, and this activation is associated with malignant tumor progression. v-Src, encoded by the v-src transforming gene of the Rous sarcoma virus, is a mutant variant of the cellular proto-oncogene c-Src. Although investigations with temperature sensitive mutants of v-Src have shown that v-Src induces many oncogenic processes, the effects on cell division are unknown. Here, we show that v-Src inhibits cellular proliferation of HCT116, HeLa S3 and NIH3T3 cells. Flow cytometry analysis indicated that inducible expression of v-Src results in an accumulation of 4N cells. Time-lapse analysis revealed that binucleation is induced throughmore » the inhibition of cytokinesis, a final step of cell division. The localization of Mklp1, which is essential for cytokinesis, to the spindle midzone is inhibited in v-Src-expressing cells. Intriguingly, Aurora B, which regulates Mklp1 localization at the midzone, is delocalized from the spindle midzone and the midbody but not from the metaphase chromosomes upon v-Src expression. Mklp2, which is responsible for the relocation of Aurora B from the metaphase chromosomes to the spindle midzone, is also lost from the spindle midzone. These results suggest that v-Src inhibits cytokinesis through the delocalization of Mklp1 and Aurora B from the spindle midzone, resulting in binucleation. -- Highlights: • v-Src inhibits cell proliferation of HCT116, HeLa S3 and NIH3T3 cells. • v-Src induces binucleation together with cytokinesis failure. • v-Src causes delocalization of Mklp1, Aurora B and INCENP from the spindle midzone.« less

Myristoylation of Src kinase mediates Src-induced and high-fat diet-accelerated prostate tumor progression in mice.

PubMed

Kim, Sungjin; Yang, Xiangkun; Li, Qianjin; Wu, Meng; Costyn, Leah; Beharry, Zanna; Bartlett, Michael G; Cai, Houjian

2017-11-10

Exogenous fatty acids provide substrates for energy production and biogenesis of the cytoplasmic membrane, but they also enhance cellular signaling during cancer cell proliferation. However, it remains controversial whether dietary fatty acids are correlated with tumor progression. In this study, we demonstrate that increased Src kinase activity is associated with high-fat diet-accelerated progression of prostate tumors and that Src kinases mediate this pathological process. Moreover, in the in vivo prostate regeneration assay, host SCID mice carrying Src(Y529F)-transduced regeneration tissues were fed a low-fat diet or a high-fat diet and treated with vehicle or dasatinib. The high-fat diet not only accelerated Src-induced prostate tumorigenesis in mice but also compromised the inhibitory effect of the anticancer drug dasatinib on Src kinase oncogenic potential in vivo We further show that myristoylation of Src kinase is essential to facilitate Src-induced and high-fat diet-accelerated tumor progression. Mechanistically, metabolism of exogenous myristic acid increased the biosynthesis of myristoyl CoA and myristoylated Src and promoted Src kinase-mediated oncogenic signaling in human cells. Of the fatty acids tested, only exogenous myristic acid contributed to increased intracellular myristoyl CoA levels. Our results suggest that targeting Src kinase myristoylation, which is required for Src kinase association at the cellular membrane, blocks dietary fat-accelerated tumorigenesis in vivo Our findings uncover the molecular basis of how the metabolism of myristic acid stimulates high-fat diet-mediated prostate tumor progression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Short-range order clustering in BCC Fe-Mn alloys induced by severe plastic deformation

NASA Astrophysics Data System (ADS)

Shabashov, V. A.; Kozlov, K. A.; Sagaradze, V. V.; Nikolaev, A. L.; Lyashkov, K. A.; Semyonkin, V. A.; Voronin, V. I.

2018-03-01

The effect of severe plastic deformation, namely, high-pressure torsion (HPT) at different temperatures and ball milling (BM) at different time intervals, has been investigated by means of Mössbauer spectroscopy in Fe100-xMnx (x = 4.1, 6.8, 9) alloys. Deformation affects the short-range clustering (SRC) in BCC lattice. Two processes occur: destruction of SRC by moving dislocations and enhancement of the SRC by migration of non-equilibrium defects. Destruction of SRC prevails during HPT at 80-293 K; whereas enhancement of SRC dominates at 473-573 K. BM starts enhancing the SRC formation at as low as 293 K due to local heating at impacts. The efficiency of HPT in terms of enhancing SRC increases with increasing temperature. The authors suppose that at low temperatures, a significant fraction of vacancies are excluded from enhancing SRC because of formation of mobile bi- and tri-vacancies having low efficiency of enhancing SRC as compared to that of mono vacancies. Milling of BCC Fe100-xMnx alloys stabilises the BCC phase with respect to α → γ transition at subsequent isothermal annealing because of a high degree of work hardening and formation of composition inhomogeneity.

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

PubMed Central

Gao, Lu; Rabbitt, Elizabeth H.; Condon, Jennifer C.; Renthal, Nora E.; Johnston, John M.; Mitsche, Matthew A.; Chambon, Pierre; Xu, Jianming; O’Malley, Bert W.; Mendelson, Carole R.

2015-01-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2–deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2–deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2–deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2–dependent production of SP-A and PAF is crucial for this process. PMID:26098214

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.

PubMed

Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C; Renthal, Nora E; Johnston, John M; Mitsche, Matthew A; Chambon, Pierre; Xu, Jianming; O'Malley, Bert W; Mendelson, Carole R

2015-07-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A-deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2-deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2-deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2-deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process.

Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway.

PubMed

Wu, Xue; Yang, Longlong; Zheng, Zhao; Li, Zhenzhen; Shi, Jihong; Li, Yan; Han, Shichao; Gao, Jianxin; Tang, Chaowu; Su, Linlin; Hu, Dahai

2016-03-01

Wound healing is a highly orchestrated, multistep process, and delayed wound healing is a significant symptomatic clinical problem. Keratinocyte migration and re-epithelialization play the most important roles in wound healing, as they determine the rate of wound healing. In our previous study, we found that Src, one of the oldest proto‑oncogenes encoding a membrane-associated, non-receptor protein tyrosine kinase, promotes keratinocyte migration. We therefore hypothesized that Src promotes wound healing through enhanced keratinocyte migration. In order to test this hypothesis, vectors for overexpressing Src and small interfering RNAs (siRNAs) for silencing of Src were used in the present study. We found that the overexpression of Src accelerated keratinocyte migration in vitro and promoted wound healing in vivo without exerting a marked effect on cell proliferation. The extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways play important roles in Src-accelerated keratinocyte migration. Further experiments demonstrated that Src induced the protein expression of matrix metalloproteinase-2 (MMP-2) and decreased the protein expression of E-cadherin. We suggest that ERK signaling is involved in the Src-mediated regulation of MMP-2 expression. The present study provided evidence that Src promotes keratinocyte migration and cutaneous wound healing, in which the regulation of MMP-2 through the ERK pathway plays an important role, and thus we also demonstrated a potential therapeutic role for Src in cutaneous wound healing.

Molecular signaling in live cells studied by FRET

NASA Astrophysics Data System (ADS)

Chien, Shu; Wang, Yingxiao

2011-11-01

Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) enables visualization of signaling events in live cells with high spatiotemporal resolution. We have used FRET to assess temporal and spatial characteristics for signaling molecules, including tyrosine kinases Src and FAK, small GTPase Rac, calcium, and a membrane-bound matrix metalloproteinase MT1-MMP. Activations of Src and Rac by platelet derived growth factor (PDGF) led to distinct subcellular patterns during cell migration on micropatterned surface, and these two enzymes interact with each other to form a feedback loop with differential regulations at different subcellular locations. We have developed FRET biosensors to monitor FAK activities at rafts vs. non-raft regions of plasma membrane in live cells. In response to cell adhesion on matrix proteins or stimulation by PDGF, the raft-targeting FAK biosensor showed a stronger FRET response than that at non-rafts. The FAK activation at rafts induced by PDGF is mediated by Src. In contrast, the FAK activation at rafts induced by adhesion is independent of Src activity, but rather is essential for Src activation. Thus, Src is upstream to FAK in response to chemical stimulation (PDGF), but FAK is upstream to Src in response to mechanical stimulation (adhesion). A novel biosensor has been developed to dynamically visualize the activity of membrane type-1-matrix metalloproteinase (MT1-MMP), which proteolytically remodels the extracellular matrix. Epidermal growth factor (EGF) directed active MT1-MMP to the leading edge of migrating live cancer cells with local accumulation of EGF receptor via a process dependent on an intact cytoskeletal network. In summary, FRET-based biosensors enable the elucidation of molecular processes and hierarchies underlying spatiotemporal regulation of biological and pathological processes, thus advancing our knowledge on how cells perceive mechanical/chemical cues in space and time to coordinate molecular/cellular functions.

Molecular signaling in live cells studied by FRET

NASA Astrophysics Data System (ADS)

Chien, Shu; Wang, Yingxiao

2012-03-01

Genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) enables visualization of signaling events in live cells with high spatiotemporal resolution. We have used FRET to assess temporal and spatial characteristics for signaling molecules, including tyrosine kinases Src and FAK, small GTPase Rac, calcium, and a membrane-bound matrix metalloproteinase MT1-MMP. Activations of Src and Rac by platelet derived growth factor (PDGF) led to distinct subcellular patterns during cell migration on micropatterned surface, and these two enzymes interact with each other to form a feedback loop with differential regulations at different subcellular locations. We have developed FRET biosensors to monitor FAK activities at rafts vs. non-raft regions of plasma membrane in live cells. In response to cell adhesion on matrix proteins or stimulation by PDGF, the raft-targeting FAK biosensor showed a stronger FRET response than that at non-rafts. The FAK activation at rafts induced by PDGF is mediated by Src. In contrast, the FAK activation at rafts induced by adhesion is independent of Src activity, but rather is essential for Src activation. Thus, Src is upstream to FAK in response to chemical stimulation (PDGF), but FAK is upstream to Src in response to mechanical stimulation (adhesion). A novel biosensor has been developed to dynamically visualize the activity of membrane type-1-matrix metalloproteinase (MT1-MMP), which proteolytically remodels the extracellular matrix. Epidermal growth factor (EGF) directed active MT1-MMP to the leading edge of migrating live cancer cells with local accumulation of EGF receptor via a process dependent on an intact cytoskeletal network. In summary, FRET-based biosensors enable the elucidation of molecular processes and hierarchies underlying spatiotemporal regulation of biological and pathological processes, thus advancing our knowledge on how cells perceive mechanical/chemical cues in space and time to coordinate molecular/cellular functions.

REVERSE SIGNALING BY GPI-LINKED MANDUCA EPHRIN REQUIRES A SRC FAMILY KINASE TO RESTRICT NEURONAL MIGRATION IN VIVO

PubMed Central

Coate, Thomas M.; Swanson, Tracy L.; Copenhaver, Philip F.

2011-01-01

Reverse signaling via GPI-linked Ephrins may help control cell proliferation and outgrowth within the nervous system, but the mechanisms underlying this process remain poorly understood. In the embryonic enteric nervous system (ENS) of the moth Manduca sexta, migratory neurons forming the enteric plexus (EP cells) express a single Ephrin ligand (GPI-linked MsEphrin), while adjacent midline cells that are inhibitory to migration express the cognate receptor (MsEph). Knocking down MsEph receptor expression in cultured embryos with antisense morpholino oligonucleotides allowed the EP cells to cross the midline inappropriately, consistent with the model that reverse signaling via MsEphrin mediates a repulsive response in the ENS. Src family kinases have been implicated in reverse signaling by type-A Ephrins in other contexts, and MsEphrin colocalizes with activated forms of endogenous Src in the leading processes of the EP cells. Pharmacological inhibition of Src within the developing ENS induced aberrant midline crossovers, similar to the effect of blocking MsEphrin reverse signaling. Hyperstimulating MsEphrin reverse signaling with MsEph-Fc fusion proteins induced the rapid activation of endogenous Src specifically within the EP cells, as assayed by Western blots of single embryonic gut explants and by whole-mount immunostaining of cultured embryos. In longer cultures, treatment with MsEph-Fc caused a global inhibition of EP cell migration and outgrowth, an effect that was prevented by inhibiting Src activation. These results support the model that MsEphrin reverse signaling induces the Src-dependent retraction of EP cell processes away from the enteric midline, thereby helping to confine the neurons to their appropriate pathways. PMID:19295147

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

PubMed Central

Geraghty, Patrick; Hardigan, Andrew

2014-01-01

The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke–exposed mice. Moreover, inhibiting Src deterred the cigarette smoke–mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

Global Impact of Oncogenic Src on a Phosphotyrosine Proteome

PubMed Central

Luo, Weifeng; Slebos, Robbert J.; Hill, Salisha; Li, Ming; Brábek, Jan; Amanchy, Ramars; Chaerkady, Raghothama; Pandey, Akhilesh; Ham, Amy-Joan L.; Hanks, Steven K.

2008-01-01

Elevated activity of Src, the first characterized protein-tyrosine kinase, is associated with progression of many human cancers, and Src has attracted interest as a therapeutic target. Src is known to act in various receptor signaling systems to impact cell behavior, yet it remains likely that the spectrum of Src protein substrates relevant to cancer is incompletely understood. To better understand the cellular impact of deregulated Src kinase activity, we extensively applied a mass spectrometry shotgun phosphotyrosine (pTyr) proteomics strategy to obtain global pTyr profiles of Src-transformed mouse fibroblasts as well as their nontransformed counterparts. A total of 867 peptides representing 563 distinct pTyr sites on 374 different proteins were identified from the Src-transformed cells, while 514 peptides representing 275 pTyr sites on 167 proteins were identified from nontransformed cells. Distinct characteristics of the two profiles were revealed by spectral counting, indicative of pTyr site relative abundance, and by complementary quantitative analysis using stable isotope labeling with amino acids in cell culture (SILAC). While both pTyr profiles are replete with sites on signaling and adhesion/cytoskeletal regulatory proteins, the Src-transformed profile is more diverse with enrichment in sites on metabolic enzymes and RNA and protein synthesis and processing machinery. Forty-three pTyr sites (32 proteins) are predicted as major biologically relevant Src targets on the basis of frequent identification in both cell populations. This select group, of particular interest as diagnostic biomarkers, includes well-established Src sites on signaling/adhesion/cytoskeletal proteins, but also uncharacterized sites of potential relevance to the transformed cell phenotype. PMID:18563927

Conflict-Specific Aging Effects Mainly Manifest in Early Information Processing Stages-An ERP Study with Different Conflict Types.

PubMed

Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

2016-01-01

Aging is usually accompanied by alterations of cognitive control functions such as conflict processing. Recent research suggests that aging effects on cognitive control seem to vary with degree and source of conflict, and conflict specific aging effects on performance measures as well as neural activation patterns have been shown. However, there is sparse information whether and how aging affects different stages of conflict processing as indicated by event related potentials (ERPs) such as the P2, N2 and P3 components. In the present study, 19 young and 23 elderly adults performed a combined Flanker conflict and stimulus-response-conflict (SRC) task. Analysis of the reaction times (RTs) revealed an increased SRC related conflict effect in elderly. ERP analysis furthermore demonstrated an age-related increase of the P2 amplitude in response to the SRC task. In addition, elderly adults exhibited an increased P3 amplitude modulation induced by incongruent SRC and Flanker conflict trials.

Additive Factors Analysis of Inhibitory Processing in the Stop-Signal Paradigm

ERIC Educational Resources Information Center

van den Wildenberg, W.P.M.; van der Molen, M.W.

2004-01-01

This article reports an additive factors analysis of choice reaction and selective stop processes manipulated in a stop-signal paradigm. Three experiments were performed in which stimulus discriminability (SD) and stimulus-response compatibility (SRC) were manipulated in a factorial fashion. In each experiment, the effects of SD and SRC were…

Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko

2014-09-26

Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore » by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.« less

Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts.

PubMed

Levy-Apter, Einat; Finkelshtein, Eynat; Vemulapalli, Vidyasiri; Li, Shawn S-C; Bedford, Mark T; Elson, Ari

2014-12-26

The non-receptor isoform of protein-tyrosine phosphatase ϵ (cyt-PTPe) supports adhesion of bone-resorbing osteoclasts by activating Src downstream of integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces resorption of mineralized matrix both in vivo and in cell culture, and induces mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr-638 by partially active Src. To understand how cyt-PTPe activates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe. The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with downstream molecules. Further studies indicated that GRB2 is required for activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture. Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr-416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2 expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt-PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src activation by integrins. Reduced GRB2 expression also reduced the ability of bone marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in which podosomal adhesion structures assume organization typical of active, resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and enables cyt-PTPe to activate Src downstream of activated integrins in OCLs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Fetal-to-maternal signaling to initiate parturition

PubMed Central

Reinl, Erin L.; England, Sarah K.

2015-01-01

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

Identification of the SRC pyrimidine-binding protein (SPy) as hnRNP K: implications in the regulation of SRC1A transcription

PubMed Central

Ritchie, Shawn A.; Pasha, Mohammed K.; Batten, Danielle J. P.; Sharma, Rajendra K.; Olson, Douglas J. H.; Ross, Andrew R. S.; Bonham, Keith

2003-01-01

The human SRC gene encodes pp60c–src, a non-receptor tyrosine kinase involved in numerous signaling pathways. Activation or overexpression of c-Src has also been linked to a number of important human cancers. Transcription of the SRC gene is complex and regulated by two closely linked but highly dissimilar promoters, each associated with its own distinct non-coding exon. In many tissues SRC expression is regulated by the housekeeping-like SRC1A promoter. In addition to other regulatory elements, three substantial polypurine:polypyrimidine (TC) tracts within this promoter are required for full transcriptional activity. Previously, we described an unusual factor called SRC pyrimidine-binding protein (SPy) that could bind to two of these TC tracts in their double-stranded form, but was also capable of interacting with higher affinity to all three pyrimidine tracts in their single-stranded form. Mutations in the TC tracts, which abolished the ability of SPy to interact with its double-stranded DNA target, significantly reduced SRC1A promoter activity, especially in concert with mutations in critical Sp1 binding sites. Here we expand upon our characterization of this interesting factor and describe the purification of SPy from human SW620 colon cancer cells using a DNA affinity-based approach. Subsequent in-gel tryptic digestion of purified SPy followed by MALDI-TOF mass spectrometric analysis identified SPy as heterogeneous nuclear ribonucleoprotein K (hnRNP K), a known nucleic-acid binding protein implicated in various aspects of gene expression including transcription. These data provide new insights into the double- and single-stranded DNA-binding specificity, as well as functional properties of hnRNP K, and suggest that hnRNP K is a critical component of SRC1A transcriptional processes. PMID:12595559

Differentiation-induced Colocalization of the KH-type Splicing Regulatory Protein with Polypyrimidine Tract Binding Protein and the c-src Pre-mRNA

PubMed Central

Hall, Megan P.; Huang, Sui; Black, Douglas L.

2004-01-01

We have examined the subcellular localization of the KH-type splicing regulatory protein (KSRP). KSRP is a multidomain RNA-binding protein implicated in a variety of cellular processes, including splicing in the nucleus and mRNA localization in the cytoplasm. We find that KSRP is primarily nuclear with a localization pattern that most closely resembles that of polypyrimidine tract binding protein (PTB). Colocalization experiments of KSRP with PTB in a mouse neuroblastoma cell line determined that both proteins are present in the perinucleolar compartment (PNC), as well as in other nuclear enrichments. In contrast, HeLa cells do not show prominent KSRP staining in the PNC, even though PTB labeling identified the PNC in these cells. Because both PTB and KSRP interact with the c-src transcript to affect N1 exon splicing, we examined the localization of the c-src pre-mRNA by fluorescence in situ hybridization. The src transcript is present in specific foci within the nucleus that are presumably sites of src transcription but are not generally perinucleolar. In normally cultured neuroblastoma cells, these src RNA foci contain PTB, but little KSRP. However, upon induced neuronal differentiation of these cells, KSRP occurs in the same foci with src RNA. PTB localization remains unaffected. This differentiation-induced localization of KSRP with src RNA correlates with an increase in src exon N1 inclusion. These results indicate that PTB and KSRP do indeed interact with the c-src transcript in vivo, and that these associations change with the differentiated state of the cell. PMID:14657238

Stimulus-response compatibility and psychological refractory period effects: implications for response selection

NASA Technical Reports Server (NTRS)

Lien, Mei-Ching; Proctor, Robert W.

2002-01-01

The purpose of this paper was to provide insight into the nature of response selection by reviewing the literature on stimulus-response compatibility (SRC) effects and the psychological refractory period (PRP) effect individually and jointly. The empirical findings and theoretical explanations of SRC effects that have been studied within a single-task context suggest that there are two response-selection routes-automatic activation and intentional translation. In contrast, all major PRP models reviewed in this paper have treated response selection as a single processing stage. In particular, the response-selection bottleneck (RSB) model assumes that the processing of Task 1 and Task 2 comprises two separate streams and that the PRP effect is due to a bottleneck located at response selection. Yet, considerable evidence from studies of SRC in the PRP paradigm shows that the processing of the two tasks is more interactive than is suggested by the RSB model and by most other models of the PRP effect. The major implication drawn from the studies of SRC effects in the PRP context is that response activation is a distinct process from final response selection. Response activation is based on both long-term and short-term task-defined S-R associations and occurs automatically and in parallel for the two tasks. The final response selection is an intentional act required even for highly compatible and practiced tasks and is restricted to processing one task at a time. Investigations of SRC effects and response-selection variables in dual-task contexts should be conducted more systematically because they provide significant insight into the nature of response-selection mechanisms.

Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1α.

PubMed

Zhao, Wei; Chang, Cunjie; Cui, Yangyan; Zhao, Xiaozhi; Yang, Jun; Shen, Lan; Zhou, Ji; Hou, Zhibo; Zhang, Zhen; Ye, Changxiao; Hasenmayer, Donald; Perkins, Robert; Huang, Xiaojing; Yao, Xin; Yu, Like; Huang, Ruimin; Zhang, Dianzheng; Guo, Hongqian; Yan, Jun

2014-04-18

Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy.

Temporal and spectral profiles of stimulus-stimulus and stimulus-response conflict processing.

PubMed

Wang, Kai; Li, Qi; Zheng, Ya; Wang, Hongbin; Liu, Xun

2014-04-01

The ability to detect and resolve conflict is an essential function of cognitive control. Laboratory studies often use stimulus-response-compatibility (SRC) tasks to examine conflict processing in order to elucidate the mechanism and modular organization of cognitive control. Inspired by two influential theories regarding cognitive control, the conflict monitoring theory (Botvinick, Braver, Barch, Carter, & Cohen, 2001) and dimensional overlap taxonomy (Kornblum, Hasbroucq, & Osman, 1990), we explored the temporal and spectral similarities and differences between processing of stimulus-stimulus (S-S) and stimulus-response (S-R) conflicts with event related potential (ERP) and time-frequency measures. We predicted that processing of S-S conflict starts earlier than that of S-R conflict and that the two types of conflict may involve different frequency bands. Participants were asked to perform two parallel SRC tasks, both combining the Stroop task (involving S-S conflict) and Simon task (involving S-R conflict). ERP results showed pronounced SRC effects (incongruent vs. congruent) on N2 and P3 components for both S-S and S-R conflicts. In both tasks, SRC effects of S-S conflict took place earlier than those of S-R conflict. Time-frequency analysis revealed that both types of SRC effects modulated theta and alpha bands, while S-R conflict effects additionally modulated power in the beta band. These results indicated that although S-S and S-R conflict processing shared considerable ERP and time-frequency properties, they differed in temporal and spectral dynamics. We suggest that the modular organization of cognitive control should take both commonality and distinction of S-S and S-R conflict processing into consideration. Copyright © 2013 Elsevier Inc. All rights reserved.

An epitope localized in c-Src negative regulatory domain is a potential marker in early stage of colonic neoplasms.

PubMed

Sakai, T; Kawakatsu, H; Fujita, M; Yano, J; Owada, M K

1998-02-01

In previous work, we established a new monoclonal antibody that specifically recognizes the active form of c-Src tyrosine kinase (Kawakatsu et al, 1996). To determine whether c-Src is active in colorectal tumorigenesis, we examined the expression of an active form of c-Src in human normal mucosa, hyperplastic polyps, adenomas, and adenocarcinomas. The tissue distribution of the active form of c-Src was studied by immunohistochemistry using this antibody, termed Clone 28. Among 66 cases of adenoma tested, 61 (92%) showed positive staining (adenoma with mild atypia, 3 of 3; adenoma with moderate atypia, 38 of 42; adenoma with severe atypia, 20 of 21). In contrast to the frequent and intense staining in adenomas, adenocarcinoma showed weak staining with less frequency in 4 of 16 (25%) cases. The number of specimens with positive staining in well- and moderately differentiated adenocarcinomas was limited to an early stage. The active form of c-Src mainly localized to the nuclear membrane and the perinuclear region. These results provide the first direct evidence that the activation of c-Src appears to be an early event in colonic carcinogenesis in situ. The findings of the present study thus allow us to propose a molecular mechanism involving c-Src activation in the process of malignant transformation of the human colonic neoplastic cells.

The imaging performance of the SRC on Mars Express

USGS Publications Warehouse

Oberst, J.; Schwarz, G.; Behnke, T.; Hoffmann, H.; Matz, K.-D.; Flohrer, J.; Hirsch, H.; Roatsch, T.; Scholten, F.; Hauber, E.; Brinkmann, B.; Jaumann, R.; Williams, D.; Kirk, R.; Duxbury, T.; Leu, C.; Neukum, G.

2008-01-01

The Mars Express spacecraft carries the pushbroom scanner high-resolution stereo camera (HRSC) and its added imaging subsystem super resolution channel (SRC). The SRC is equipped with its own optical system and a 1024??1024 framing sensor. SRC produces snapshots with 2.3 m ground pixel size from the nominal spacecraft pericenter height of 250 km, which are typically embedded in the central part of the large HRSC scenes. The salient features of the SRC are its light-weight optics, a reliable CCD detector, and high-speed read-out electronics. The quality and effective visibility of details in the SRC images unfortunately falls short of what has been expected. In cases where thermal balance cannot be reached, artifacts, such as blurring and "ghost features" are observed in the images. In addition, images show large numbers of blemish pixels and are plagued by electronic noise. As a consequence, we have developed various image improving algorithms, which are discussed in this paper. While results are encouraging, further studies of image restoration by dedicated processing appear worthwhile. The SRC has obtained more than 6940 images at the time of writing (1 September 2007), which often show fascinating details in surface morphology. SRC images are highly useful for a variety of applications in planetary geology, for studies of the Mars atmosphere, and for astrometric observations of the Martian satellites. This paper will give a full account of the design philosophy, technical concept, calibration, operation, integration with HRSC, and performance, as well as science accomplishments of the SRC. ?? 2007 Elsevier Ltd. All rights reserved.

What is the definition of sports-related concussion: a systematic review.

PubMed

McCrory, Paul; Feddermann-Demont, Nina; Dvořák, Jiří; Cassidy, J David; McIntosh, Andrew; Vos, Pieter E; Echemendia, Ruben J; Meeuwisse, Willem; Tarnutzer, Alexander A

2017-06-01

Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC. This is a systematic literature review. Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016). Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data. Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation. SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology

PubMed Central

Fleet, Tiffany; Stashi, Erin; Zhu, Bokai; Rajapakshe, Kimal; Marcelo, Kathrina L.; Kettner, Nicole M.; Gorman, Blythe K.; Coarfa, Cristian; Fu, Loning; O’Malley, Bert W.; York, Brian

2017-01-01

Circadian rhythmicity is a fundamental process that synchronizes behavioral cues with metabolic homeostasis. Disruption of daily cycles due to jet lag or shift work results in severe physiological consequences including advanced aging, metabolic syndrome, and even cancer. Our understanding of the molecular clock, which is regulated by intricate positive feedforward and negative feedback loops, has expanded to include an important metabolic transcriptional coregulator, Steroid Receptor Coactivator-2 (SRC-2), that regulates both the central clock of the suprachiasmatic nucleus (SCN) and peripheral clocks including the liver. We hypothesized that an environmental uncoupling of the light-dark phases, termed chronic circadian disruption (CCD), would lead to pathology similar to the genetic circadian disruption observed with loss of SRC-2. We found that CCD and ablation of SRC-2 in mice led to a common comorbidity of metabolic syndrome also found in humans with circadian disruption, non-alcoholic fatty liver disease (NAFLD). The combination of SRC-2−/− and CCD results in a more robust phenotype that correlates with human non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) gene signatures. Either CCD or SRC-2 ablation produces an advanced aging phenotype leading to increased mortality consistent with other circadian mutant mouse models. Collectively, our studies demonstrate that SRC-2 provides an essential link between the behavioral activities influenced by light cues and the metabolic homeostasis maintained by the liver. PMID:27432117

Ground Observation of the Hayabusa Reentry: The Third Opportunity of Man-made Fireball from Interplanetary Orbit

NASA Astrophysics Data System (ADS)

Ishihara, Y.; Yamamoto, M.; Hiramatsu, Y.; Furumoto, M.; Fujita, K.

2010-12-01

After 7 years and 6,000,000,000 km of challenging cruise in the solar system, the Hayabusa did come back to the Earth on June 13, 2010. The Hayabusa, the first sample-return explorer to NEA, landed on 25243 Itokawa in 2005, capturing surface particles on the S-type asteroid into its sample return capsule (SRC). Following to the reentries of the Genesis in 2004 and the Stardust in 2006, the return of the Hayabusa SRC was the third direct reentry event from the interplanetary transfer orbit to the Earth at a velocity of over 11.2 km/s. In addition, it was world first case of direct reentry of spacecraft from interplanetary transfer orbit. After the successful resumption of the SRC, it was carefully sent to ISAS/JAXA, and at present, small particles expected to be the first sample-return materials from the minor planet are carefully investigated. In order to obtain precise trajectory information to ensure the quick procedure for the Hayabusa SRC resumption team, we observed the Hayabusa SRC reentry by optically in Australian night sky. High-resolution imaging and spectroscopy were carried out with several high-sensitivity instruments to investigate thermal-protection process of thermal protection ablator (TPA) as well as interaction process between SRC surface materials and upper atmospheric neutral and plasma components. Moreover, shockwaves were observed by infrasound/seismic sensor arrays on ground to investigate reentry related shockwaves as well as air-to-ground coupling process at the extremely rare opportunity. With respect to nominal trajectory of the Hayabusa SRC reentry, four optical stations were set inside and near the Woomera Prohibited Area, Australia, targeting on peak-heat and/or front-heat profiles of ablating TPA for engineering aspect. Infrasound and seismic sensors were also deployed as three arrayed stations and three single stations to realize direction findings of sonic boom type shockwaves from the SRC and spacecraft and point source type shockwaves from explosion of the Hayabusa itself as well as investigate precise parameters of pressure waves and energy transforming processes through the air-to-ground couplings. At 23:21 local time (13:51 UT) on June 13, 2010, the reentry of the SRC and the Hayabusa itself were successfully operated on the exact schedule and trajectory, giving us fruitful images and signals on almost all cameras and infrasound/seismic sensors. Moreover, several audible sound signals were detected at an observation site about 70 km apart from the trajectory. In this talk, we introduce our ground observations and preliminary results of infrasound/seismic observation part of this ground observation campaign. Acknowledgement: This research was partially supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (B), Field Research in Abroad, 22403005, 2010 (PI: Y.H.).

Probing short-range correlations in asymmetric nuclei with quasi-free pair knockout reactions

NASA Astrophysics Data System (ADS)

Stevens, Sam; Ryckebusch, Jan; Cosyn, Wim; Waets, Andreas

2018-02-01

Short-range correlations (SRC) in asymmetric nuclei with an unusual neutron-to-proton ratio can be studied with quasi-free two-nucleon knockout processes following the collision between accelerated ions and a proton target. We derive an approximate factorized cross section for those SRC-driven p (A ,p‧N1N2) reactions. Our reaction model hinges on the factorization properties of SRC-driven A (e ,e‧N1N2) reactions for which strong indications are found in theory-experiment comparisons. In order to put our model to the test we compare its predictions with results of 12C (p ,p‧ pn) measurements conducted at Brookhaven National Laboratory (BNL) and find a fair agreement. The model can also reproduce characteristic features of SRC-driven two-nucleon knockout reactions, like back-to-back emission of the correlated nucleons. We study the asymmetry dependence of nuclear SRC by providing predictions for the ratio of proton-proton to proton-neutron knockout cross sections for the carbon isotopes 9-15C thereby covering neutron excess values (N - Z) / Z between -0.5 and +0.5.

Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases.

PubMed

Cooper, J A; Simon, M A; Kussick, S J

1996-11-01

Vertebrate Src can be activated by specific mutations to become oncogenic. Analogous mutations in Drosophila Src64 (DSrc) induce abnormal differentiation of photoreceptor cells when expressed ectopically in the developing Drosophila adult eye. We have investigated the roles that the adapter protein, Downstream of receptor kinases (Drk), and the SH2 domain-containing tyrosine phosphatase, Corkscrew (Csw), play in this process. We find that dominant-negative mutations in either the drk or csw genes ameliorate the developmental abnormalities induced by activated DSrc. This suggests that Drk and Csw are required downstream of, or parallel to, DSrc. Csw does not act solely as an upstream activator of DSrc. The results are discussed in relation to potential roles for the vertebrate homologues of Drk and Csw (Grb2 and SHP2, respectively) in the transformation of fibroblasts by vertebrate Src.

Ageing differentially affects neural processing of different conflict types-an fMRI study.

PubMed

Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

2014-01-01

Interference control and conflict resolution is affected by ageing. There is increasing evidence that ageing does not compromise interference control in general but rather shows distinctive effects on different components of interference control. Different conflict types, [e.g., stimulus-stimulus (S-S) or stimulus-response (S-R) conflicts] trigger different cognitive processes and thus activate different neural networks. In the present functional magnetic resonance imaging (fMRI) study, we used a combined Flanker and Stimulus Response Conflict (SRC) task to investigate the effect of ageing on S-S and S-R conflicts. Behavioral data analysis revealed larger SRC effects in elderly. fMRI Results show that both age groups recruited similar regions [caudate nucleus, cingulate gyrus and middle occipital gyrus (MOG)] during Flanker conflict processing. Furthermore, elderly show an additional activation pattern in parietal and frontal areas. In contrast, no common activation of both age groups was found in response to the SRC. These data suggest that ageing has distinctive effects on S-S and S-R conflicts.

SRC-induced disintegration of adherens junctions of madin-darby canine kidney cells is dependent on endocytosis of cadherin and antagonized by Tiam-1.

PubMed

Palovuori, Riitta; Sormunen, Raija; Eskelinen, Sinikka

2003-12-01

The effects of Src tyrosine kinase activation in subconfluent temperature sensitive (ts)-Src-transformed Madin-Darby canine kidney (MDCK) cells were analyzed by shifting them from nonpermissive (40.5 degrees C) to permissive (35 degrees C) temperature. Already, in 15 minutes, adherens junction components were released from the lateral walls and accumulated to basal surfaces. Simultaneously, membranous actin staining vanished, actin bundles appeared at the basal surface, and the cells flattened. The only component phosphorylated and translocated after the shift to 35 degrees C was p120ctn. The epithelial-mesenchymal transition could be inhibited by a specific inhibitor of Src kinase, PP2, or by inhibiting endocytosis. Therefore, Src activation was responsible for the transition, but not because of phosphorylation of adherens junction components but by way of activation of endocytic machinery and RhoGTPase. Expression of an RacGEF, Tiam-1 (T-lymphoma invasion and metastasis gene 1), prevented flattening of Src-transformed MDCK cells at 35 degrees C and resulted in accumulation of cadherin to lateral membranes. In the case where the Src-MDCK cells were cultivated at 35 degrees C and shifted for short time periods to 40.5 degrees C, cadherin rapidly returned to lateral membranes, whereas actin and p120ctn followed hours afterward. This further supports the view that cadherin internalization is the primary target of Src kinase. We also looked at the cell morphology and distribution of cadherin and Tiam-1 in cells grown in three-dimensional gels composed of collagen and laminin or in Matrigel. At nonpermissive temperature, both Src-MDCK and Tiam-1-transfected Src-MDCK cells exhibited nonpolarized morphology in collagen I, a loose cluster in the mixture of collagen I and laminin, and a differentiated cyst in Matrigel. In growth factor-depleted Matrigel, the Src-MDCK cells grew in nondifferentiated clusters, whereas Tiam-1-transfected cells went to apoptosis. The differentiated phenotype of both cell lines could be rescued by Matrigel-conditioned medium, platelet-derived growth factor, or cholera toxin. Concomitantly, both cadherin and Tiam-1 were recruited to lateral membranes. Therefore, cadherin and Tiam-1 seem to be the key players in the differentiation process of MDCK cells.

Evaluation of a direct injection nebulizer interface for flow injection analysis and high performance liquid chromatography with inductively coupled plasma-atomic emission spectroscopic detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaFreniere, K.E.

A direct injection nebulizer (DIN) was designed, developed, and evaluated to determine its potential utilization as an effective interface for flow injection analysis (FIA) and high performance liquid chromatography (HPLC) coupled with inductively coupled plasma-atomic emission spectroscopic detection. The analytical figures of merit for the DIN when used as an interface for FIA-ICP-AES were found to be comparable to or better than those obtained with conventional pneumatic nebulization in terms of limits of detection (LODs), reproducibility, linearity, and interelement effects. Stable plasma operation was maintained for the DIN sample introduction of a variety of pure organic solvents, including acetonitrile, methanol,more » methylisobutylketone, and pyridine. The HPLC-DIN-ICP-AES facility was specifically applied for the speciation of inorganic and organometallic species contained in synthetic mixtures, vanilla extracts, and a variety of energy-related materials, such as shale oil process water, coal extracts, shale oil, crude oil, and an SRC II. Suggestions for future research are also considered. 227 refs., 44 figs., 15 tabs.« less

The Transmodulation of HER2 and EGFR by Substance P in Breast Cancer Cells Requires c-Src and Metalloproteinase Activation.

PubMed

Garcia-Recio, Susana; Pastor-Arroyo, Eva M; Marín-Aguilera, Mercedes; Almendro, Vanessa; Gascón, Pedro

2015-01-01

Substance P (SP) is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC) aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R) signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator) and of metalloproteinases (ligand-dependent mediators) in HER2/EGFR activation. Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines. Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process.

The Activation of c-Src Tyrosine Kinase: Conformational Transition Pathway and Free Energy Landscape.

PubMed

Fajer, Mikolai; Meng, Yilin; Roux, Benoît

2017-04-20

Tyrosine kinases are important cellular signaling allosteric enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Their activity must be tightly controlled, and malfunction can lead to a variety of diseases, particularly cancer. The nonreceptor tyrosine kinase c-Src, a prototypical model system and a representative member of the Src-family, functions as complex multidomain allosteric molecular switches comprising SH2 and SH3 domains modulating the activity of the catalytic domain. The broad picture of self-inhibition of c-Src via the SH2 and SH3 regulatory domains is well characterized from a structural point of view, but a detailed molecular mechanism understanding is nonetheless still lacking. Here, we use advanced computational methods based on all-atom molecular dynamics simulations with explicit solvent to advance our understanding of kinase activation. To elucidate the mechanism of regulation and self-inhibition, we have computed the pathway and the free energy landscapes for the "inactive-to-active" conformational transition of c-Src for different configurations of the SH2 and SH3 domains. Using the isolated c-Src catalytic domain as a baseline for comparison, it is observed that the SH2 and SH3 domains, depending upon their bound orientation, promote either the inactive or active state of the catalytic domain. The regulatory structural information from the SH2-SH3 tandem is allosterically transmitted via the N-terminal linker of the catalytic domain. Analysis of the conformational transition pathways also illustrates the importance of the conserved tryptophan 260 in activating c-Src, and reveals a series of concerted events during the activation process.

Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases

PubMed Central

Lesslie, D P; Summy, J M; Parikh, N U; Fan, F; Trevino, J G; Sawyer, T K; Metcalf, C A; Shakespeare, W C; Hicklin, D J; Ellis, L M; Gallick, G E

2006-01-01

Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process. PMID:16685275

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis.

PubMed

Silva, Corinne M

2004-10-18

The signal transducers and activators of transcription (STATs) were originally identified in the signaling pathway activated by the nontyrosine kinase containing cytokine receptors. The role of these STATs in hematopoietic cell signaling has been well described. In the case of cytokine receptors, activation of STAT tyrosine phosphorylation occurs through ligand-induced recruitment, and activation of the intracellular JAK kinases. However, STATs can also be activated by growth factor receptors, particularly the EGFR; as well as by members of the Src Family of Kinases (SFKs), particularly c-Src. In many cases, there is a differential activation of the STATs by these tyrosine kinases as compared to activation by the cytokine receptors. This difference provides for the potential of unique actions of STATs in response to growth factor receptor and SFK activation. Since there are many cancers in which SFKs and c-Src in particular, are co-overexpressed with growth factor receptors, it is not surprising that STATs play an important role in the tumorigenesis process induced by c-Src. The activation paradigm and role of STATs in these cancers, with particular emphasis on breast cancer models, is discussed.

The targeted delivery of the c-Src peptide complexed with schizophyllan to macrophages inhibits polymicrobial sepsis and ulcerative colitis in mice.

PubMed

Kim, Ye-Ram; Hwang, Jangsun; Koh, Hyun-Jung; Jang, Kiseok; Lee, Jong-Dae; Choi, Jonghoon; Yang, Chul-Su

2016-05-01

Hyper-inflammatory responses triggered by intracellular reactive oxygen species (ROS) can lead to a variety of diseases, including sepsis and colitis. However, the regulators of this process remain poorly defined. In this study, we demonstrate that c-Src is a negative regulator of cellular ROS generation through its binding to p47phox. This molecule also competitively inhibits the NADPH oxidase complex (NOX) assembly. Furthermore, we developed the schizophyllan (SPG)-c-Src SH3 peptide, which is a β-1,3-glucan conjugated c-Src SH3-derived peptide composed of amino acids 91-108 and 121-140 of c-Src. The SPG-SH3 peptide has a significant therapeutic effect on mouse ROS-mediated inflammatory disease models, cecal-ligation-puncture-induced sepsis, and dextran sodium sulfate-induced colitis. It does so by inhibiting the NOX subunit assembly and proinflammatory mediator production. Therefore, the SPG-SH3 peptide is a potential therapeutic agent for ROS-associated lethal inflammatory diseases. Our findings provide clues for the development of new peptide-base drugs that will target p47phox. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chunfa, E-mail: chunfa.huang@case.edu; Department of Medicine, Case Western Reserve University; Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106

The glomerular capillary wall, composed of endothelial cells, the glomerular basement membrane and the podocytes, is continually subjected to hemodynamic force arising from tractional stress due to blood pressure and shear stress due to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as hyperfiltration is associated with glomerular injury and progressive renal disease, and the conversion of mechanical stimuli to chemical signals in the regulation of the process is poorly understood in podocytes. By examining DNA fragmentation, apoptotic nuclear changes and cytochrome c release, we found that shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes exposedmore » to shear stress also stimulated c-Src phosphorylation, phospholipase D (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the antibodies against c-Src, PLD{sub 1}, and PLD{sub 2} to perform reciprocal co-immunoprecipitations and in vitro PLD activity assay, our data indicated that c-Src interacted with and activated PLD{sub 1} but not PLD{sub 2}. The inhibition of shear stress-induced c-Src phosphorylation by PP{sub 2} (a specific inhibitor of c-Src kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte hypertrophy and apoptosis.« less

v-Src-driven transformation is due to chromosome abnormalities but not Src-mediated growth signaling.

PubMed

Honda, Takuya; Morii, Mariko; Nakayama, Yuji; Suzuki, Ko; Yamaguchi, Noritaka; Yamaguchi, Naoto

2018-01-18

v-Src is the first identified oncogene product and has a strong tyrosine kinase activity. Much of the literature indicates that v-Src expression induces anchorage-independent and infinite cell proliferation through continuous stimulation of growth signaling by v-Src activity. Although all of v-Src-expressing cells are supposed to form transformed colonies, low frequencies of v-Src-induced colony formation have been observed so far. Using cells that exhibit high expression efficiencies of inducible v-Src, we show that v-Src expression causes cell-cycle arrest through p21 up-regulation despite ERK activation. v-Src expression also induces chromosome abnormalities and unexpected suppression of v-Src expression, leading to p21 down-regulation and ERK inactivation. Importantly, among v-Src-suppressed cells, only a limited number of cells gain the ability to re-proliferate and form transformed colonies. Our findings provide the first evidence that v-Src-driven transformation is attributed to chromosome abnormalities, but not continuous stimulation of growth signaling, possibly through stochastic genetic alterations.

Lack of Csk-mediated negative regulation in a unicellular SRC kinase.

PubMed

Schultheiss, Kira P; Suga, Hiroshi; Ruiz-Trillo, Iñaki; Miller, W Todd

2012-10-16

Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans.

Dasatinib is preclinically active against Src-overexpressing human transitional cell carcinoma of the urothelium with activated Src signaling.

PubMed

Levitt, Jonathan M; Yamashita, Hideyuki; Jian, Weiguo; Lerner, Seth P; Sonpavde, Guru

2010-05-01

Dasatinib is an orally administered multitargeted kinase inhibitor that targets Src family tyrosine kinases, Abl, c-Kit, and PDGFR. A preclinical study was conducted to evaluate dasatinib alone or combined with cisplatin for human transitional cell carcinoma (TCC). Expression of Src in a human TCC tissue microarray was evaluated by immunohistochemistry. The activity of dasatinib and/or cisplatin was evaluated in six human TCC cell lines. Western blot was done to assess Src and phosphorylated-Src (p-Src) expression. The activity of dasatinib alone and in combination with cisplatin was determined in murine subcutaneous xenografts. Sixty-two percent to 75% of human TCC expressed Src. Dasatinib displayed significant antiproliferative activity at nanomolar concentrations against two human TCC cell lines (RT4 and Hu456) that exhibited high Src and p-Src expression and were cisplatin-resistant. RT4 cells were the most sensitive and displayed the highest level of Src pathway activation (p-Src/Src ratio). Dasatinib downregulated p-Src in either sensitive or resistant cells. TCC cells that were sensitive to cisplatin (5637 and TCC-SUP) were highly resistant to dasatinib and exhibited low Src expression. Dasatinib showed antitumor activity in RT4 murine xenografts, and the combination of dasatinib and cisplatin was significantly more active than placebo. Combination dasatinib plus cisplatin significantly inhibited proliferation and promoted apoptosis in vivo. In conclusion, dasatinib displayed significant preclinical antitumor activity against Src-overexpressing human TCC with active Src signaling and was highly active in combination with cisplatin in vivo. Further clinical development might be warranted in selected human subjects.

Endothelial Barrier Protection by Local Anesthetics: Ropivacaine and Lidocaine Block Tumor Necrosis Factor-α–induced Endothelial Cell Src Activation

PubMed Central

Piegeler, Tobias; Votta-Velis, E. Gina; Bakhshi, Farnaz R.; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G.; Schwartz, David E.; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D.

2014-01-01

Background Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase–Akt–nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Methods Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Results Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10−10 M for ropivacaine; IC50 = 5.864 × 10−10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10−10 M for ropivacaine; IC50 = 6.377 × 10−10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Conclusions Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory “side-effect” of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease. PMID:24525631

Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation.

PubMed

Piegeler, Tobias; Votta-Velis, E Gina; Bakhshi, Farnaz R; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G; Schwartz, David E; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D

2014-06-01

Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase-Akt-nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10 M for ropivacaine; IC50 = 5.864 × 10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10 M for ropivacaine; IC50 = 6.377 × 10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory "side-effect" of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease.

Aldosterone rapidly activates Src kinase in M-1 cells involving the mineralocorticoid receptor and HSP84.

PubMed

Braun, Sabine; Lösel, Ralf; Wehling, Martin; Boldyreff, Brigitte

2004-07-16

We investigated the effect of aldosterone on Src kinase. In the kidney cell line, M-1 aldosterone leads to a >2-fold transient activation of Src kinase seen as early as 2 min after aldosterone administration. Maximal Src kinase activation was measured at an aldosterone concentration of 1 nM. In parallel to activation, autophosphorylation at Tyr-416 of Src kinase increased. Src kinase activation was blocked by spironolactone. Aldosterone led to increased association of Src with HSP84. Furthermore, rapamycin blocked aldosterone-induced Src activation. We conclude that Src activation by aldosterone is mediated through the mineralocorticoid receptor and HSP84.

Roles of Raft-Anchored Adaptor Cbp/PAG1 in Spatial Regulation of c-Src Kinase

PubMed Central

Oneyama, Chitose; Suzuki, Takashi; Okada, Masato

2014-01-01

The tyrosine kinase c-Src is upregulated in numerous human cancers, implying a role for c-Src in cancer progression. Previously, we have shown that sequestration of activated c-Src into lipid rafts via a transmembrane adaptor, Cbp/PAG1, efficiently suppresses c-Src-induced cell transformation in Csk-deficient cells, suggesting that the transforming activity of c-Src is spatially regulated via Cbp in lipid rafts. To dissect the molecular mechanisms of the Cbp-mediated regulation of c-Src, a combined analysis was performed that included mathematical modeling and in vitro experiments in a c-Src- or Cbp-inducible system. c-Src activity was first determined as a function of c-Src or Cbp levels, using focal adhesion kinase (FAK) as a crucial c-Src substrate. Based on these experimental data, two mathematical models were constructed, the sequestration model and the ternary model. The computational analysis showed that both models supported our proposal that raft localization of Cbp is crucial for the suppression of c-Src function, but the ternary model, which includes a ternary complex consisting of Cbp, c-Src, and FAK, also predicted that c-Src function is dependent on the lipid-raft volume. Experimental analysis revealed that c-Src activity is elevated when lipid rafts are disrupted and the ternary complex forms in non-raft membranes, indicating that the ternary model accurately represents the system. Moreover, the ternary model predicted that, if Cbp enhances the interaction between c-Src and FAK, Cbp could promote c-Src function when lipid rafts are disrupted. These findings underscore the crucial role of lipid rafts in the Cbp-mediated negative regulation of c-Src-transforming activity, and explain the positive role of Cbp in c-Src regulation under particular conditions where lipid rafts are perturbed. PMID:24675741

SH2 Ligand-Like Effects of Second Cytosolic Domain of Na/K-ATPase α1 Subunit on Src Kinase.

PubMed

Banerjee, Moumita; Duan, Qiming; Xie, Zijian

2015-01-01

Our previous studies have suggested that the α1 Na/K-ATPase interacts with Src to form a receptor complex. In vitro binding assays indicate an interaction between second cytosolic domain (CD2) of Na/K-ATPase α1 subunit and Src SH2 domain. Since SH2 domain targets Src to specific signaling complexes, we expressed CD2 as a cytosolic protein and studied whether it could act as a Src SH2 ligand in LLC-PK1 cells. Co-immunoprecipitation analyses indicated a direct binding of CD2 to Src, consistent with the in vitro binding data. Functionally, CD2 expression increased basal Src activity, suggesting a Src SH2 ligand-like property of CD2. Consistently, we found that CD2 expression attenuated several signaling pathways where Src plays an important role. For instance, although it increased surface expression of Na/K-ATPase, it decreased ouabain-induced activation of Src and ERK by blocking the formation of Na/K-ATPase/Src complex. Moreover, it also attenuated cell attachment-induced activation of Src/FAK. Consequently, CD2 delayed cell spreading, and inhibited cell proliferation. Furthermore, these effects appear to be Src-specific because CD2 expression had no effect on EGF-induced activation of EGF receptor and ERK. Hence, the new findings indicate the importance of Na/K-ATPase/Src interaction in ouabain-induced signal transduction, and support the proposition that the CD2 peptide may be utilized as a Src SH2 ligand capable of blocking Src-dependent signaling pathways via a different mechanism from a general Src kinase inhibitor.

Identification and functional characterization of an Src homology domain 3 domain-binding site on Cbl.

PubMed

Sanjay, Archana; Miyazaki, Tsuyoshi; Itzstein, Cecile; Purev, Enkhtsetseg; Horne, William C; Baron, Roland

2006-12-01

Cbl is an adaptor protein and ubiquitin ligase that binds and is phosphorylated by the nonreceptor tyrosine kinase Src. We previously showed that the primary interaction between Src and Cbl is mediated by the Src homology domain 3 (SH3) of Src binding to proline-rich sequences of Cbl. The peptide Cbl RDLPPPPPPDRP(540-551), which corresponds to residues 540-551 of Cbl, inhibited the binding of a GST-Src SH3 fusion protein to Cbl, whereas RDLAPPAPPPDR(540-551) did not, suggesting that Src binds to this site on Cbl in a class I orientation. Mutating prolines 543-548 reduced Src binding to the Cbl 479-636 fragment significantly more than mutating the prolines in the PPVPPR(494-499) motif, which was previously reported to bind Src SH3. Mutating Cbl prolines 543-548 to alanines substantially reduced Src binding to Cbl, Src-induced phosphorylation of Cbl, and the inhibition of Src kinase activity by Cbl. Expressing the mutated Cbl in osteoclasts induced a moderate reduction in bone-resorbing activity and increased amounts of Src protein. In contrast, disabling the tyrosine kinase-binding domain of full-length Cbl by mutating glycine 306 to glutamic acid, and thereby preventing the previously described binding of the tyrosine kinase-binding domain to the Src phosphotyrosine 416, had no effect on Cbl phosphorylation, the inhibition of Src activity by full-length Cbl, or bone resorption. These data indicate that the Cbl RDLPPPP(540-546) sequence is a functionally important binding site for Src.

Scleroderma renal crisis in a case of mixed connective tissue disease.

PubMed

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K.

PubMed

Sánchez-Margalet, V; Najib, S

1999-07-23

The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling. We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis 68 may be part of the signaling complexes of insulin receptor along with p85. In vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.

SGT1 is required in PcINF1/SRC2-1 induced pepper defense response by interacting with SRC2-1

PubMed Central

Liu, Zhi-qin; Liu, Yan-yan; Shi, Lan-ping; Yang, Sheng; Shen, Lei; Yu, Huan-xin; Wang, Rong-zhang; Wen, Jia-yu; Tang, Qian; Hussain, Ansar; Khan, Muhammad Ifnan; Hu, Jiong; Liu, Cai-ling; Zhang, Yang-wen; Cheng, Wei; He, Shui-lin

2016-01-01

PcINF1 was previously found to induce pepper defense response by interacting with SRC2-1, but the underlying mechanism remains uninvestigated. Herein, we describe the involvement of SGT1 in the PcINF1/SRC2-1-induced immunity. SGT1 was observed to be up-regulated by Phytophthora capsici inoculation and synergistically transient overexpression of PcINF1/SRC2-1 in pepper plants. SGT1-silencing compromised HR cell death, blocked H2O2 accumulation, and downregulated HR-associated and hormones-dependent marker genes’ expression triggered by PcINF1/SRC2-1 co-overexpression. The interaction between SRC2-1 and SGT1 was found by the yeast two hybrid system and was further confirmed by bimolecular fluorescence complementation and co-immunoprecipitation analyses. The SGT1/SRC2-1 interaction was enhanced by transient overexpression of PcINF1 and Phytophthora capsici inoculation, and SGT1-silencing attenuated PcINF1/SRC2-1 interaction. Additionally, by modulating subcellular localizations of SRC2-1, SGT1, and the interacting complex of SGT1/SRC2-1, it was revealed that exclusive nuclear targeting of the SGT1/SRC2-1 complex blocks immunity triggered by formation of SGT1/SRC2-1, and a translocation of the SGT1/SRC2-1 complex from the plasma membrane and cytoplasm to the nuclei upon the inoculation of P. capsici. Our data demonstrate that the SGT1/SRC2-1 interaction, and its nucleocytoplasmic partitioning, is involved in pepper’s immunity against P. capsici, thus providing a molecular link between Ca2+ signaling associated SRC2-1 and SGT1-mediated defense signaling. PMID:26898479

Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: evidence for haploinsufficiency.

PubMed

Weiss, Roy E; Gehin, Martine; Xu, Jianming; Sadow, Peter M; O'Malley, Bert W; Chambon, Pierre; Refetoff, Samuel

2002-04-01

Steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)-2 are homologous nuclear receptor coactivators. We have investigated their possible redundancy as thyroid hormone (TH) coactivators by measuring thyroid function in compound SRC-1 and TIF-2 knock out (KO) mice. Whereas SRC-1 KO (SRC-1(-/-)) mice are resistant to TH and SRC-1(+/-) are not, we now demonstrate that TIF-2 KO (TIF-2(-/-)) mice have normal thyroid function. Yet double heterozygous, SRC-1(+/-)/TIF-2(+/-) mice manifested resistance to TH of a similar degree as that in mice completely deficient in SRC-1. KO of both SRC-1 and TIF-2 resulted in marked increases of serum TH and thyrotropin concentrations. This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2.

Cbl Associates with Pyk2 and Src to Regulate Src Kinase Activity, αvβ3 Integrin-Mediated Signaling, Cell Adhesion, and Osteoclast Motility

PubMed Central

Sanjay, Archana; Houghton, Adam; Neff, Lynn; DiDomenico, Emilia; Bardelay, Chantal; Antoine, Evelyne; Levy, Joan; Gailit, James; Bowtell, David; Horne, William C.; Baron, Roland

2001-01-01

The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts and transfected 293 cells, we find that a molecular complex comprising Src, Pyk2, and Cbl functions to regulate cell adhesion and motility. The activation of integrin αvβ3 induces the [Ca2+]i-dependent phosphorylation of Pyk2 Y402, its association with Src SH2, Src activation, and the Src SH3-dependent recruitment and phosphorylation of c-Cbl. Furthermore, the PTB domain of Cbl is shown to bind to phosphorylated Tyr-416 in the activation loop of Src, the autophosphorylation site of Src, inhibiting Src kinase activity and integrin-mediated adhesion. Finally, we show that deletion of c Src or c-Cbl leads to a decrease in osteoclast migration. Thus, binding of αvβ3 integrin induces the formation of a Pyk2/Src/Cbl complex in which Cbl is a key regulator of Src kinase activity and of cell adhesion and migration. These findings may explain the osteopetrotic phenotype in the Src−/− mice. PMID:11149930

Changing concentration, lifetime and climate forcing of atmospheric methane

NASA Astrophysics Data System (ADS)

Lelieveld, Jos; Crutzen, Paul J.; Dentener, Frank J.

1998-04-01

Previous studies on ice core analyses and recent in situ measurements have shown that CH4 has increased from about 0.75 1.73μmol/mol during the past 150years. Here, we review sources and sink estimates and we present global 3D model calculations, showing that the main features of the global CH4 distribution are well represented. The model has been used to derive the total CH4 emission source, being about 600 Tg yr-1. Based on published results of isotope measurements the total contribution of fossil fuel related CH4 emissions has been estimated to be about 110 Tg yr-1. However, the individual coal, natural gas and oil associated CH4 emissions can not be accurately quantified. In particular natural gas and oil associated emissions remain speculative. Since the total anthropogenic CH4 source is about 410 Tg yr-1 (70% of the total source) and the mean recent atmospheric CH4 increase is 20 Tg yr-1 an anthropogenic source reduction of 5% could stabilize the atmospheric CH4 level. We have calculated the indirect chemical effects of increasing CH4 on climate forcing on the basis of global 3D chemistry-transport and radiative transfer calculations. These indicate an enhancement of the direct radiative effect by about 30%, in agreement with previous work. The contribution of CH4 (direct and indirect effects) to climate forcing during the past 150years is 0.57W m2 (direct 0.44W m2, indirect 0.13 W m2). This is about 35% of the climate forcing by CO2 (1.6W m2) and about 22% of the forcing by all long-lived greenhouse gases (2.6 W m2). Scenario calculations (IPCC-IS92a) indicate that the CH4 lifetime in the atmosphere increased by about 25 30%during the past 150years to a current value of 7.9years. Future lifetime changes are expected to be much smaller, about 6%, mostly due to the expected increase of tropospheric O3 (→OH) in the tropics. The global mean concentration of CH4 may increase to about 2.55μmol/mol, its lifetime is expected to increase to 8.4years in the year 2050. Further, we have calculated a CH4 global warming potential (GWP) of 21 (kgCH4/kgCO2) over a time horizon of 100years, in agreement with IPCC (1996). Scenario calculations indicate that the importance of the climate forcing by CH4 (including indirect effects) relative to that of CO2 will decrease in future; currently this is about 35%, while this is expected to decrease to about 15% in the year 2050.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, S. P.N.; Peterson, G. R.

Coal beneficiation is a generic term used for processes that prepare run-of-mine coal for specific end uses. It is also referred to as coal preparation or coal cleaning and is a means of reducing the sulfur and the ash contents of coal. Information is presented regarding current and potential coal beneficiation processes. Several of the processes reviewed, though not yet commercial, are at various stages of experimental development. Process descriptions are provided for these processes commensurate with the extent of information and time available to perform the evaluation of these processes. Conceptual process designs, preliminary cost estimates, and economic evaluationsmore » are provided for the more advanced (from a process development hierarchy viewpoint) processes based on production levels of 1500 and 15,000 tons/day (maf) of cleaned product coal. Economic evaluations of the coal preparation plants are conducted for several project financing schemes and at 12 and 15% annual after-tax rates of return on equity capital. A 9% annual interest rate is used on the debt fraction of the plant capital. Cleaned product coal prices are determined using the discounted cash flow procedure. The study is intended to provide information on publicly known coal beneficiation processes and to indicate the relative costs of various coal beneficiation processes. Because of severe timeconstraints, several potential coal beneficiation processes are not evaluated in great detail. It is recommended that an additional study be conducted to complement this study and to more fully appreciate the potentially significant role of coal beneficiation in the clean burning of coal.« less

Phosphopeptide occupancy and photoaffinity cross-linking of the v-Src SH2 domain attenuates tyrosine kinase activity.

PubMed

Garcia, P; Shoelson, S E; Drew, J S; Miller, W T

1994-12-02

Phosphorylation of c-Src at carboxyl-terminal Tyr-527 suppresses tyrosine kinase activity and transforming potential, presumably by facilitating the intramolecular interaction of the C terminus of Src with its SH2 domain. In addition, it has been shown previously that occupancy of the c-Src SH2 domain with a phosphopeptide stimulates c-Src kinase catalytic activity. We have performed analogous studies with v-Src, the transforming protein from Rous sarcoma virus, which has extensive homology with c-Src. v-Src lacks an autoregulatory phosphorylation site, and its kinase domain is constitutively active. Phosphopeptides corresponding to the sequences surrounding c-Src Tyr-527 and a Tyr-Glu-Glu-Ile motif from the hamster polyoma virus middle T antigen inhibit tyrosine kinase activity of baculovirus-expressed v-Src 2- and 4-fold, respectively. To determine the mechanism of this regulation, the Tyr-527 phosphopeptide was substituted with the photoactive amino acid p-benzoylphenylalanine at the adjacent positions (N- and C-terminal) to phosphotyrosine. These peptides photoinactivate the v-Src tyrosine kinase 5-fold in a time- and concentration-dependent manner. Furthermore, the peptides cross-link an isolated Src SH2 domain with similar rates and specificity. These data indicate that occupancy of the v-Src SH2 domain induces a conformational change that is transmitted to the kinase domain and attenuates tyrosine kinase activity.

Royal Society, Discussion on New Coal Chemistry, London, England, May 21, 22, 1980, Proceedings

NASA Astrophysics Data System (ADS)

1981-03-01

A discussion of new coal chemistry is presented. The chemical and physical structure of coal is examined in the first section, including structural studies of coal extracts, metal and metal complexes in coal and coal microporosity. The second section presents new advances in applied coal technology. The development of liquid fuels and chemicals from coal is given especial emphasis, with papers on the Sasol Synthol process, the Shell-Koppers gasification process, liquefaction and gasification in Germany, the Solvent Refined Coal process, the Exxon Donor Solvent liquefaction process and the Mobil Methanol-to-Gasoline process. Finally, some developments that will be part of the future of coal chemistry in the year 2000 are examined in the third section, including coal-based chemical complexes and the use of coal as an alternative source to oil for chemical feedstocks.

Comparative reduction of Giardia cysts, F+ coliphages, sulphite reducing clostridia and fecal coliforms by wastewater treatment processes.

PubMed

Nasser, Abidelfatah M; Benisti, Neta-Lee; Ofer, Naomi; Hovers, Sivan; Nitzan, Yeshayahu

2017-01-28

Advanced wastewater treatment processes are applied to prevent the environmental dissemination of pathogenic microorganisms. Giardia lamblia causes a severe disease called giardiasis, and is highly prevalent in untreated wastewater worldwide. Monitoring the microbial quality of wastewater effluents is usually based on testing for the levels of indicator microorganisms in the effluents. This study was conducted to compare the suitability of fecal coliforms, F+ coliphages and sulfide reducing clostridia (SRC) as indicators for the reduction of Giardia cysts in two full-scale wastewater treatment plants. The treatment process consists of activated sludge, coagulation, high rate filtration and either chlorine or UV disinfection. The results of the study demonstrated that Giardia cysts are highly prevalent in raw wastewater at an average concentration of 3600 cysts/L. Fecal coliforms, F+ coliphages and SRC were also detected at high concentrations in raw wastewater. Giardia cysts were efficiently removed (3.6 log 10 ) by the treatment train. The greatest reduction was observed for fecal coliforms (9.6 log 10 ) whereas the least reduction was observed for F+ coliphages (2.1 log 10 ) following chlorine disinfection. Similar reduction was observed for SRC by filtration and disinfection by either UV (3.6 log 10 ) or chlorine (3.3 log 10 ). Since F+ coliphage and SRC were found to be more resistant than fecal coliforms for the tertiary treatment processes, they may prove to be more suitable as indicators for Giardia. The results of this study demonstrated that advanced wastewater treatment may prove efficient for the removal of Giardia cysts and may prevent its transmission when treated effluents are applied for crop irrigation or streams restoration.

Immunohistochemical localization of steroid receptor coactivators in chondrosarcoma: an in vivo tissue microarray study.

PubMed

Li, Wei; Fu, Jingshu; Bian, Chen; Zhang, Jiqiang; Xie, Zhao

2014-12-01

Chondrosarcoma is the second most common type of primary bone malignancy following up osteosarcoma, characterized by resistance to conventional chemotherapeutic agents and radiation regimens. The p160 family members steroid receptor coactivator-1 and -3 (SRC-1 and SRC-3) have been implied in the regulation of cancer growth, migration, invasion, metastasis and chemotherapeutic resistance; but we still lack detailed information about the levels of SRCs in chondrosarcoma. In this study, expression of SRC-1 and SRC-3 in chondrosarcoma was examined by immunohistochemistry with tissue microarrays; the four score system (0, 1, 2 and 3) was used to evaluate the staining. The results showed that there were no gender-, site- or age-differences regarding the expression of SRC-1 or SRC-3 (p>0.05); organ (bone or cartilage) -differences were only detected for SRC-1 but not SRC-3 (p<0.05). Significant higher levels of SRC-1 and SRC-3 were detected in MDC and PDC when compared to WDC. Our study clearly demonstrated differentiation-dependant expression of SRC-1 and SRC-3 in chondrosarcoma, may be novel targets for the prognosis and/or treatment of chondrosarcoma, would have opened a new avenue and established foundation for studying chondrosarcoma. Copyright © 2014 Elsevier GmbH. All rights reserved.

The use of assistive technology in the everyday lives of young people living with dementia and their caregivers. Can a simple remote control make a difference?

PubMed

Jentoft, Rita; Holthe, Torhild; Arntzen, Cathrine

2014-12-01

This study was a part of a larger study exploring the impact of assistive technology on the lives of young people living with dementia (YPD). This paper focuses on one of the most useful devices, the simple remote control (SRC). The objective was to explore the reason why the SRC is significant and beneficial in the everyday lives of YPD and their caregivers. This qualitative longitudinal study had a participatory design. Eight participants received an SRC. The range for using it was 0-15 months. In-depth interviews and observations were conducted at baseline and repeated every third month up to 18 months. A situated learning approach was used in the analysis to provide a deeper understanding of the significance and use of SRC. Young people having dementia spend a substantial amount of time alone. Watching television was reported to be important, but handling remote controls was challenging and created a variety of problems. YPD learned to use SRC, which made important differences in the everyday lives of all family members. Comprehensive support from caregivers and professionals was important for YPD in the learning process. The SRC was deemed a success because it solved challenges regarding the use of television in everyday lives of families. The design was recognizable and user-friendly, thus allowing YPD to learn its operation. Access to professional support and advice regarding assistive technology is vital for establishing a system for follow-up and continued collaboration to make future adaptations and adjustments.

Src binds cortactin through an SH2 domain cystine-mediated linkage.

PubMed

Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

2012-12-15

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

Src binds cortactin through an SH2 domain cystine-mediated linkage

PubMed Central

Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

2012-01-01

Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045

Ableson Kinases Negatively Regulate Invadopodia Function and Invasion in Head and Neck Squamous Cell Carcinoma by Inhibiting an HB-EGF Autocrine Loop

PubMed Central

Hayes, Karen E.; Walk, Elyse L.; Ammer, Amanda Gatesman; Kelley, Laura C.; Martin, Karen H.; Weed, Scott A.

2014-01-01

Head and neck squamous cell carcinoma (HNSCC) has a proclivity for locoregional invasion. HNSCC mediates invasion in part through invadopodia-based proteolysis of the extracellular matrix (ECM). Activation of Src, Erk1/2, Abl and Arg downstream of epidermal growth factor receptor (EGFR) modulates invadopodia activity through phosphorylation of the actin regulatory protein cortactin. In MDA-MB-231 breast cancer cells, Abl and Arg function downstream of Src to phosphorylate cortactin, promoting invadopodia ECM degradation activity and thus assigning a pro-invasive role for Ableson kinases. We report that Abl kinases have an opposite, negative regulatory role in HNSCC where they suppress invadopodia and tumor invasion. Impairment of Abl expression or Abl kinase activity with imatinib mesylate enhanced HNSCC matrix degradation and 3D collagen invasion, functions that were impaired in MDA-MB-231. HNSCC lines with elevated EGFR and Src activation did not contain increased Abl or Arg kinase activity, suggesting Src could bypass Abl/Arg to phosphorylate cortactin and promote invadopodia ECM degradation. Src transformed Abl−/−/Arg−/− fibroblasts produced ECM degrading invadopodia containing pY421 cortactin, indicating that Abl/Arg are dispensable for invadopodia function in this system. Imatinib treated HNSCC cells had increased EGFR, Erk1/2 and Src activation, enhancing cortactin pY421 and pS405/418 required for invadopodia function. Imatinib stimulated shedding of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) from HNSCC cells, where soluble HB-EGF enhanced invadopodia ECM degradation in HNSCC but not in MDA-MB-231. HNSCC cells treated with inhibitors of the EGFR invadopodia pathway indicated that EGFR and Src are required for invadopodia function. Collectively our results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating a EGFR-Src-cortactin cascade, in contrast to the invasion promoting functions of Abl kinases in breast and other cancer types. Our results provide mechanistic support for recent failed HNSCC clinical trials utilizing imatinib. PMID:23146907

Calcium-permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors Trigger Neuronal Nitric-oxide Synthase Activation to Promote Nerve Cell Death in an Src Kinase-dependent Fashion*

PubMed Central

Socodato, Renato; Santiago, Felipe N.; Portugal, Camila C.; Domingues, Ana F.; Santiago, Ana R.; Relvas, João B.; Ambrósio, António F.; Paes-de-Carvalho, Roberto

2012-01-01

In the retina information decoding is dependent on excitatory neurotransmission and is critically modulated by AMPA glutamate receptors. The Src-tyrosine kinase has been implicated in modulating neurotransmission in CNS. Thus, our main goal was to correlate AMPA-mediated excitatory neurotransmission with the modulation of Src activity in retinal neurons. Cultured retinal cells were used to access the effects of AMPA stimulation on nitric oxide (NO) production and Src phosphorylation. 4-Amino-5-methylamino-2′,7′-difluorofluorescein diacetate fluorescence mainly determined NO production, and immunocytochemistry and Western blotting evaluated Src activation. AMPA receptors activation rapidly up-regulated Src phosphorylation at tyrosine 416 (stimulatory site) and down-regulated phosphotyrosine 527 (inhibitory site) in retinal cells, an effect mainly mediated by calcium-permeable AMPA receptors. Interestingly, experiments confirmed that neuronal NOS was activated in response to calcium-permeable AMPA receptor stimulation. Moreover, data suggest NO pathway as a key regulatory signaling in AMPA-induced Src activation in neurons but not in glial cells. The NO donor SNAP (S-nitroso-N-acetyl-dl-penicillamine) and a soluble guanylyl cyclase agonist (YC-1) mimicked AMPA effect in Src Tyr-416 phosphorylation, reinforcing that Src activation is indeed modulated by the NO pathway. Gain and loss-of-function data demonstrated that ERK is a downstream target of AMPA-induced Src activation and NO signaling. Furthermore, AMPA stimulated NO production in organotypic retinal cultures and increased Src activity in the in vivo retina. Additionally, AMPA-induced apoptotic retinal cell death was regulated by both NOS and Src activity. Because Src activity is pivotal in several CNS regions, the data presented herein highlight that Src modulation is a critical step in excitatory retinal cell death. PMID:22992730

Src kinase regulation by phosphorylation and dephosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roskoski, Robert

2005-05-27

Src and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTP{alpha}, PTP{epsilon}, and PTP{lambda}. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shownmore » to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined.« less

miR-137 Targets p160 Steroid Receptor Coactivators SRC1, SRC2, and SRC3 and Inhibits Cell Proliferation

PubMed Central

Eedunuri, Vijay Kumar; Rajapakshe, Kimal; Fiskus, Warren; Geng, Chuandong; Chew, Sue Anne; Foley, Christopher; Shah, Shrijal S.; Shou, John; Mohamed, Junaith S.; O'Malley, Bert W.

2015-01-01

The p160 family of steroid receptor coactivators (SRCs) are pleiotropic transcription factor coactivators and “master regulators” of gene expression that promote cancer cell proliferation, survival, metabolism, migration, invasion, and metastasis. Cancers with high p160 SRC expression exhibit poor clinical outcomes and resistance to therapy, highlighting the SRCs as critical oncogenic drivers and, thus, therapeutic targets. microRNAs are important epigenetic regulators of protein expression. To examine the regulation of p160 SRCs by microRNAs, we used and combined 4 prediction algorithms to identify microRNAs that could target SRC1, SRC2, and SRC3 expression. For validation of these predictions, we assessed p160 SRC protein expression and cell viability after transfection of corresponding microRNA mimetics in breast cancer, uveal melanoma, and prostate cancer (PC) cell lines. Transfection of selected microRNA mimetics into breast cancer, uveal melanoma, and PC cells depleted SRC protein expression levels and exerted potent antiproliferative activity in these cell types. In particular, microRNA-137 (miR-137) depleted expression of SRC1, SRC2, and very potently, SRC3. The latter effect can be attributed to the presence of 3 miR-137 recognition sequences within the SRC3 3′-untranslated region. Using reverse phase protein array analysis, we identified a network of proteins, in addition to SRC3, that were modulated by miR-137 in PC cells. We also found that miR-137 and its host gene are epigenetically silenced in human cancer specimens and cell lines. These results support the development and testing of microRNA-based therapies (in particular based on restoring miR-137 levels) for targeting the oncogenic family of p160 SRCs in cancer. PMID:26066330

Calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors trigger neuronal nitric-oxide synthase activation to promote nerve cell death in an Src kinase-dependent fashion.

PubMed

Socodato, Renato; Santiago, Felipe N; Portugal, Camila C; Domingues, Ana F; Santiago, Ana R; Relvas, João B; Ambrósio, António F; Paes-de-Carvalho, Roberto

2012-11-09

In the retina information decoding is dependent on excitatory neurotransmission and is critically modulated by AMPA glutamate receptors. The Src-tyrosine kinase has been implicated in modulating neurotransmission in CNS. Thus, our main goal was to correlate AMPA-mediated excitatory neurotransmission with the modulation of Src activity in retinal neurons. Cultured retinal cells were used to access the effects of AMPA stimulation on nitric oxide (NO) production and Src phosphorylation. 4-Amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence mainly determined NO production, and immunocytochemistry and Western blotting evaluated Src activation. AMPA receptors activation rapidly up-regulated Src phosphorylation at tyrosine 416 (stimulatory site) and down-regulated phosphotyrosine 527 (inhibitory site) in retinal cells, an effect mainly mediated by calcium-permeable AMPA receptors. Interestingly, experiments confirmed that neuronal NOS was activated in response to calcium-permeable AMPA receptor stimulation. Moreover, data suggest NO pathway as a key regulatory signaling in AMPA-induced Src activation in neurons but not in glial cells. The NO donor SNAP (S-nitroso-N-acetyl-DL-penicillamine) and a soluble guanylyl cyclase agonist (YC-1) mimicked AMPA effect in Src Tyr-416 phosphorylation, reinforcing that Src activation is indeed modulated by the NO pathway. Gain and loss-of-function data demonstrated that ERK is a downstream target of AMPA-induced Src activation and NO signaling. Furthermore, AMPA stimulated NO production in organotypic retinal cultures and increased Src activity in the in vivo retina. Additionally, AMPA-induced apoptotic retinal cell death was regulated by both NOS and Src activity. Because Src activity is pivotal in several CNS regions, the data presented herein highlight that Src modulation is a critical step in excitatory retinal cell death.

Differential subcellular membrane recruitment of Src may specify its downstream signalling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diesbach, Philippe de; Medts, Thierry; Carpentier, Sarah

2008-04-15

Most Src family members are diacylated and constitutively associate with membrane 'lipid rafts' that coordinate signalling. Whether the monoacylated Src, frequently hyperactive in carcinomas, also localizes at 'rafts' remains controversial. Using polarized MDCK cells expressing the thermosensitive v-Src/tsLA31 variant, we here addressed how Src tyrosine-kinase activation may impact on its (i) membrane recruitment, in particular to 'lipid rafts'; (ii) subcellular localization; and (iii) signalling. The kinetics of Src-kinase thermoactivation correlated with its recruitment from the cytosol to sedimentable membranes where Src largely resisted solubilisation by non-ionic detergents at 4 deg. C and floated into sucrose density gradients like caveolin-1 andmore » flotillin-2, i.e. 'lipid rafts'. By immunofluorescence, activated Src showed a dual localization, at apical endosomes/macropinosomes and at the apical plasma membrane. The plasma membrane Src pool did not colocalize with caveolin-1 and flotillin-2, but extensively overlapped GM1 labelling by cholera toxin. Severe ({approx} 70%) cholesterol extraction with methyl-{beta}-cyclodextrin (M{beta}CD) did not abolish 'rafts' floatation, but strongly decreased Src association with floating 'rafts' and abolished its localization at the apical plasma membrane. Src activation independently activated first the MAP-kinase - ERK1/2 pathway, then the PI3-kinase - Akt pathway. MAP-kinase - ERK1/2 activation was insensitive to M{beta}CD, which suppressed Akt phosphorylation and apical endocytosis induced by Src, both depending on the PI3-kinase pathway. We therefore suggest that activated Src is recruited at two membrane compartments, allowing differential signalling, first via ERK1/2 at 'non-raft' domains on endosomes, then via PI3-kinase-Akt on a distinct set of 'rafts' at the apical plasma membrane. Whether this model is applicable to c-Src remains to be examined.« less

Differential Prognostic Implications of Gastric Signet Ring Cell Carcinoma

PubMed Central

Chon, Hong Jae; Hyung, Woo Jin; Kim, Chan; Park, Sohee; Kim, Jie-Hyun; Park, Chan Hyuk; Ahn, Joong Bae; Kim, Hyunki; Chung, Hyun Cheol; Rha, Sun Young; Noh, Sung Hoon; Jeung, Hei-Cheul

2017-01-01

Objective: The aim of this study was to analyze the clinicopathologic characteristics and prognosis of signet ring cell carcinoma (SRC) according to disease status (early vs advanced gastric cancer) in gastric cancer patients. Background: The prognostic implication of gastric SRC remains a subject of debate. Methods: A retrospective analysis was performed using the clinical records of 7667 patients including 1646 SRC patients who underwent radical gastrectomy between 2001 and 2010. A further analysis was also performed after dividing patients into three groups according to histologic subtype: SRC, well-to-moderately differentiated (WMD), and poorly differentiated adenocarcinoma. Results: SRC patients have younger age distribution and female predominance compared with other histologic subtypes. Notably, the distribution of T stage of SRC patients was distinct, located in extremes (T1: 66.2% and T4: 20%). Moreover, the prognosis of SRC in early gastric cancer and advanced gastric cancer was contrasting. In early gastric cancer, SRC demonstrated more favorable prognosis than WMD after adjusting for age, sex, and stage. In contrast, SRC in advanced gastric cancer displayed worse prognosis than WMD. As stage increased, survival outcomes of SRC continued to worsen compared with WMD. Conclusions: Although conferring favorable prognosis in early stage, SRC has worse prognostic impact as disease progresses. The longstanding controversy of SRC on prognosis may result from disease status at presentation, which leads to differing prognosis compared with tubular adenocarinoma. PMID:27232252

Variant estrogen receptor-c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation.

PubMed

Li, Lei; Hisamoto, Koji; Kim, Kyung Hee; Haynes, M Page; Bauer, Philip M; Sanjay, Archana; Collinge, Mark; Baron, Roland; Sessa, William C; Bender, Jeffrey R

2007-10-16

Little is known about the tyrosine kinase c-Src's function in the systemic circulation, in particular its role in arterial responses to hormonal stimuli. In human aortic and venous endothelial cells, c-Src is indispensable for 17beta-estradiol (E2)-stimulated phosphatidylinositol 3-kinase/Akt/endothelial NO synthase (eNOS) pathway activation, a possible mechanism in E2-mediated vascular protection. Here we show that c-Src supports basal and E2-stimulated NO production and is required for E2-induced vasorelaxation in murine aortas. Only membrane c-Src is structurally and functionally involved in E2-induced eNOS activation. Independent of c-Src kinase activity, c-Src is associated with an N-terminally truncated estrogen receptor alpha variant (ER46) and eNOS in the plasma membrane through its "open" (substrate-accessible) conformation. In the presence of E2, c-Src kinase is activated by membrane ER46 and in turn phosphorylates ER46 for subsequent ER46 and c-Src membrane recruitment, the assembly of an eNOS-centered membrane macrocomplex, and membrane-initiated eNOS activation. Overall, these results provide insights into a critical role for the tyrosine kinase c-Src in estrogen-stimulated arterial responses, and in membrane-initiated rapid signal transduction, for which obligate complex assembly and localization require the c-Src substrate-accessible structure.

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

PubMed Central

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-01-01

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration. PMID:26681405

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

PubMed

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-12-18

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

Preliminary study of semi-refined carrageenan (SRC) as secondary gelling agent in natural rubber (NR) latex foam

NASA Astrophysics Data System (ADS)

Norhazariah, S.; Azura, A. R.; Azahari, B.; Sivakumar, R.

2017-12-01

Semi-refined carrageenan (SRC) product is considerably cheaper and easier to produce as a natural polysaccharide, which was utilized in food and other product application. However, the application in latex is limited. The aim of this work is to evaluate the SRC produced from low industrial grade seaweed (LIGS) in the latex foam application. The FTIR spectra showed the SRC produced as kappa type carrageenan with lower sulfur content compared to native LIGS. NR latex foam is produced by using the Dunlop method with some modifications. The effect of SRC loading as a secondary gelling agent in NR latex foam is investigated. The density and morphology of the NR latex foam with the addition of the SRC are analyzed. NR latex foam density increased with SRC loading and peaked at 1.8 phr SRC. The addition of SRC has induced the bigger cell size compared to the cell size of the control NR latex foam, as shown in the optical micrograph. It can be concluded that SRC LIGS could be acted as secondary gelling agent in NR latex foam.

Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions.

PubMed

Tu, Chun; Ortega-Cava, Cesar F; Winograd, Paul; Stanton, Marissa Jo; Reddi, Alagarsamy Lakku; Dodge, Ingrid; Arya, Ranjana; Dimri, Manjari; Clubb, Robert J; Naramura, Mayumi; Wagner, Kay-Uwe; Band, Vimla; Band, Hamid

2010-09-14

Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs requires the endosomal-sorting complexes required for transport (ESCRT) pathway. Tsg101 deletion also led to impaired Src-dependent activation of STAT3 and focal adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or Rab7 function led to the accumulation of active Src at aberrant LE/LY compartments followed by its loss. Analyses using fluorescence recovery after photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway-dependent. These results reveal a critical role for an ESCRT pathway-dependent LE/LY trafficking step in Src function by promoting localization of active Src to FAs.

SRC activates TAZ for intestinal tumorigenesis and regeneration.

PubMed

Byun, Mi Ran; Hwang, Jun-Ha; Kim, A Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Hwang, Eun Sook; Hong, Jeong-Ho

2017-12-01

Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, Apc Min/+ , activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective equipment and player characteristics associated with the incidence of sport-related concussion in high school football players: a multifactorial prospective study.

PubMed

McGuine, Timothy A; Hetzel, Scott; McCrea, Michael; Brooks, M Alison

2014-10-01

The incidence of sport-related concussion (SRC) in high school football is well documented. However, limited prospective data are available regarding how player characteristics and protective equipment affect the incidence of SRC. To determine whether the type of protective equipment (helmet and mouth guard) and player characteristics affect the incidence of SRC in high school football players. Cohort study; Level of evidence, 2. Certified athletic trainers (ATs) at each high school recorded the type of helmet worn (brand, model, purchase year, and recondition status) by each player as well as information regarding players' demographics, type of mouth guard used, and history of SRC. The ATs also recorded the incidence and days lost from participation for each SRC. Incidence of SRC was compared for various helmets, type of mouth guard, history of SRC, and player demographics. A total of 2081 players (grades 9-12) enrolled during the 2012 and/or 2013 football seasons (2287 player-seasons) and participated in 134,437 football (practice or competition) exposures. Of these players, 206 (9%) sustained a total of 211 SRCs (1.56/1000 exposures). There was no difference in the incidence of SRC (number of helmets, % SRC [95% CI]) for players wearing Riddell (1171, 9.1% [7.6%-11.0%]), Schutt (680, 8.7% [6.7%-11.1%]), or Xenith (436, 9.2% [6.7%-12.4%]) helmets. Helmet age and recondition status did not affect the incidence of SRC. The rate of SRC (hazard ratio [HR]) was higher in players who wore a custom mouth guard (HR = 1.69 [95% CI, 1.20-2.37], P < .001) than in players who wore a generic mouth guard. The rate of SRC was also higher (HR = 1.96 [95% CI, 1.40-2.73], P < .001) in players who had sustained an SRC within the previous 12 months (15.1% of the 259 players [95% CI, 11.0%-20.1%]) than in players without a previous SRC (8.2% of the 2028 players [95% CI, 7.1%-9.5%]). Incidence of SRC was similar regardless of the helmet brand (manufacturer) worn by high school football players. Players who had sustained an SRC within the previous 12 months were more likely to sustain an SRC than were players without a history of SRC. Sports medicine providers who work with high school football players need to realize that factors other than the type of protective equipment worn affect the risk of SRC in high school players. © 2014 The Author(s).

Genesis failure investigation report : JPL Failure Review Board, Avionics Sub-Team

NASA Technical Reports Server (NTRS)

Klein, John; Manning, Rob; Barry, Ed; Donaldson, Jim; Rivellini, Tom; Battel, Steven; Savino, Joe; Lee, Wayne; Dalton, Jerry; Underwood, Mark;

Restoration Of MEX SRC Images For Improved Topography: A New Image Product

NASA Astrophysics Data System (ADS)

Duxbury, T. C.

2012-12-01

Surface topography is an important constraint when investigating the evolution of solar system bodies. Topography is typically obtained from stereo photogrammetric or photometric (shape from shading) analyses of overlapping / stereo images and from laser / radar altimetry data. The ESA Mars Express Mission [1] carries a Super Resolution Channel (SRC) as part of the High Resolution Stereo Camera (HRSC) [2]. The SRC can build up overlapping / stereo coverage of Mars, Phobos and Deimos by viewing the surfaces from different orbits. The derivation of high precision topography data from the SRC raw images is degraded because the camera is out of focus. The point spread function (PSF) is multi-peaked, covering tens of pixels. After registering and co-adding hundreds of star images, an accurate SRC PSF was reconstructed and is being used to restore the SRC images to near blur free quality. The restored images offer a factor of about 3 in improved geometric accuracy as well as identifying the smallest of features to significantly improve the stereo photogrammetric accuracy in producing digital elevation models. The difference between blurred and restored images provides a new derived image product that can provide improved feature recognition to increase spatial resolution and topographic accuracy of derived elevation models. Acknowledgements: This research was funded by the NASA Mars Express Participating Scientist Program. [1] Chicarro, et al., ESA SP 1291(2009) [2] Neukum, et al., ESA SP 1291 (2009). A raw SRC image (h4235.003) of a Martian crater within Gale crater (the MSL landing site) is shown in the upper left and the restored image is shown in the lower left. A raw image (h0715.004) of Phobos is shown in the upper right and the difference between the raw and restored images, a new derived image data product, is shown in the lower right. The lower images, resulting from an image restoration process, significantly improve feature recognition for improved derived topographic accuracy.

Sex Differences in Time to Return-to-Play Progression After Sport-Related Concussion.

PubMed

Stone, Sarah; Lee, Bobby; Garrison, J Craig; Blueitt, Damond; Creed, Kalyssa

2016-10-03

Recently, female sports participation has increased, and there is a tendency for women to experience more symptoms and variable presentation after sport-related concussion (SRC). The purpose of this study was to determine whether sex differences exist in time to begin a return-to-play (RTP) progression after an initial SRC. After initial SRC, female athletes (11-20 years old) would take longer to begin an RTP progression compared with age-matched male athletes. Retrospective cohort study. Level 3. A total of 579 participants (365 males [mean age, 15.0 ± 1.7 years], 214 females [mean age, 15.2 ± 1.5 years]), including middle school, high school, and collegiate athletes who participated in various sports and experienced an initial SRC were included and underwent retrospective chart review. The following information was collected: sex, age at injury, sport, history of prior concussion, date of injury, and date of initiation of RTP progression. Participants with a history of more than 1 concussion or injury sustained from non-sport-related activity were excluded. Despite American football having the greatest percentage (49.2%) of sport participation, female athletes took significantly longer to start an RTP progression after an initial SRC (29.1 ± 26.3 days) compared with age-matched male athletes (22.7 ± 18.3 days; P = 0.002). On average, female athletes took approximately 6 days longer to begin an RTP progression compared with age-matched male athletes. This suggests that sex differences exist between athletes, ages 11 to 20 years, with regard to initiation of an RTP progression after SRC. Female athletes may take longer to recover after an SRC, and therefore, may take longer to return to sport. Sex should be considered as part of the clinical decision-making process when determining plan of care for this population. © 2016 The Author(s).

Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

Measurement science and manufacturing science research

NASA Technical Reports Server (NTRS)

Phillips, D. Howard

1987-01-01

The research program of Semiconductor Research Corp. is managed as three overlapping areas: Manufacturing Sciences, Design Sciences and Microstructure Sciences. A total of 40 universities are participating in the performance of over 200 research tasks. The goals and direction of Manufacturing Sciences research became more clearly focused through the efforts of the Manufacturing Sciences Committee of the SRC Technical Advisory Board (TAB). The mission of the SRC Manufacturing Research is the quantification, control, and understanding of semiconductor manufacturing process necessary to achieve a predictable and profitable product output in the competitive environment of the next decade. The 1994 integrated circuit factory must demonstrate a three level hierarchy of control: (1) operation control, (2) process control, and (3) process design. These levels of control are briefly discussed.

--No Title--

Science.gov Websites

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Sex Differences in High School Athletes' Knowledge of Sport-Related Concussion Symptoms and Reporting Behaviors.

PubMed

Wallace, Jessica; Covassin, Tracey; Beidler, Erica

2017-07-01

  Recent researchers have reported that athletes' knowledge of sport-related concussion (SRC) has increased but that athletes still lack knowledge of all the signs and symptoms of SRC. Understanding the signs and symptoms of SRC and the dangers of playing while symptomatic are critical to reporting behaviors in high school athletes.   To examine sex differences in knowledge of SRC symptoms and reasons for not reporting a suspected SRC to an authoritative figure in high school athletes.   Cross-sectional study.   Survey.   A total of 288 athletes across 7 sports (198 males [68.8%] and 90 females [31.2%]).   A validated knowledge-of-SRC survey consisted of demographic questions, a list of 21 signs and symptoms of SRC, and reasons why athletes would not report their SRC. The independent variable was sex. Athlete knowledge of SRC symptoms was assessed by having participants identify the signs and symptoms of SRC from a list of 21 symptoms. Knowledge scores were calculated by summing the number of correct answers; scores ranged from 0 to 21, with a score closer to 21 representing greater knowledge. Reporting-behavior questions asked athletes to choose reasons why they decided not to report any possible SRC signs and symptoms to an authoritative figure.   A sex difference in total SRC symptom knowledge was found (F 286 = 4.97, P = .03, d = 0.26). Female high school athletes had more total SRC symptom knowledge (mean ± standard deviation = 15.06 ± 2.63; 95% confidence interval = 14.54, 15.57) than males (14.36 ± 2.76; 95% confidence interval = 13.97, 14.74). Chi-square tests identified significant relationships between sex and 8 different reasons for not reporting an SRC.   High school males and females had similar SRC symptom knowledge; however, female athletes were more likely to report their concussive symptoms to an authoritative figure.

Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture

PubMed Central

Tan, Boon Siang Nicholas; Kwek, Joly; Wong, Chong Kum Edwin; Saner, Nicholas J.; Yap, Charlotte; Felquer, Fernando; Morris, Michael B.; Gardner, David K.; Rathjen, Peter D.; Rathjen, Joy

2016-01-01

Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation. PMID:27723793

Cyr61 as mediator of Src signaling in triple negative breast cancer cells

PubMed Central

Molinari, Agnese; Wagner, Kay-Uwe; Losada, Jesús Pérez; Ciordia, Sergio; Albar, Juan Pablo; Martín-Pérez, Jorge

2015-01-01

SFKs are involved in tumorigenesis and metastasis. Here we analyzed c-Src contribution to initial steps of metastasis by tetracycline-dependent expression of a specific shRNA-c-Src, which suppressed c-Src mRNA and protein levels in metastatic MDA-MB-231 cells. c-Src suppression did not alter cell proliferation or survival, but it significantly reduced anchorage-independent growth. Concomitantly with diminished tyrosine-phosphorylation/activation of Fak, caveolin-1, paxillin and p130CAS, c-Src depletion also inhibited cellular migration, invasion and transendothelial migration. Quantitative proteomic analyses of the secretome showed that Cyr61 levels, which were detected in the exosomal fraction, were diminished upon shRNA-c-Src expression. In contrast, Cyr61 expression was unaltered inside cells. Cyr61 partially colocalized with cis-Golgi gp74 marker and with exosomal marker CD63, but c-Src depletion did not alter their cellular distribution. In SUM159PT cells, transient c-Src suppression also reduced secreted exosomal Cyr61 levels. Furthermore, conditional expression of a c-Src dominant negative mutant (SrcDN, c-Src-K295M/Y527F) in MDA-MB-231 and in SUM159PT diminished secreted Cyr61 as well. Cyr61 transient suppression in MDA-MB-231 inhibited invasion and transendothelial migration. Finally, in both MDA-MB-231 and SUM159PT, a neutralizing Cyr61 antibody restrained migration. Collectively, these results suggest that c-Src regulates secreted proteins, including the exosomal Cyr61, which are involved in modulating the metastatic potential of triple negative breast cancer cells. PMID:25980494

Application studies of RFID technology in the process of coal logistics transport

NASA Astrophysics Data System (ADS)

Qiao, Bingqin; Chang, Xiaoming; Hao, Meiyan; Kong, Dejin

2012-04-01

For quality control problems in coal transport, RFID technology has been proposed to be applied to coal transportation process. The whole process RFID traceability system from coal production to consumption has been designed and coal supply chain logistics tracking system integration platform has been built, to form the coal supply chain traceability and transport tracking system and providing more and more transparent tracking and monitoring of coal quality information for consumers of coal. Currently direct transport and combined transport are the main forms of coal transportation in China. The means of transport are cars, trains and ships. In the booming networking environment of RFID technology, the RFID technology will be applied to coal logistics and provide opportunity for the coal transportation tracking in the process transportation.

The Tyrosine Kinase Activity of c-Src Regulates Actin Dynamics and Organization of Podosomes in Osteoclasts

PubMed Central

Destaing, Olivier; Sanjay, Archana; Itzstein, Cecile; Horne, William C.; Toomre, Derek

2008-01-01

Podosomes are dynamic actin-rich structures composed of a dense F-actin core surrounded by a cloud of more diffuse F-actin. Src performs one or more unique functions in osteoclasts (OCLs), and podosome belts and bone resorption are impaired in the absence of Src. Using Src−/− OCLs, we investigated the specific functions of Src in the organization and dynamics of podosomes. We found that podosome number and the podosome-associated actin cloud were decreased in Src−/− OCLs. Videomicroscopy and fluorescence recovery after photobleaching analysis revealed that the life span of Src−/− podosomes was increased fourfold and that the rate of actin flux in the core was decreased by 40%. Thus, Src regulates the formation, structure, life span, and rate of actin polymerization in podosomes and in the actin cloud. Rescue of Src−/− OCLs with Src mutants showed that both the kinase activity and either the SH2 or the SH3 binding domain are required for Src to restore normal podosome organization and dynamics. Moreover, inhibition of Src family kinase activities in Src−/− OCLs by Src inhibitors or by expressing dominant-negative SrcK295M induced the formation of abnormal podosomes. Thus, Src is an essential regulator of podosome structure, dynamics and organization. PMID:17978100

The effect of processing temperature and time on the structure and fracture characteristics of self-reinforced composite poly(methyl methacrylate).

PubMed

Wright, D D; Gilbert, J L; Lautenschlager, E P

1999-08-01

A novel material, self-reinforced composite poly(methyl methacrylate) (SRC-PMMA) has been previously developed in this laboratory. It consists of high-strength PMMA fibers embedded in a matrix of PMMA derived from the fibers. As a composite material, uniaxial SRC-PMMA has been shown to have greatly improved flexural, tensile, fracture toughness and fatigue properties when compared to unreinforced PMMA. Previous work examined one empirically defined processing condition. This work systematically examines the effect of processing time and temperature on the thermal properties, fracture toughness and fracture morphology of SRC-PMMA produced by a hot compaction method. Differential scanning calorimetry (DSC) shows that composites containing high amounts of retained molecular orientation exhibit both endothermic and exothermic peaks which depend on processing times and temperatures. An exothermic release of energy just above Tg is related to the release of retained molecular orientation in the composites. This release of energy decreases linearly with increasing processing temperature or time for the range investigated. Fracture toughness results show a maximum fracture toughness of 3.18 MPa m1/2 for samples processed for 65 min at 128 degrees C. Optimal structure and fracture toughness are obtained in composites which have maximum interfiber bonding and minimal loss of molecular orientation. Composite fracture mechanisms are highly dependent on processing. Low processing times and temperatures result in more interfiber/matrix fracture, while higher processing times and temperatures result in higher ductility and more transfiber fracture. Excessive processing times result in brittle failure. Copyright 1999 Kluwer Academic Publishers

76 FR 21404 - National Park Service Alaska Region's Subsistence Resource Commission (SRC) Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... Resource Commission (SRC) program. SUMMARY: The Gates of the Arctic National Park SRC will meet to develop... to do so. Gates of the Arctic National Park SRC Meeting Date and Location: The Gates of the Arctic... weather or local circumstances. For Further Information on the Gates of the Arctic National Park SRC...

75 FR 51103 - Notice of Public Meetings for the National Park Service (NPS) Alaska Region's Subsistence...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... SRC and Wrangell-St. Elias SRC plan to meet to develop and continue work on National Park Service (NPS... SRC Meeting Date and Location: The Lake Clark National Park SRC meeting will be held on Tuesday... Alaska Regional Office, at (907) 644- 3603. Aniakchak National Monument SRC Meeting Date and Location...

Proceedings: Fourteenth annual EPRI conference on fuel science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-05-01

EPRI's Fourteenth Annual Contractors' Conference on Fuel Science was held on May 18--19, 1989 in Palo Alto, CA. The conference featured results of work on coal science, coal liquefaction, methanol production, and coal oil coprocessing and coal upgrading. The following topics were discussed: recent development in coal liquefaction at the Wilsonville Clean Coal Research Center; British coal's liquid solvent extraction (LSE) process; feedstock reactivity in coal/oil co-processing; utility applications for coal-oil coprocessed fuels; effect of coal rank and quality on two-stage liquefaction; organic sulfur compounds in coals; the perchloroethylene refining process of high-sulfur coals; extraction of sulfur coals; extraction ofmore » sulfur from coal; agglomeration of bituminous and subbituminous coals; solubilization of coals by cell-free extracts derived from polyporus versicolor; remediation technologies and services; preliminary results from proof-of-concept testing of heavy liquid cyclone cleaning technology; clean-up of soil contaminated with tarry/oily organics; midwest ore processing company's coal benefication technology: recent prep plant, scale and laboratory activities; combustion characterization of coal-oil agglomerate fuels; status report on the liquid phase methanol project; biomimetic catalysis; hydroxylation of C{sub 2} {minus} C{sub 3} and cycloc{sub 6} hydrocarbons with Fe cluster catalysts as models for methane monooxygenase enzyme; methanol production scenarios; and modeling studies of the BNL low temperature methanol catalyst. Individual projects are processed separately for the data bases.« less

The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing.

PubMed

Hannemann, Sebastian; Madrid, Ricardo; Stastna, Jana; Kitzing, Thomas; Gasteier, Judith; Schönichen, André; Bouchet, Jerome; Jimenez, Alberto; Geyer, Matthias; Grosse, Robert; Benichou, Serge; Fackler, Oliver T

2008-10-10

Diaphanous-related formins (DRFs) mediate GTPase-triggered actin rearrangements to regulate central cellular processes, such as cell motility and cytokinesis. The DRF FHOD1 interacts with the Rho-GTPase Rac1 and mediates formation of actin stress fibers in its deregulated form; the physiologically relevant activities and molecular mechanisms of endogenous FHOD1, however, are still unknown. Here we report that FHOD1 physically associates via the N-terminal part of its FH2 domain with the central domain of ROCK1. Although FHOD1 does not affect the kinase activity of ROCK1, the DRF is an efficient substrate for phosphorylation by ROCK1. Co-expression of FHOD1 and ROCK1 results in the generation of nonapoptotic plasma membrane (PM) blebs, to which the DRF is efficiently recruited. Blebbing induced by FHOD1 and ROCK1 depends on F-actin integrity, the Rho-ROCK cascade, and Src activity and is reminiscent of the recently described PM blebs triggered by expression of Src homology 4 (SH4) domain PM targeting signals. Consistently, endogenous FHOD1 is required in SH4 domain expressing cells for efficient PM blebbing and rounded cell morphology in two-dimensional cultures or three-dimensional matrices, respectively. Efficient association of FHOD1 with ROCK1, as well as recruitment of the DRF to blebs, depends on Src activity, suggesting that the functional interaction between both proteins is regulated by Src. These results define a role for endogenous FHOD1 in SH4 domain-induced blebbing and suggest that its activity is regulated by ROCK1 in a Src-dependent manner.

Simultaneous inhibition of aryl hydrocarbon receptor (AhR) and Src abolishes androgen receptor signaling.

PubMed

Ghotbaddini, Maryam; Cisse, Keyana; Carey, Alexis; Powell, Joann B

2017-01-01

Altered c-Src activity has been strongly implicated in the development, growth, progression, and metastasis of human cancers including prostate cancer. Src is known to regulate several biological functions of tumor cells, including proliferation. There are several Src inhibitors under evaluation for clinical effectiveness but have shown little activity in monotherapy trials of solid tumors. Combination studies are being explored by in vitro analysis and in clinical trials. Here we investigate the effect of simultaneous inhibition of the aryl hydrocarbon receptor (AhR) and Src on androgen receptor (AR) signaling in prostate cancer cells. AhR has also been reported to interact with the Src signaling pathway during prostate development. c-Src protein kinase is associated with the AhR complex in the cytosol and upon ligand binding to AhR, c-Src is activated and released from the complex. AhR has also been shown to regulate AR signaling which remains functionally important in the development and progression of prostate cancer. We provide evidence that co-inhibition of AhR and Src abolish AR activity. Evaluation of total protein and cellular fractions revealed decreased pAR expression and AR nuclear localization. Assays utilizing an androgen responsive element (ARE) and qRT-PCR analysis of AR genes revealed decreased AR promoter activity and transcriptional activity in the presence of both AhR and Src inhibitors. Furthermore, co-inhibition of AhR and Src reduced the growth of prostate cancer cells compared to individual treatments. Several studies have revealed that AhR and Src individually inhibit cellular proliferation. However, this study is the first to suggest simultaneous inhibition of AhR and Src to inhibit AR signaling and prostate cancer cell growth.

Differential effects of phosphotyrosine phosphatase expression on hormone-dependent and independent pp60c-src activity.

PubMed

Way, B A; Mooney, R A

1994-10-26

pp60c-src kinase activity can be increased by phosphotyrosine dephosphorylation or growth factor-dependent phosphorylation reactions. Expression of the transmembrane phosphotyrosine phosphatase (PTPase) CD45 has been shown to inhibit growth factor receptor signal transduction (Mooney, RA, Freund, GG, Way, BA and Bordwell, KL (1992) J Biol Chem 267, 23443-23446). Here it is shown that PTPase expression decreased platelet-derived growth factor (PDGF)-dependent activation of pp60c-src but failed to increase hormone independent (basal) pp60c-src activity. PDGF-dependent tyrosine phosphorylation of its receptor was reduced by approximately 60% in cells expressing the PTPase. In contrast, a change in phosphotyrosine content of pp60c-src was not detected in response to PDGF or in PTPase+ cells. PDGF increased the intrinsic tyrosine kinase activity of pp60c-src in both control and PTPase+ cells, but the effect was smaller in PTPase+ cells. In an in vitro assay, hormone-stimulated pp60c-src autophosphorylation from PTPase+ cells was decreased 64 +/- 22%, and substrate phosphorylation by pp60c-src was reduced 54 +/- 16% compared to controls. Hormone-independent pp60c-src kinase activity was unchanged by expression of the PTPase. pp60c-src was, however, an in vitro substrate for CD45, being dephosphorylated at both the regulatory (Tyr527) and kinase domain (Tyr416) residues. In addition, in vitro dephosphorylation by CD45 increased pp60c-src activity. These findings suggest that the PDGF receptor was an in vivo substrate of CD45 but pp60c-src was not. The lack of activation of pp60c-src in the presence of expressed PTPase may demonstrate the importance of compartmentalization and/or accessory proteins to PTPase-substrate interactions.

v-Src-induced nuclear localization of YAP is involved in multipolar spindle formation in tetraploid cells.

PubMed

Kakae, Keiko; Ikeuchi, Masayoshi; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

2017-01-01

The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells. Upon v-Src expression, the proportion of multinucleated cells is increased in a time-dependent manner. Flow cytometry analysis revealed that v-Src increases the number of cells having a ≥4N DNA content. Microscopic analysis showed that v-Src induces the formation of multipolar spindles with excess centrosomes. These results suggest that v-Src induces multipolar spindle formation by generating multinucleated cells. Tetraploidy activates the tetraploidy checkpoint, leading to a cell cycle arrest of tetraploid cells at the G1 phase, in which the nuclear exclusion of the transcription co-activator YAP plays a critical role. In multinucleated cells that are induced by cytochalasin B and the Plk1 inhibitor, YAP is excluded from the nucleus. However, v-Src prevents this nuclear exclusion of YAP through a decrease in the phosphorylation of YAP at Ser127 in multinucleated cells. Furthermore, v-Src decreases the expression level of p53, which also plays a critical role in the cell cycle arrest of tetraploid cells. These results suggest that v-Src promotes abnormal spindle formation in at least two ways: generation of multinucleated cells and a weakening of the tetraploidy checkpoint. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective Equipment and Player Characteristics Associated With the Incidence of Sport-Related Concussion in High School Football Players

PubMed Central

McGuine, Timothy A.; Hetzel, Scott; McCrea, Michael; Brooks, M. Alison

2015-01-01

Background The incidence of sport-related concussion (SRC) in high school football is well documented. However, limited prospective data are available regarding how player characteristics and protective equipment affect the incidence of SRC. Purpose To determine whether the type of protective equipment (helmet and mouth guard) and player characteristics affect the incidence of SRC in high school football players. Design Cohort study; Level of evidence, 2. Methods Certified athletic trainers (ATs) at each high school recorded the type of helmet worn (brand, model, purchase year, and recondition status) by each player as well as information regarding players’ demographics, type of mouth guard used, and history of SRC. The ATs also recorded the incidence and days lost from participation for each SRC. Incidence of SRC was compared for various helmets, type of mouth guard, history of SRC, and player demographics. Results A total of 2081 players (grades 9–12) enrolled during the 2012 and/or 2013 football seasons (2287 player-seasons) and participated in 134,437 football (practice or competition) exposures. Of these players, 206 (9%) sustained a total of 211 SRCs (1.56/1000 exposures). There was no difference in the incidence of SRC (number of helmets, % SRC [95% CI]) for players wearing Riddell (1171, 9.1% [7.6%–11.0%]), Schutt (680, 8.7% [6.7%–11.1%]), or Xenith (436, 9.2% [6.7%–12.4%]) helmets. Helmet age and recondition status did not affect the incidence of SRC. The rate of SRC (hazard ratio [HR]) was higher in players who wore a custom mouth guard (HR = 1.69 [95% CI, 1.20–2.37], P <.001) than in players who wore a generic mouth guard. The rate of SRC was also higher (HR = 1.96 [95% CI, 1.40–2.73], P <.001) in players who had sustained an SRC within the previous 12 months (15.1% of the 259 players [95% CI, 11.0%–20.1%]) than in players without a previous SRC (8.2% of the 2028 players [95% CI, 7.1%–9.5%]). Conclusion Incidence of SRC was similar regardless of the helmet brand (manufacturer) worn by high school football players. Players who had sustained an SRC within the previous 12 months were more likely to sustain an SRC than were players without a history of SRC. Sports medicine providers who work with high school football players need to realize that factors other than the type of protective equipment worn affect the risk of SRC in high school players. PMID:25060072

c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched Into Prostate Cancer Cell Exosomes.

PubMed

DeRita, Rachel M; Zerlanko, Brad; Singh, Amrita; Lu, Huimin; Iozzo, Renato V; Benovic, Jeffrey L; Languino, Lucia R

2017-01-01

It is well known that Src tyrosine kinase, insulin-like growth factor 1 receptor (IGF-IR), and focal adhesion kinase (FAK) play important roles in prostate cancer (PrCa) development and progression. Src, which signals through FAK in response to integrin activation, has been implicated in many aspects of tumor biology, such as cell proliferation, metastasis, and angiogenesis. Furthermore, Src signaling is known to crosstalk with IGF-IR, which also promotes angiogenesis. In this study, we demonstrate that c-Src, IGF-IR, and FAK are packaged into exosomes (Exo), c-Src in particular being highly enriched in Exo from the androgen receptor (AR)-positive cell line C4-2B and AR-negative cell lines PC3 and DU145. Furthermore, we show that the active phosphorylated form of Src (Src pY416 ) is co-expressed in Exo with phosphorylated FAK (FAK pY861 ), a known target site of Src, which enhances proliferation and migration. We further demonstrate for the first time exosomal enrichment of G-protein-coupled receptor kinase (GRK) 5 and GRK6, both of which regulate Src and IGF-IR signaling and have been implicated in cancer. Finally, Src pY416 and c-Src are both expressed in Exo isolated from the plasma of prostate tumor-bearing TRAMP mice, and those same mice have higher levels of exosomal c-Src than their wild-type counterparts. In summary, we provide new evidence that active signaling molecules relevant to PrCa are enriched in Exo, and this suggests that the Src signaling network may provide useful biomarkers detectable by liquid biopsy, and may contribute to PrCa progression via Exo. J. Cell. Biochem. 118: 66-73, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Heterogeneity of signal transduction by Na-K-ATPase α-isoforms: role of Src interaction.

PubMed

Yu, Hui; Cui, Xiaoyu; Zhang, Jue; Xie, Joe X; Banerjee, Moumita; Pierre, Sandrine V; Xie, Zijian

2018-02-01

Of the four Na-K-ATPase α-isoforms, the ubiquitous α1 Na-K-ATPase possesses both ion transport and Src-dependent signaling functions. Mechanistically, we have identified two putative pairs of domain interactions between α1 Na-K-ATPase and Src that are critical for α1 signaling function. Our subsequent report that α2 Na-K-ATPase lacks these putative Src-binding sites and fails to carry on Src-dependent signaling further supported our proposed model of direct interaction between α1 Na-K-ATPase and Src but fell short of providing evidence for a causative role. This hypothesis was specifically tested here by introducing key residues of the two putative Src-interacting domains present on α1 but not α2 sequence into the α2 polypeptide, generating stable cell lines expressing this mutant, and comparing its signaling properties to those of α2-expressing cells. The mutant α2 was fully functional as a Na-K-ATPase. In contrast to wild-type α2, the mutant gained α1-like signaling function, capable of Src interaction and regulation. Consistently, the expression of mutant α2 redistributed Src into caveolin-1-enriched fractions and allowed ouabain to activate Src-mediated signaling cascades, unlike wild-type α2 cells. Finally, mutant α2 cells exhibited a growth phenotype similar to that of the α1 cells and proliferated much faster than wild-type α2 cells. These findings reveal the structural requirements for the Na-K-ATPase to function as a Src-dependent receptor and provide strong evidence of isoform-specific Src interaction involving the identified key amino acids. The sequences surrounding the putative Src-binding sites in α2 are highly conserved across species, suggesting that the lack of Src binding may play a physiologically important and isoform-specific role.

H-Ras Modulates N-Methyl-d-aspartate Receptor Function via Inhibition of Src Tyrosine Kinase Activity*

PubMed Central

Thornton, Claire; Yaka, Rami; Dinh, Son; Ron, Dorit

2005-01-01

Tyrosine phosphorylation of the NR2A and NR2B subunits of the N-methyl-d-aspartate (NMDA) receptor by Src protein-tyrosine kinases modulates receptor channel activity and is necessary for the induction of long term potentiation (LTP). Deletion of H-Ras increases both NR2 tyrosine phosphorylation and NMDA receptor-mediated hippocampal LTP. Here we investigated whether H-Ras regulates phosphorylation and function of the NMDA receptor via Src family protein-tyrosine kinases. We identified Src as a novel H-Ras binding partner. H-Ras bound to Src but not Fyn both in vitro and in brain via the Src kinase domain. Cotransfection of H-Ras and Src inhibited Src activity and decreased NR2A tyrosine phosphorylation. Treatment of rat brain slices with Tat-H-Ras depleted NR2A from the synaptic membrane, decreased endogenous Src activity and NR2A phosphorylation, and decreased the magnitude of hip-pocampal LTP. No change was observed for NR2B. We suggest that H-Ras negatively regulates Src phosphorylation of NR2A and retention of NR2A into the synaptic membrane leading to inhibition of NMDA receptor function. This mechanism is specific for Src and NR2A and has implications for studies in which regulation of NMDA receptor-mediated LTP is important, such as synaptic plasticity, learning, and memory and addiction. PMID:12695509

Targeting the yin and the yang: combined inhibition of the tyrosine kinase c-Src and the tyrosine phosphatase SHP-2 disrupts pancreatic cancer signaling and biology in vitro and tumor formation in vivo.

PubMed

Gomes, Evan G; Connelly, Sarah F; Summy, Justin M

2013-07-01

Although c-Src (Src) has emerged as a potential pancreatic cancer target in preclinical studies, Src inhibitors have not demonstrated a significant therapeutic benefit in clinical trials. The objective of these studies was to examine the effects of combining Src inhibition with inhibition of the protein tyrosine phosphatase SHP-2 in pancreatic cancer cells in vitro and in vivo. SHP-2 and Src functions were inhibited by siRNA or small molecule inhibitors. The effects of dual Src/SHP-2 functional inhibition were evaluated by Western blot analysis of downstream signaling pathways; cell biology assays to examine caspase activity, viability, adhesion, migration, and invasion in vitro; and an orthotopic nude mouse model to observe pancreatic tumor formation in vivo. Dual targeting of Src and SHP-2 induces an additive or supra-additive loss of phosphorylation of Akt and ERK-1/2 and corresponding increases in expression of apoptotic markers, relative to targeting either protein individually. Combinatorial inhibition of Src and SHP-2 significantly reduces viability, adhesion, migration, and invasion of pancreatic cancer cells in vitro and tumor formation in vivo, relative to individual Src/SHP-2 inhibition. These data suggest that the antitumor effects of Src inhibition in pancreatic cancer may be enhanced through simultaneous inhibition of SHP-2.

SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer

PubMed Central

Zhou, Xiaorong; Comerford, Sarah A.; York, Brian; O’Donnell, Kathryn A.

2017-01-01

Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in Src-2-/- liver tumors. We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver. PMID:28273073

Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.

PubMed

Huang, Chao; Zhang, Zhe; Chen, Lihan; Lee, Hank W; Ayrapetov, Marina K; Zhao, Ting C; Hao, Yimei; Gao, Jinsong; Yang, Chunzhang; Mehta, Gautam U; Zhuang, Zhengping; Zhang, Xiaoren; Hu, Guohong; Chin, Y Eugene

2018-06-01

Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G 2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation. Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR . ©2018 American Association for Cancer Research.

Rosebud SynCoal Partnership, SynCoal{reg_sign} demonstration technology update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheldon, R.W.

1997-12-31

An Advanced Coal Conversion Process (ACCP) technology being demonstrated in eastern Montana (USA) at the heart of one of the world`s largest coal deposits is providing evidence that the molecular structure of low-rank coals can be altered successfully to produce a unique product for a variety of utility and industrial applications. The product is called SynCoal{reg_sign} and the process has been developed by the Rosebud SynCoal Partnership (RSCP) through the US Department of Energy`s multi-million dollar Clean Coal Technology Program. The ACCP demonstration process uses low-pressure, superheated gases to process coal in vibrating fluidized beds. Two vibratory fluidized processing stagesmore » are used to heat and convert the coal. This is followed by a water spray quench and a vibratory fluidized stage to cool the coal. Pneumatic separators remove the solid impurities from the dried coal. There are three major steps to the SynCoal{reg_sign} process: (1) thermal treatment of the coal in an inert atmosphere, (2) inert gas cooling of the hot coal, and (3) removal of ash minerals. When operated continuously, the demonstration plant produces over 1,000 tons per day (up to 300,000 tons per year) of SynCoal{reg_sign} with a 2% moisture content, approximately 11,800b Btu/lb and less than 1.0 pound of SO{sub 2} per million Btu. This product is obtained from Rosebud Mine sub-bituminous coal which starts with 25% moisture, 8,600 Btu/lb and approximately 1.6 pounds of SO{sub 2} per million Btu.« less

Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

PubMed

Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

2005-07-08

The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

Process for coal liquefaction employing selective coal feed

DOEpatents

Hoover, David S.; Givens, Edwin N.

1983-01-01

An improved coal liquefaction process is provided whereby coal conversion is improved and yields of pentane soluble liquefaction products are increased. In this process, selected feed coal is pulverized and slurried with a process derived solvent, passed through a preheater and one or more dissolvers in the presence of hydrogen-rich gases at elevated temperatures and pressures, following which solids, including mineral ash and unconverted coal macerals, are separated from the condensed reactor effluent. The selected feed coals comprise washed coals having a substantial amount of mineral matter, preferably from about 25-75%, by weight, based upon run-of-mine coal, removed with at least 1.0% by weight of pyritic sulfur remaining and exhibiting vitrinite reflectance of less than about 0.70%.

Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

PubMed

He, Yi-Xin; Liu, Jin; Guo, Baosheng; Wang, Yi-Xiang; Pan, Xiaohua; Li, Defang; Tang, Tao; Chen, Yang; Peng, Songlin; Bian, Zhaoxiang; Liang, Zicai; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

2015-03-09

To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

GROWTH REGULATION IN ROUS SARCOMA VIRUS INFECTED CHICKEN EMBRYO FIBROBLASTS: THE ROLE OF THE src GENE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parry, G.; Bartholomew, J.A.; Blssell, M.J.

1980-07-01

We report here a study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in this process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. The two principal findings were (1) the stationary phase of the cell cycle (G{sub 1}) in chick embryo fibroblasts seems to have two distinct regulatory compartments (using the terminology of Brooks et al. we refer to these as 'Q' and 'A' states).more » When rendered stationary at 41.5 C by serum deprivation, normal cells enter a Q state, but cells infected with the ts-mutant occupy an A state. (2) Whereas normal cells can occupy either state depending on culture conditions, the ts-infected cells, at 41.5 C, do not seem to enter Q even though a known src gene product, a kinase, is reported to be inactive at this temperature. We discuss the possibility that viral factors other than the active src protein kinase influence growth control in infected cultures.« less

30 CFR 784.25 - Return of coal processing waste to abandoned underground workings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Return of coal processing waste to abandoned... ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL MINING AND RECLAMATION OPERATIONS PERMITS AND COAL... RECLAMATION AND OPERATION PLAN § 784.25 Return of coal processing waste to abandoned underground workings. (a...

30 CFR 784.25 - Return of coal processing waste to abandoned underground workings.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Return of coal processing waste to abandoned... ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL MINING AND RECLAMATION OPERATIONS PERMITS AND COAL... RECLAMATION AND OPERATION PLAN § 784.25 Return of coal processing waste to abandoned underground workings. (a...

30 CFR 784.25 - Return of coal processing waste to abandoned underground workings.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Return of coal processing waste to abandoned... ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL MINING AND RECLAMATION OPERATIONS PERMITS AND COAL... RECLAMATION AND OPERATION PLAN § 784.25 Return of coal processing waste to abandoned underground workings. (a...

Signaling network of the Btk family kinases.

PubMed

Qiu, Y; Kung, H J

2000-11-20

The Btk family kinases represent new members of non-receptor tyrosine kinases, which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCgamma and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, differentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunodeficiency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.

Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion

PubMed Central

Knuchel, Sarah; Anderle, Pascale; Werfelli, Patricia; Diamantis, Eva; Rüegg, Curzio

2015-01-01

Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC) invasion by secreting motility factors and extracellular matrix processing enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by contact-dependent mechanisms. To address this question we characterized the interaction between fibroblasts and SW620 and HT29 colorectal cancer cells in 2D and 3D co-culture models in vitro. Here we show that fibroblasts induce contact-dependent cancer cell elongation, motility and invasiveness independently of deposited matrix or secreted factors. These effects depend on fibroblast cell surface-associated fibroblast growth factor (FGF) -2. Inhibition of FGF-2 or FGF receptors (FGFRs) signaling abolishes these effects. FGFRs activate SRC in cancer cells and inhibition or silencing of SRC in cancer cells, but not in fibroblasts, prevents fibroblasts-mediated effects. Using an RGD-based integrin antagonist and function-blocking antibodies we demonstrate that cancer cell adhesion to fibroblasts requires integrin αvβ5. Taken together, these results demonstrate that fibroblasts induce cell-contact-dependent colorectal cancer cell migration and invasion under 2D and 3D conditions in vitro through fibroblast cell surface-associated FGF-2, FGF receptor-mediated SRC activation and αvβ5 integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2-FGFRs-SRC-αvβ5 integrin loop might be explored as candidate therapeutic target to block colorectal cancer invasion. PMID:25973543

Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion.

PubMed

Knuchel, Sarah; Anderle, Pascale; Werfelli, Patricia; Diamantis, Eva; Rüegg, Curzio

2015-06-10

Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC) invasion by secreting motility factors and extracellular matrix processing enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by contact-dependent mechanisms. To address this question we characterized the interaction between fibroblasts and SW620 and HT29 colorectal cancer cells in 2D and 3D co-culture models in vitro. Here we show that fibroblasts induce contact-dependent cancer cell elongation, motility and invasiveness independently of deposited matrix or secreted factors. These effects depend on fibroblast cell surface-associated fibroblast growth factor (FGF) -2. Inhibition of FGF-2 or FGF receptors (FGFRs) signaling abolishes these effects. FGFRs activate SRC in cancer cells and inhibition or silencing of SRC in cancer cells, but not in fibroblasts, prevents fibroblasts-mediated effects. Using an RGD-based integrin antagonist and function-blocking antibodies we demonstrate that cancer cell adhesion to fibroblasts requires integrin αvβ5. Taken together, these results demonstrate that fibroblasts induce cell-contact-dependent colorectal cancer cell migration and invasion under 2D and 3D conditions in vitro through fibroblast cell surface-associated FGF-2, FGF receptor-mediated SRC activation and αvβ5 integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2-FGFRs-SRC-αvβ5 integrin loop might be explored as candidate therapeutic target to block colorectal cancer invasion.

Advanced coal conversion process demonstration. Technical progress report for the period July 1, 1995--September 30, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1997-05-01

This report describes the technical progress made on the Advanced Coal Conversion Process (ACCP) Demonstration Project from July 1, 1995 through September 30, 1995. The ACCP Demonstration Project is a US Department of Energy (DOE) Clean Coal Technology Project. This project demonstrates an advanced, thermal, coal upgrading process, coupled with physical cleaning techniques, that is designed to upgrade high-moisture, low-rank coals to a high-quality, low-sulfur fuel, registered as the SynCoal process. The coal is processed through three stages (two heating stages followed by an inert cooling stage) of vibrating fluidized bed reactors that remove chemically bound water, carboxyl groups, andmore » volatile sulfur compounds. After thermal upgrading, the cola is put through a deep-bed stratifier cleaning process to separate the pyrite-rich ash from the coal.« less

A Kinase-Independent Function of c-Src Mediates p130Cas Phosphorylation at the Serine-639 Site in Pressure Overloaded Myocardium.

PubMed

Palanisamy, Arun P; Suryakumar, Geetha; Panneerselvam, Kavin; Willey, Christopher D; Kuppuswamy, Dhandapani

2015-12-01

Early work in pressure overloaded (PO) myocardium shows that integrins mediate focal adhesion complex formation by recruiting the adaptor protein p130Cas (Cas) and nonreceptor tyrosine kinase c-Src. To explore c-Src role in Cas-associated changes during PO, we used a feline right ventricular in vivo PO model and a three-dimensional (3D) collagen-embedded adult cardiomyocyte in vitro model that utilizes a Gly-Arg-Gly-Asp-Ser (RGD) peptide for integrin stimulation. Cas showed slow electrophoretic mobility (band-shifting), recruitment to the cytoskeleton, and tyrosine phosphorylation at 165, 249, and 410 sites in both 48 h PO myocardium and 1 h RGD-stimulated cardiomyocytes. Adenoviral mediated expression of kinase inactive (negative) c-Src mutant with intact scaffold domains (KN-Src) in cardiomyocytes did not block the RGD stimulated changes in Cas. Furthermore, expression of KN-Src or kinase active c-Src mutant with intact scaffold function (A-Src) in two-dimensionally (2D) cultured cardiomyocytes was sufficient to cause Cas band-shifting, although tyrosine phosphorylation required A-Src. These data indicate that c-Src's adaptor function, but not its kinase function, is required for a serine/threonine specific phosphorylation(s) responsible for Cas band-shifting. To explore this possibility, Chinese hamster ovary cells that stably express Cas were infected with either β-gal or KN-Src adenoviruses and used for Cas immunoprecipitation combined with mass spectrometry analysis. In the KN-Src expressing cells, Cas showed phosphorylation at the serine-639 (human numbering) site. A polyclonal antibody raised against phospho-serine-639 detected Cas phosphorylation in 24-48 h PO myocardium. Our studies indicate that c-Src's adaptor function mediates serine-639 phosphorylation of Cas during integrin activation in PO myocardium. © 2015 Wiley Periodicals, Inc.

Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery

PubMed Central

Knock, Greg A.; Snetkov, Vladimir A.; Shaifta, Yasin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Aims We investigated the role of src-family kinases (srcFKs) in hypoxic pulmonary vasoconstriction (HPV) and how this relates to Rho-kinase-mediated Ca2+ sensitization and changes in intracellular Ca2+ concentration ([Ca2+]i). Methods and results Intra-pulmonary arteries (IPAs) were obtained from male Wistar rats. HPV was induced in myograph-mounted IPAs. Auto-phosphorylation of srcFKs and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and myosin light-chain (MLC20) in response to hypoxia were determined by western blotting. Translocation of Rho-kinase and effects of siRNA knockdown of src and fyn were examined in cultured pulmonary artery smooth muscle cells (PASMCs). [Ca2+]i was estimated in Fura-PE3-loaded IPA. HPV was inhibited by two blockers of srcFKs, SU6656 and PP2. Hypoxia enhanced phosphorylation of three srcFK proteins at Tyr-416 (60, 59, and 54 kDa, corresponding to src, fyn, and yes, respectively) and enhanced srcFK-dependent tyrosine phosphorylation of multiple target proteins. Hypoxia caused a complex, time-dependent enhancement of MYPT-1 and MLC20 phosphorylation, both in the absence and presence of pre-constriction. The sustained component of this enhancement was blocked by SU6656 and the Rho-kinase inhibitor Y27632. In PASMCs, hypoxia caused translocation of Rho-kinase from the nucleus to the cytoplasm, and this was prevented by anti-src siRNA and to a lesser extent by anti-fyn siRNA. The biphasic increases in [Ca2+]i that accompany HPV were also inhibited by PP2. Conclusion Hypoxia activates srcFKs and triggers protein tyrosine phosphorylation in IPA. Hypoxia-mediated Rho-kinase activation, Ca2+ sensitization, and [Ca2+]i responses are depressed by srcFK inhibitors and/or siRNA knockdown, suggesting a central role of srcFKs in HPV. PMID:18682436

Divergent modulation of Rho‐kinase and Ca2+ influx pathways by Src family kinases and focal adhesion kinase in airway smooth muscle

PubMed Central

Shaifta, Yasin; Irechukwu, Nneka; Prieto‐Lloret, Jesus; MacKay, Charles E; Marchon, Keisha A; Ward, Jeremy P T

2015-01-01

Background and Purpose The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src‐family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR‐mediated ASM contraction and associated signalling events. Experimental Approach Contraction was recorded in intact or α‐toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light‐chain‐20 (MLC20) and myosin phosphatase targeting subunit‐1 (MYPT‐1) was evaluated in cultured human ASM cells (hASMC). [Ca2+]i was evaluated in Fura‐2 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined. Key Results Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho‐kinase, while after α‐toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho‐kinase, but not FAK. CCh and BK increased phosphorylation of MYPT‐1 and MLC20 and auto‐phosphorylation of SrcFK and FAK. MYPT‐1 phosphorylation was sensitive to inhibition of Rho‐kinase and SrcFK, but not FAK. Contraction induced by SR Ca2+ depletion and equivalent [Ca2+]i responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization‐induced contraction was sensitive to FAK inhibition only. SrcFK auto‐phosphorylation was partially FAK‐dependent, while FAK auto‐phosphorylation was SrcFK‐independent. Conclusions and Implications SrcFK mediates Ca2+‐sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca2+ influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease. PMID:26294392

Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Haiyan; Department of Pharmacology, Tianjin Medical University, Tianjin 300070; Huh, Jin

Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphinemore » reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced mitochondrial ROS generation by inhibiting complex I via Src.« less

Review of Sparse Representation-Based Classification Methods on EEG Signal Processing for Epilepsy Detection, Brain-Computer Interface and Cognitive Impairment

PubMed Central

Wen, Dong; Jia, Peilei; Lian, Qiusheng; Zhou, Yanhong; Lu, Chengbiao

2016-01-01

At present, the sparse representation-based classification (SRC) has become an important approach in electroencephalograph (EEG) signal analysis, by which the data is sparsely represented on the basis of a fixed dictionary or learned dictionary and classified based on the reconstruction criteria. SRC methods have been used to analyze the EEG signals of epilepsy, cognitive impairment and brain computer interface (BCI), which made rapid progress including the improvement in computational accuracy, efficiency and robustness. However, these methods have deficiencies in real-time performance, generalization ability and the dependence of labeled sample in the analysis of the EEG signals. This mini review described the advantages and disadvantages of the SRC methods in the EEG signal analysis with the expectation that these methods can provide the better tools for analyzing EEG signals. PMID:27458376

Cooperative Atmosphere-Surface Exchange Study-1999.

NASA Astrophysics Data System (ADS)

Moeng, Chin-Hoh; Poulos, Gregory S.; Lemone, Margaret A.

2003-10-01

Surface-station, radiosonde, and Doppler minisodar data from the Cooperative Atmosphere-Surface Exchange Study-1997 (CASES-97) field project, collected in a 60-km-wide array in the lower Walnut River watershed (terrain variation 150 m) southeast of Wichita, Kansas, are used to study the relationship of the change of the 2-m potential temperature 2m with station elevation ze, 2m/ze ,ze to the ambient wind and thermal stratification /z ,z during fair-weather nights. As in many previous studies, predawn 2m varies linearly with ze, and ,ze ,z over a depth h that represents the maximum elevation range of the stations. Departures from the linear 2m-elevation relationship (,ze line) are related to vegetation (cool for vegetation, warm for bare ground), local terrain (drainage flows from nearby hills, although a causal relationship is not established), and the formation of a cold pool at lower elevations on some days.The near-surface flow and its evolution are functions of the Froude number Fr = S/(Nh), where S is the mean wind speed from the surface to h, and N is the corresponding Brunt-Väisälä frequency. The near-surface wind is coupled to the ambient flow for Fr = 3.3, based on where the straight line relating ,ze to ln Fr intersects the ln Fr axis. Under these conditions, 2m is constant horizontally even though ,z > 0, suggesting that near-surface air moves up- and downslope dry adiabatically. However, 2m cools (or warms) everywhere at the same rate. The lowest Froude numbers are associated with drainage flows, while intermediate values characterize regimes with intermediate behavior. The evolution of 2m horizontal variability σ through the night is also a function of the predawn Froude number. For the nights with the lowest Fr, the σ maximum occurs in the last 1-3 h before sunrise. For nights with Fr 3.3 (,ze 0) and for intermediate values, σ peaks 2-3 h after sunset. The standard deviations relative to the ,ze line reach their lowest values in the last hours of darkness. Thus, it is not surprising that the relationships of ,ze to Fr and ,z based on data through the night show more scatter, and ,ze 0.5,z in contrast to the predawn relationship. However, ,ze 0 for ln Fr = 3.7, a value similar to that just before sunrise.A heuristic Lagrangian parcel model is used to explain the horizontal uniformity of time-evolving 2m when the surface flow is coupled with the ambient wind, as well as both the linear variation of 2m with elevation and the time required to reach maximum values of σ under drainage-flow conditions.

Distribution and associations of intraocular pressure in 7- and 12-year-old Chinese children: The Anyang Childhood Eye Study.

PubMed

Li, Shuning; Li, Shi-Ming; Wang, Xiao-Lei; Kang, Meng-Tian; Liu, Luo-Ru; Li, He; Wei, Shi-Fei; Ran, An-Ran; Zhan, Siyan; Thomas, Ravi; Wang, Ningli

2017-01-01

To report the intraocular pressure (IOP) and its association with myopia and other factors in 7 and 12-year-old Chinese children. All children participating in the Anyang Childhood Eye Study underwent non-contact tonometry as well as measurement of central corneal thickness (CCT), axial length, cycloplegic auto-refraction, blood pressure, height and weight. A questionnaire was used to collect other relevant information. Univariable and multivariable analysis were performed to determine the associations of IOP. A total of 2760 7-year-old children (95.4%) and 2198 12-year-old children (97.0%) were included. The mean IOP was 13.5±3.1 mmHg in the younger cohort and 15.8±3.5 mmHg in older children (P<0.0001). On multivariable analysis, higher IOP in the younger cohort was associated with female gender (standardized regression coefficient [SRC], 0.11, P<0.0001), increasing central corneal thickness (SRC, 0.39, P<0.0001), myopia (SRC, 0.05, P = 0.03), deep anterior chamber (SRC, 0.07, P<0.01), smaller waist (SRC, 0.07, P<0.01) and increasing mean arterial pressure (SRC, 0.13, P<0.0001). In the older cohort, higher IOP was again associated with female gender (SRC, 0.16, P<0.0001), increasing central corneal thickness (SRC, 0.43, P<0.0001), deep anterior chamber (SRC, 0.09, P<0.01), higher body mass index (SRC, 0.07, P = 0.04) and with increasing mean arterial pressure (SRC, 0.09, P = 0.01), age at which reading commenced (SRC, 0.10, P<0.01) and birth method (SRC, 0.09, P = 0.01), but not with myopia (SRC, 0.09, P = 0.20). In Chinese children, higher IOP was associated with female gender, older age, thicker central cornea, deeper anterior chamber and higher mean arterial pressure. Higher body mass index, younger age at commencement of reading and being born of a caesarean section was also associated with higher IOP in adolescence.

Effect of wheat flour characteristics on sponge cake quality.

PubMed

Moiraghi, Malena; de la Hera, Esther; Pérez, Gabriela T; Gómez, Manuel

2013-02-01

To select the flour parameters that relate strongly to cake-making performance, in this study the relationship between sponge cake quality, solvent retention capacity (SRC) profile and flour physicochemical characteristics was investigated using 38 soft wheat samples of different origins. Particle size average, protein, damaged starch, water-soluble pentosans, total pentosans, SRC and pasting properties were analysed. Sponge cake volume and crumb texture were measured to evaluate cake quality. Cluster analysis was applied to assess differences in flour quality parameters among wheat lines based on the SRC profile. Cluster 1 showed significantly higher sponge cake volume and crumb softness, finer particle size and lower SRC sucrose, SRC carbonate, SRC water, damaged starch and protein content. Particle size, damaged starch, protein, thickening capacity and SRC parameters correlated negatively with sponge cake volume, while total pentosans and pasting temperature showed the opposite effect. The negative correlations between cake volume and SRC parameters along with the cluster analysis results indicated that flours with smaller particle size, lower absorption capacity and higher pasting temperature had better cake-making performance. Some simple analyses, such as SRC, particle size distribution and pasting properties, may help to choose flours suitable for cake making. Copyright © 2012 Society of Chemical Industry.

Association of spiritual/religious coping with depressive symptoms in high- and low-risk pregnant women.

PubMed

Vitorino, Luciano M; Chiaradia, Raíssa; Low, Gail; Cruz, Jonas Preposi; Pargament, Kenneth I; Lucchetti, Alessandra L G; Lucchetti, Giancarlo

2018-02-01

To investigate the role of spiritual/religious coping (SRC) on depressive symptoms in high- and low-risk pregnant women. Spiritual/religious coping is associated with physical and mental health outcomes. However, only few studies investigated the role of these strategies during pregnancy and whether low- and high-risk pregnant women have different coping mechanisms. This study is a cross-sectional comparative study. This study included a total of 160 pregnant women, 80 with low-risk pregnancy and 80 with high-risk pregnancy. The Beck Depression Inventory, the brief SRC scale and a structured questionnaire on sociodemographic and obstetric aspects were used. General linear model regression analysis was used to identify the factors associated with positive and negative SRC strategies in both groups of pregnant women. Positive SRC use was high, whereas negative SRC use was low in both groups. Although we found no difference in SRC strategies between the two groups, negative SRC was associated with depression in women with high-risk pregnancy, but not in those with low-risk pregnancy. Furthermore, positive SRC was not associated with depressive symptoms in both groups. Results showed that only the negative SRC strategies of Brazilian women with high-risk pregnancies were associated with worsened mental health outcomes. Healthcare professionals, obstetricians and nurse midwives should focus on the use of negative SRC strategies in their pregnant patients. © 2017 John Wiley & Sons Ltd.

Mössbauer study of the inorganic sulfur removal from coals

NASA Astrophysics Data System (ADS)

Reyes Caballero, F.; Martínez Ovalle, S. A.

2014-01-01

Mössbauer Spectroscopy (MS) was applied to study the occurrence and behavior of the iron-sulfur-containing minerals in coal and coal fractions obtained by different separation methods: hydrocyclonic, flotation and chemical removal process. Samples of one high sulfur coal from Guachinte mine (Valle, Colombia) and three low sulfur coals from the El Salitre zone (Paipa-Boyacá, Colombia) were analyzed. MS evidenced only the presence of pyrite in Esmeralda and Las Casitas coals, while it identified pyrite and siderite on Cerezo coal. MS and SEM- EDX confirm the inorganic sulfur removal on Guachinte coal submitted to hydrocyclonic removal process. MS of the precipitated coal fraction from Las Casitas mine obtained by flotation in water showed the presence of ferrous sulfate because of coal-weathering process. Treatment with hot diluted HNO3 equal to 27 acid on raw coal sample from Las Casitas mine showed that almost all of the pyrite in raw coal was removed.

Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.

PubMed

Gomes, Pedro; Saito, Tomoaki; Del Corsso, Cris; Alioua, Abderrahmane; Eghbali, Mansoureh; Toro, Ligia; Stefani, Enrico

2008-10-01

Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.

Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression.

PubMed

Chen, Wenbo; Lu, Xuqiang; Chen, Yuan; Li, Ming; Mo, Pingli; Tong, Zhangwei; Wang, Wei; Wan, Wei; Su, Guoqiang; Xu, Jianming; Yu, Chundong

2017-02-15

Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3 -/- ) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection. Based on these findings, we hypothesized that SRC-3 is involved in host defense against attaching and effacing bacterial infection. We compared the responses of SRC-3 -/- and wild-type mice to intestinal C. rodentium infection. We found that SRC-3 -/- mice exhibited delayed clearance of C. rodentium and more severe tissue pathology after oral infection with C. rodentium compared with wild-type mice. SRC-3 -/- mice expressed normal antimicrobial peptides in the colons but exhibited delayed recruitment of neutrophils into the colonic mucosa. Accordingly, SRC-3 -/- mice showed a delayed induction of CXCL2 and CXCL5 in colonic epithelial cells, which are responsible for neutrophil recruitment. At the molecular level, we found that SRC-3 can activate the NF-κB signaling pathway to promote CXCL2 expression at the transcriptional level. Collectively, we show that SRC-3 contributes to host defense against enteric bacteria, at least in part via upregulating CXCL2 expression to recruit neutrophils. Copyright © 2017 by The American Association of Immunologists, Inc.

Novel Bioluminescent Activatable Reporter for Src Tyrosine Kinase Activity in Living Mice

PubMed Central

Leng, Weibing; Li, Dezhi; Chen, Liang; Xia, Hongwei; Tang, Qiulin; Chen, Baoqin; Gong, Qiyong; Gao, Fabao; Bi, Feng

2016-01-01

Aberrant activation of the Src kinase is implicated in the development of a variety of human malignancies. However, it is almost impossible to monitor Src activity in an in vivo setting with current biochemical techniques. To facilitate the noninvasive investigation of the activity of Src kinase both in vitro and in vivo, we developed a genetically engineered, activatable bioluminescent reporter using split-luciferase complementation. The bioluminescence of this reporter can be used as a surrogate for Src activity in real time. This hybrid luciferase reporter was constructed by sandwiching a Src-dependent conformationally responsive unit (SH2 domain-Srcpep) between the split luciferase fragments. The complementation bioluminescence of this reporter was dependent on the Src activity status. In our study, Src kinase activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to clinical small-molecular kinase inhibitors, dasatinib and saracatinib. This system was also applied for high-throughput screening of Src inhibitors against a kinase inhibitor library in living cells. These results provide unique insights into drug development and pharmacokinetics/phoarmocodynamics of therapeutic drugs targeting Src signaling pathway enabling the optimization of drug administration schedules for maximum benefit. Using both Firefly and Renilla luciferase imaging, we have successfully monitored Src tyrosine kinase activity and Akt serine/threonine kinase activity concurrently in one tumor xenograft. This dual luciferase reporter imaging system will be helpful in exploring the complex signaling networks in vivo. The strategies reported here can also be extended to study and image other important kinases and the cross-talks among them. PMID:26941850

Experimental validation of arthroscopic cartilage stiffness measurement using enzymatically degraded cartilage samples

NASA Astrophysics Data System (ADS)

Lyyra, T.; Arokoski, J. P. A.; Oksala, N.; Vihko, A.; Hyttinen, M.; Jurvelin, J. S.; Kiviranta, I.

1999-02-01

In order to evaluate the ability of the arthroscopic indentation instrument, originally developed for the measurement of cartilage stiffness during arthroscopy, to detect cartilage degeneration, we compared changes in the stiffness with the structural and constitutional alterations induced by enzymes on the tissue in vitro. The culturing of osteochondral plugs on Petri dishes was initiated in Minimum Essential Medium with Earle's salts and the baseline stiffness was measured. Then, the experimental specimens were digested using trypsin for 24 h, chondroitinase ABC or purified collagenase (type VII) for 24 h or 48 h ( n = 8-15 per group). The control specimens were incubated in the medium. After the enzyme digestion, the end-point stiffness was measured and the specimens for the microscopic analyses were processed. The proteoglycan (PG) distribution was analysed using quantitative microspectrophotometry and the quantitative evaluation of the collagen network was made using a computer-based polarized light microscopy analysis. Decrease of cartilage stiffness was found after 24 h trypsin (36%) and 48 h chondroitinase ABC (24%) digestion corresponding to a decrease of up to 80% and up to 30% in the PG content respectively. Decrease of the superficial zone collagen content or arrangement (78%, ) after 48 h collagenase digestion also induced a decrease (30%, ) in cartilage stiffness. We conclude that our instrument is capable of detecting early structural and compositional changes related to cartilage degeneration.

Process to improve boiler operation by supplemental firing with thermally beneficiated low rank coal

DOEpatents

Sheldon, Ray W.

2001-01-01

The invention described is a process for improving the performance of a commercial coal or lignite fired boiler system by supplementing its normal coal supply with a controlled quantity of thermally beneficiated low rank coal, (TBLRC). This supplemental TBLRC can be delivered either to the solid fuel mill (pulverizer) or directly to the coal burner feed pipe. Specific benefits are supplied based on knowledge of equipment types that may be employed on a commercial scale to complete the process. The thermally beneficiated low rank coal can be delivered along with regular coal or intermittently with regular coal as the needs require.

Significance of ERa and c-Src Interaction in the Progression of Hormone Independent Breast Cancer

DTIC Science & Technology

2005-12-01

defects in estrogen signaling [1]. Because of global defects in estrogen signaling observed in these c-Src deficient mice, we have recently generated...1998). Interestingly, the region of the kinase domain of ErbB-2 that correlates with c-Src association, referred to as TK2 (Segatto et al., 1991...ductive organs that are dependent on ERa in c-Src- deficient mice. We show that the loss of the c-Src tyrosine kinase correlates with defects in ductal

EG-1 interacts with c-Src and activates its signaling pathway.

PubMed

Lu, Ming; Zhang, Liping; Sartippour, Maryam R; Norris, Andrew J; Brooks, Mai N

2006-10-01

EG-1 is significantly elevated in breast, colorectal, and prostate cancers. Overexpression of EG-1 stimulates cellular proliferation, and targeted inhibition blocks mouse xenograft tumor growth. To further clarify the function of EG-1, we investigated its role in c-Src activation. We observed that EG-1 overexpression results in activation of c-Src, but found no evidence that EG-1 is a direct Src substrate. EG-1 also binds to other members of the Src family. Furthermore, EG-1 shows interaction with multiple other SH3- and WW-containing molecules involved in various signaling pathways. These observations suggest that EG-1 may be involved in signaling pathways including c-Src activation.

Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account.

PubMed

Di Rosa, Elisa; Bardi, Lara; Umiltà, Carlo; Masina, Fabio; Forgione, Margherita; Mapelli, Daniela

2017-08-01

The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

76 FR 3653 - Alaska Region's Subsistence Resource Commission (SRC) Program; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... subsistence management issues. The NPS SRC program is authorized under Title VIII, Section 808 of the Alaska...: 1. Call to order. 2. SRC Roll Call and Confirmation of Quorum. 3. Welcome and Introductions. 4.... c. Resource Management Program Update. 14. Public and other Agency Comments. 15. SRC Work Session...

OH REACTION KINETICS OF GAS-PHASE A- AND G-HEXACHLOROCYCLOHEXANE AND HEXACHLOROBENZENE. (R825377)

EPA Science Inventory

Rate constants for the gas-phase reactions of the hydroxyl
radical (OH) with - and -hexachlorocyclohexane (-
and 78 FR 51207 - Kobuk Valley National Park Subsistence Resource Commission (SRC) and the Denali National Park SRC...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-AKR-DENA-KOVA-DTS-13608; PPAKAKROR4; PPMPRLE1Y.LS0000] Kobuk Valley National Park Subsistence Resource Commission (SRC) and the Denali National Park SRC; Meetings AGENCY: National Park Service, Interior. ACTION: Meeting notice. SUMMARY: As...

76 FR 57763 - Alaska Region's Subsistence Resource Commission (SRC) Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

...) program. SUMMARY: The Gates of the Arctic National Park SRC will meet to develop and continue work on NPS... changed based on inclement weather or exceptional circumstances. Gates of the Arctic National Park SRC Meeting Dates and Location: The Gates of the Arctic National Park SRC will meet at Sophie Station Hotel...

Dynamic activation of Src induced by low-power laser irradiation in living cells mediated by reactive oxygen species

NASA Astrophysics Data System (ADS)

Zhang, Juntao; Gao, Xuejuan; Xing, Da; Liu, Lei

2007-11-01

Low-power laser irradiation (LPLI) leads to photochemical reaction and then activates intracellular several signaling pathway. Reactive oxygen species (ROS) are considered to be the primary messengers produced by LPLI. Here, we studied the signaling pathway mediated by ROS upon the stimulation of LPLI. Src tyrosine kinases are well-known targets of ROS and can be activated by oxidative events. Using a Src reporter based on fluorescence resonance energy transfer (FRET) technique, we visualized the dynamic Src activation in Hela cells immediately after LPLI. Moreover, Src activity was enhanced by increasing the duration of LPLI. In addition, our results suggested that ROS were key mediators of Src activation, as ROS scavenger, vitamin C decreased and exogenous H IIO II increased the activity of Src. Meanwhile, Gö6983 loading did not block the effect of LPLI. CCK-8 experiments proved that cell vitality was prominently improved by LPLI with all the doses we applied in our experiments ranging from 3 to 25J/cm2. The results indicated that LPLI/ROS/Src pathway may be involved in the LPLI biostimulation effects.

Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I1,2

PubMed Central

Ivakine, Evgueni A.; Lam, Emily; Deurloo, Marielle; Dida, Joana; Zirngibl, Ralph A.

2015-01-01

Abstract Src is a nonreceptor protein tyrosine kinase that is expressed widely throughout the central nervous system and is involved in diverse biological functions. Mice homozygous for a spontaneous mutation in Src (Src thl/thl) exhibited hypersociability and hyperactivity along with impairments in visuospatial, amygdala-dependent, and motor learning as well as an increased startle response to loud tones. The phenotype of Src thl/thl mice showed significant overlap with Williams-Beuren syndrome (WBS), a disorder caused by the deletion of several genes, including General Transcription Factor 2-I (GTF2I). Src phosphorylation regulates the movement of GTF2I protein (TFII-I) between the nucleus, where it is a transcriptional activator, and the cytoplasm, where it regulates trafficking of transient receptor potential cation channel, subfamily C, member 3 (TRPC3) subunits to the plasma membrane. Here, we demonstrate altered cellular localization of both TFII-I and TRPC3 in the Src mutants, suggesting that disruption of Src can phenocopy behavioral phenotypes observed in WBS through its regulation of TFII-I. PMID:26464974

A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

PubMed

Moroco, Jamie A; Baumgartner, Matthew P; Rust, Heather L; Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S; Camacho, Carlos J; Smithgall, Thomas E

2015-08-01

The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. © 2014 John Wiley & Sons A/S.

Association of p60c-src with endosomal membranes in mammalian fibroblasts

PubMed Central

1992-01-01

We have examined the subcellular localization of p60c-src in mammalian fibroblasts. Analysis of indirect immunofluorescence by three- dimensional optical sectioning microscopy revealed a granular cytoplasmic staining that co-localized with the microtubule organizing center. Immunofluorescence experiments with antibodies against a number of membrane markers demonstrated a striking co-localization between p60c-src and the cation-dependent mannose-6-phosphate receptor (CI- MPR), a marker that identifies endosomes. Both p60c-src and the CI-MPR were found to cluster at the spindle poles throughout mitosis. In addition, treatment of interphase and mitotic cells with brefeldin A resulted in a clustering of p60c-src and CI-MPR at a peri-centriolar position. Biochemical fractionation of cellular membranes showed that a major proportion of p60c-src co-enriched with endocytic membranes. Treatment of membranes containing HRP to alter their apparent density also altered the density of p60c-src-containing membranes. Similar density shift experiments with total cellular membranes revealed that the majority of membrane-associated p60c-src in the cell is associated with endosomes, while very little is associated with plasma membranes. These results support a role for p60c-src in the regulation of endosomal membranes and protein trafficking. PMID:1378446

Coactivator SRC-2–dependent metabolic reprogramming mediates prostate cancer survival and metastasis

PubMed Central

Dasgupta, Subhamoy; Putluri, Nagireddy; Long, Weiwen; Zhang, Bin; Wang, Jianghua; Kaushik, Akash K.; Arnold, James M.; Bhowmik, Salil K.; Stashi, Erin; Brennan, Christine A.; Rajapakshe, Kimal; Coarfa, Cristian; Mitsiades, Nicholas; Ittmann, Michael M.; Chinnaiyan, Arul M.; Sreekumar, Arun; O’Malley, Bert W.

2015-01-01

Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2–driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer. PMID:25664849

A Kinase-Independent Function of c-Src Mediates p130Cas Phosphorylation at the Serine-639 Site in Pressure Overloaded Myocardium

PubMed Central

Palanisamy, Arun P.; Suryakumar, Geetha; Panneerselvam, Kavin; Willey, Christopher D.; Kuppuswamy, Dhandapani

2017-01-01

Early work in pressure overloaded (PO) myocardium shows that integrins mediate focal adhesion complex formation by recruiting the adaptor protein p130Cas (Cas) and nonreceptor tyrosine kinase c-Src. To explore c-Src role in Cas-associated changes during PO, we used a feline right ventricular in vivo PO model and a three-dimensional (3D) collagen-embedded adult cardiomyocyte in vitro model that utilizes a Gly-Arg-Gly-Asp-Ser (RGD) peptide for integrin stimulation. Cas showed slow electrophoretic mobility (band-shifting), recruitment to the cytoskeleton, and tyrosine phosphorylation at 165, 249, and 410 sites in both 48 h PO myocardium and 1 h RGD-stimulated cardiomyocytes. Adenoviral mediated expression of kinase inactive (negative) c-Src mutant with intact scaffold domains (KN-Src) in cardiomyocytes did not block the RGD stimulated changes in Cas. Furthermore, expression of KN-Src or kinase active c-Src mutant with intact scaffold function (A-Src) in two-dimensionally (2D) cultured cardiomyocytes was sufficient to cause Cas band-shifting, although tyrosine phosphorylation required A-Src. These data indicate that c-Src’s adaptor function, but not its kinase function, is required for a serine/threonine specific phosphorylation(s) responsible for Cas band-shifting. To explore this possibility, Chinese hamster ovary cells that stably express Cas were infected with either β-gal or KN-Src adenoviruses and used for Cas immunoprecipitation combined with mass spectrometry analysis. In the KN-Src expressing cells, Cas showed phosphorylation at the serine-639 (human numbering) site. A polyclonal antibody raised against phospho-serine-639 detected Cas phosphorylation in 24–48 h PO myocardium. Our studies indicate that c-Src’s adaptor function mediates serine-639 phosphorylation of Cas during integrin activation in PO myocardium. PMID:25976166

Antiangiogenic and Antitumor Effects of Src Inhibition in Ovarian Carcinoma

PubMed Central

Han, Liz Y.; Landen, Charles N.; Trevino, Jose G.; Halder, Jyotsnabaran; Lin, Yvonne G.; Kamat, Aparna A.; Kim, Tae-Jin; Merritt, William M.; Coleman, Robert L.; Gershenson, David M.; Shakespeare, William C.; Wang, Yihan; Sundaramoorth, Raji; Metcalf, Chester A.; Dalgarno, David C.; Sawyer, Tomi K.; Gallick, Gary E.; Sood, Anil K.

2011-01-01

Src, a nonreceptor tyrosine kinase, is a key mediator for multiple signaling pathways that regulate critical cellular functions and is often aberrantly activated in a number of solid tumors, including ovarian carcinoma. The purpose of this study was to determine the role of activated Src inhibition on tumor growth in an orthotopic murine model of ovarian carcinoma. In vitro studies on HeyA8 and SKOV3ip1 cell lines revealed that Src inhibition by the Src-selective inhibitor, AP23846, occurred within 1 hour and responded in a dose-dependent manner. Furthermore, Src inhibition enhanced the cytotoxicity of docetaxel in both chemosensitive and chemoresistant ovarian cancer cell lines, HeyA8 and HeyA8-MDR, respectively. In vivo, Src inhibition by AP23994, an orally bioavailable analogue of AP23846, significantly decreased tumor burden in HeyA8 (P = 0.02), SKOV3ip1 (P = 0.01), as well as HeyA8-MDR (P < 0.03) relative to the untreated controls. However, the greatest effect on tumor reduction was observed in combination therapy with docetaxel (P < 0.001, P = 0.002, and P = 0.01, for the above models, respectively). Proliferating cell nuclear antigen staining showed that Src inhibition alone (P = 0.02) and in combination with docetaxel (P = 0.007) significantly reduced tumor proliferation. In addition, Src inhibition alone and in combination with docetaxel significantly down-regulated tumoral production of vascular endothelial growth factor and interleukin 8, whereas combination therapy decreased the microvessel density (P = 0.02) and significantly affected vascular permeability (P < 0.05). In summary, Src inhibition with AP23994 has potent antiangiogenic effects and significantly reduces tumor burden in preclinical ovarian cancer models. Thus, Src inhibition may be an attractive therapeutic approach for patients with ovarian carcinoma. PMID:16951177

v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins.

PubMed

Sobue, S; Murakami, M; Banno, Y; Ito, H; Kimura, A; Gao, S; Furuhata, A; Takagi, A; Kojima, T; Suzuki, M; Nozawa, Y; Murate, T

2008-10-09

Sphingosine kinase 1 (SPHK1) is overexpressed in solid tumors and leukemia. However, the mechanism of SPHK1 overexpression by oncogenes has not been defined. We found that v-Src-transformed NIH3T3 cells showed a high SPHK1 mRNA, SPHK1 protein and SPHK enzyme activity. siRNA of SPHK1 inhibited the growth of v-Src-NIH3T3, suggesting the involvement of SPHK1 in v-Src-induced oncogenesis. v-Src-NIH3T3 showed activations of protein kinase C-alpha, signal transducers and activators of transcription 3 and c-Jun NH(2)-terminal kinase. Their inhibition suppressed SPHK1 expression in v-Src-NIH3T3, whereas their overexpression increased SPHK1 mRNA in NIH3T3. Unexpectedly, the nuclear run-on assay and the promoter analysis using 5'-promoter region of mouse SPHK1 did not show any significant difference between mock- and v-Src-NIH3T3. Furthermore, the half-life of SPHK1 mRNA in mock-NIH3T3 was nearly 15 min, whereas that of v-Src-NIH3T3 was much longer. Examination of two AU-rich region-binding proteins, AUF1 and HuR, that regulate mRNA decay reciprocally, showed decreased total AUF1 protein associated with increased tyrosine-phosphorylated form and increased serine-phosphorylated HuR protein in v-Src-NIH3T3. Modulation of AUF1 and HuR by their overexpression or siRNA revealed that SPHK1 mRNA in v-Src- and mock-NIH3T3 was regulated reciprocally by these factors. Our results showed, for the first time, a novel mechanism of v-Src-induced SPHK1 overexpression.

Platelet-derived growth factor-dependent association of the GTPase-activating protein of Ras and Src.

PubMed Central

Schlesinger, T K; Demali, K A; Johnson, G L; Kazlauskas, A

1999-01-01

Here we report that the platelet-derived growth factor beta receptor (betaPDGFR) is not the only tyrosine kinase able to associate with the GTPase-activating protein of Ras (RasGAP). The interaction of non-betaPDGFR kinase(s) with RasGAP was dependent on stimulation with platelet-derived growth factor (PDGF) and seemed to require tyrosine phosphorylation of RasGAP. Because the tyrosine phosphorylation site of RasGAP is in a sequence context that is favoured by the Src homology 2 ('SH2') domain of Src family members, we tested the possibility that Src was the kinase that associated with RasGAP. Indeed, Src interacted with phosphorylated RasGAP fusion proteins; immunodepletion of Src markedly decreased the recovery of the RasGAP-associated kinase activity. Thus PDGF-dependent tyrosine phosphorylation of RasGAP results in the formation of a complex between RasGAP and Src. To begin to address the relevance of these observations, we focused on the consequences of the interaction of Src and RasGAP. We found that a receptor mutant that did not activate Src was unable to efficiently mediate the tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Taken together, these observations support the following hypothesis. When RasGAP is recruited to the betaPDGFR, it is phosphorylated and associates with Src. Once bound to RasGAP, Src is no longer able to promote the phosphorylation of PLCgamma. This hypothesis offers a mechanistic explanation for our previously published findings that the recruitment of RasGAP to the betaPDGFR attenuates the tyrosine phosphorylation of PLCgamma. Finally, these findings suggest a novel way in which RasGAP negatively regulates signal relay by the betaPDGFR. PMID:10567236

Removal of mercury from coal via a microbial pretreatment process

DOEpatents

Borole, Abhijeet P [Knoxville, TN; Hamilton, Choo Y [Knoxville, TN

2011-08-16

A process for the removal of mercury from coal prior to combustion is disclosed. The process is based on use of microorganisms to oxidize iron, sulfur and other species binding mercury within the coal, followed by volatilization of mercury by the microorganisms. The microorganisms are from a class of iron and/or sulfur oxidizing bacteria. The process involves contacting coal with the bacteria in a batch or continuous manner. The mercury is first solubilized from the coal, followed by microbial reduction to elemental mercury, which is stripped off by sparging gas and captured by a mercury recovery unit, giving mercury-free coal. The mercury can be recovered in pure form from the sorbents via additional processing.

Coal liquefaction process utilizing coal/CO.sub.2 slurry feedstream

DOEpatents

Comolli, Alfred G.; McLean, Joseph B.

1989-01-01

A coal hydrogenation and liquefaction process in which particulate coal feed is pressurized to an intermediate pressure of at least 500 psig and slurried with CO.sub.2 liquid to provide a flowable coal/CO.sub.2 slurry feedstream, which is further pressurized to at least 1000 psig and fed into a catalytic reactor. The coal particle size is 50-375 mesh (U.S. Sieve Series) and provides 50-80 W % coal in the coal/CO.sub.2 slurry feedstream. Catalytic reaction conditions are maintained at 650.degree.-850.degree. F. temperature, 1000-4000 psig hydrogen partial pressure and coal feed rate of 10-100 lb coal/hr ft.sup.3 reactor volume to produce hydrocarbon gas and liquid products. The hydrogen and CO.sub.2 are recovered from the reactor effluent gaseous fraction, hydrogen is recycled to the catalytic reactor, and CO.sub.2 is liquefied and recycled to the coal slurrying step. If desired, two catalytic reaction stages close coupled together in series relation can be used. The process advantageously minimizes the recycle and processing of excess hydrocarbon liquid previously needed for slurrying the coal feed to the reactor(s).

A characterization and evaluation of coal liquefaction process streams. Quarterly technical progress report, October 1--December 31, 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, G.A.; Brandes, S.D.; Winschel, R.A.

1995-05-01

The objectives of this project are to support the DOE direct coal liquefaction process development program and to improve the useful application of analytical chemistry to direct coal liquefaction process development. Independent analyses by well-established methods will be obtained of samples produced in direct coal liquefaction processes under evaluation by DOE. Additionally, analytical instruments and techniques which are currently underutilized for the purpose of examining coal-derived samples will be evaluated. The data obtained from this study will be used to help guide current process development and to develop an improved data base on coal and coal liquids properties. A samplemore » bank will be established and maintained for use in this project and will be available for use by other researchers. The reactivity of the non-distillable resids toward hydrocracking at liquefaction conditions (i.e., resid reactivity) will be examined. From the literature and data experimentally obtained, a mathematical kinetic model of resid conversion will be constructed. It is anticipated that such a model will provide insights useful for improving process performance and thus the economics of direct coal liquefaction. During this quarter, analyses were completed on 65 process samples from representative periods of HRI Run POC-2 in which coal, coal/plastics, and coal/rubber were the feedstocks. A sample of the oil phase of the oil/water separator from HRI Run POC-1 was analyzed to determine the types and concentrations of phenolic compounds. Chemical analyses and microautoclave tests were performed to monitor the oxidation and measure the reactivity of the standard coal (Old Ben Mine No. 1) which has been used for the last six years to determine solvent quality of process oils analyzed in this and previous DOE contracts.« less

Microbial products activate monocytic cells through detergent-resistant membrane microdomains.

PubMed

Epelman, Slava; Berenger, Byron; Stack, Danuta; Neely, Graham G; Ma, Ling Ling; Mody, Christopher H

2008-12-01

Patients with cystic fibrosis suffer recurrent pulmonary infections that are characterized by an overactive yet ineffective and destructive inflammatory response that is associated with respiratory infections by Pseudomonas aeruginosa, a pathogen that produces a number of phlogistic molecules. To better understand this process, we used exoenzyme S (ExoS), one of the key P. aeruginosa-secreted exoproducts, which is known to stimulate cells via the Toll-like receptor (TLR) pathway. We found that ExoS induced proinflammatory cytokine production via the NF-kappaB, Erk1/2, and Src kinase pathways. Because Src kinases are concentrated within cholesterol-containing, detergent-resistant membrane microdomains (DRM) (also called lipid rafts) and DRM act as signaling platforms and amplifiers on the surface of cells, we addressed the role of DRM in ExoS signaling. ExoS bound directly to a subset of DRM and induced the phosphorylation of multiple proteins within DRM, including Src kinases. Disruption of DRM by cholesterol extraction prevented NF-kappaB and Erk 1/2 activation and TNF-alpha production in response to ExoS. Activation of monocytic cells by other TLR and Nod-like receptor agonists, such as lipoteichoic acid, lipopolysaccharide, and peptidoglycan, were also dependent on DRM, and disruption prevented TNF-alpha production. Disruption of DRM did not prevent ExoS binding but did release the Src kinase, Lyn, from the DRM fraction into the detergent-soluble fraction, a site in which Src kinases are not active. These studies show that ExoS, a TLR agonist, requires direct binding to DRM for optimal signaling, which suggests that DRM are possible therapeutic targets in cystic fibrosis.

The Src SH2 domain interacts dynamically with the focal adhesion kinase binding site as demonstrated by paramagnetic NMR spectroscopy.

PubMed

Lindfors, Hanna E; Drijfhout, Jan Wouter; Ubbink, Marcellus

2012-06-01

The interaction between the tyrosine kinases Src and focal adhesion kinase (FAK) is a key step in signaling processes from focal adhesions. The phosphorylated tyrosine residue 397 in FAK is able to bind the Src SH2 domain. To establish the extent of the FAK binding motif, the binding affinity of the SH2 domain for phosphorylated and unphosphorylated FAK-derived peptides of increasing length was determined and compared with that of the internal Src SH2 binding site. It is shown that the FAK peptides have higher affinity than the internal binding site and that seven negative residues adjacent to the core SH2 binding motif increase the binding constant 30-fold. A rigid spin-label incorporated in the FAK peptides was used to establish on the basis of paramagnetic relaxation enhancement whether the peptide-protein complex is well defined. A large spread of the paramagnetic effects on the surface of the SH2 domain suggests that the peptide-protein complex exhibits dynamics, despite the high affinity of the peptide. The strong electrostatic interaction between the positive side of the SH2 domain and the negative peptide results in a high affinity but may also favor a dynamic interaction. Copyright © 2012 Wiley Periodicals, Inc.

Literature survey of properties of synfuels derived from coal

NASA Technical Reports Server (NTRS)

Flores, F.

1982-01-01

A literature survey of the properties of synfuels for ground-based turbine applications is presented. The four major concepts for converting coal into liquid fuels (solvent extraction, catalytic liquefaction, pyrolysis, and indirect liquefaction), and the most important concepts for coal gasification (fixed bed, fluidized bed, entrained flow, and underground gasification) are described. Upgrading processes for coal derived liquid fuels are also described. Data presented for liquid fuels derived from various processes, including H-coal, synthoil, solvent refined coal, COED, donor solvent, zinc chloride hydrocracking, co-steam, and flash pyrolysis. Typical composition, and property data is also presented for low and medium-BTU gases derived from the various coal gasification processes.

Inhibition of src family kinases by a combinatorial action of 5'-AMP and small heat shock proteins, identified from the adult heart.

PubMed

Kasi, V S; Kuppuswamy, D

1999-10-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5'-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5'-AMP and to a lesser extent 5'-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including alphaB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5'-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5'-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5'-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state.

Structure-based design of an osteoclast-selective, nonpeptide Src homology 2 inhibitor with in vivo antiresorptive activity

PubMed Central

Shakespeare, William; Yang, Michael; Bohacek, Regine; Cerasoli, Franklin; Stebbins, Karin; Sundaramoorthi, Raji; Azimioara, Mihai; Vu, Chi; Pradeepan, Selvi; Metcalf, Chester; Haraldson, Chad; Merry, Taylor; Dalgarno, David; Narula, Surinder; Hatada, Marcos; Lu, Xiaode; van Schravendijk, Marie Rose; Adams, Susan; Violette, Shelia; Smith, Jeremy; Guan, Wei; Bartlett, Catherine; Herson, Jay; Iuliucci, John; Weigele, Manfred; Sawyer, Tomi

2000-01-01

Targeted disruption of the pp60src (Src) gene has implicated this tyrosine kinase in osteoclast-mediated bone resorption and as a therapeutic target for the treatment of osteoporosis and other bone-related diseases. Herein we describe the discovery of a nonpeptide inhibitor (AP22408) of Src that demonstrates in vivo antiresorptive activity. Based on a cocrystal structure of the noncatalytic Src homology 2 (SH2) domain of Src complexed with citrate [in the phosphotyrosine (pTyr) binding pocket], we designed 3′,4′-diphosphonophenylalanine (Dpp) as a pTyr mimic. In addition to its design to bind Src SH2, the Dpp moiety exhibits bone-targeting properties that confer osteoclast selectivity, hence minimizing possible undesired effects on other cells that have Src-dependent activities. The chemical structure AP22408 also illustrates a bicyclic template to replace the post-pTyr sequence of cognate Src SH2 phosphopeptides such as Ac-pTyr-Glu-Glu-Ile (1). An x-ray structure of AP22408 complexed with Lck (S164C) SH2 confirmed molecular interactions of both the Dpp and bicyclic template of AP22408 as predicted from molecular modeling. Relative to the cognate phosphopeptide, AP22408 exhibits significantly increased Src SH2 binding affinity (IC50 = 0.30 μM for AP22408 and 5.5 μM for 1). Furthermore, AP22408 inhibits rabbit osteoclast-mediated resorption of dentine in a cellular assay, exhibits bone-targeting properties based on a hydroxyapatite adsorption assay, and demonstrates in vivo antiresorptive activity in a parathyroid hormone-induced rat model. PMID:10944210

Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling.

PubMed

Archer-Lahlou, Elodie; Audet, Nicolas; Amraei, Mohammad Gholi; Huard, Karine; Paquin-Gobeil, Mélanie; Pineyro, Graciela

2009-01-01

Abstract An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre-treatment with Src inhibitor PP2 (20 microM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post-endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR-Galphal3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.

The Endoplasmic Reticulum Is a Reservoir for WAVE/SCAR Regulatory Complex Signaling in the Arabidopsis Leaf1[W][OA

PubMed Central

Zhang, Chunhua; Mallery, Eileen; Reagan, Sara; Boyko, Vitaly P.; Kotchoni, Simeon O.; Szymanski, Daniel B.

2013-01-01

During plant cell morphogenesis, signal transduction and cytoskeletal dynamics interact to locally organize the cytoplasm and define the geometry of cell expansion. The WAVE/SCAR (for WASP family verprolin homologous/suppressor of cyclic AMP receptor) regulatory complex (W/SRC) is an evolutionarily conserved heteromeric protein complex. Within the plant kingdom W/SRC is a broadly used effector that converts Rho-of-Plants (ROP)/Rac small GTPase signals into Actin-Related Protein2/3 and actin-dependent growth responses. Although the components and biochemistry of the W/SRC pathway are well understood, a basic understanding of how cells partition W/SRC into active and inactive pools is lacking. In this paper, we report that the endoplasmic reticulum (ER) is an important organelle for W/SRC regulation. We determined that a large intracellular pool of the core W/SRC subunit NAP1, like the known positive regulator of W/SRC, the DOCK family guanine nucleotide-exchange factor SPIKE1 (SPK1), localizes to the surface of the ER. The ER-associated NAP1 is inactive because it displays little colocalization with the actin network, and ER localization requires neither activating signals from SPK1 nor a physical association with its W/SRC-binding partner, SRA1. Our results indicate that in Arabidopsis (Arabidopsis thaliana) leaf pavement cells and trichomes, the ER is a reservoir for W/SRC signaling and may have a key role in the early steps of W/SRC assembly and/or activation. PMID:23613272

A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.

PubMed

Kashiwagi, Kenji; Ito, Sadahiro; Maeda, Shuichiro; Kato, Goro

2017-12-01

Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole retinas was significantly lower than that in young SD/SD mice in the absence of inflammation and elevated intraocular pressure, resembling the pathogenesis of progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice exhibited no age-related RGC loss. The age-related retinal RGC number reduction was greater in the peripheral rather than the mid-peripheral region of the retina in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of ageing SD/SD mice was significantly higher than that in young SD/SD mice. These results suggest that Src regulates RGC survival during ageing in a manner that depends on Ser75 phosphorylation.

Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion

PubMed Central

Zhou, Xiaoxu; Liu, Lirong; Masucci, Monica V.; Tang, Jinhua; Li, Xuezhu; Liu, Na; Bayliss, George; Zhao, Ting C.; Zhuang, Shougang

2017-01-01

Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage. PP1 treatment also suppressed renal expression of neutrophil gelatinase-associated lipocalin and reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented downregulation of several adherens and tight junction proteins, including E-cadherin, ZO-1, and claudins-1/−4 in the kidney after I/R injury as well as in cultured renal proximal tubular cells following oxidative stress. Finally, PP1 inhibited I/R–induced renal expression of matrix metalloproteinase-2 and -9, phosphorylation of extracellular signal–regulated kinases1/2, signal transducer and activator of transcription-3, and nuclear factor-κB, and the infiltration of macrophages into the kidney. These data indicate that Src is a pivotal mediator of renal epithelial injury and that its inhibition may have a therapeutic potential to treat AKI. PMID:28415724

Clinicopathological Characteristics and Prognostic Value of Signet Ring Cells in Gastric Carcinoma: A Meta-Analysis.

PubMed

Nie, Run-Cong; Yuan, Shu-Qiang; Li, Yuan-Fang; Chen, Yong-Ming; Chen, Xiao-Jiang; Zhu, Bao-Yan; Xu, Li-Pu; Zhou, Zhi-Wei; Chen, Shi; Chen, Ying-Bo

2017-01-01

Background and Objectives: Previous studies of the prognostic value of the signet ring cell (SRC) type have yielded inconsistent results. Therefore, the aim of the present meta-analysis is to explore the clinicopathological characteristics and prognostic value of SRCs. Methods: Relevant articles that compared SRC and non-SRC type in PubMed and Web of Science were comprehensively searched. Then, a meta-analysis was performed. Results: A total of 19 studies including 35947 cases were analyzed. Compared with non-SRC patients, SRC patients tended to be younger (WMD: -3.88, P=0.001) and predominantly female (OR: 1.60, P<0.001). Additionally, SRC patients exhibited less upper third tumor location (OR: 0.62, P<0.001) and less frequent hematogenous metastasis (OR: 0.41, P<0.001). There was no difference in overall survival (OS) between SRC and non-SRC patients in the total population (HR: 1.02, P=0.830). Early gastric cancer with SRCs was associated with better OS (HR: 0.57, P=0.002), while advanced gastric cancer with non-SRCs was associated with a worse prognosis (HR: 1.17, P<0.001). Conclusions: This meta-analysis revealed that SRC tends to affect young females and tends to be located in the middle and lower third of the stomach. Early SRCs are associated with better prognoses, while advanced SRCs are associated with worse prognoses.

40 CFR Appendix V to Part 86 - The Standard Road Cycle (SRC)

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false The Standard Road Cycle (SRC) V... Appendix V to Part 86—The Standard Road Cycle (SRC) 1. The standard road cycle (SRC) is a mileage accumulation cycle that may be used for any vehicle which is covered by the applicability provisions of § 86...

N-terminal deletions in Rous sarcoma virus p60src: effects on tyrosine kinase and biological activities and on recombination in tissue culture with the cellular src gene.

PubMed Central

Cross, F R; Garber, E A; Hanafusa, H

1985-01-01

We have constructed deletions within the region of cloned Rous sarcoma virus DNA coding for the N-terminal 30 kilodaltons of p60src. Infectious virus was recovered after transfection. Deletions of amino acids 15 to 149, 15 to 169, or 149 to 169 attenuated but did not abolish transforming activity, as assayed by focus formation and anchorage-independent growth. These deletions also had only slight effects on the tyrosine kinase activity of the mutant src protein. Deletion of amino acids 169 to 264 or 15 to 264 completely abolished transforming activity, and src kinase activity was reduced at least 10-fold. However, these mutant viruses generated low levels of transforming virus by recombination with the cellular src gene. The results suggest that as well as previously identified functional domains for p60src myristylation and membrane binding (amino acids 1 to 14) and tyrosine kinase activity (amino acids 250 to 526), additional N-terminal sequences (particularly amino acids 82 to 169) can influence the transforming activity of the src protein. Images PMID:2426576

c-Src activity is differentially required by cancer cell motility modes.

PubMed

Logue, Jeremy S; Cartagena-Rivera, Alexander X; Chadwick, Richard S

2018-04-01

Cancer cell migration requires that cells respond and adapt to their surroundings. In the absence of extracellular matrix cues, cancer cells will undergo a mesenchymal to ameboid transition, whereas a highly confining space will trigger a switch to "leader bleb-based" migration. To identify oncogenic signaling pathways mediating these transitions, we undertook a targeted screen using clinically useful inhibitors. Elevated Src activity was found to change actin and focal adhesion dynamics, whereas inhibiting Src triggered focal adhesion disassembly and blebbing. On non-adherent substrates and in collagen matrices, amoeboid-like, blebbing cells having high Src activity formed protrusions of the plasma membrane. To evaluate the role of Src in confined cells, we use a novel approach that places cells under a slab of polydimethylsiloxane (PDMS), which is held at a defined height. Using this method, we find that leader bleb-based migration is resistant to Src inhibition. High Src activity was found to markedly change the architecture of cortical actomyosin, reduce cell mechanical properties, and the percentage of cells that undergo leader bleb-based migration. Thus, Src is a signal transducer that can potently influence transitions between migration modes with implications for the rational development of metastasis inhibitors.

Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn; Luo, Xiaoyong; Nie, Peipei

SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuatingmore » AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.« less

30 CFR 905.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 905.764 Section 905.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE CALIFORNIA § 905.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 910.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 910.764 Section 910.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE GEORGIA § 910.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 912.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 912.764 Section 912.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE IDAHO § 912.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 903.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 903.764 Section 903.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE ARIZONA § 903.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

Pilot Plant Program for the AED Advanced Coal Cleaning System. Phase II. Interim final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-08-01

Advanced Energy Dynamics, Inc. (AED), has developed a proprietary coal cleaning process which employs a combination of ionization and electrostatic separation to remove both sulfur and ash from dry pulverized coal. The Ohio Department of Energy sponsored the first part of a program to evaluate, develop, and demonstrate the process in a continuous-flow pilot plant. Various coals used by Ohio electric utilities were characterized and classified, and sulfur reduction, ash reduction and Btu recovery were measured. Sulfur removal in various coals ranged from 33 to 68% (on a Btu basis). Ash removal ranged from 17 to 59% (on a Btumore » basis). Ash removal of particles greater than 53 microns ranged from 46 to 88%. Btu recovery ranged from 90 to 97%. These results, especially the large percentage removal of ash particles greater than 53 microns, suggest that the AED system can contribute materially to improved boiler performance and availability. The study indicated the following potential areas for commercial utilization of the AED process: installation between the pulverizer and boiler of conventional coal-fired power utilities; reclamation of fine coal refuse; dry coal cleaning to supplement, and, if necessary, to take the place of conventional coal cleaning; upgrading coal used in: (1) coal-oil mixtures, (2) gasification and liquefaction processes designed to handle pulverized coal; and (3) blast furnaces for making steel, as a fuel supplement to the coke. Partial cleaning of coking coal blends during preheating may also prove economically attractive. Numerous other industrial processes which use pulverized coal such as the production of activated carbon and direct reduction of iron ore may also benefit from the use of AED coal cleaning.« less

40 CFR 60.254 - Standards for coal processing and conveying equipment, coal storage systems, transfer and loading...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standards for coal processing and conveying equipment, coal storage systems, transfer and loading systems, and open storage piles. 60.254... (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Coal Preparation...

Evaluation of a direct injection nebulizer interface for flow injection analysis and high performance liquid chromatography with inductively coupled plasma-atomic emission spectroscopic detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaFreniere, K.E.

A direct injection nebulizer (DIN) was designed, developed and evaluated to determine its potential utilization as an effective interface for flow injection analysis (FIA) and high performance liquid chromatography (HPLC) coupled with inductively coupled plasma-atomic emission spectroscopic detection. The analytical figures of merit for the DIN when used as an interface for FIA-ICP-AES were found to be comparable to or better than those obtained with conventional pneumatic nebulization in terms of limits of detection (LODs), reproducibility, linearity, and interelement effects. In the HPLC mode, the LODDs were found to be comparable to those obtained by continuous-flow sample introduction into themore » ICP, or inferior by up to only a factor of four. Stable plasma operation was maintained for the DIN sample introduction of a variety of pure organic solvents, including acetonitrile, methanol, methyl-isobutylketone, and pyridine. The HPLC-DIN-ICP-AES facility was specifically applied for the speciation of inorganic and organo-metallic species contained in synthetic mixtures, vanilla extracts and a variety of energy-related materials, such as shale oil process water, coal extracts, shale oil, crude oil, and an SRC II. Suggestions for future research are also considered.« less

Fluidized bed coal desulfurization

NASA Technical Reports Server (NTRS)

Ravindram, M.

1983-01-01

Laboratory scale experiments were conducted on two high volatile bituminous coals in a bench scale batch fluidized bed reactor. Chemical pretreatment and posttreatment of coals were tried as a means of enhancing desulfurization. Sequential chlorination and dechlorination cum hydrodesulfurization under modest conditions relative to the water slurry process were found to result in substantial sulfur reductions of about 80%. Sulfur forms as well as proximate and ultimate analyses of the processed coals are included. These studies indicate that a fluidized bed reactor process has considerable potential for being developed into a simple and economic process for coal desulfurization.

Fluidized-bed bioreactor process for the microbial solubiliztion of coal

DOEpatents

Scott, Charles D.; Strandberg, Gerald W.

1989-01-01

A fluidized-bed bioreactor system for the conversion of coal into microbially solubilized coal products. The fluidized-bed bioreactor continuously or periodically receives coal and bio-reactants and provides for the production of microbially solubilized coal products in an economical and efficient manner. An oxidation pretreatment process for rendering coal uniformly and more readily susceptible to microbial solubilization may be employed with the fluidized-bed bioreactor.

Considerations on coal gasification

NASA Technical Reports Server (NTRS)

Franzen, J. E.

1978-01-01

Commercial processes for the gasification of coal with oxygen are discussed. The Koppers-Totzek process for the gasification of coal dust entrained in a stream of gasifying agents is described in particular detail. The outlook for future applications of coal gasification is presented.

Prognostic Significance of Signet Ring Gastric Cancer

PubMed Central

Taghavi, Sharven; Jayarajan, Senthil N.; Davey, Adam; Willis, Alliric I.

2012-01-01

Purpose Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States. Patients and Methods The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007. Results We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001). Conclusion In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis. PMID:22927530

Lemongrass essential oil and citral inhibit Src/Stat3 activity and suppress the proliferation/survival of small-cell lung cancer cells, alone or in combination with chemotherapeutic agents.

PubMed

Maruoka, Takayuki; Kitanaka, Akira; Kubota, Yoshitsugu; Yamaoka, Genji; Kameda, Tomohiro; Imataki, Osamu; Dobashi, Hiroaki; Bandoh, Shuji; Kadowaki, Norimitsu; Tanaka, Terukazu

2018-03-13

Small-cell lung cancer (SCLC) is intractable due to its high propensity for relapse. Novel agents are thus needed for SCLC treatment. Lemongrass essential oil (LG-EO) and its major constituent, citral, have been reported to inhibit the proliferation and survival of several types of cancer cells. However, the precise mechanisms through which LG-EO and citral exert their effects on SCLC cells have not been fully elucidated. SCLC cells express Src and have high levels of Src-tyrosine kinase (Src-TK) activity. In most SCLC cell lines, constitutive phosphorylation of Stat3(Y705), which is essential for its activation, has been detected. Src-TK can phosphorylate Stat3(Y705), and activated Stat3 promotes the expression of the anti-apoptotic factors Bcl-xL and Mcl-1. In the present study, LG-EO and citral prevented Src-TK from phosphorylating Stat3(Y705), resulting in decreased Bcl-xL and Mcl-1 expression, in turn suppressing the proliferation/survival of SCLC cells. To confirm these findings, the wild-type-src gene was transfected into the LU135 SCLC cell line (LU135‑wt-src), in which Src and activated phospho-Stat3(Y705) were overexpressed. The suppression of cell proliferation and the induction of apoptosis by treatment with LG-EO or citral were significantly attenuated in the LU135-wt-src cells compared with the control LU135-mock cells. The signal transducer and activator of transcription 3 (Stat3) signaling pathway is also associated with intrinsic drug resistance. LU135-wt-src cells were significantly resistant to conventional chemotherapeutic agents compared with LU135-mock cells. The combined effects of citral and each conventional chemotherapeutic agent on SCLC cells were also evaluated. The combination treatment exerted additive or more prominent effects on LU135-wt-src, LU165 and MN1112 cells, which are relatively chemoresistant SCLC cells. These findings suggest that either LG-EO or citral, alone or in combination with chemotherapeutic agents, may be a novel therapeutic option for SCLC patients.

The role of Src kinase in the biology and pathogenesis of Acanthamoeba castellanii

PubMed Central

2012-01-01

Background Acanthamoeba species are the causative agents of fatal granulomatous encephalitis in humans. Haematogenous spread is thought to be a primary step, followed by blood–brain barrier penetration, in the transmission of Acanthmaoeba into the central nervous system, but the associated molecular mechanisms remain unclear. Here, we evaluated the role of Src, a non-receptor protein tyrosine kinase in the biology and pathogenesis of Acanthamoeba. Methods Amoebistatic and amoebicidal assays were performed by incubating amoeba in the presence of Src kinase-selective inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and its inactive analog, PP3 (4-amino-7-phenylpyrazolo[3,4-d]pyrimidine). Using this inhibitor, the role of Src kinase in A. castellanii interactions with Escherichia coli was determined. Zymographic assays were performed to study effects of Src kinase on extracellular proteolytic activities of A. castellanii. The human brain microvascular endothelial cells were used to determine the effects of Src kinase on A. castellanii adhesion to and cytotoxicity of host cells. Results Inhibition of Src kinase using a specific inhibitor, PP2 (4-amino-5-(4 chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d] pyrimidine) but not its inactive analog, PP3 (4-amino-7-phenylpyrazolo[3,4-d] pyrimidine), had detrimental effects on the growth of A. castellanii (keratitis isolate, belonging to the T4 genotype). Interestingly, inhibition of Src kinase hampered the phagocytic ability of A. castellanii, as measured by the uptake of non-invasive bacteria, but, on the contrary, invasion by pathogenic bacteria was enhanced. Zymographic assays revealed that inhibition of Src kinases reduced extracellular protease activities of A. castellanii. Src kinase inhibition had no significant effect on A. castellanii binding to and cytotoxicity of primary human brain microvascular endothelial cells, which constitute the blood–brain barrier. Conclusions For the first time, these findings demonstrated that Src kinase is involved in A. castellanii proliferation, protease secretions and phagocytic properties. Conversely, invasion of Acanthamoeba by pathogenic bacteria was stimulated by Src kinase inhibition. PMID:22676352

Process for forming coal compacts and product thereof

DOEpatents

Gunnink, Brett; Kanunar, Jayanth; Liang, Zhuoxiong

2002-01-01

A process for forming durable, mechanically strong compacts from coal particulates without use of a binder is disclosed. The process involves applying a compressive stress to a particulate feed comprising substantially water-saturated coal particles while the feed is heated to a final compaction temperature in excess of about 100.degree. C. The water present in the feed remains substantially in the liquid phase throughout the compact forming process. This is achieved by heating and compressing the particulate feed and cooling the formed compact at a pressure sufficient to prevent water present in the feed from boiling. The compacts produced by the process have a moisture content near their water saturation point. As a result, these compacts absorb little water and retain exceptional mechanical strength when immersed in high pressure water. The process can be used to form large, cylindrically-shaped compacts from coal particles (i.e., "coal logs") so that the coal can be transported in a hydraulic coal log pipeline.

FGF-mediated mesoderm induction involves the Src-family kinase Laloo.

PubMed

Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A

1998-08-27

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

Retirement-from-sport considerations following pediatric sports-related concussion: case illustrations and institutional approach.

PubMed

Ellis, Michael J; McDonald, Patrick J; Cordingley, Dean; Mansouri, Behzad; Essig, Marco; Ritchie, Lesley

2016-04-01

The decision to advise an athlete to retire from sports following sports-related concussion (SRC) remains a persistent challenge for physicians. In the absence of strong empirical evidence to support recommendations, clinical decision making must be individualized and should involve a multidisciplinary team of experts in concussion and traumatic brain injury. Although previous authors have advocated for a more conservative approach to these issues in child and adolescent athletes, there are few reports outlining considerations for this process among this unique population. Here, the authors use multiple case illustrations to discuss 3 subgroups of clinical considerations for sports retirement among pediatric SRC patients including the following: those with structural brain abnormalities identified on neuroimaging, those presenting with focal neurological deficits and abnormalities on physical examination, and those in whom the cumulative or prolonged effects of concussion are suspected or demonstrated. The authors' evolving multidisciplinary institutional approach to return-to-play and retirement decision making in pediatric SRC is also presented.

Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

PubMed

Schlaepfer, D D; Hunter, T

1996-10-01

Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is required for Grb2 binding to FAK. Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. In vitro, c-Src phosphorylated FAK Tyr-925 in a glutathione S-transferase-FAK C-terminal domain fusion protein, whereas FAK did not. Using epitope-tagged FAK constructs, transiently expressed in human 293 cells, we determined the effect of site-directed mutations on c-Src and Grb2 binding to FAK. Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. These results support a model whereby Src-family PTKs are recruited to FAK and focal adhesions following integrin-induced autophosphorylation and exposure of FAK Tyr-397. Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src.

PubMed

Willey, Christopher D; Balasubramanian, Sundaravadivel; Rodríguez Rosas, María C; Ross, Robert S; Kuppuswamy, Dhandapani

2003-06-01

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.

v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

PubMed

Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

1994-10-01

We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

Impregnating Coal With Calcium Carbonate

NASA Technical Reports Server (NTRS)

Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

1991-01-01

Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

Novel electrochemical process for coal conversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farooque, M.

1989-07-01

The feasibility of two distinctly different routes to coal conversion at low severity conditions was investigated. An electrochemical approach utilizing both the electro-oxidation and electro-reduction routes was employed. The electro-oxidation route consists of an electrochemical reaction involving H{sub 2}O and coal, leading to the breakup of coal molecules. The observed reaction rate has been explained as a combination of the coal and pyrite electro-oxidation currents. Organic sulfur has been identified as the contributing factor for the observation of more than 100% H{sub 2} production current efficiency with several coal samples. Also, an attractive coal pre-treatment process has been identified whichmore » results in production of useful products and simultaneous upgrading of the coal. Electrochemical oxidation of coal with H{sub 2}O leads to the production of hydrogen, CO{sub 2}, simultaneous removal of pyritic sulfur, and significant reduction of ash content. There is also indirect evidence that the organic sulfur may be removed in the process. A preliminary economic evaluation of this process has projected a cost advantage of > $8 per ton of Illinois {number sign}2 coal. A lab-scale cell has been successfully employed in this study for generating process data useful for future design calculations. This study also explored the electro-reduction route of coal conversion and has successfully demonstrated production of liquid products from different coal types at low severity conditions. A variety of aliphatic and aromatic compounds have been identified in the products. Coal type appeared to be the most important parameter affecting the product spectrum. 32 refs., 26 figs., 19 tabs.« less

Coal liquefaction process with enhanced process solvent

DOEpatents

Givens, Edwin N.; Kang, Dohee

1984-01-01

In an improved coal liquefaction process, including a critical solvent deashing stage, high value product recovery is improved and enhanced process-derived solvent is provided by recycling second separator underflow in the critical solvent deashing stage to the coal slurry mix, for inclusion in the process solvent pool.

Inhibition of Src Family Kinases by a Combinatorial Action of 5′-AMP and Small Heat Shock Proteins, Identified from the Adult Heart

PubMed Central

Kasi, Vijaykumar S.; Kuppuswamy, Dhandapani

1999-01-01

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5′-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5′-AMP and to a lesser extent 5′-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including αB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5′-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5′-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5′-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state. PMID:10490624

Discovery of Diffuse Hard X-Ray Emission from the Vicinity of PSR J1648-4611 with Suzaku

NASA Astrophysics Data System (ADS)

Sakai, Michito; Matsumoto, Hironori; Haba, Yoshito; Kanou, Yasufumi; Miyamoto, Youhei

2013-06-01

We observed the pulsar PSR J1648-4611 with Suzaku. Two X-ray sources, Suzaku J1648-4610 (Src A) and Suzaku J1648-4615 (Src B), were found in the field of view. Src A is coincident with the pulsar PSR J1648-4611, which was also detected by the Fermi Gamma-ray Space Telescope. A hard-band image indicates that Src A is spatially extended. We found point sources in the vicinity of Src A by using a Chandra image of the same region, but the point sources have soft X-ray emission, and cannot explain the hard X-ray emission of Src A. The hard-band spectrum of Src A can be reproduced by a power-law model with a photon index of 2.0+0.9-0.7. The X-ray flux in the 2-10 keV band is 1.4 × 10-13 erg cm-2 s-1. The diffuse emission suggests a pulsar wind nebula around PSR J1648&"8211;4611, but the luminosity of Src A is much larger than that expected from the spin-down luminosity of the pulsar. Parts of the very-high-energy γ-ray emission of HESS J1646-458 may be powered by this pulsar wind nebula driven by PSR J1648-4611. Src B has soft emission, and its X-ray spectrum can be described by a power-law model with a photon index of 3.0+1.4-0.8. The X-ray flux in the 0.4-10 keV band is 6.4 × 10-14 erg s-1 cm-2. No counterpart for Src B has been found in the literature.

Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro.

PubMed

Chellaiah, Meenakshi A; Schaller, Michael D

2009-08-01

PTP-PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP-PEST on dephosphorylation of c-Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over-expression of PTP-PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP-PEST over-expression as compared with control osteoclasts. Cells expressing constitutively active-Src (527YDeltaF) simulate the effects mediated by PTP-PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src-mediated phosphorylation of cortactin and WASP as well as the formation of WASP.cortactin.Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates.

The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells.

PubMed

Endo, Akinori; Ly, Tony; Pippa, Raffaella; Bensaddek, Dalila; Nicolas, Armel; Lamond, Angus I

2017-01-06

Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Scavenger Receptor C Mediates Phagocytosis of White Spot Syndrome Virus and Restricts Virus Proliferation in Shrimp

PubMed Central

Yang, Ming-Chong; Shi, Xiu-Zhen; Yang, Hui-Ting; Sun, Jie-Jie; Xu, Ling; Wang, Xian-Wei; Zhao, Xiao-Fan

2016-01-01

Scavenger receptors are an important class of pattern recognition receptors that play several important roles in host defense against pathogens. The class C scavenger receptors (SRCs) have only been identified in a few invertebrates, and their role in the immune response against viruses is seldom studied. In this study, we firstly identified an SRC from kuruma shrimp, Marsupenaeus japonicus, designated MjSRC, which was significantly upregulated after white spot syndrome virus (WSSV) challenge at the mRNA and protein levels in hemocytes. The quantity of WSSV increased in shrimp after knockdown of MjSRC, compared with the controls. Furthermore, overexpression of MjSRC led to enhanced WSSV elimination via phagocytosis by hemocytes. Pull-down and co-immunoprecipitation assays demonstrated the interaction between MjSRC and the WSSV envelope protein. Electron microscopy observation indicated that the colloidal gold-labeled extracellular domain of MjSRC was located on the outer surface of WSSV. MjSRC formed a trimer and was internalized into the cytoplasm after WSSV challenge, and the internalization was strongly inhibited after knockdown of Mjβ-arrestin2. Further studies found that Mjβ-arrestin2 interacted with the intracellular domain of MjSRC and induced the internalization of WSSV in a clathrin-dependent manner. WSSV were co-localized with lysosomes in hemocytes and the WSSV quantity in shrimp increased after injection of lysosome inhibitor, chloroquine. Collectively, this study demonstrated that MjSRC recognized WSSV via its extracellular domain and invoked hemocyte phagocytosis to restrict WSSV systemic infection. This is the first study to report an SRC as a pattern recognition receptor promoting phagocytosis of a virus. PMID:28027319

Multiple Kernel Sparse Representation based Orthogonal Discriminative Projection and Its Cost-Sensitive Extension.

PubMed

Zhang, Guoqing; Sun, Huaijiang; Xia, Guiyu; Sun, Quansen

2016-07-07

Sparse representation based classification (SRC) has been developed and shown great potential for real-world application. Based on SRC, Yang et al. [10] devised a SRC steered discriminative projection (SRC-DP) method. However, as a linear algorithm, SRC-DP cannot handle the data with highly nonlinear distribution. Kernel sparse representation-based classifier (KSRC) is a non-linear extension of SRC and can remedy the drawback of SRC. KSRC requires the use of a predetermined kernel function and selection of the kernel function and its parameters is difficult. Recently, multiple kernel learning for SRC (MKL-SRC) [22] has been proposed to learn a kernel from a set of base kernels. However, MKL-SRC only considers the within-class reconstruction residual while ignoring the between-class relationship, when learning the kernel weights. In this paper, we propose a novel multiple kernel sparse representation-based classifier (MKSRC), and then we use it as a criterion to design a multiple kernel sparse representation based orthogonal discriminative projection method (MK-SR-ODP). The proposed algorithm aims at learning a projection matrix and a corresponding kernel from the given base kernels such that in the low dimension subspace the between-class reconstruction residual is maximized and the within-class reconstruction residual is minimized. Furthermore, to achieve a minimum overall loss by performing recognition in the learned low-dimensional subspace, we introduce cost information into the dimensionality reduction method. The solutions for the proposed method can be efficiently found based on trace ratio optimization method [33]. Extensive experimental results demonstrate the superiority of the proposed algorithm when compared with the state-of-the-art methods.

Mouse fibroblasts homozygous for c-Src oncogene disruption shows dramatic suppression of expression of the gene encoding osteopontin, and adhesive phosphoprotein implicated in bone differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chackalaparampil, I.; Mukherjee, B.B.; Peri, A.

1994-09-01

Osteopetrosis, affecting mice and humans alike, arises from reduced or impaired bone resorption, causing abnormally dense bone formation. Normal bone differentiation requires continuous resorption and remodeling by osteoclasts which are derived from monocyte/macrophage lineage in the bone marrow. It has been reported that targeted homozygous disruption of c-src proto-oncogene in mice results in the development of osteopetrosis due to impaired bone-resorbing function of osteoclast cells. However, the molecular mechanism(s) which leads to osteoclast dysfunction in c-src deficient (src{sup -/-}) mice remains unclear. Here, we report that in embryonic fibroblasts derived from homozygous Src{sup -/-} mice, the expression of the genemore » coding for osteopontin (OP), a phosphorylated glycoprotein involved in bone differentiation, is drastically repressed. OP gene expression is not, however, affected in the heterozygous (Src{sup +/-}) mutant cells of identical origin, or in the c-src expression and OP production. Moreover, OP expression in c-src-deficient cells could be rescued upon treatment with 12-0-tetradecanoyl phorbol-13-myristate-acetate or okadaic acid. These observations indicate that OP expression is regulated via an src-mediated protein kinase C signaling pathway. Since it is known that OP mediates osteoclast adherence to the bone matrix, a key event in bone differentiation, our data is most significant in that they strongly suggest that drastic inhibition of synthesis of OP prevents osteoclasts in Src{sup -/-} mice from anchoring to the bone matrix. Consequently, this disruption of osteoclast adherence impairs their ability to form bone-resorbing ruffled border, causing osteopetrosis.« less

Advanced liquefaction using coal swelling and catalyst dispersion techniques. Quarterly progress report, July--September 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curtis, C.W.; Gutterman, C.; Chander, S.

The overall objective of this project is to develop a new approach for the direct liquefaction of coal to produce an all-distillate product slate at a sizable cost reduction over current technology. The approach integrates coal selection, pretreatment, coal swelling with catalyst impregnation, liquefaction, product recovery with characterization, alternate bottoms processing, and carrying out a technical assessment including an economic evaluation. The primary coal of this program, Black Thunder subbituminous coal, can be effectively beneficiated to about 3.5 wt % ash using aqueous sulfurous acid pretreatment. This treated coal can be further beneficiated to about 2 wt % ash usingmore » commercially available procedures. All three coals used in this study (Black Thunder, Burning Star bituminous, and Martin Lake lignite) are effectively swelled by a number of solvents. The most effective solvents are those having hetero-functionality. laboratory- and bench-scale liquefaction experimentation is underway using swelled and catalyst impregnated coal samples. Higher coal conversions were observed for the SO{sub 2}-treated subbituminous coal than the raw coal, regardless of catalyst type. Conversions of swelled coal were highest when Molyvan L, molybdenum naphthenate, and nickel octoate, respectively, were added to the liquefaction solvent. The study of bottoms processing consists of combining the ASCOT process which consists of coupling solvent deasphalting with delayed coking to maximize the production of coal-derived liquids while rejecting solids within the coke drum. The asphalt production phase has been completed; representative product has been evaluated. The solvent system for the deasphalting process has been established. Two ASCOT tests produced overall liquid yields (63.3 wt % and 61.5 wt %) that exceeded the combined liquid yields from the vacuum tower and ROSE process.« less

A Multifactorial Approach to Sport-Related Concussion Prevention and Education: Application of the Socioecological Framework.

PubMed

Register-Mihalik, Johna; Baugh, Christine; Kroshus, Emily; Y Kerr, Zachary; Valovich McLeod, Tamara C

2017-03-01

To offer an overview of sport-related concussion (SRC) prevention and education strategies in the context of the socioecological framework (SEF). Athletic trainers (ATs) will understand the many factors that interact to influence SRC prevention and the implications of these interactions for effective SRC education. Concussion is a complex injury that is challenging to identify and manage, particularly when athletes fail to disclose symptoms to their health care providers. Education is 1 strategy for increasing disclosure. However, limited information addresses how ATs can integrate the many factors that may influence the effectiveness of SRC education into their specific settings. Public health models provide an example through the SEF, which highlights the interplay among various levels of society and sport that can facilitate SRC prevention strategies, including education. For ATs to develop appropriate SRC prevention strategies, a framework for application is needed. A growing body of information concerning SRC prevention indicates that knowledge alone is insufficient to change concussion-related behaviors. The SEF allows this information to be considered at levels such as policy and societal, community, interpersonal (relationships), and intrapersonal (athlete). The use of such a framework will facilitate more comprehensive SRC prevention efforts that can be applied in all athletic training practice settings. Clinical Applications: Athletic trainers can use this information as they plan SRC prevention strategies in their specific settings. This approach will aid in addressing the layers of complexity that exist when developing a concussion-management policy and plan.

Short-term residential care for dementia patients: predictors for utilization and expected quality from a family caregiver's point of view.

PubMed

Donath, Carolin; Winkler, Angelika; Grässel, Elmar

2009-08-01

Short-term residential care (SRC) has proved to be effective in reducing the burden on family caregivers of dementia patients. Nevertheless, little is known about the factors which influence its usage or the expectations of family caregivers regarding quality. In this paper we address the following questions: (i) which variables of the care situation, the caregivers and their attitudes act as predictors for the utilization of SRC facilities? (ii) What are the views of caregivers about the quality of SRC? The cross-sectional study was carried out as an anonymous written survey of family caregivers of dementia patients in four regions of Germany. With a 20% response it was possible to analyze the quantitative and qualitative data from 404 and 254 family caregivers respectively. Predictors for utilization were evaluated using binary logistic regression analysis. The answers to questions of quality were evaluated using qualitative content analysis. Significant predictors for the utilization of SRC are the assessment of the helpfulness of SRC and the caregiver's knowledge of the accessibility of SRC facilities. Family caregivers who had already used SRC most frequently expressed the wish for "good care" in SRC facilities, followed by a program of suitable activities for dementia patients. In order to increase the rate of utilization, family caregivers must be convinced of the relevant advantages of using SRC facilities. The staff should be trained in caring for dementia patients and appropriate activities should be available.

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

PubMed Central

Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

2017-01-01

Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway. PMID:29187825

Time phased alternate blending of feed coals for liquefaction

DOEpatents

Schweigharett, Frank; Hoover, David S.; Garg, Diwaker

1985-01-01

The present invention is directed to a method for reducing process performance excursions during feed coal or process solvent changeover in a coal hydroliquefaction process by blending of feedstocks or solvents over time. ,

Coal-oil coprocessing at HTI - development and improvement of the technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stalzer, R.H.; Lee, L.K.; Hu, J.

1995-12-31

Co-Processing refers to the combined processing of coal and petroleum-derived heavy oil feedstocks. The coal feedstocks used are those typically utilized in direct coal liquefaction: bituminous, subbituminous, and lignites. Petroleum-derived oil, is typically a petroleum residuum, containing at least 70 W% material boiling above 525{degrees}C. The combined coal and oil feedstocks are processed simultaneously with the dual objective of liquefying the coal and upgrading the petroleum-derived residuum to lower boiling (<525{degrees}C) premium products. HTI`s investigation of the Co-Processing technology has included work performed in laboratory, bench and PDU scale operations. The concept of co-processing technology is quite simple and amore » natural outgrowth of the work done with direct coal liquefaction. A 36 month program to evaluate new process concepts in coal-oil coprocessing at the bench-scale was begun in September 1994 and runs until September 1997. Included in this continuous bench-scale program are provisions to examine new improvements in areas such as: interstage product separation, feedstock concentrations (coal/oil), improved supported/dispersed catalysts, optimization of reactor temperature sequencing, and in-line hydrotreating. This does not preclude other ideas from DOE contracts and other sources that can lead to improved product quality and economics. This research work has led to important findings which significantly increased liquid yields, improved product quality, and improved process economics.« less

The importance of student research projects in dental education.

PubMed

Guven, Y; Uysal, O

2011-05-01

In this article, our aim was to summarise students' research over 15 years at Istanbul University Faculty of Dentistry and to evaluate both the research activities from the students' perspectives and the effect of this activity on their undergraduate and postgraduate success. In 1992, dental students formed 'a Student Research Club' (SRC), which new students attend voluntarily and carry out a scientific project out with the normal curriculum every year. In total, 409 different students have presented 193 research projects at these meetings over 15 years. Seventy-four of these students were from other universities and presented 37 projects. In this research, a questionnaire containing 20 items was administered to 93 students who were the members of SRC to learn their own perception of the development of their academic and research skills and the broader impact of the club on their career. It was evaluated using Likert scale (ranged from strongly disagree to strongly agree). Student feedback was very positive and over three quarters (81%) of answers ranged between 'agree' and 'strongly agree'. When the cumulative grade point average (CGPA) of the 88 SRC members in the last 6 years (2003/2004 to 2008/2009) was evaluated as the school success rate, significant difference was found between the grades obtained by members and non-members (P<0.001). There was also significant difference between the CGPA of 25 members of SRC who were randomly chosen, before and after membership to the club (P<0.001). While the 141 members of SRC applied to postgraduate education to Istanbul University Faculty of Dentistry over the last 5 years, 74 of them accepted for PhD (52.6%). There is a statistically significant difference between the member and non-member groups (P<0.001). In addition, of the 58 teaching assistants who stayed in academic life after postgraduate studies at Istanbul University Faculty of Dentistry, 16 of them had been a member of the SRC (31%). However, no statistical difference was found between members of SRC and non-members. These data showed that although the students had an intensive programme in the school, they were able to carry out this voluntary activity successfully and this activity contributed to their educational process. Students also believe that participation of them to this activity effects positively on both personal development and academic success. © 2011 John Wiley & Sons A/S.

New cleaning technologies advance coal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onursal, B.

1984-05-01

Alternative options are discussed for reducing sulfur dioxide emissions from coal burning utility and industrial sources. Test results indicate that it may be most advantageous to use the AED Process after coal preparation or on coals that do not need much ash removal. However, the developer claims that research efforts after 1981 have led to process improvements for producing clean coals containing 1.5% to 3% ash. This paper describes the test facility where a full-scale test of the AED Process is underway.

Addition to the Lewis Chemical Equilibrium Program to allow computation from coal composition data

NASA Technical Reports Server (NTRS)

Sevigny, R.

1980-01-01

Changes made to the Coal Gasification Project are reported. The program was developed by equilibrium combustion in rocket engines. It can be applied directly to the entrained flow coal gasification process. The particular problem addressed is the reduction of the coal data into a form suitable to the program, since the manual process is involved and error prone. A similar problem in relating the normal output of the program to parameters meaningful to the coal gasification process is also addressed.

Histochemical assessment for osteoblastic activity coupled with dysfunctional osteoclasts in c-src deficient mice.

PubMed

Toray, Hisashi; Hasegawa, Tomoka; Sakagami, Naoko; Tsuchiya, Erika; Kudo, Ai; Zhao, Shen; Moritani, Yasuhito; Abe, Miki; Yoshida, Taiji; Yamamoto, Tomomaya; Yamamoto, Tsuneyuki; Oda, Kimimitsu; Udagawa, Nobuyuki; Luiz de Freitas, Paulo Henrique; Li, Minqi

2017-01-01

Since osteoblastic activities are believed to be coupled with osteoclasts, we have attempted to histologically verify which of the distinct cellular circumstances, the presence of osteoclasts themselves or bone resorption by osteoclasts, is essential for coupled osteoblastic activity, by examining c-fos -/- or c-src -/- mice. Osteopetrotic c-fos deficient (c-fos -/- ) mice have no osteoclasts, while c-src deficient (c-src -/- ) mice, another osteopetrotic model, develop dysfunctional osteoclasts due to a lack of ruffled borders. c-fos -/- mice possessed no tartrate-resistant acid phosphatase (TRAPase)-reactive osteoclasts, and showed very weak tissue nonspecific alkaline phosphatase (TNALPase)-reactive mature osteoblasts. In contrast, c-src -/- mice had many TNALPase-positive osteoblasts and TRAPase-reactive osteoclasts. Interestingly, the parallel layers of TRAPase-reactive/osteopontin-positive cement lines were observed in the superficial region of c-src -/- bone matrix. This indicates the possibility that in c-src -/- mice, osteoblasts were activated to deposit new bone matrices on the surfaces that osteoclasts previously passed along, even without bone resorption. Transmission electron microscopy demonstrated cell-to-cell contacts between mature osteoblasts and neighboring ruffled border-less osteoclasts, and osteoid including many mineralized nodules in c-src -/- mice. Thus, it seems likely that osteoblastic activities would be maintained in the presence of osteoclasts, even if they are dysfunctional.

v-src induces clonal sarcomas and rapid metastasis following transduction with a replication-defective retrovirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoker, A.W.; Sieweke, M.H.

1989-12-01

v-src is an effective carcinogen when expressed from Rous sarcoma virus (RSV) in vivo. Whereas RSV tumors require sustained oncogene expression, their growth is largely a balance between viral recruitment of tissues and host immune destruction of infected cells. The authors have therefore examined the tumorigenic potential of v-src in the absence of viral recruitment and viral antigen expression. v-src was introduced with high efficiency into chicken wing web tissues using replication-defective (rd) retroviral vectors. Clonal sarcomas were induced rapidly, and furthermore, v-src potentiated metastatic progression in {approx} 0.1%-1% of tumor clones with unexpectedly short latency. rd vectors proved effectivemore » not only in transducing v-src into tissues but also as insertional markers of tumor clonality. The rd vector present in most primary and metastatic tumors was a highly truncated form of RSV derived by viral transmission of spliced v-src mRNA; this vector should thus avoid viral recruitment and host anti-viral immune reaction through its complete lack of viral structural genes. Under such conditions v-src maintains strong carcinogenicity in vivo when restricted to clonal tumor growth and can confer rapid metastatic potential on a discrete subset of tumor clones.« less

Two Sides of the Same Coin: The Positive and Negative Impact of Spiritual Religious Coping on Quality of Life and Depression in Dialysis Patients.

PubMed

Vitorino, Luciano Magalhães; Soares, Renata de Castro E Santos; Santos, Ana Eliza Oliveira; Lucchetti, Alessandra Lamas Granero; Cruz, Jonas Preposi; Cortez, Paulo José Oliveira; Lucchetti, Giancarlo

2017-08-01

Studies have shown that spiritual/religious beliefs are associated with mental health and health-related quality of life (HRQoL). However, few studies evaluated how spiritual/religious coping (SRC) could affect hemodialysis patients. The present study investigated the role of SRC behaviors on HRQoL and depressive symptoms in hemodialysis patients. This was cross-sectional study with 184 patients. Patients completed the Beck Depression Inventory, Brief SRC Scale, Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and a Sociodemographic and Health Characterization Questionnaire. From 218 patients, 184 (84.4%) were included (53.8% male with a median age of 55.9 years). Negative SRC, but not positive SRC, was associated with depressive symptoms. Positive SRC presented significant effects in SF-36 pain and physical and social functioning. On the other hand, negative SRC exhibited significant effects in SF-36 role emotional, energy/fatigue, pain, and physical functioning. SRC influences the mental health and HRQoL in Brazilian hemodialysis patients in two distinct ways. If used positively, it may have positive outcomes. However, if used negatively, it may lead to dysfunctional consequences such as greater depressive symptomatology and affect HRQoL. Health professionals must be aware of these "two sides of the same coin."

Role of c-Src in cellular events associated with colony-stimulating factor-1-induced spreading in osteoclasts.

PubMed

Insogna, K; Tanaka, S; Neff, L; Horne, W; Levy, J; Baron, R

1997-01-01

We and others have observed that in response to treatment with Colony Stimulating Factor-1 (CSF-1) neonatal rat osteoclasts demonstrate rapid cytoplasmic spreading. The receptor for CSF-1, c-Fms, is expressed in osteoclasts, possesses intrinsic tyrosine-kinase activity, and signals via rapid phosphorylation of selected proteins. It has been reported previously that c-Src becomes tyrosine phosphorylated following CSF-1 treatment of fibroblasts overexpressing c-Fms. We therefore examined the cellular events associated with CSF-1-induced spreading in osteoclasts and what role, if any, c-Src played in these processes. Confocal microscopic studies using phosphotyrosine (P-tyr) monoclonal antibodies demonstrated that CSF-1 induced a significant dose- and time-dependent increase in P-tyr labeling of neonatal rat osteoclasts. Phalloidin staining was consistent with partial to complete disassembly of the actin attachment ring with redistribution of actin to the spreading cytoplasmic edge of the cell. Quantitation of cellular F-actin using NBD-phallicidin confirmed a decrease in polymerized actin following exposure to CSF-1. In contrast, CSF-1 failed to induce any cytoplasmic spreading in osteoclasts isolated from mice with targeted disruption of the src gene. Further, in src- osteoclasts no well defined attachment ring could be identified. To investigate cell-signaling events associated with osteoclast spreading, detergent lysates were made from purified multinucleated osteoclast-like cells (OCLs) obtained by coculturing murine bone marrow and osteoblasts with calcitriol. Western blot analyses of lysates from control and CSF-1-treated normal cells indicated that several proteins were specifically phosphorylated in response to CSF-1, most notably proteins of 165, 60, and 85-90 kDa. Immunoprecipitation studies revealed that the 165 and 60 kDa proteins were, respectively, c-Fms and c-Src. The c-Src kinase activity was increased 2.9-fold following CSF-1 treatment. The 85-90 kDa protein is as yet unidentified. Since activated receptor tyrosine kinases may induce spreading in part by reducing phosphoinositol 4,5-bisphosphate (PIP2) binding to actin-associated proteins, a monoclonal antibody to PIP2 was used to assess the nature of PIP2 binding proteins in OCLs. Proteins of 85-90 kDa, 43 kDa, and 30 kDa were consistently demonstrated to bind PIP2. Further, the PIP2 content of the 85-90 kDa protein appeared to decrease with CSF-1 treatment. Whether this protein represents the phosphoprotein of the same M.W. is unclear. We also examined the effect of CSF-1 on the PIP2 content of alpha-actinin. Alpha-actinin showed low-level PIP2 binding, which was demonstrable only after immuno-precipitation and did not change with CSF-1 treatment. However, CSF-1 did cause a significant decline in the phosphotyrosine content of alpha-actinin. In contrast, in src- OCLs, CSF-1 induced more prolonged phosphorylation of c-Fms, and the 85-90 kDa protein was markedly hypophosphorylated. Further, alpha-actinin did not dephosphorylate in src- cells. We conclude that CSF-1-induced osteoclast spreading is accompanied by rapid reorganization of the actin cytoskeleton and phosphorylation of several cellular substrates, including c-Fms and c-Src. PIP2 binding to at least one protein appears to decrease with CSF-1 treatment, which may favor actin depolymerization. The reduced tyrosine phosphorylation of alpha-actinin could effect its ability to bind to actin. Thus c-Src may play an important role in these cellular events since in its absence, osteoclasts do not spread and signaling events downstream are altered. Whether these changes relate in part to the basal abnormalities in the cytoskeletal organization of src- osteoclasts remains to be determined.

Approach to investigation and treatment of persistent symptoms following sport-related concussion: a systematic review.

PubMed

Makdissi, Michael; Schneider, Kathryn J; Feddermann-Demont, Nina; Guskiewicz, Kevin M; Hinds, Sidney; Leddy, John J; McCrea, Michael; Turner, Michael; Johnston, Karen M

2017-06-01

To conduct a systematic review of the literature regarding assessment and treatment modalities in patients with persistent symptoms following sport-related concussion (SRC). We searched Medline, Embase, SPORTSDiscus, PsycINFO, CINAHL, Cochrane library and ProQuest Dissertation & Theses Global electronic databases. Studies were included if they were original research, reported on SRC as the primary source of injury, included patients with persistent postconcussive symptoms (>10 days) and investigated the role of assessment or treatment modalities. Of 3225 articles identified in the preliminary search, 25 articles met the inclusion criteria. 11 articles were concerned with assessment and 14 articles with treatment of persistent symptoms following SRC. There were three randomised control trials and one quasi-experimental study. The remainder consisting of cross-sectional studies, historical cohorts and case series. 'Persistent symptoms' following SRC can be defined as clinical recovery that falls outside expected time frames (ie, >10-14 days in adults and >4 weeks in children). It does not reflect a single pathophysiological entity, but describes a constellation of non-specific post-traumatic symptoms that may be linked to coexisting and/or confounding pathologies. A detailed multimodal clinical assessment is required to identify specific primary and secondary processes, and treatment should target specific pathologies identified. There is preliminary evidence supporting the use of symptom-limited aerobic exercise, targeted physical therapy and a collaborative approach that includes cognitive behavioural therapy. Management of patients with persistent symptoms is challenging and should occur in a multidisciplinary collaborative setting, with healthcare providers with experience in SRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Coal liquefaction quenching process

DOEpatents

Thorogood, Robert M.; Yeh, Chung-Liang; Donath, Ernest E.

1983-01-01

There is described an improved coal liquefaction quenching process which prevents the formation of coke with a minimum reduction of thermal efficiency of the coal liquefaction process. In the process, the rapid cooling of the liquid/solid products of the coal liquefaction reaction is performed without the cooling of the associated vapor stream to thereby prevent formation of coke and the occurrence of retrograde reactions. The rapid cooling is achieved by recycling a subcooled portion of the liquid/solid mixture to the lower section of a phase separator that separates the vapor from the liquid/solid products leaving the coal reactor.

Microbial desulfurization of coal

NASA Technical Reports Server (NTRS)

Dastoor, M. N.; Kalvinskas, J. J.

1978-01-01

Experiments indicate that several sulfur-oxidizing bacteria strains have been very efficient in desulfurizing coal. Process occurs at room temperature and does not require large capital investments of high energy inputs. Process may expand use of abundant reserves of high-sulfur bituminous coal, which is currently restricted due to environmental pollution. On practical scale, process may be integrated with modern coal-slurry transportation lines.

SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2

NASA Astrophysics Data System (ADS)

Naudin, Cécile; Sirvent, Audrey; Leroy, Cédric; Larive, Romain; Simon, Valérie; Pannequin, Julie; Bourgaux, Jean-François; Pierre, Josiane; Robert, Bruno; Hollande, Frédéric; Roche, Serge

2014-01-01

The adaptor SLAP is a negative regulator of receptor signalling in immune cells but its role in human cancer is ill defined. Here we report that SLAP is abundantly expressed in healthy epithelial intestine but strongly downregulated in 50% of colorectal cancer. SLAP overexpression suppresses cell tumorigenicity and invasiveness while SLAP silencing enhances these transforming properties. Mechanistically, SLAP controls SRC/EPHA2/AKT signalling via destabilization of the SRC substrate and receptor tyrosine kinase EPHA2. This activity is independent from CBL but requires SLAP SH3 interaction with the ubiquitination factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2. SRC phosphorylates EPHA2 on Tyr594, thus creating a feedback loop that promotes EPHA2 destruction and thereby self-regulates its transforming potential. SLAP silencing enhances SRC oncogenicity and sensitizes colorectal tumour cells to SRC inhibitors. Collectively, these data establish a tumour-suppressive role for SLAP in colorectal cancer and a mechanism of SRC oncogenic induction through stabilization of its cognate substrates.

Lipid binding by the Unique and SH3 domains of c-Src suggests a new regulatory mechanism

PubMed Central

Pérez, Yolanda; Maffei, Mariano; Igea, Ana; Amata, Irene; Gairí, Margarida; Nebreda, Angel R.; Bernadó, Pau; Pons, Miquel

2013-01-01

c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase, SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation. PMID:23416516

Management of local economic and ecological system of coal processing company

NASA Astrophysics Data System (ADS)

Kiseleva, T. V.; Mikhailov, V. G.; Karasev, V. A.

2016-10-01

The management issues of local ecological and economic system of coal processing company - coal processing plant - are considered in the article. The objectives of the research are the identification and the analysis of local ecological and economic system (coal processing company) performance and the proposals for improving the mechanism to support the management decision aimed at improving its environmental safety. The data on the structure of run-of-mine coal processing products are shown. The analysis of main ecological and economic indicators of coal processing enterprises, characterizing the state of its environmental safety, is done. The main result of the study is the development of proposals to improve the efficiency of local enterprise ecological and economic system management, including technical, technological and business measures. The results of the study can be recommended to industrial enterprises to improve their ecological and economic efficiency.

Comparison Analysis of Coal Biodesulfurization and Coal's Pyrite Bioleaching with Acidithiobacillus ferrooxidans

PubMed Central

Hong, Fen-Fen; He, Huan; Liu, Jin-Yan; Tao, Xiu-Xiang; Zheng, Lei; Zhao, Yi-Dong

2013-01-01

Acidithiobacillus ferrooxidans (A. ferrooxidans) was applied in coal biodesulfurization and coal's pyrite bioleaching. The result showed that A. ferrooxidans had significantly promoted the biodesulfurization of coal and bioleaching of coal's pyrite. After 16 days of processing, the total sulfur removal rate of coal was 50.6%, and among them the removal of pyritic sulfur was up to 69.9%. On the contrary, after 12 days of processing, the coal's pyrite bioleaching rate was 72.0%. SEM micrographs showed that the major pyrite forms in coal were massive and veinlets. It seems that the bacteria took priority to remove the massive pyrite. The sulfur relative contents analysis from XANES showed that the elemental sulfur (28.32%) and jarosite (18.99%) were accumulated in the biotreated residual coal. However, XRD and XANES spectra of residual pyrite indicated that the sulfur components were mainly composed of pyrite (49.34%) and elemental sulfur (50.72%) but no other sulfur contents were detected. Based on the present results, we speculated that the pyrite forms in coal might affect sulfur biooxidation process. PMID:24288464

Desulfurizing Coal With an Alkali Treatment

NASA Technical Reports Server (NTRS)

Ravindram, M.; Kalvinskas, J. J.

1987-01-01

Experimental coal-desulfurization process uses alkalies and steam in fluidized-bed reactor. With highly volatile, high-sulfur bituminous coal, process removed 98 percent of pyritic sulfur and 47 percent of organic sulfur. Used in coal liquefaction and in production of clean solid fuels and synthetic liquid fuels. Nitrogen or steam flows through bed of coal in reactor. Alkalies react with sulfur, removing it from coal. Nitrogen flow fluidizes bed while heating or cooling; steam is fluidizing medium during reaction.

A New Use for High-Sulfur Coal

NASA Technical Reports Server (NTRS)

Lawson, D. D.; England, C.

1982-01-01

New process recovers some of economic value of high-sulfur coal. Although high-sulfur content is undesirable in most coal-utilization schemes (such as simple burning), proposed process prefers high-sulfur coal to produce electrical power or hydrogen. Potential exists for widespread application in energy industry.

Zinc sulfide liquefaction catalyst

DOEpatents

Garg, Diwakar

1984-01-01

A process for the liquefaction of carbonaceous material, such as coal, is set forth wherein coal is liquefied in a catalytic solvent refining reaction wherein an activated zinc sulfide catalyst is utilized which is activated by hydrogenation in a coal derived process solvent in the absence of coal.

Technological and economic aspects of coal biodesulfurisation.

PubMed

Klein, J

1998-01-01

The sulfur found in coal is either part of the molecular coal structure (organically bound sulfur), is contained in minerals such as pyrite (FeS2), or occurs in minor quantities in the form of sulfate and elemental sulfur. When pyrite crystals are finely distributed within the coal matrix, mechanical cleaning can only remove part of the pyrite. It can, however, be removed by microbial action requiring only mild conditions. The process involves simple equipment, almost no chemicals, but relatively long reaction times, and treatment of iron sulfate containing process water. Different process configurations are possible, depending on the coal particle size. Coal with particle sizes of less than 0.5 mm is preferably desulfurised in slurry reactors, while lump coal (> 0.5 mm) should be treated in heaps. Investment and operating costs are estimated for different process configurations on an industrial scale. Concerning the organically bound sulfur in coal there is up to now no promising biochemical pathway for the degradation and/or desulfurisation of such compounds.

Coal desulfurization by chlorinolysis production and combustion test evaluation of product coals

NASA Technical Reports Server (NTRS)

Kalvinskas, J. J.; Daly, D.

1982-01-01

Laboratory-scale screening tests were carried out on coal from Harrison County, Ohio to establish chlorination and hydrodesulfurization conditions for the batch reactor production of chlorinolysis and chlorinolysis-hydrodesulfurized coals. In addition, three bituminous coals, were treated on the lab scale by the chlorinolysis process to provide 39 to 62% desulfurization. Two bituminous coals and one subbituminous coal were then produced in 11 to 15 pound lots as chlorinolysis and hydrodesulfurized coals. The chlorinolysis coals had a desulfurization of 29-69%, reductions in voltatiles and hydrogen. Hydrodesulfurization provided a much greater desulfurization (56-86%), reductions in volatiles and hydrogen. The three coals were combustion tested in the Penn State ""plane flame furnace'' to determine ignition and burning characteristics. All three coals burned well to completion as: raw coals, chlorinolysis processed coals, and hydrodesulfurized coals. The hydrodesulfurized coals experienced greater ignition delays and reduced burning rates than the other coals because of the reduced volatile content. It is thought that the increased open pore volume in the desulfurized-devolatilized coals compensates in part for the decreased volatiles effect on ignition and burning.

Mobil process converts methanol to high-quality synthetic gasoline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, A.

1978-12-11

If production of gasoline from coal becomes commercially attractive in the United States, a process under development at the Mobil Research and Development Corp. may compete with better known coal liquefaction processes. Mobil process converts methanol to high-octane, unleaded gasoline; methanol can be produced commercially from coal. If gasoline is the desired product, the Mobil process offers strong technical and cost advantages over H-coal, Exxon donor solvent, solvent-refined coal, and Fischer--Tropsch processes. The cost analysis, contained in a report to the Dept. of Energy, concludes that the Mobil process produces more-expensive liquid products than any other liquefaction process except Fischer--Tropsch.more » But Mobil's process produces ready-to-use gasoline, while the others produce oils which require further expensive refining to yield gasoline. Disadvantages and advantages are discussed.« less

Pretreatment of coal during transport

DOEpatents

Johnson, Glenn E.; Neilson, Harry B.; Forney, Albert J.; Haynes, William P.

1977-04-19

Many available coals are "caking coals" which possess the undesirable characteristic of fusing into a solid mass when heated through their plastic temperature range (about 400.degree. C.) which temperature range is involved in many common treatment processes such as gasification, hydrogenation, carbonization and the like. Unless the caking properties are first destroyed, the coal cannot be satisfactorily used in such processes. A process is disclosed herein for decaking finely divided coal during its transport to the treating zone by propelling the coal entrained in an oyxgen-containing gas through a heated transport pipe whereby the separate transport and decaking steps of the prior art are combined into a single step.

Research on coal-water fuel combustion in a circulating fluidized bed / Badanie spalania zawiesinowych paliw węglowo-wodnych w cyrkulacyjnej warstwie fluidalnej

NASA Astrophysics Data System (ADS)

Kijo-Kleczkowska, Agnieszka

2012-10-01

In the paper the problem of heavily-watered fuel combustion has been undertaken as the requirements of qualitative coals combusted in power stations have been growing. Coal mines that want to fulfill expectations of power engineers have been forced to extend and modernize the coal enrichment plants. This causes growing quantity of waste materials that arise during the process of wet coal enrichment containing smaller and smaller under-grains. In this situation the idea of combustion of transported waste materials, for example in a hydraulic way to the nearby power stations appears attractive because of a possible elimination of the necessary deep dehydration and drying as well as because of elimination of the finest coal fraction loss arising during discharging of silted water from coal wet cleaning plants. The paper presents experimental research results, analyzing the process of combustion of coal-water suspension depending on the process conditions. Combustion of coal-water suspensions in fluidized beds meets very well the difficult conditions, which should be obtained to use the examined fuel efficiently and ecologically. The suitable construction of the research stand enables recognition of the mechanism of coal-water suspension contact with the inert material, that affects the fluidized bed. The form of this contact determines conditions of heat and mass exchange, which influence the course of a combustion process. The specificity of coal-water fuel combustion in a fluidized bed changes mechanism and kinetics of the process.

Refining and end use study of coal liquids II - linear programming analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, C.; Tam, S.

1995-12-31

A DOE-funded study is underway to determine the optimum refinery processing schemes for producing transportation fuels that will meet CAAA regulations from direct and indirect coal liquids. The study consists of three major parts: pilot plant testing of critical upgrading processes, linear programming analysis of different processing schemes, and engine emission testing of final products. Currently, fractions of a direct coal liquid produced form bituminous coal are being tested in sequence of pilot plant upgrading processes. This work is discussed in a separate paper. The linear programming model, which is the subject of this paper, has been completed for themore » petroleum refinery and is being modified to handle coal liquids based on the pilot plant test results. Preliminary coal liquid evaluation studies indicate that, if a refinery expansion scenario is adopted, then the marginal value of the coal liquid (over the base petroleum crude) is $3-4/bbl.« less

Low-Cost Aqueous Coal Desulfurization

NASA Technical Reports Server (NTRS)

Kalvinskas, J. J.; Vasilakos, N.; Corcoran, W. H.; Grohmann, K.; Rohatgi, N. K.

1982-01-01

Water-based process for desulfurizing coal not only eliminates need for costly organic solvent but removes sulfur more effectively than an earlier solvent-based process. New process could provide low-cost commercial method for converting high-sulfur coal into environmentally acceptable fuel.

Process for preparing a stabilized coal-water slurry

DOEpatents

Givens, E.N.; Kang, D.

1987-06-23

A process is described for preparing a stabilized coal particle suspension which includes the steps of providing an aqueous media substantially free of coal oxidizing constituents, reducing, in a nonoxidizing atmosphere, the particle size of the coal to be suspended to a size sufficiently small to permit suspension thereof in the aqueous media and admixing the coal of reduced particle size with the aqueous media to release into the aqueous media coal stabilizing constituents indigenous to and carried by the reduced coal particles in order to form a stabilized coal particle suspension. The coal stabilizing constituents are effective in a nonoxidizing atmosphere to maintain the coal particle suspension at essentially a neutral or alkaline pH. The coal is ground in a nonoxidizing atmosphere such as an inert gaseous atmosphere to reduce the coal to a sufficient particle size and is admixed with an aqueous media that has been purged of oxygen and acid-forming gases. 2 figs.

Process for preparing a stabilized coal-water slurry

DOEpatents

Givens, Edwin N.; Kang, Doohee

1987-01-01

A process for preparing a stabilized coal particle suspension which includes the steps of providing an aqueous media substantially free of coal oxidizing constituents, reducing, in a nonoxidizing atmosphere, the particle size of the coal to be suspended to a size sufficiently small to permit suspension thereof in the aqueous media and admixing the coal of reduced particle size with the aqueous media to release into the aqueous media coal stabilizing constituents indigenous to and carried by the reduced coal particles in order to form a stabilized coal particle suspension. The coal stabilizing constituents are effective in a nonoxidizing atmosphere to maintain the coal particle suspension at essentially a neutral or alkaline pH. The coal is ground in a nonoxidizing atmosphere such as an inert gaseous atmosphere to reduce the coal to a sufficient particle size and is admixed with an aqueous media that has been purged of oxygen and acid-forming gases.

Reducing Greenhouse Gas Emissions from Agricultural Wetlands in Borneo

NASA Astrophysics Data System (ADS)

Abdul, H.; Fatah, L.; Nursyamsi, D.; Kazuyuki, I.

2011-12-01

At the forum G20 meeting in 2009, Indonesian President delivered Indonesia's commitment to reduce national greenhouse gas (GHG) emissions by 26% in 2020 by unilateral action and by 41% with support of other countries. To achieve the target, Indonesian government has put forestry, agriculture (including peatlands), energy, industry and transportation as main responsible sectors. Development of crop with low GHG emissions, increasing C sequestration and the use of organic fertilizers are among the activities to be carried out in 2010-2020 period to minimize GHG emissions from agricultural sectors. Three experiments have been carried out to elucidate the reflectivity of crop selection, soil ameliorants and organic fertilizers on GHG emissions from agricultural wetlands in Borneo. Firstly, gas samples were collected in weekly basis from oil palm, paddy, and vegetables fields and analyzed for methane (CH4) and nitrous oxide (N2O) concentrations by a gas chromatography. Secondly, coal fly ash, dolomite and ZnSO4 were incorporated into a pot containing peat and/or alluvial soils taken from wetlands in South Kalimantan. The air samples were taken and analyzed for CH4 by a gas chromatography. Finally, microbial consortium are isolated from soil, sediment and cow dung. The microbes were then propagated and used in a rice straw composting processes. The CO2, CH4 and N2O emissions from composting vessel were measured at one, two and four weeks of composting processes. The results showed that shifting the use of peatlands for oil palm to vegetable field reduced the GHG emissions by about 74% and that to paddy field reduce the GHG emissions by about 82%. The CH4 emissions from paddy field can be further reduced by applying dolomite. However, the use of coal fly ash and ZnSO4 increased CH4 emissions from peat soil cultivated to rice. The use of microbe isolated from saline soil could reduce GHG emissions during the composting of rice straw. The social aspect of GHG reduction in Borneo will also be discussed.

Interfacial properties and coal cleaning in the LICADO process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, S.M.B.

1986-01-01

The LICADO LIquid CArbon DiOxide process is currently being investigated as a new technique for cleaning coal. It relies on the relative wettability of clean coal and mineral particles between liquid CO/sub 2/ and water so that when liquid CO/sub 2/ is dispersed into a coal-water slurry, it tends to form agglomerates with the clean coal particles and float them to the liquid CO/sub 2/ phase. The mineral particles, on the other hand, remain in the aqueous phase as refuse. Since the surface/interfacial properties of fine coal particles play such an important role in this coal cleaning operation, an understandingmore » of their behavior becomes indispensable. In order to understand the separation mechanisms involved in the LICADO process, it is necessary to study the interfacial interactions occurring in the CO/sub 2/-water-coal system. It is believed that a relationship between the process performance and the wetting characteristics of the coal/refuse particles can be established. Upper Freeport -200 mesh coal from Indiana County, PA with 23.5% ash content was selected for the experimental work. A specially designed high pressure experimental unit, equipped with necessary optical and photographic accessories, was constructed for this study. Contact angles were also measured on the coal surface under two different sample pretreatment conditions: water-first-wet and liquid CO/sub 2/-first-wet. The results infer that an optimum mixing is necessary to provide sufficient shear force to expose the clean coal particles to the CO/sub 2/ droplets. The coal maceral and mineral association on the coal particle surface was determined based on the reflective grey level distinction between the mineral and Litho-type of various coal components.« less

Energy Conversion Alternatives Study (ECAS), General Electric Phase 1. Volume 3: Energy conversion subsystems and components. Part 3: Gasification, process fuels, and balance of plant

NASA Technical Reports Server (NTRS)

Boothe, W. A.; Corman, J. C.; Johnson, G. G.; Cassel, T. A. V.

1976-01-01

Results are presented of an investigation of gasification and clean fuels from coal. Factors discussed include: coal and coal transportation costs; clean liquid and gas fuel process efficiencies and costs; and cost, performance, and environmental intrusion elements of the integrated low-Btu coal gasification system. Cost estimates for the balance-of-plant requirements associated with advanced energy conversion systems utilizing coal or coal-derived fuels are included.

Improvement of storage, handling, and transportability of fine coal. Quarterly technical progress report number 8, October 1--December 31, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Mulled Coal process was developed as a means of overcoming the adverse handling characteristics of wet fine coal without thermal drying. The process involves the addition of a low cost, harmless reagent to wet fine coal using off-the-shelf mixing equipment. Based on laboratory- and bench-scale testing, Mulled coal can be stored, shipped, and burned without causing any of the plugging, pasting, carryback and freezing problems normally associated with wet coal. On the other hand, Mulled Coal does not cause the fugitive and airborne dust problems normally associated with thermally dried coal. The objectives of this project are to demonstratemore » that: the Mulled Coal process, which has been proved to work on a wide range of wet fine coals at bench scale, will work equally well on a continuous basis, producing consistent quality, and at a convincing rate of production in a commercial coal preparation plant; the wet product from a fine coal cleaning circuit can be converted to a solid fuel form for ease of handling and cost savings in storage and rail car transportation; and a wet fine coal product thus converted to a solid fuel form, can be stored, shipped, and burned with conventional fuel handling, transportation, and combustion systems.« less

Process for electrochemically gasifying coal using electromagnetism

DOEpatents

Botts, Thomas E.; Powell, James R.

1987-01-01

A process for electrochemically gasifying coal by establishing a flowing stream of coal particulate slurry, electrolyte and electrode members through a transverse magnetic field that has sufficient strength to polarize the electrode members, thereby causing them to operate in combination with the electrolyte to electrochemically reduce the coal particulate in the slurry. Such electrochemical reduction of the coal produces hydrogen and carbon dioxide at opposite ends of the polarized electrode members. Gas collection means are operated in conjunction with the process to collect the evolved gases as they rise from the slurry and electrolyte solution.

Development of clean coal and clean soil technologies using advanced agglomeration techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ignasiak, B.; Ignasiak, T.; Szymocha, K.

1990-01-01

Three major topics are discussed in this report: (1) Upgrading of Low Rank Coals by the Agflotherm Process. Test data, procedures, equipment, etc., are described for co-upgrading of subbituminous coals and heavy oil; (2) Upgrading of Bituminous Coals by the Agflotherm Process. Experimental procedures and data, bench and pilot scale equipments, etc., for beneficiating bituminous coals are described; (3) Soil Clean-up and Hydrocarbon Waste Treatment Process. Batch and pilot plant tests are described for soil contaminated by tar refuse from manufactured gas plant sites. (VC)

Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

PubMed Central

van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

2013-01-01

Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

Interfacing with USSTRATCOM and UTTR during Stardust Earth Return

NASA Technical Reports Server (NTRS)

Jefferson, David C.; Baird, Darren T.; Cangahuala, Laureano A.; Lewis, George D.

2006-01-01

The Stardust Sample Return Capsule separated from the main spacecraft four hours prior to atmospheric entry. Between this time and the time at which the SRC touched down at the Utah Test and Training Range, two organizations external to JPL were involved in tracking the Sample Return Capsule. Orbit determination for the Stardust spacecraft during deep space cruise, the encounters of asteroid Annefrank and comet Wild 2, and the final approach to Earth used X-band radio metric Doppler and range data obtained through the Deep Space Network. The SRC lacked the electronics needed for coherently transponded radio metric tracking, so the DSN was not able to track the SRC after it separated from the main spacecraft. Although the expected delivery accuracy at atmospheric entry was well within the capability needed to target the SRC to the desired ground location, it was still desirable to obtain direct knowledge of the SRC trajectory in case of anomalies. For this reason U.S. Strategic Command was engaged to track the SRC between separation and atmospheric entry. Once the SRC entered the atmosphere, ground sensors at UTTR were tasked to acquire the descending SRC and maintain track during the descent in order to determine the landing location, to which the ground recovery team was then directed. This paper discusses organizational interfaces, data products, and delivery schedules, and the actual tracking operations are described.

Coal desulfurization by low temperature chlorinolysis, phase 3

NASA Technical Reports Server (NTRS)

Kalvinskas, J. J.; Rohatgi, N. K.; Ernest, J.

1981-01-01

Laboratory scale, bench scale batch reactor, and minipilot plant tests were conducted on 22 bituminous, subbituminous, and lignite coals. Chemical pretreatment and post treatment of coals relative to the chlorination were tried as a means of enhancing desulfurization by the chlorinolysis process. Elevated temperature (500-700 C) hydrogen treatment of chlorinolysis-processed coal at atmospheric pressure was found to substantially increase coal desulfurization up to 90 percent. Sulfur forms, proximate and ultimate analyses of the processed coal are included. Minipilot plant operation indicates that the continuous flow reactor provides coal desulfurization results comparable to those obtained in the batch reactor. Seven runs were conducted at coal feed rates of 1.5 to 8.8 kg per hour using water and methylchloroform solvents, gaseous chlorine feed of 3 to 31.4 SCFH at 21 to 70 C, and atmospheric pressure for retention times of 20 to 120 minutes.

Bench-scale performance testing and economic analyses of electrostatic dry coal cleaning. Final report, October 1980-July 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rich, S.R.

1987-02-01

The report gives results of preliminary performance evaluations and economic analyses of the Advanced Energy Dynamics (AED) electrostatic dry coal-cleaning process. Grab samples of coal-feed-product coals were obtained from 25 operating physical coal-cleaning (PCC) plants. These samples were analyzed for ash, sulfur, and energy content and splits of the original samples of feed run-of-mine coal were provided for bench-scale testing in an electrostatic separation apparatus. The process showed superior sulfur-removal performance at equivalent cost and energy-recovery levels. The ash-removal capability of the process was not evaluated completely: overall, ash-removal results indicated that the process did not perform as well asmore » the PCC plants.« less

PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells

PubMed Central

Lee, Luke J.; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

2013-01-01

Elevated levels of intracellular Ca2+ ([Ca2+]i) inhibit Na+/H+ exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca2+]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca2+ signaling proteins necessary for regulation of NHE3 activity. [Ca2+]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca2+]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y416 phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca2+]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca2+]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca2+]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3. PMID:23703528

Targeting Drug-Sensitive and -Resistant Strains of Mycobacterium tuberculosis by Inhibition of Src Family Kinases Lowers Disease Burden and Pathology.

PubMed

Chandra, Pallavi; Rajmani, R S; Verma, Garima; Bhavesh, Neel Sarovar; Kumar, Dhiraj

2016-01-01

In view of emerging drug resistance among bacterial pathogens, including Mycobacterium tuberculosis, the development of novel therapeutic strategies is increasingly being sought. A recent paradigm in antituberculosis (anti-TB) drug development is to target the host molecules that are crucial for intracellular survival of the pathogen. We previously showed the importance of Src tyrosine kinases in mycobacterial pathogenesis. Here, we report that inhibition of Src significantly reduced survival of H37Rv as well as multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of M. tuberculosis in THP-1 macrophages. Src inhibition was also effective in controlling M. tuberculosis infection in guinea pigs. In guinea pigs, reduced M. tuberculosis burden due to Src inhibition also led to a marked decline in the disease pathology. In agreement with the theoretical framework of host-directed approaches against the pathogen, Src inhibition was equally effective against an XDR strain in controlling infection in guinea pigs. We propose that Src inhibitors could be developed into effective host-directed anti-TB drugs, which could be indiscriminately used against both drug-sensitive and drug-resistant strains of M. tuberculosis. IMPORTANCE The existing treatment regimen for tuberculosis (TB) suffers from deficiencies like high doses of antibiotics, long treatment duration, and inability to kill persistent populations in an efficient manner. Together, these contribute to the emergence of drug-resistant tuberculosis. Recently, several host factors were identified which help intracellular survival of Mycobacterium tuberculosis within the macrophage. These factors serve as attractive targets for developing alternate therapeutic strategies against M. tuberculosis. This strategy promises to be effective against drug-resistant strains. The approach also has potential to considerably lower the risk of emergence of new drug-resistant strains. We explored tyrosine kinase Src as a host factor exploited by virulent M. tuberculosis for intracellular survival. We show that Src inhibition can effectively control tuberculosis in infected guinea pigs. Moreover, Src inhibition ameliorated TB-associated pathology in guinea pigs. Thus, Src inhibitors have strong potential to be developed as possible anti-TB drugs.

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

PubMed

Kiechle, Karin; Bazarian, Jeffrey J; Merchant-Borna, Kian; Stoecklein, Veit; Rozen, Eric; Blyth, Brian; Huang, Jason H; Dayawansa, Samantha; Kanz, Karl; Biberthaler, Peter

2014-01-01

The on-field diagnosis of sports-related concussion (SRC) is complicated by the lack of an accurate and objective marker of brain injury. To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion. Longitudinal cohort study. From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels. Forty-six athletes (30 Munich, 16 Rochester) underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich) sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002). Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively). A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC. Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells.

PubMed

Zachos, Nicholas C; Lee, Luke J; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

2013-08-01

Elevated levels of intracellular Ca(2+) ([Ca(2+)]i) inhibit Na(+)/H(+) exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca(2+)]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca(2+) signaling proteins necessary for regulation of NHE3 activity. [Ca(2+)]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca(2+)]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y(416) phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca(2+)]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca(2+)]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca(2+)]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.

The American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator Does Not Accurately Predict Risk of 30-Day Complications Among Patients Undergoing Microvascular Head and Neck Reconstruction.

PubMed

Arce, Kevin; Moore, Eric J; Lohse, Christine M; Reiland, Matthew D; Yetzer, Jacob G; Ettinger, Kyle S

2016-09-01

The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) is a novel universal risk calculator designed to aid in risk stratification of patients undergoing various types of major surgery. The purpose of this study was to assess the validity of the ACS NSQIP SRC in predicting postoperative complications in patients undergoing microvascular head and neck reconstruction. A retrospective cohort study of patients undergoing head and neck microvascular reconstruction with fibular free flaps at a single institution was completed. The NSQIP SRC was used to compute complication risk estimates and length of stay (LOS) estimates for all patients under study. Associations between complication risk estimates generated by the SRC and actual rates of observed complications were evaluated using logistic regression models. Logistic regression models also were used to evaluate the SRC estimates for LOS duration compared with the actual observed LOS after surgery. Of 153 patients under study, 46 (30%) developed a postoperative complication corresponding to those defined by NSQIP SRC. Thirty-eight patients (25%) developed a postoperative complication categorized as severe in the parameters of the NSQIP SRC. None of the SRC complication estimates showed a statistically relevant association with the corresponding observed rates of complications. The mean LOS predicted by the SRC was 8.0 days (median, 7.5 days; interquartile range [IQR], 6.5 to 9; range, 5.0 to 18.5 days). The mean observed LOS for the study group was 9.6 days (median, 7.0 days; IQR, 6 to 9; range, 5 to 67 days). Lin's (Biometrics 45:255, 1989) concordance correlation coefficient to measure agreement between observed and predicted LOS was 0.10, indicating only slight agreement between the 2 values. The ACS NSQIP SRC is not a useful risk-stratifying metric for patients undergoing major head and neck reconstruction with microvascular fibular free flaps. The SRC also does not accurately predict hospital LOS for this same patient cohort. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Iron catalyzed coal liquefaction process

DOEpatents

Garg, Diwakar; Givens, Edwin N.

1983-01-01

A process is described for the solvent refining of coal into a gas product, a liquid product and a normally solid dissolved product. Particulate coal and a unique co-catalyst system are suspended in a coal solvent and processed in a coal liquefaction reactor, preferably an ebullated bed reactor. The co-catalyst system comprises a combination of a stoichiometric excess of iron oxide and pyrite which reduce predominantly to active iron sulfide catalysts in the reaction zone. This catalyst system results in increased catalytic activity with attendant improved coal conversion and enhanced oil product distribution as well as reduced sulfide effluent. Iron oxide is used in a stoichiometric excess of that required to react with sulfur indigenous to the feed coal and that produced during reduction of the pyrite catalyst to iron sulfide.

Recovery of Rare Earth Elements from Coal and Coal Byproducts via a Closed Loop Leaching Process: Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, Richard; Heinrichs, Michael; Argumedo, Darwin

Objectives: Through this grant, Battelle proposes to address Area of Interest (AOI) 1 to develop a bench-scale technology to economically separate, extract, and concentrate mixed REEs from coal ash. U.S. coal and coal byproducts provide the opportunity for a domestic source of REEs. The DOE’s National Energy Technology Laboratory (NETL) has characterized various coal and coal byproducts samples and has found varying concentrations of REE ranging up to 1,000 parts per million by weight. The primary project objective is to validate the economic viability of recovering REEs from the coal byproduct coal ash using Battelle’s patented closed-loop Acid Digestion Processmore » (ADP). This will be accomplished by selecting coal sources with the potential to provide REE concentrations above 300 parts per million by weight, collecting characterization data for coal ash samples generated via three different methods, and performing a Techno-Economic Analysis (TEA) for the proposed process. The regional availability of REE-laden coal ash, the regional market for rare earth concentrates, and the system capital and operating costs for rare earth recovery using the ADP technology will be accounted for in the TEA. Limited laboratory testing will be conducted to generate the parameters needed for the design of a bench scale system for REE recovery. The ultimate project outcome will be the design for an optimized, closed loop process to economically recovery REEs such that the process may be demonstrated at the bench scale in a Phase 2 project. Project Description: The project will encompass evaluation of the ADP technology for the economic recovery of REEs from coal and coal ash. The ADP was originally designed and demonstrated for the U.S. Army to facilitate demilitarization of cast-cured munitions via acid digestion in a closed-loop process. Proof of concept testing has been conducted on a sample of Ohio-based Middle Kittanning coal and has demonstrated the feasibility of recovering REEs using the ADP technology. In AOI 1, Ohio coal sources with the potential to provide a consistent source of rare earth element concentrations above 300 parts per million will be identified. Coal sample inventories from West Virginia and Pennsylvania will also be assessed for purposes of comparison. Three methods of preparing the coal ash will be evaluated for their potential to enhance the technical feasibility and economics of REE recovery. Three sources of coal ash are targeted for evaluation of the economics of REE recovery in this project: (1) coal ash from power generation stations, to include fly ash and/or bottom ash, (2) ash generated in a lower temperature ashing process, and (3) ash residual from Battelle’s coal liquefaction process. Making use of residual ash from coal liquefaction processes directly leverages work currently being conducted by Battelle for DOE NETL in response to DE-FOA-0000981 entitled “Greenhouse Gas Emissions Reductions Research and Development Leading to Cost-Competitive Coal-to-Liquids Based Jet Fuel Production.” Using the sample characterization results and regional information regarding REE concentration, availability and cost, a TEA will be developed. The previously generated laboratory testing results for leaching and REE recovery via the ADP will be used to perform the TEA, along with common engineering assumptions for scale up of equipment and labor costs. Finally, upon validation of the economic feasibility of the process by the TEA, limited laboratory testing will be performed to support the design of a bench scale system. In a future project phase, it is envisioned that the bench scale system will be constructed and operated to prove the process on a continuous basis.« less

Design and implementation of the monitoring system for underground coal fires in Xinjiang region, China

NASA Astrophysics Data System (ADS)

Li-bo, Dang; Jia-chun, Wu; Yue-xing, Liu; Yuan, Chang; Bin, Peng

2017-04-01

Underground coal fire (UCF) is serious in Xinjiang region of China. In order to deal with this problem efficiently, a UCF monitoring System, which is based on the use of wireless communication technology and remote sensing images, was designed and implemented by Xinjiang Coal Fire Fighting Bureau. This system consists of three parts, i.e., the data collecting unit, the data processing unit and the data output unit. For the data collecting unit, temperature sensors and gas sensors were put together on the sites with depth of 1.5 meter from the surface of coal fire zone. Information on these sites' temperature and gas was transferred immediately to the data processing unit. The processing unit was developed by coding based on GIS software. Generally, the processed datum were saved in the computer by table format, which can be displayed on the screen as the curve. Remote sensing image for each coal fire was saved in this system as the background for each monitoring site. From the monitoring data, the changes of the coal fires were displayed directly. And it provides a solid basis for analyzing the status of coal combustion of coal fire, the gas emission and possible dominant direction of coal fire propagation, which is helpful for making-decision of coal fire extinction.

Process for clean-burning fuel from low-rank coal

DOEpatents

Merriam, Norman W.; Sethi, Vijay; Brecher, Lee E.

1994-01-01

A process for upgrading and stabilizing low-rank coal involving the sequential processing of the coal through three fluidized beds; first a dryer, then a pyrolyzer, and finally a cooler. The fluidizing gas for the cooler is the exit gas from the pyrolyzer with the addition of water for cooling. Overhead gas from pyrolyzing is likely burned to furnish the energy for the process. The product coal exits with a tar-like pitch sealant to enhance its safety during storage.

Process for clean-burning fuel from low-rank coal

DOEpatents

Merriam, N.W.; Sethi, V.; Brecher, L.E.

1994-06-21

A process is described for upgrading and stabilizing low-rank coal involving the sequential processing of the coal through three fluidized beds; first a dryer, then a pyrolyzer, and finally a cooler. The fluidizing gas for the cooler is the exit gas from the pyrolyzer with the addition of water for cooling. Overhead gas from pyrolyzing is likely burned to furnish the energy for the process. The product coal exits with a tar-like pitch sealant to enhance its safety during storage. 1 fig.

Sensing underground coal gasification by ground penetrating radar

NASA Astrophysics Data System (ADS)

Kotyrba, Andrzej; Stańczyk, Krzysztof

2017-12-01

The paper describes the results of research on the applicability of the ground penetrating radar (GPR) method for remote sensing and monitoring of the underground coal gasification (UCG) processes. The gasification of coal in a bed entails various technological problems and poses risks to the environment. Therefore, in parallel with research on coal gasification technologies, it is necessary to develop techniques for remote sensing of the process environment. One such technique may be the radar method, which allows imaging of regions of mass loss (voids, fissures) in coal during and after carrying out a gasification process in the bed. The paper describes two research experiments. The first one was carried out on a large-scale model constructed on the surface. It simulated a coal seam in natural geological conditions. A second experiment was performed in a shallow coal deposit maintained in a disused mine and kept accessible for research purposes. Tests performed in the laboratory and in situ conditions showed that the method provides valuable data for assessing and monitoring gasification surfaces in the UCG processes. The advantage of the GPR method is its high resolution and the possibility of determining the spatial shape of various zones and forms created in the coal by the gasification process.

Using stable isotopes to monitor forms of sulfur during desulfurization processes: A quick screening method

USGS Publications Warehouse

Liu, Chao-Li; Hackley, Keith C.; Coleman, D.D.; Kruse, C.W.

1987-01-01

A method using stable isotope ratio analysis to monitor the reactivity of sulfur forms in coal during thermal and chemical desulfurization processes has been developed at the Illinois State Geological Survey. The method is based upon the fact that a significant difference exists in some coals between the 34S/32S ratios of the pyritic and organic sulfur. A screening method for determining the suitability of coal samples for use in isotope ratio analysis is described. Making these special coals available from coal sample programs would assist research groups in sorting out the complex sulfur chemistry which accompanies thermal and chemical processing of high sulfur coals. ?? 1987.

Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.

PubMed

Montagner, Alexandra; Delgado, Maria B; Tallichet-Blanc, Corinne; Chan, Jeremy S K; Sng, Ming K; Mottaz, Hélén; Degueurce, Gwendoline; Lippi, Yannick; Moret, Catherine; Baruchet, Michael; Antsiferova, Maria; Werner, Sabine; Hohl, Daniel; Saati, Talal Al; Farmer, Pierre J; Tan, Nguan S; Michalik, Liliane; Wahli, Walter

2014-01-01

Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers.

Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma

PubMed Central

Agarwal, Saurabh; Ghosh, Rajib; Chen, Zaowen; Lakoma, Anna; Gunaratne, Preethi H.; Kim, Eugene S.; Shohet, Jason M.

2016-01-01

(NB) is the most common extracranial pediatric solid tumor with high mortality rates. The tyrosine kinase c-Src has been known to play an important role in differentiation of NB cells, but the mechanism of c-Src regulation has not been defined. Here, we characterize PAG1 (Cbp, Csk binding protein), a central inhibitor of c-Src and other Src family kinases, as a novel tumor suppressor in NB. Clinical cohort analysis demonstrate that low expression of PAG1 is a significant prognostic factor for high stage disease, increased relapse, and worse overall survival for children with NB. PAG1 knockdown in NB cells promotes proliferation and anchorage-independent colony formation with increased activation of AKT and ERK downstream of c-Src, while PAG1 overexpression significantly rescues these effects. In vivo, PAG1 overexpression significantly inhibits NB tumorigenicity in an orthotopic xenograft model. Our results establish PAG1 as a potent tumor suppressor in NB by inhibiting c-Src and downstream effector pathways. Thus, reactivation of PAG1 and inhibition of c-Src kinase activity represents an important novel therapeutic approach for high-risk NB. PMID:26993602

An adaptor role for cytoplasmic Sam68 in modulating Src activity during cell polarization.

PubMed

Huot, Marc-Etienne; Brown, Claire M; Lamarche-Vane, Nathalie; Richard, Stéphane

2009-04-01

The Src-associated substrate during mitosis with a molecular mass of 68 kDa (Sam68) is predominantly nuclear and is known to associate with proteins containing the Src homology 3 (SH3) and SH2 domains. Although Sam68 is a Src substrate, little is known about the signaling pathway that link them. Src is known to be activated transiently after cell spreading, where it modulates the activity of small Rho GTPases. Herein we report that Sam68-deficient cells exhibit loss of cell polarity and cell migration. Interestingly, Sam68-deficient cells exhibited sustained Src activity after cell attachment, resulting in the constitutive tyrosine phosphorylation and activation of p190RhoGAP and its association with p120rasGAP. Consistently, we observed that Sam68-deficient cells exhibited deregulated RhoA and Rac1 activity. By using total internal reflection fluorescence microscopy, we observed Sam68 near the plasma membrane after cell attachment coinciding with phosphorylation of its C-terminal tyrosines and association with Csk. These findings show that Sam68 localizes near the plasma membrane during cell attachment and serves as an adaptor protein to modulate Src activity for proper signaling to small Rho GTPases.

Relationships of flour solvent retention capacity, secondary structure and rheological properties with the cookie making characteristics of wheat cultivars.

PubMed

Kaur, Amritpal; Singh, Narpinder; Kaur, Seeratpreet; Ahlawat, Arvind Kumar; Singh, Anju Mahendru

2014-09-01

The relationships of grain, flour solvent retention capacity (SRC) and dough rheological properties with the cookie making properties of wheat cultivars were evaluated. Cultivars with higher proportion of intermolecular-β-sheets+antiparallel β sheets and lower α-helix had greater gluten strength. The grain weight and diameter positively correlated with the proportion of fine particles and the cookie spread factor (SF) and negatively to the grain hardness (GH) and Na2CO3 SRC. The SF was higher in the flour with a higher amount of fine particle and with a lower Na2CO3 SRC and dough stability (DS). The breaking strength (BS) of cookies was positively correlated to lactic acid (LA) SRC, DS, peak time, sedimentation value (SV), G' and G″. Na2CO3 SRC and GH were strongly correlated. The gluten performance index showed a strong positive correlation with SV, DS, G' and G″. The water absorption had a significant positive correlation with sucrose SRC and LASRC. Cultivars with higher GH produced higher amount of coarse particles in flours that had higher Na2CO3 SRC and lower cookie SF. Copyright © 2014 Elsevier Ltd. All rights reserved.

SRC family kinases as novel therapeutic targets to treat breast cancer brain metastases.

PubMed

Zhang, Siyuan; Huang, Wen-Chien; Zhang, Lin; Zhang, Chenyu; Lowery, Frank J; Ding, Zhaoxi; Guo, Hua; Wang, Hai; Huang, Suyun; Sahin, Aysegul A; Aldape, Kenneth D; Steeg, Patricia S; Yu, Dihua

2013-09-15

Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2(+) brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. ©2013 AACR.

Pilot-Scale Demonstration of Pefi's Oxygenated Transportation Fuels Production Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Coal-cleaning processes have been utilized to increase the heating value of coal by extracting ash-forming minerals in the coal. These processes involve the crushing or grinding of raw coal followed by physical separation processes, taking advantage of the density difference between carbonaceous particles and mineral particles. In addition to the desired increase in the heating value of coal, a significant reduction of the sulfur content of the coal fed to a combustion unit is effected by the removal of pyrite and other sulfides found in the mineral matter. WRI is assisting PulseWave to develop an alternate, more efficient method ofmore » liberating and separating the undesirable mineral matter from the carbonaceous matter in coal. The approach is based on PulseWave's patented resonance disintegration technology that reduces that particle size of materials by application of destructive resonance, shock waves, and vortex generating forces. Illinois No.5 coal, a Wyodak coal, and a Pittsburgh No.8 coal were processed using the resonance disintegration apparatus then subjected to conventional density separations. Initial microscopic results indicate that up to 90% of the pyrite could be liberated from the coal in the machine, but limitations in the density separations reduced overall effectiveness of contaminant removal. Approximately 30-80% of the pyritic sulfur and 30-50% of the mercury was removed from the coal. The three coals (both with and without the pyritic phase separated out) were tested in WRI's 250,000 Btu/hr Combustion Test Facility, designed to replicate a coal-fired utility boiler. The flue gases were characterized for elemental, particle bound, and total mercury in addition to sulfur. The results indicated that pre-combustion cleaning could reduce a large fraction of the mercury emissions.« less

Coal: Its Structure and Some of Its Uses.

ERIC Educational Resources Information Center

Phillips, P. S.

1981-01-01

Describes the formation, chemical structure, and several uses of coal. The history of coal usage, production processes, coal tar products, and production of petroleum and other hydrocarbons from coal are also described. (DS)

SRC: A Model of Industry-University Cooperation.

ERIC Educational Resources Information Center

Cavin, Ralph K., III; Phillips, D. Howard

1988-01-01

Describes the Semiconductor Research Corporation (SRC), a non-profit research cooperative designed to conduct research in the field of integrated circuits, principally in U.S. universities, with membership restricted to U.S.-owned companies. Analyzes SRC's impact on the U.S. educational system. (TW)

Role of SRC-3delta4 in the Progression and Metastasis of Castration-Resistant Prostate Cancer

DTIC Science & Technology

2014-12-01

tyrosine phosphorylation of SRC-3∆4, which was inhibited by the treatment with EGFR inhibitor AG1478. Mutation of Y1159 to phenylalanine (Y1159F...Y1159 to phenylalanine (Y1159F) greatly reduced SRC-3∆4/AR interaction that is stimulated by EGF. Figure 7 Overexpression of SRC-3∆4 promoted...adhesion turnover and matrix metalloproteinase expression. Cancer research 68, 5460-5468. 6. Chung, A.C., Zhou, S., Liao, L ., Tien, J.C., Greenberg

Src is a major signaling component for CTGF induction by TGF-β1 in osteoblasts

PubMed Central

X, Zhang; JA, Arnott; S, Rehman; WG, DeLong; A, Sanjay; FF, Safadi; SN, Popoff

2010-01-01

Connective tissue growth factor (CTGF/CCN2) is induced by transforming growth factor beta 1(TGF-β1) where it acts as a downstream mediator of TGF-β1 induced matrix production in osteoblasts. We have shown the requirement of Src, Erk and Smad signaling for CTGF induction by TGF-β1 in osteoblasts, however the potential interaction among these signaling pathways remains undetermined. In this study we demonstrate that TGF-β1 activates Src kinase in ROS17/2.8 cells and that treatment with the Src family kinase inhibitor PP2 prevents Src activation and CTGF induction by TGF-β1. Additionally, inhibiting Src activation prevented Erk activation, Smad 2 & 3 activation and nuclear translocation by TGF-β1, demonstrating that Src is an essential upstream signaling partner of both Erk and Smads in osteoblasts. MAPKs such as Erk can modulate the Smad pathway through directly mediating the phosphorylation of Smads or indirectly through activation/inactivation of required nuclear co-activators that mediate Smad DNA binding. When we treated cells with the Erk inhibitor, PD98059 it inhibited TGF-β1-induced CTGF protein expression but had no effect on Src activation, Smad activation or Smad nuclear translocation. However PD98059 impaired transcriptional complex formation on the Smad binding element (SBE) on the CTGF promoter, demonstrating that Erk activation was required for SBE transactivation. This data demonstrates that Src is an essential upstream signaling transducer of Erk and Smad signaling with respect to TGF-β1 in osteoblasts and that Smads and Erk function independently but are both essential for forming a transcriptionally active complex on the CTGF promoter in osteoblasts. PMID:20432467

Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon

PubMed Central

Wang, Zhe; Yan, Wei; Sun, Huimin; Xue, Peipei; Fan, Xiaoming; Zeng, Xiaoyu; Chen, Juan; Shao, Chen; Zhu, Feng

2016-01-01

T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is highly expressed in a variety of tumors and associated with a poor prognosis of human malignancies. However, the activation mechanism of TOPK is still unrevealed. Herein, first we found that Src directly bound with and phosphorylated TOPK at Y74 and Y272 in vitro. Anti-phospho-TOPK at Y74 was prepared, the endogenous phosphorylation of TOPK at Y74 was detected in colon cancer cells, and the phosphorylation was inhibited in cells expressing low levels of Src. Subsequently, we stably transfected Y74 and Y272 double mutated TOPK (TOPK-FF) into JB6 or SW480 cells, and observed that both the anchorage-independent growth ability and tumorigenesis of TOPK-FF cells were suppressed compared with those of wild type TOPK (TOPK-WT) ex vivo and in vivo. The phosphorylation level of TOPK substrate, Histone H3 at Ser10 also decreased dramatically ex vivo or in vivo. Moreover, we showed that Src could inhibit the ubiquitination of TOPK. Transiently expressed TOPK-WT was more stable than TOPK-FF in pause and chase experiment. Endogenous TOPK was more stable in Src wild type (Src+/+) MEFs than in Src knockout (Src−/−). Taken together, our results indicate that Src is a novel upstream kinase of TOPK. The phosphorylation of TOPK at Y74 and Y272 by Src increases the stability and activity of TOPK, and promotes the tumorigenesis of colon cancer. It may provide opportunities for TOPK based prognosis and targeted therapy for colon cancer patients. PMID:27016416

Explanatory characteristics for nutrient concentrations and loads in the Sava River Catchment and cross-regionally

NASA Astrophysics Data System (ADS)

Levi, L.; Cvetkovic, V.; Destouni, G.

2015-12-01

This study compiles estimates of waterborne nutrient concentrations and loads in the Sava River Catchment (SRC). Based on this compilation, we investigate hotspots of nutrient inputs and retention along the river, as well as concentration and load correlations with river discharge and various human drivers of excess nutrient inputs to the SRC. For cross-regional assessment and possible generalization, we also compare corresponding results between the SRC and the Baltic Sea Drainage Basin (BSDB). In the SRC, one small incremental subcatchment, which is located just downstream of Zagreb and has the highest population density among the SRC subcatchments, is identified as a major hotspot for net loading (input minus retention) of both total nitrogen (TN) and total phosphorus (TP) to the river and through it to downstream areas of the SRC. The other SRC subcatchments exhibit relatively similar characteristics with smaller net nutrient loading. The annual loads of both TN and TP along the Sava River exhibit dominant temporal variability with considerably higher correlation with annual river discharge (R2 = 0.51 and 0.28, respectively) than that of annual average nutrient concentrations (R2 = 0.0 versus discharge for both TN and TP). Nutrient concentrations exhibit instead dominant spatial variability with relatively high correlation with population density among the SRC subcatchments (R2=0.43-0.64). These SRC correlation characteristics compare well with corresponding ones for the BSDB, even though the two regions are quite different in their hydroclimatic, agricultural and wastewater treatment conditions. Such cross-regional consistency in dominant variability type and explanatory catchment characteristics may be a useful generalization basis, worthy of further investigation, for at least first-order estimation of nutrient concentration and load conditions in less data-rich regions.

Atypical protein kinase C activity is required for extracellular matrix degradation and invasion by Src-transformed cells.

PubMed

Rodriguez, Elena M; Dunham, Elizabeth E; Martin, G Steven

2009-10-01

Atypical protein kinase C (aPKC) isoforms have been shown to mediate Src-dependent signaling in response to growth factor stimulation. To determine if aPKC activity contributes to the transformed phenotype of cells expressing oncogenic Src, we have examined the activity and function of aPKCs in 3T3 cells expressing viral Src (v-Src). aPKC activity and tyrosine phosphorylation were found to be elevated in some but not all clones of mouse fibroblasts expressing v-Src. aPKC activity was inhibited either by addition of a membrane-permeable pseudosubstrate, by expression of a dominant-negative aPKC, or by RNAi-mediated knockdown of specific aPKC isoforms. aPKC activity contributes to morphological transformation and stress fiber disruption, and is required for migration of Src-transformed cells and for their ability to polarize at the edge of a monolayer. The lambda isoform of aPKC is specifically required for invasion through extracellular matrix in Boyden chamber assays and for degradation of the extracellular matrix in in situ zymography assays. Tyrosine phosphorylation of aPKClambda is required for its ability to promote cell invasion. The defect in invasion upon aPKC inhibition appears to result from a defect in the assembly and/or function of podosomes, invasive adhesions on the ventral surface of the cell that are sites of protease secretion. aPKC was also found to localize to podosomes of v-Src transformed cells, suggesting a direct role for aPKC in podosome assembly and/or function. We conclude that basal or elevated aPKC activity is required for the ability of Src-transformed cells to degrade and invade the extracellular matrix. Copyright 2009 Wiley-Liss, Inc.

1α,25(OH)2-Vitamin D3 Inhibits C2C12 Cell Differentiation by Activating c-Src and ERK1/2.

PubMed

Wang, Zhonghua; Jiang, Aijun; Mei, Jingwei; Zhang, Xinyan

2018-05-01

The steroid hormone 1α,25(OH)2-vitamin D3 (1,25-D3) induced some biological responses through activation of MAPK cascades in various cell types. It seems that 1,25-D3 plays different roles at different stages of proliferating, differentiating, and differentiated C2C12 cells. We wanted to detect the effect of 1,25-D3 on myogenic differentiation and the role of ERK1/2 in differentiating stage induced by 2% horse serum with 1,25-D3. In this study, cells were induced to differentiate with 2% horse serum until the 7th day (with addition of 1,25-D3 every two days). The protein level of MHC (myosin heavy chain) and phosphorylation level of Src and ERK1/2 were determined with western blot. U0126 (MEK inhibitor) and PP2 (Src specific inhibitor) were used to confirm the relationship between 1,25-D3, MHC, Src, and ERK1/2. 1,25-D3 inhibited differentiation of C2C12 cells and fusion of myotubes by phosphorylating and activating Src and ERK1/2. Phosphorylation of ERK1/2 was inhibited, not only by U0126 but also by PP2 (a Src specific inhibitor) which led to the promotion of differentiation of C2C12 cells; however, U0126 did not inhibit Src phosphorylation. These results suggested that 1,25-D3 possibly inhibited C2C12 differentiation through Src and ERK1/2, and Src played an upstream role in this signaling pathway.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer.

PubMed

Bauman, Julie E; Duvvuri, Umamaheswar; Gooding, William E; Rath, Tanya J; Gross, Neil D; Song, John; Jimeno, Antonio; Yarbrough, Wendell G; Johnson, Faye M; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T; Ferris, Robert L; Kim, Seungwon; Hirsch, Fred R; Ellison, Kimberly; Flaherty, John T; Mills, Gordon B; Grandis, Jennifer R

2017-03-23

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms ( P = 0.0014); however, no effect was seen with dasatinib alone ( P = 0.24). High baseline pMAPK expression was associated with response to erlotinib ( P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib ( P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer

PubMed Central

Bauman, Julie E.; Duvvuri, Umamaheswar; Gooding, William E.; Rath, Tanya J.; Gross, Neil D.; Song, John; Jimeno, Antonio; Yarbrough, Wendell G.; Johnson, Faye M.; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T.; Ferris, Robert L.; Kim, Seungwon; Hirsch, Fred R.; Ellison, Kimberly; Flaherty, John T.; Mills, Gordon B.

2017-01-01

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II–IVa HNSCC were randomized to 7–21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms (P = 0.0014); however, no effect was seen with dasatinib alone (P = 0.24). High baseline pMAPK expression was associated with response to erlotinib (P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib (P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma. PMID:28352657

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice

PubMed Central

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y.; DeMayo, Francesco J.; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W.

2005-01-01

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, ARGAL4DBD, which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators. PMID:15983373

Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice.

PubMed

Ye, Xiangcang; Han, Sang Jun; Tsai, Sophia Y; DeMayo, Francesco J; Xu, Jianming; Tsai, Ming-Jer; O'Malley, Bert W

2005-07-05

Genetic disruption of the steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes. To quantify their roles in the function of androgen receptor (AR) transcriptional activity in vivo, we generated a unique transgenic AR-reporter mouse and analyzed the cell-specific contributions of SRC-1 and TIF2 to the activity of AR in mouse testis. Transgenic AR-luciferase and transgenic AR-lacZ mice harbor a recombinant mouse AR gene, AR(GAL4DBD), which is functionally coupled with a upstream activation sequence-mediated reporter gene (AR activity indicator). After characterization of these mice in terms of AR function, we further derived bigenic mice by crossing AR activity indicator mice with the SRC-1-/- or TIF2+/- mutant mice. Analyses of the resultant bigenic mice by in vivo imaging and luciferase assays showed that testicular AR activity was decreased significantly in those with the TIF2+/- mutation but not in the SRC-1+/- background, suggesting that TIF2 serves as the preferential coactivator for AR in testis. Immunohistological analysis confirmed that AR and TIF2 coexist in mouse testicular Sertoli cell nuclei under normal conditions. Although SRC-1 concentrates in Sertoli cell nuclei in the absence of TIF2, nuclear SRC-1 is not able to rescue AR activity in the TIF2 mutant background. Interestingly, SRC-1 appears to negatively influence AR activity, thereby counterbalancing the TIF2-stimulated AR activity. Our results provide unique in vivo insights to the multidimensional cell-type-specific interactions between AR and coregulators.

Control of vascular smooth muscle function by Src-family kinases and reactive oxygen species in health and disease

PubMed Central

MacKay, Charles E; Knock, Greg A

2015-01-01

Abstract Reactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src-family kinases (SrcFKs), a multi-functional group of non-receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS-induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G-protein-coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca2+ concentration, including transient receptor potential channels, voltage-gated Ca2+ channels and various types of K+ channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase-2, Janus kinase, other focal adhesion-associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro-proliferative and anti-apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth-factor receptor transactivation and downstream signalling, hypoxia-inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension. PMID:25384773

Randolph Plant passes 60-million-ton milestone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sprouls, M.W.; Adam, B.O.

1983-09-01

Peabody Coal Co.'s Randolph coal preparation plant has processed 60 million tons of coal during 10 years of operation. The plant, which is in Illinois, receives coal from 3 mines and 2 more will eventually send their output for cleaning. Coal from one mine travels 2 miles overland to a 30,000 ton conical bunker constructed of Reinforced Earth. Clean coal is supplied for electricity generation. The plant uses water-only processes, with a jig and three stages of hydrocyclones. A flowsheet of the scalper circuit is given.

Integrated coal cleaning, liquefaction, and gasification process

DOEpatents

Chervenak, Michael C.

1980-01-01

Coal is finely ground and cleaned so as to preferentially remove denser ash-containing particles along with some coal. The resulting cleaned coal portion having reduced ash content is then fed to a coal hydrogenation system for the production of desirable hydrocarbon gases and liquid products. The remaining ash-enriched coal portion is gasified to produce a synthesis gas, the ash is removed from the gasifier usually as slag, and the synthesis gas is shift converted with steam and purified to produce the high purity hydrogen needed in the coal hydrogenation system. This overall process increases the utilization of as-mined coal, reduces the problems associated with ash in the liquefaction-hydrogenation system, and permits a desirable simplification of a liquids-solids separation step otherwise required in the coal hydrogenation system.

Continuous coal processing method

NASA Technical Reports Server (NTRS)

Ryason, P. R. (Inventor)

1980-01-01

A coal pump is provided in which solid coal is heated in the barrel of an extruder under pressure to a temperature at which the coal assumes plastic properties. The coal is continuously extruded, without static zones, using, for example, screw extrusion preferably without venting through a reduced diameter die to form a dispersed spray. As a result, the dispersed coal may be continuously injected into vessels or combustors at any pressure up to the maximum pressure developed in the extrusion device. The coal may be premixed with other materials such as desulfurization aids or reducible metal ores so that reactions occur, during or after conversion to its plastic state. Alternatively, the coal may be processed and caused to react after extrusion, through the die, with, for example, liquid oxidizers, whereby a coal reactor is provided.

Microbial solubilization of coal

DOEpatents

Strandberg, G.W.; Lewis, S.N.

1988-01-21

The present invention relates to a cell-free preparation and process for the microbial solubilization of coal into solubilized coal products. More specifically, the present invention relates to bacterial solubilization of coal into solubilized coal products and a cell-free bacterial byproduct useful for solubilizing coal. 5 tabs.

77 FR 58868 - Teleconference for the National Park Service Alaska Region's Subsistence Resource Commission Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... Park Subsistence Resource Commission (SRC) and the Wrangell-St. Elias National Park SRC will meet to... and Location for Next Meeting 12. Adjourn Meeting Wrangell-St. Elias National Park SRC Meeting Date and Location: The [[Page 58869

Process for electrochemically gasifying coal

DOEpatents

Botts, T.E.; Powell, J.R.

1985-10-25

A process is claimed for electrochemically gasifying coal by establishing a flowing stream of coal particulate slurry, electrolyte and electrode members through a transverse magnetic field that has sufficient strength to polarize the electrode members, thereby causing them to operate in combination with the electrolyte to electrochemically reduce the coal particulate in the slurry. Such electrochemical reduction of the coal produces hydrogen and carbon dioxide at opposite ends of the polarized electrode members. Gas collection means are operated in conjunction with the process to collect the evolved gases as they rise from the slurry and electrolyte solution. 7 figs.

Phosphatidylinositol Phosphate 5-Kinase Iγi2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells*

PubMed Central

Thapa, Narendra; Choi, Suyong; Hedman, Andrew; Tan, Xiaojun; Anderson, Richard A.

2013-01-01

A fundamental property of tumor cells is to defy anoikis, cell death caused by a lack of cell-matrix interaction, and grow in an anchorage-independent manner. How tumor cells organize signaling molecules at the plasma membrane to sustain oncogenic signals in the absence of cell-matrix interactions remains poorly understood. Here, we describe a role for phosphatidylinositol 4-phosphate 5-kinase (PIPK) Iγi2 in controlling anchorage-independent growth of tumor cells in coordination with the proto-oncogene Src. PIPKIγi2 regulated Src activation downstream of growth factor receptors and integrins. PIPKIγi2 directly interacted with the C-terminal tail of Src and regulated its subcellular localization in concert with talin, a cytoskeletal protein targeted to focal adhesions. Co-expression of PIPKIγi2 and Src synergistically induced the anchorage-independent growth of nonmalignant cells. This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKIγi2, functions with the proto-oncogene Src, to regulate oncogenic signaling. PMID:24151076

Hsp90 dependence of a kinase is determined by its conformational landscape

PubMed Central

Luo, Qi; Boczek, Edgar E.; Wang, Qi; Buchner, Johannes; Kaila, Ville R. I.

2017-01-01

Heat shock protein 90 (Hsp90) is an abundant molecular chaperone, involved in the folding and activation of 60% of the human kinome. The oncogenic tyrosine kinase v-Src is one of the most stringent client proteins of Hsp90, whereas its almost identical homolog c-Src is only weakly affected by the chaperone. Here, we perform atomistic molecular simulations and in vitro kinase assays to explore the mechanistic differences in the activation of v-Src and c-Src. While activation in c-Src is strictly controlled by ATP-binding and phosphorylation, we find that activating conformational transitions are spontaneously sampled in Hsp90-dependent Src mutants. Phosphorylation results in an enrichment of the active conformation and in an increased affinity for Hsp90. Thus, the conformational landscape of the mutated kinase is reshaped by a broken “control switch”, resulting in perturbations of long-range electrostatics, higher activity and increased Hsp90-dependence. PMID:28290541

Desulfurization of Coal in Fluidized Beds

NASA Technical Reports Server (NTRS)

Maddury, R.; Kalvinskas, J.

1985-01-01

Experimental dry chemical process for removing sulfur from coal-and thereby reducing harmful sulfur emissions from coal-fired electric powerplants-promises more economical and effective than older wet chemical processes. New process faster, requires smaller amounts of chemical reagents, and produces no liquid effluents, which poses disposal problem.

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes

PubMed Central

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation. PMID:28736554

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes.

PubMed

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation.

Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3Kδ/Akt and NFκB induction in a murine asthma model.

PubMed

El-Hashim, Ahmed Z; Khajah, Maitham A; Renno, Waleed M; Babyson, Rhema S; Uddin, Mohib; Benter, Ibrahim F; Ezeamuzie, Charles; Akhtar, Saghir

2017-08-30

The molecular mechanisms underlying asthma pathogenesis are poorly characterized. In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kδ/Akt and NF-κB are signaling effectors downstream of Src/EGFR activation; and (3) if upstream inhibition of Src/EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways. Allergic inflammation resulted in increased phosphorylation of EGFR, Akt, ERK1/2 and IκB in the lung tissues from ovalbumin (OVA)-challenged BALB/c mice. Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness. Treatment with pathway-selective inhibitors for ERK1/2 (PD89059) and PI3Kδ/Akt (IC-87114) respectively, or an inhibitor of NF-κB (BAY11-7085) also reduced the OVA-induced asthmatic phenotype but to a lesser extent compared to Src/EGFR inhibition. Thus, Src via EGFR transactivation and subsequent downstream activation of multiple pathways regulates the allergic airway inflammatory response. Furthermore, a broader upstream inhibition of Src/EGFR offers an attractive therapeutic alternative in the treatment of asthma relative to selectively targeting the individual downstream signaling effectors.

Examining Recovery Trajectories Following Sport-related Concussion Using a Multi-Modal Clinical Assessment Approach

PubMed Central

Henry, Luke C.; Elbin, RJ; Collins, Michael W.; Marchetti, Gregory; Kontos, Anthony P.

2016-01-01

Background Previous research estimates that the majority of athletes with sport-related concussion (SRC) will recover between 7–10 days following injury. This short, temporal window of recovery is predominately based on symptom resolution and cognitive improvement, and does not accurately reflect recent advances to the clinical assessment model. Objective To characterize SRC recovery at 1-week post-injury time intervals on symptom, neurocognitive, and vestibular-oculomotor outcomes, and examine gender differences on SRC recovery time. Methods A prospective, repeated measures design was used to examine the temporal resolution of neurocognitive, symptom, and vestibular-oculomotor impairment in 66 subjects (16.5 ± 1.9 years, range 14–23, 64% male) with SRC. Results Recovery time across all outcomes was between 21–28 days post SRC for most athletes. Symptoms demonstrated the greatest improvement in the first 2 weeks, while neurocognitive impairment lingered across various domains up to 28 days post SRC. Vestibular-oculomotor decrements also resolved between one to three weeks post injury. There were no gender differences in neurocognitive recovery. Males were more likely to be asymptomatic by the fourth week and reported less vestibular-oculomotor impairment than females at weeks 1 and 2. Conclusion When utilizing the recommended “comprehensive” approach for concussion assessment, recovery time for SRC is approximately three to four weeks, which is longer than the commonly reported 7–14 days. Sports medicine clinicians should use a variety of complementing assessment tools to capture the heterogeneity of SRC. PMID:26445375

The transcriptional coactivators p/CIP and SRC-1 control insulin resistance through IRS1 in obesity models.

PubMed

Wang, Zhiyong; Shah, O Jameel; Hunter, Tony

2012-01-01

Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as transcriptional coactivators for nuclear hormone receptors and other transcription factors in vitro. In a previous study, we reported initial characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double knockout (DKO) mice, which exhibit increased energy expenditure, and suggested that nuclear hormone receptor target genes were involved in these phenotypes. In this study, we demonstrate that p/CIP and SRC1 control insulin signaling in a cell-autonomous manner both in vitro and in vivo. Genetic deletion of p/CIP and SRC-1 increases glucose uptake and enhances insulin sensitivity in both regular chow- and high fat diet-fed DKO mice despite increased food intake. Interestingly, we discover that loss of p/CIP and SRC-1 results in resistance to age-related obesity and glucose intolerance. We show that expression levels of a key insulin signaling component, insulin receptor substrate 1 (IRS1), are significantly increased in two cell lines representing fat and muscle lineages with p/CIP and SRC-1 deletions and in white adipose tissue and skeletal muscle of DKO mice; this may account for increased glucose metabolism and insulin sensitivity. This is the first evidence that the p160 coactivators control insulin signaling and glucose metabolism through IRS1. Therefore, our studies indicate that p/CIP and SRC-1 are potential therapeutic targets not only for obesity but also for diabetes.

The Transcriptional Coactivators p/CIP and SRC-1 Control Insulin Resistance through IRS1 in Obesity Models

PubMed Central

Wang, Zhiyong; Shah, O. Jameel; Hunter, Tony

2012-01-01

Three p160 family members, p/CIP, SRC1, and TIF2, have been identified as transcriptional coactivators for nuclear hormone receptors and other transcription factors in vitro. In a previous study, we reported initial characterization of the obesity-resistant phenotypes of p/CIP and SRC-1 double knockout (DKO) mice, which exhibit increased energy expenditure, and suggested that nuclear hormone receptor target genes were involved in these phenotypes. In this study, we demonstrate that p/CIP and SRC1 control insulin signaling in a cell-autonomous manner both in vitro and in vivo. Genetic deletion of p/CIP and SRC-1 increases glucose uptake and enhances insulin sensitivity in both regular chow- and high fat diet-fed DKO mice despite increased food intake. Interestingly, we discover that loss of p/CIP and SRC-1 results in resistance to age-related obesity and glucose intolerance. We show that expression levels of a key insulin signaling component, insulin receptor substrate 1 (IRS1), are significantly increased in two cell lines representing fat and muscle lineages with p/CIP and SRC-1 deletions and in white adipose tissue and skeletal muscle of DKO mice; this may account for increased glucose metabolism and insulin sensitivity. This is the first evidence that the p160 coactivators control insulin signaling and glucose metabolism through IRS1. Therefore, our studies indicate that p/CIP and SRC-1 are potential therapeutic targets not only for obesity but also for diabetes. PMID:22859932

Examining Recovery Trajectories After Sport-Related Concussion With a Multimodal Clinical Assessment Approach.

PubMed

Henry, Luke C; Elbin, R J; Collins, Michael W; Marchetti, Gregory; Kontos, Anthony P

2016-02-01

Previous research estimates that the majority of athletes with sport-related concussion (SRC) will recover between 7 and 10 days after injury. This short temporal window of recovery is based predominately on symptom resolution and cognitive improvement and does not accurately reflect recent advances in the clinical assessment model. To characterize SRC recovery at 1-week postinjury time intervals on symptom, neurocognitive, and vestibular-oculomotor outcomes and to examine sex differences in SRC recovery time. A prospective, repeated-measures design was used to examine the temporal resolution of neurocognitive, symptom, and vestibular-oculomotor impairment in 66 subjects (age, 16.5 ± 1.9 years; range, 14-23 years; 64% male) with SRC. Recovery time across all outcomes was between 21 and 28 days after SRC for most athletes. Symptoms demonstrated the greatest improvement in the first 2 weeks, although neurocognitive impairment lingered across various domains up to 28 days after SRC. Vestibular-oculomotor decrements also resolved between 1 and 3 weeks after injury. There were no sex differences in neurocognitive recovery. Male subjects were more likely to be asymptomatic by the fourth week and reported less vestibular-oculomotor impairment than female subjects at weeks 1 and 2. When the recommended "comprehensive" approach is used for concussion assessment, recovery time for SRC is approximately 3 to 4 weeks, which is longer than the commonly reported 7 to 14 days. Sports medicine clinicians should use a variety of complementing assessment tools to capture the heterogeneity of SRC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, S.C.; Manwani, P.

Coal-water slurries have been regarded as a potential substitute for heavy fuel oil. Various demonstrations of coal-water slurry combustion have been performed; however, a fundamental understanding of how the combustion process of a slurry fuel is enhanced is still not adequate. The combustion of coal-water mixture droplets suspended on microthermocouples has been investigated. It was found that droplets of lignite coal (which is a noncaking coal) burn effectively; however, droplets of bituminous coal (which is a caking coal) are relatively difficult to burn. During the heat-up of bituminous coal-water slurry droplets may turn to ''popcorn'' and show significant agglomeration. Themore » incomplete combustion of coal-water slurry droplets in furnaces has been reported, and this is a drawback of this process. The objective of the present study is to explore the possibility of enhancing the combustion of coal-water slurry droplets with the use of a combustible emulsified oil.« less

40 CFR 63.7499 - What are the subcategories of boilers and process heaters?

Code of Federal Regulations, 2013 CFR

2013-07-01

... process heaters, as defined in § 63.7575 are: (a) Pulverized coal/solid fossil fuel units. (b) Stokers designed to burn coal/solid fossil fuel. (c) Fluidized bed units designed to burn coal/solid fossil fuel... liquid fuel. (r) Units designed to burn coal/solid fossil fuel. (s) Fluidized bed units with an...

40 CFR 63.7499 - What are the subcategories of boilers and process heaters?

Code of Federal Regulations, 2014 CFR

2014-07-01

... process heaters, as defined in § 63.7575 are: (a) Pulverized coal/solid fossil fuel units. (b) Stokers designed to burn coal/solid fossil fuel. (c) Fluidized bed units designed to burn coal/solid fossil fuel... liquid fuel. (r) Units designed to burn coal/solid fossil fuel. (s) Fluidized bed units with an...

Flash hydrogenation of coal

DOEpatents

Manowitz, Bernard; Steinberg, Meyer; Sheehan, Thomas V.; Winsche, Warren E.; Raseman, Chad J.

1976-01-01

A process for the hydrogenation of coal comprising the contacting of powdered coal with hydrogen in a rotating fluidized bed reactor. A rotating fluidized bed reactor suitable for use in this process is also disclosed. The coal residence time in the reactor is limited to less than 5 seconds while the hydrogen contact time is not in excess of 0.2 seconds.

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

PubMed

Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

2017-09-07

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

Soil CO2 flux from three ecosystems in tropical peatland of Sarawak, Malaysia

NASA Astrophysics Data System (ADS)

Melling, Lulie; Hatano, Ryusuke; Goh, Kah Joo

2005-02-01

Soil CO2 flux was measured monthly over a year from tropical peatland of Sarawak, Malaysia using a closed-chamber technique. The soil CO2 flux ranged from 100 to 533 mg C m2 h1 for the forest ecosystem, 63 to 245 mg C m2 h1 for the sago and 46 to 335 mg C m2 h1 for the oil palm. Based on principal component analysis (PCA), the environmental variables over all sites could be classified into three components, namely, climate, soil moisture and soil bulk density, which accounted for 86% of the seasonal variability. A regression tree approach showed that CO2 flux in each ecosystem was related to different underlying environmental factors. They were relative humidity for forest, soil temperature at 5 cm for sago and water-filled pore space for oil palm. On an annual basis, the soil CO2 flux was highest in the forest ecosystem with an estimated production of 2.1 kg C m2 yr1 followed by oil palm at 1.5 kg C m2 yr1 and sago at 1.1 kg C m2 yr1. The different dominant controlling factors in CO2 flux among the studied ecosystems suggested that land use affected the exchange of CO2 between tropical peatland and the atmosphere.

Process for changing caking coals to noncaking coals

DOEpatents

Beeson, Justin L.

1980-01-01

Caking coals are treated in a slurry including alkaline earth metal hydroxides at moderate pressures and temperatures in air to form noncaking carbonaceous material. Hydroxides such as calcium hydroxide, magnesium hydroxide or barium hydroxide are contemplated for slurrying with the coal to interact with the agglomerating constituents. The slurry is subsequently dewatered and dried in air at atmospheric pressure to produce a nonagglomerating carbonaceous material that can be conveniently handled in various coal conversion and combustion processes.

Assessment of Coal Geology, Resources, and Reserves in the Gillette Coalfield, Powder River Basin, Wyoming

USGS Publications Warehouse

Luppens, James A.; Scott, David C.; Haacke, Jon E.; Osmonson, Lee M.; Rohrbacher, Timothy J.; Ellis, Margaret S.

2008-01-01

The Gillette coalfield, within the Powder River Basin in east-central Wyoming, is the most prolific coalfield in the United States. In 2006, production from the coalfield totaled over 431 million short tons of coal, which represented over 37 percent of the Nation's total yearly production. The Anderson and Canyon coal beds in the Gillette coalfield contain some of the largest deposits of low-sulfur subbituminous coal in the world. By utilizing the abundance of new data from recent coalbed methane development in the Powder River Basin, this study represents the most comprehensive evaluation of coal resources and reserves in the Gillette coalfield to date. Eleven coal beds were evaluated to determine the in-place coal resources. Six of the eleven coal beds were evaluated for reserve potential given current technology, economic factors, and restrictions to mining. These restrictions included the presence of railroads, a Federal interstate highway, cities, a gas plant, and alluvial valley floors. Other restrictions, such as thickness of overburden, thickness of coal beds, and areas of burned coal were also considered. The total original coal resource in the Gillette coalfield for all eleven coal beds assessed, and no restrictions applied, was calculated to be 201 billion short tons. Available coal resources, which are part of the original coal resource that is accessible for potential mine development after subtracting all restrictions, are about 164 billion short tons (81 percent of the original coal resource). Recoverable coal, which is the portion of available coal remaining after subtracting mining and processing losses, was determined for a stripping ratio of 10:1 or less. After mining and processing losses were subtracted, a total of 77 billion short tons of coal were calculated (48 percent of the original coal resource). Coal reserves are the portion of the recoverable coal that can be mined, processed, and marketed at a profit at the time of the economic evaluation. With a discounted cash flow at 8 percent rate of return, the coal reserves estimate for the Gillette coalfield is10.1 billion short tons of coal (6 percent of the original resource total) for the 6 coal beds evaluated.

Automatic crack detection method for loaded coal in vibration failure process

PubMed Central

Li, Chengwu

2017-01-01

In the coal mining process, the destabilization of loaded coal mass is a prerequisite for coal and rock dynamic disaster, and surface cracks of the coal and rock mass are important indicators, reflecting the current state of the coal body. The detection of surface cracks in the coal body plays an important role in coal mine safety monitoring. In this paper, a method for detecting the surface cracks of loaded coal by a vibration failure process is proposed based on the characteristics of the surface cracks of coal and support vector machine (SVM). A large number of cracked images are obtained by establishing a vibration-induced failure test system and industrial camera. Histogram equalization and a hysteresis threshold algorithm were used to reduce the noise and emphasize the crack; then, 600 images and regions, including cracks and non-cracks, were manually labelled. In the crack feature extraction stage, eight features of the cracks are extracted to distinguish cracks from other objects. Finally, a crack identification model with an accuracy over 95% was trained by inputting the labelled sample images into the SVM classifier. The experimental results show that the proposed algorithm has a higher accuracy than the conventional algorithm and can effectively identify cracks on the surface of the coal and rock mass automatically. PMID:28973032

Automatic crack detection method for loaded coal in vibration failure process.

PubMed

Li, Chengwu; Ai, Dihao

2017-01-01

In the coal mining process, the destabilization of loaded coal mass is a prerequisite for coal and rock dynamic disaster, and surface cracks of the coal and rock mass are important indicators, reflecting the current state of the coal body. The detection of surface cracks in the coal body plays an important role in coal mine safety monitoring. In this paper, a method for detecting the surface cracks of loaded coal by a vibration failure process is proposed based on the characteristics of the surface cracks of coal and support vector machine (SVM). A large number of cracked images are obtained by establishing a vibration-induced failure test system and industrial camera. Histogram equalization and a hysteresis threshold algorithm were used to reduce the noise and emphasize the crack; then, 600 images and regions, including cracks and non-cracks, were manually labelled. In the crack feature extraction stage, eight features of the cracks are extracted to distinguish cracks from other objects. Finally, a crack identification model with an accuracy over 95% was trained by inputting the labelled sample images into the SVM classifier. The experimental results show that the proposed algorithm has a higher accuracy than the conventional algorithm and can effectively identify cracks on the surface of the coal and rock mass automatically.

Novel Autophosphorylation Sites of Src Family Kinases Regulate Kinase Activity and SH2 Domain Binding Capacity

PubMed Central

Weir, Marion E.; Mann, Jacqueline E.; Corwin, Thomas; Fulton, Zachary W.; Hao, Jennifer M.; Maniscalco, Jeanine F.; Kenney, Marie C.; Roque, Kristal M. Roman; Chapdelaine, Elizabeth F.; Stelzl, Ulrich; Deming, Paula B.; Ballif, Bryan A.; Hinkle, Karen L.

2016-01-01

Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly-regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly-phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the site C-terminal to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. PMID:27001024

Sport-Related Concussions

ERIC Educational Resources Information Center

Brady, Don; Brady, Flo

2011-01-01

Sport-related concussions (SRC) are not limited to specific age ranges, professional athletes, or gender. The primary focus of much of SRC research pertains to the assessment, management, and return to play (RTP) of the concussed athlete. This article highlights some major issues of SRC along with some controversies that presently exist within the…

Sex differences in sport-related concussion long-term outcomes.

PubMed

Covassin, Tracey; Savage, Jennifer L; Bretzin, Abigail C; Fox, Meghan E

2017-09-18

Approximately 1.6 to 3.8 million recreational and sports-related concussions (SRC) occur each year in the Unites States. Research suggest that female athletes are at a greater risk for a SRC compared to male athletes competing in comparable sports (i.e., soccer, basketball). Moreover, female athletes have reported more total symptoms and greater neurocognitive impairments following a SRC. Female athletes have been found to report greater symptom provocation as measured by the Vestibular/Ocular Motor Screening (VOMS), and increased brain activation compared to males. There is a scarcity of research on long-term effects of SRC in male and female athletes. Therefore, the aim of this review article is to summarize the existing literature on sex differences in acute and sub-acute SRC outcomes. Copyright © 2017. Published by Elsevier B.V.

Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages.

PubMed

Maa, Ming-Chei; Leu, Tzeng-Horng

2016-06-01

As an evolutionarily conserved mechanism, innate immunity controls self-nonself discrimination to protect a host from invasive pathogens. Macrophages are major participants of the innate immune system. Through the activation of diverse Toll-like receptors (TLRs), macrophages are triggered to initiate a variety of functions including locomotion, phagocytosis, and secretion of cytokines that requires the participation of tyrosine kinases. Fgr, Hck, and Lyn are myeloid-specific Src family kinases. Despite their constitutively high expression in macrophages, their absence does not impair LPS responsiveness. In contrast, Src, a barely detectable tyrosine kinase in resting macrophages, becomes greatly inducible in response to TLR engagement, implicating its role in macrophage activation. Indeed, silencing Src suppresses the activated TLR-mediated migration, phagocytosis, and interferon-beta (IFN-β) secretion in macrophages. And these physiological defects can be restored by the introduction of siRNA-resistant Src. Notably, the elevated expression and activity of Src is inducible nitric oxide synthase (iNOS)-dependent. Due to (1) iNOS being a NF-κB target, which can be induced by various TLR ligands, (2) Src can mediate NF-κB activation, therefore, there ought to exist a loop of signal amplification that regulates macrophage physiology in response to the engagement of TLRs.

Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling.

PubMed

Fusaki, N; Iwamatsu, A; Iwashima, M; Fujisawa, J i

1997-03-07

The Src family protein-tyrosine kinase, Fyn, is associated with the T cell receptor (TCR) and plays an important role in TCR-mediated signaling. We found that a human T cell leukemia virus type 1-infected T cell line, Hayai, overexpressed Fyn. To identify the molecules downstream of Fyn, we analyzed the tyrosine phosphorylation of cellular proteins in the cells. In Hayai, a 68-kDa protein was constitutively tyrosine-phosphorylated. The 68-kDa protein was coimmunoprecipitated with various signaling proteins such as phospholipase C gamma1, the phosphatidylinositol 3-kinase p85 subunit, Grb2, SHP-1, Cbl, and Jak3, implying that the protein might function as an adapter. Purification and microsequencing of this protein revealed that it was the RNA-binding protein, Sam68 (Src associated in mitosis, 68 kDa). Sam68 was associated with the Src homology 2 and 3 domains of Fyn and also those of another Src family kinase, Lck. CD3 cross-linking induced tyrosine phosphorylation of Sam68 in uninfected T cells. These data suggest that Sam68 participates in the signal transduction pathway downstream of TCR-coupled Src family kinases Fyn and Lck in lymphocytes, that is not only in the mitotic pathway downstream of c-Src in fibroblasts.

Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

PubMed Central

Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

2014-01-01

Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

Dynamic organization of myristoylated Src in the live cell plasma membrane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Adam W.; Huang, Hector H.; Endres, Nicholas F.

The spatial organization of lipid-anchored proteins in the plasma membrane directly influences cell signaling, but measuring such organization in situ is experimentally challenging. The canonical oncogene, c-Src, is a lipid anchored protein that plays a key role in integrin-mediated signal transduction within focal adhesions and cell–cell junctions. Because of its activity in specific plasma membrane regions, structural motifs within the protein have been hypothesized to play an important role in its subcellular localization. This study used a combination of time-resolved fluorescence fluctuation spectroscopy and super-resolution microscopy to quantify the dynamic organization of c-Src in live cell membranes. Pulsed-interleaved excitation fluorescencemore » cross-correlation spectroscopy (PIE–FCCS) showed that a small fraction of c-Src transiently sorts into membrane clusters that are several times larger than the monomers. Photoactivated localization microscopy (PALM) confirmed that c-Src partitions into clusters with low probability and showed that the characteristic size of the clusters is 10–80 nm. Finally, time-resolved fluorescence anisotropy measurements were used to quantify the rotational mobility of c-Src to determine how it interacts with its local environment. Altogether, these results build a quantitative description of the mobility and clustering behavior of the c-Src nonreceptor tyrosine kinase in the live cell plasma membrane.« less

Dynamic organization of myristoylated Src in the live cell plasma membrane

DOE PAGES

Smith, Adam W.; Huang, Hector H.; Endres, Nicholas F.; ...

2016-01-15

The spatial organization of lipid-anchored proteins in the plasma membrane directly influences cell signaling, but measuring such organization in situ is experimentally challenging. The canonical oncogene, c-Src, is a lipid anchored protein that plays a key role in integrin-mediated signal transduction within focal adhesions and cell–cell junctions. Because of its activity in specific plasma membrane regions, structural motifs within the protein have been hypothesized to play an important role in its subcellular localization. This study used a combination of time-resolved fluorescence fluctuation spectroscopy and super-resolution microscopy to quantify the dynamic organization of c-Src in live cell membranes. Pulsed-interleaved excitation fluorescencemore » cross-correlation spectroscopy (PIE–FCCS) showed that a small fraction of c-Src transiently sorts into membrane clusters that are several times larger than the monomers. Photoactivated localization microscopy (PALM) confirmed that c-Src partitions into clusters with low probability and showed that the characteristic size of the clusters is 10–80 nm. Finally, time-resolved fluorescence anisotropy measurements were used to quantify the rotational mobility of c-Src to determine how it interacts with its local environment. Altogether, these results build a quantitative description of the mobility and clustering behavior of the c-Src nonreceptor tyrosine kinase in the live cell plasma membrane.« less

The src-family protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation.

PubMed

Möhn, H; Le Cabec, V; Fischer, S; Maridonneau-Parini, I

1995-07-15

The src-family protein-tyrosine kinase p59hck is mainly expressed in neutrophils; however, its functional role in these cells is unknown. Several other src-family members are localized on secretory vesicles and have been proposed to regulate intracellular traffic. We have established here the subcellular localization of p59hck in human neutrophils. Immunoblotting of subcellular fractions showed that approx. 60% of the p59hck per cell is localized on the secretory granules; the other 40% is distributed equally between non-granular membranes and the cytosol. Immunofluorescence of neutrophils and HL60 cells suggests that the p59hck-positive granules are azurophil granules. Granular p59hck is highly susceptible to degradation by an azurophil-granule proteinase. Different forms of p59hck occur in the three subcellular compartments: a 61 kDa form is mainly found in the granules, a 59 kDa form is predominant in the non-granular membranes, whereas cytosolic p59hck migrates as a doublet at 63 kDa. During the process of phagocytosis-linked degranulation, induced by serum-opsonized zymosan in neutrophils or HL60 cells, granular p59hck translocates towards the phagosome. The subcellular localization of p59hck suggests that the enzyme could be involved in the regulation of the degranulation process.

Altered cortical activation and connectivity patterns for visual attention processing in young adults post-traumatic brain injury: A functional near infrared spectroscopy study.

PubMed

Wu, Ziyan; Mazzola, Catherine A; Catania, Lori; Owoeye, Oyindamola; Yaramothu, Chang; Alvarez, Tara; Gao, Yu; Li, Xiaobo

2018-06-01

This study aimed at understanding the neurobiological mechanisms associated with inattention induced by traumatic brain injury (TBI). To eliminate the potential confounding caused by the heterogeneity of TBI, we focused on young adults postsports-related concussion (SRC). Functional near-infrared spectroscopy (fNIRS) data were collected from 27 young adults post-SRC and 27 group-matched normal controls (NCs), while performing a visual sustained attention task. Task responsive cortical activation maps and pairwise functional connectivity among six regions of interest were constructed for each subject. Correlations among the brain imaging measures and clinical measures of attention were calculated in each group. Compared to the NCs, the SRC group showed significantly increased brain activation in left middle frontal gyrus (MFG) and increased functional connectivity between right inferior occipital cortex (IOC) bilateral calcarine gyri (CG). The left MFG activation magnitude was significantly negatively correlated with the hyperactive/impulsive symptom severity measure in the NCs, but not in the patients. The right hemisphere CG-IOC functional connectivity showed a significant positive correlation with the hyperactive/impulsive symptom severity measure in patients, but not in NCs. The current data suggest that abnormal left MFG activation and hyper-communications between right IOC and bilateral CG during visual attention processing may significantly contribute to behavioral manifestations of attention deficits in patients with TBI. © 2018 John Wiley & Sons Ltd.

ELECTROKINETIC DENSIFICATION OF COAL FINES IN WASTE PONDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

E. James Davis

1999-12-18

The objective of this research was to demonstrate that electrokinetics can be used to remove colloidal coal and mineral particles from coal-washing ponds and lakes without the addition of chemical additives such as salts and polymeric flocculants. The specific objectives were: Design and develop a scaleable electrophoresis apparatus to clarify suspensions of colloidal coal and clay particles; Demonstrate the separation process using polluted waste water from the coal-washing facilities at the coal-fired power plants in Centralia, WA; Develop a mathematical model of the process to predict the rate of clarification and the suspension electrical properties needed for scale up.

Electrical Resistivity Tomography for coal fire mapping over Jharia coal field, India

NASA Astrophysics Data System (ADS)

Pal, S. K.; Kumar, S.; Bharti, A. K.; Pathak, V. K.; Kumar, R.

2016-12-01

Over the decades, coal fires are serious global concern posing grievous hazards to the valuable energy resources, local environments and human life. The coal seam and coal mine fires may be initiated due to improper mining activities, exothermic reactions, lighting, forest fire and other anthropic activities, which burn the coal and may continue underground for decades. The burning of concealed coal seams is a complex process involving numerous ill-defined parameters. Generally, the coal exhibits resistivity of 100 to 500Ωm at normal temperature conditions. During the pyrolysis process, at temperatures greater than 6500C coal became a good conductor with a resistivity of approximately 1 Ωm. The present study deals with the mapping of coal fire over Jharia coal field, India using Electrical Resistivity Tomography (ERT). A state-of-the-art 61-channel 64 electrode FlashRES-Universal ERT data acquisition system has been used for data acquisition in the field. The ERT data have been collected using Gradient array and processed in FlashRES Universal survey data checking program for removing noisy data. Then, filtered output data have been inverted using a 2.5D resistivity inversion program. Low resistivity anomalies over 80m-125m and 320m-390m along the profile are inferred to be active coal fire in seam- XVI at a depth of 25m -35m(Figure 1). High resistivity anomaly over 445m - 510m at a depth of 25m -35m has been delineated, due to void associated with complete combustion of seam- XVI coal, followed by char and ash formation resulting from the coal seam fire. Results prove the efficacy of the ERT study comprising Gradient array for coal fire mapping over, Jharia coal field, India.

Coal Mining Machinery Development As An Ecological Factor Of Progressive Technologies Implementation

NASA Astrophysics Data System (ADS)

Efremenkov, A. B.; Khoreshok, A. A.; Zhironkin, S. A.; Myaskov, A. V.

2017-01-01

At present, a significant amount of energy spent for the work of mining machines and coal mining equipment on coal mines and open pits goes to the coal grinding in the process of its extraction in mining faces. Meanwhile, the increase of small fractions in mined coal does not only reduce the profitability of its production, but also causes a further negative impact on the environment and degrades labor conditions for miners. The countermeasure to the specified processes is possible with the help of coal mining equipment development. However, against the background of the technological decrease of coal mine equipment applied in Russia the negative impact on the environment is getting reinforced.

Eye-Tracking and Corpus-Based Analyses of Syntax-Semantics Interactions in Complement Coercion

PubMed Central

Lowder, Matthew W.; Gordon, Peter C.

2016-01-01

Previous work has shown that the difficulty associated with processing complex semantic expressions is reduced when the critical constituents appear in separate clauses as opposed to when they appear together in the same clause. We investigated this effect further, focusing in particular on complement coercion, in which an event-selecting verb (e.g., began) combines with a complement that represents an entity (e.g., began the memo). Experiment 1 compared reading times for coercion versus control expressions when the critical verb and complement appeared together in a subject-extracted relative clause (SRC) (e.g., The secretary that began/wrote the memo) compared to when they appeared together in a simple sentence. Readers spent more time processing coercion expressions than control expressions, replicating the typical coercion cost. In addition, readers spent less time processing the verb and complement in SRCs than in simple sentences; however, the magnitude of the coercion cost did not depend on sentence structure. In contrast, Experiment 2 showed that the coercion cost was reduced when the complement appeared as the head of an object-extracted relative clause (ORC) (e.g., The memo that the secretary began/wrote) compared to when the constituents appeared together in an SRC. Consistent with the eye-tracking results of Experiment 2, a corpus analysis showed that expressions requiring complement coercion are more frequent when the constituents are separated by the clause boundary of an ORC compared to when they are embedded together within an SRC. The results provide important information about the types of structural configurations that contribute to reduced difficulty with complex semantic expressions, as well as how these processing patterns are reflected in naturally occurring language. PMID:28529960

Measurement of the Energy and High-Pressure Dependence of X-ray-Induced Decomposition of Crystalline Strontium Oxalate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldberger, David; Evlyukhin, Egor; Cifligu, Petrika

We report measurements of the X-ray-induced decomposition of crystalline strontium oxalate (SrC2O4) as a function of energy and high pressure in two separate experiments. SrC2O4 at ambient conditions was irradiated with monochromatic synchrotron X-rays ranging in energy from 15 to 28 keV. A broad resonance of the decomposition yield was observed with a clear maximum when irradiating with ~20 keV X-rays and ambient pressure. Little or no decomposition was observed at 15 keV, which is below the Sr K-shell energy of 16.12 keV, suggesting that excitation of core electrons may play an important role in the destabilization of the C2O42–more » anion. A second experiment was performed to investigate the high-pressure dependence of the X-ray-induced decomposition of strontium oxalate at fixed energy. SrC2O4 was compressed in a diamond anvil cell (DAC) in the pressure range from 0 to 7.6 GPa with 1 GPa increments and irradiated in situ with 20 keV X-rays. A marked pressure dependence of the decomposition yield of SrC2O4 was observed with a decomposition yield maximum at around 1 GPa, suggesting that different crystal structures of the material play an important role in the decomposition process. This may be due in part to a phase transition observed near this pressure.« less

TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

PubMed Central

Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

2014-01-01

ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.

PubMed

Karim, Ahmad Faisal; Chandra, Pallavi; Chopra, Aanchal; Siddiqui, Zaved; Bhaskar, Ashima; Singh, Amit; Kumar, Dhiraj

2011-11-18

Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbiased manner. The analysis superimposes differentially regulated genes between contrasting environments onto the network of functional protein associations followed by a series of iterative enrichments and network analysis. To test the utility of the approach, we infected THP1 macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the attenuated non-virulent strain H37Ra as contrasting perturbations and generated the temporal global expression profiles. EPA of the results provided details of response-specific and time-dependent host molecular network perturbations. Further analysis identified tyrosine kinase Src as the major regulatory hub discriminating the responses between wild-type and attenuated Mtb infection. We were then able to verify this novel role of Src experimentally and show that Src executes its role through regulating two vital antimicrobial processes of the host cells (i.e. autophagy and acidification of phagolysosome). These results bear significant potential for developing novel anti-tuberculosis therapy. We propose that EPA could prove extremely useful in understanding complex cellular responses for a variety of perturbations, including pathogenic infections.

Measurement of the Energy and High-Pressure Dependence of X-ray-Induced Decomposition of Crystalline Strontium Oxalate.

PubMed

Goldberger, David; Evlyukhin, Egor; Cifligu, Petrika; Wang, Yonggang; Pravica, Michael

2017-09-28

We report measurements of the X-ray-induced decomposition of crystalline strontium oxalate (SrC 2 O 4 ) as a function of energy and high pressure in two separate experiments. SrC 2 O 4 at ambient conditions was irradiated with monochromatic synchrotron X-rays ranging in energy from 15 to 28 keV. A broad resonance of the decomposition yield was observed with a clear maximum when irradiating with ∼20 keV X-rays and ambient pressure. Little or no decomposition was observed at 15 keV, which is below the Sr K-shell energy of 16.12 keV, suggesting that excitation of core electrons may play an important role in the destabilization of the C 2 O 4 2- anion. A second experiment was performed to investigate the high-pressure dependence of the X-ray-induced decomposition of strontium oxalate at fixed energy. SrC 2 O 4 was compressed in a diamond anvil cell (DAC) in the pressure range from 0 to 7.6 GPa with 1 GPa increments and irradiated in situ with 20 keV X-rays. A marked pressure dependence of the decomposition yield of SrC 2 O 4 was observed with a decomposition yield maximum at around 1 GPa, suggesting that different crystal structures of the material play an important role in the decomposition process. This may be due in part to a phase transition observed near this pressure.

Process for removing pyritic sulfur from bituminous coals

DOEpatents

Pawlak, Wanda; Janiak, Jerzy S.; Turak, Ali A.; Ignasiak, Boleslaw L.

1990-01-01

A process is provided for removing pyritic sulfur and lowering ash content of bituminous coals by grinding the feed coal, subjecting it to micro-agglomeration with a bridging liquid containing heavy oil, separating the microagglomerates and separating them to a water wash to remove suspended pyritic sulfur. In one embodiment the coal is subjected to a second micro-agglomeration step.

Underground Coal Preparation System and Applications

NASA Astrophysics Data System (ADS)

Wei, Cao; DeYong, Shang; BaoNing, Zhang

2018-03-01

The underground coal preparation is a cutting-edge technology of the coal industry worldwide. This paper introduced the meaning of implementing the underground coal preparation, and the practical applications of underground mechanical moving screen jig, underground heavy medium shallow slot and underground air jigger. Through analyzing the main separation equipment and the advantages and disadvantages of three primary processes from aspects of process complexity, slime water treatment, raw coal preparation, etc., the difference among technology investment, construction scale, production cost and economic benefit is concluded.

Coal pump development phase 3

NASA Technical Reports Server (NTRS)

Kushida, R. O.; Sankur, V. D.; Gerbracht, F. G.; Mahajan, V.

1980-01-01

Techniques for achieving continuous coal sprays were studied. Coazial injection with gas and pressure atomization were studied. Coal particles, upon cooling, were found to be porous and fragile. Reactivity tests on the extruded coal showed overall conversion to gases and liquids unchanged from that of the raw coal. The potentials for applications of the coal pump to eight coal conversion processes were examined.

Hydrogen production from coal using a nuclear heat source

NASA Technical Reports Server (NTRS)

Quade, R. N.

1976-01-01

A strong candidate for hydrogen production in the intermediate time frame of 1985 to 1995 is a coal-based process using a high-temperature gas-cooled reactor (HTGR) as a heat source. Expected process efficiencies in the range of 60 to 70% are considerably higher than all other hydrogen production processes except steam reforming of a natural gas. The process involves the preparation of a coal liquid, hydrogasification of that liquid, and steam reforming of the resulting gaseous or light liquid product. A study showing process efficiency and cost of hydrogen vs nuclear reactor core outlet temperature has been completed, and shows diminishing returns at process temperatures above about 1500 F. A possible scenario combining the relatively abundant and low-cost Western coal deposits with the Gulf Coast hydrogen users is presented which provides high-energy density transportation utilizing coal liquids and uranium.

Liquefaction Of Coal With Surfactant And Disposable Catalyst

NASA Technical Reports Server (NTRS)

Hickey, Gregory S.; Sharma, Pramod K.

1996-01-01

Fuels derived from coal more competitive with petroleum products. Improved coal-liquefaction process exploits synergistic effects of disposable iron oxide catalyst and cheap anionic surfactant. Efficiency of conversion achieved in significantly higher than efficiencies obtained with addition of either surfactant or catalyst alone. No costly pretreatment necessary, and increase in conversion achieved under processing conditions milder than those used heretofore in liquefaction of coal. Quality of distillates obtained after liquefaction in process expected superior to distillates obtained after liquefaction by older techniques.

Hydrogen production from coal

NASA Technical Reports Server (NTRS)

1975-01-01

The gasification reactions necessary for the production of hydrogen from montana subbituminous coal are presented. The coal composition is given. The gasifier types mentioned include: suspension (entrained) combustion; fluidized bed; and moving bed. Each gasification process is described. The steam-iron process, raw and product gas compositions, gasifier feed quantities, and process efficiency evaluations are also included.

Hydrogen manufacture by Lurgi gasification of Oklahoma coal

NASA Technical Reports Server (NTRS)

1975-01-01

Advantages and disadvantages of using the Lurgi gasification process to produce hydrogen from Oklahoma coal are listed. Special attention was given to the production of heat for the process; heat is generated by burning part of pretreated coal in the steam generator. Overall performance of the Lurgi process is summarized in tabular form.

From in situ coal to the final coal product: A case study of the Danville Coal Member (Indiana)

USGS Publications Warehouse

Mastalerz, Maria; Padgett, P.L.

1999-01-01

A surface coal mine operation and preparation plant in southwestern Indiana was sampled to examine variations in coal quality and coal petrography parameters for the Danville Coal Member of the Dugger Formation (Pennsylvanian-Desmoinesian, Westphalian D). Representative samples from in situ coal, preparation plant feeds, and a final coal product were collected in order to compare coal quality, coal petrography, trace element concentrations, and ash chemistry of the coal to those of the product. Coal quality parameters of the in situ samples and various feeds, coarse refuse, and final product were variable. The quality of the final coal product was best predicted by the coal quality of the clean coal feed (from the middle portions of the seam). Some trace element contents, especially lead and arsenic, varied between the coal feeds and the product. Lead contents increased in the feeds and product compared to the channel sample of the raw coal, possibly due to contamination in the handling process.A surface coal mine operation and preparation plant in southwestern Indiana was sampled to examine variations in coal quality and coal petrography parameters for the Danville Coal Member of the Dugger Formation (Pennsylvanian-Desmoinesian, Westphalian D). Representative samples from in situ coal, preparation plant feeds, and a final coal product were collected in order to compare coal quality, coal petrography, trace element concentrations, and ash chemistry of the coal to those of the product. Coal quality parameters of the in situ samples and various feeds, coarse refuse, and final product were variable. The quality of the final coal product was best predicted by the coal quality of the clean coal feed (from the middle portions of the seam). Some trace element contents, especially lead and arsenic, varied between the coal feeds and the product. Lead contents increased in the feeds and product compared to the channel sample of the raw coal, possibly due to contamination in the handling process.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looney, J.H.; Im, C.J.

Under the sponsorship of DOE/METC, UCC Research completed a program in 1984 concerned with the development, testing, and manufacture of an ultra-clean coal-water mixture fuel using the UCC two-stage physical beneficiation and coal-water mixture preparation process. Several gallons of ultra-clean coal-water slurry produced at the UCC Research pilot facility was supplied to DOE/METC for combustion testing. The finalization of this project resulted in the presentation of a conceptual design and economic analysis of an ultra-clean coal-water mixture processing facility sufficient in size to continuously supply fuel to a 100 MW turbine power generation system. Upon completion of the above program,more » it became evident that substantial technological and economic improvement could be realized through further laboratory and engineering investigation of the UCC two-stage physical beneficiation process. Therefore, as an extension to the previous work, the purpose of the present program was to define the relationship between the controlling technical parameters as related to coal-water slurry quality and product price, and to determine the areas of improvement in the existing flow-scheme, associated cost savings, and the overall effect of these savings on final coal-water slurry price. Contents of this report include: (1) introduction; (2) process refinement (improvement of coal beneficiation process, different source coals and related cleanability, dispersants and other additives); (3) coal beneficiation and cost parametrics summary; (4) revised conceptual design and economic analysis; (5) operating and capital cost reduction; (6) conclusion; and (7) appendices. 24 figs., 12 tabs.« less

Liquefaction of black thunder coal with counterflow reactor technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, R.J.; Simpson, P.L.

There is currently a resurgence of interest in the use of carbon monoxide and water to promote the solubilization of low rank coals in liquefaction processes. The mechanism for the water shift gas reaction (WGSR) is well documented and proceeds via a formate ion intermediate at temperatures up to about 400{degrees}C. Coal solubilization is enhanced by CO/H{sub 2}O and by the solvent effect of the supercritical water. The WGSR is catalyzed by bases (alkali metal carbonates, hydroxides, acetates, aluminates). Many inorganic salts which promote catalytic hydrogenation are rendered inactive in CO/H{sub 2}O, although there is positive evidence for the benefitmore » of using pyrite for both the WGSR and as a hydrogenation catalyst. The temperatures at which coal solubilization occurs are insufficient to promote extensive cracking or upgrading of the solubilized coal. Therefore, a two step process might achieve these two reactions sequentially. Alberta Research Council (ARC) has developed a two-stage process for the coprocessing of low rank coals and petroleum resids/bitumens. This process was further advanced by utilizing the counterflow reactor (CFR) concept pioneered by Canadian Energy Developments (CED) and ARC. The technology is currently being applied to coal liquefaction. The two-stage process employs CO/H{sub 2}O at relatively mid temperature and pressure to solubilize the coal, followed by a more severe hydrocracking step. This paper describes the results of an autoclave study conducted to support a bench unit program on the direct liquefaction of coals.« less

NEPRILYSIN REGULATES PULMONARY ARTERY SMOOTH MUSCLE CELL PHENOTYPE THROUGH A PDGF RECEPTOR DEPENDENT MECHANISM

PubMed Central

Karoor, Vijaya; Oka, Masahiko; Walchak, Sandra J.; Hersh, Louis B.; Miller, York E.; Dempsey, Edward C.

2013-01-01

Reduced neprilysin (NEP), a cell surface metallopeptidase, which cleaves and inactivates pro-inflammatory and vasoactive peptides, predisposes the lung vasculature to exaggerated remodeling in response to hypoxia. We hypothesize that loss of NEP in pulmonary artery smooth muscle cells (PASMCs) results in increased migration and proliferation. PASMCs isolated from NEP−/− mice exhibited enhanced migration and proliferation in response to serum and PDGF, which was attenuated by NEP replacement. Inhibition of NEP by overexpression of a peptidase dead mutant or knockdown by siRNA in NEP+/+ cells increased migration and proliferation. Loss of NEP led to an increase in Src kinase activity and phosphorylation of PTEN resulting in activation of the PDGF receptor (PDGFR). Knockdown of Src kinase with siRNA or inhibition with PP2 a src kinase inhibitor decreased PDGFRY751 phosphorylation and attenuated migration and proliferation in NEP−/− SMCs. NEP substrates, endothelin-1(ET-1) or fibroblast growth factor-2 (FGF2), increased activation of Src and PDGFR in NEP+/+ cells, which was decreased by an ETAR antagonist, neutralizing antibody to FGF2 and Src inhibitor. Similar to the observations in PASMCs levels of p-PDGFR, p-Src and p-PTEN were elevated in NEP−/− lungs. ETAR antagonist also attenuated the enhanced responses in NEP−/−PASMCs and lungs. Taken together our results suggest a novel mechanism for regulation of PDGFR signaling by NEP substrates involving Src and PTEN. Strategies that increase lung NEP activity/expression or target key downstream effectors, like Src, PTEN or PDGFR, may be of therapeutic benefit in pulmonary vascular disease. PMID:23381789

Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions.

PubMed

Groveman, Bradley R; Xue, Sheng; Marin, Vedrana; Xu, Jindong; Ali, Mohammad K; Bienkiewicz, Ewa A; Yu, Xian-Min

2011-02-01

Previous studies demonstrated that intra-domain interactions between Src family kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2 domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the molecules in a closed conformation, disrupt the kinase active site, and inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate receptors (NMDARs) induced by expression of constitutively active neuronal Src (n-Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F), is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role than the SH3 domain. Our data also show that n-Src binds directly to the C-terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent, and dysfunctions of the SH2 and/or SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src, which is important in the regulation of NMDAR functions. © 2010 The Authors Journal compilation © 2010 FEBS.

Integrated Waste Treatment Unit (IWTU) Input Coal Analyses and Off-Gass Filter (OGF) Content Analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jantzen, Carol M.; Missimer, David M.; Guenther, Chris P.

A full engineering scale Fluidized Bed Steam Reformer (FBSR) system is being used at the Idaho Nuclear Technology and Engineering Center (INTEC) to stabilize acidic Low Activity Waste (LAW) known as Sodium Bearing Waste (SBW). The INTEC facility, known as the Integrated Waste Treatment Unit (IWTU), underwent an Operational Readiness Review (ORR) and a Technology Readiness Assessment (TRA) in March 2014. The IWTU began non-radioactive simulant processing in late 2014 and by January, 2015 ; the IWTU had processed 62,000 gallons of simulant. The facility is currently in a planned outage for inspection of the equipment and will resume processingmore » simulated waste feed before commencing to process 900,000 gallons of radioactive SBW. The SBW acidic waste will be made into a granular FBSR product (carbonate based) for disposal in the Waste Isolation Pilot Plant (WIPP). In the FBSR process calcined coal is used to create a CO2 fugacity to force the waste species to convert to carbonate species. The quality of the coal, which is a feed input, is important because the reactivity, moisture, and volatiles (C,H,N,O, and S) in the coal impact the reactions and control of the mineralizing process in the primary steam reforming vessel, the Denitration and Mineralizing Reformer (DMR). Too much moisture in the coal can require that additional coal be used. However since moisture in the coal is only a small fraction of the moisture from the fluidizing steam this can be self-correcting. If the coal reactivity or heating value is too low then the coal feedrate needs to be adjusted to achieve the desired heat generation. Too little coal and autothermal heat generation in the DMR cannot be sustained and/or the carbon dioxide fugacity will be too low to create the desired carbonate mineral species. Too much coal and excess S and hydroxide species can form. Excess sulfur from coal that (1) is too rich in sulfur or (2) from overfeeding coal can promote wall scale and contribute to corrosion in process piping and materials, in excessive off-gas absorbent loading, and in undesired process emissions. The ash content of the coal is important as the ash adds to the DMR and other vessel products which affect the final waste product mass and composition. The amount and composition of the ash also affects the reaction kinetics. Thus ash content and composition contributes to the mass balance. In addition, sodium, potassium, calcium, sulfur, and maybe silica and alumina in the ash may contribute to wall-scale formation. Sodium, potassium, and alumina in the ash will be overwhelmed by the sodium, potassium, and alumina from the feed but the impact from the other ash components needs to be quantified. A maximum coal particle size is specified so the feed system does not plug and a minimum particle size is specified to prevent excess elutriation from the DMR to the Process Gas Filter (PGF). A vendor specification was used to procure the calcined coal for IWTU processing. While the vendor supplied a composite analysis for the 22 tons of coal (Appendix A), this study compares independent analyses of the coal performed at the Savannah River National Laboratory (SRNL) and at the National Energy Technology Laboratory (NETL). Three supersacks a were sampled at three different heights within the sack in order to determine within bag variability and between bag variability of the coal. These analyses were also compared to the vendor’s composite analyses and to the coal specification. These analyses were also compared to historic data on Bestac coal analyses that had been performed at Hazen Research Inc. (HRI) between 2004-2011.« less

Coal liquefaction and hydrogenation

DOEpatents

Schindler, Harvey D.; Chen, James M.

1985-01-01

Disclosed is a coal liquefaction process using two stages. The first stage liquefies the coal and maximizes the product while the second stage hydrocracks the remainder of the coal liquid to produce solvent.

Organic coal-water fuel: Problems and advances (Review)

NASA Astrophysics Data System (ADS)

Glushkov, D. O.; Strizhak, P. A.; Chernetskii, M. Yu.

2016-10-01

The study results of ignition of organic coal-water fuel (OCWF) compositions were considered. The main problems associated with investigation of these processes were identified. Historical perspectives of the development of coal-water composite fuel technologies in Russia and worldwide are presented. The advantages of the OCWF use as a power-plant fuel in comparison with the common coal-water fuels (CWF) were emphasized. The factors (component ratio, grinding degree of solid (coal) component, limiting temperature of oxidizer, properties of liquid and solid components, procedure and time of suspension preparation, etc.) affecting inertia and stability of the ignition processes of suspensions based on the products of coaland oil processing (coals of various types and metamorphism degree, filter cakes, waste motor, transformer, and turbine oils, water-oil emulsions, fuel-oil, etc.) were analyzed. The promising directions for the development of modern notions on the OCWF ignition processes were determined. The main reasons limiting active application of the OCWF in power generation were identified. Characteristics of ignition and combustion of coal-water and organic coal-water slurry fuels were compared. The effect of water in the composite coal fuels on the energy characteristics of their ignition and combustion, as well as ecological features of these processes, were elucidated. The current problems associated with pulverization of composite coal fuels in power plants, as well as the effect of characteristics of the pulverization process on the combustion parameters of fuel, were considered. The problems hindering the development of models of ignition and combustion of OCWF were analyzed. It was established that the main one was the lack of reliable experimental data on the processes of heating, evaporation, ignition, and combustion of OCWF droplets. It was concluded that the use of high-speed video recording systems and low-inertia sensors of temperature and gas concentration could help in providing the lacking experimental information.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cada, G.F.

H-coal is a process for the direct liquefaction of coal to produce synthetic fuels. Its development has progressed from bench-scale testing through operation of a 2.7 Mg/d (3 ton/d) Process Development Unit. A large-scale H-Coal pilot plant is presently operating at Catlettsburg, Kentucky, and there are plans for the construction of a commercial H-Coal liquefaction facility by the end of the decade. Two of the environmental concerns of the developing direct coal liquefaction industry are accidental spills of synthetic oils and treatment/storage of solid wastes. As a means of obtaining preliminary information on the severity of these potential impacts wellmore » in advance of commercialization, samples of product oils and solid wastes were obtained from the H-Coal Process Development Unit (PDU). These samples were subjected to a battery of rapid screening tests, including chemical characterization and bioassays with a variety of aquatic and terrestrial organisms. Water-soluble fraction (WSFs) of H-Coal PDU oils had considerably higher concentrations of phenols and anilines and were commonly one to two orders of magnitude more toxic to aquatic organisms than WSFs of analogous petroleum crude oil. Whole H-Coal PDU oils were also more toxic to the cricket than petroleum-based oils, and some H-Coal samples showed evidence of teratogenicity. Leachates from H-Coal PDU solid wastes, on the other hand, had relatively low concentrations of selected elements and had essentially no acute toxicity to a variety of aquatic and terrestrial species. These studies indicate that environmental effects of product oil spills from a commercial H-Coal liquefaction plant are likely to be more severe than those of conventional petroleum spills. Product upgrading or special transportation and storage techniques may be needed to ensure environmentally sound commercialization of the H-Coal process.« less

Catalysts and process developments for two-stage liquefaction. Fourth quarterly technical progress report, July 1, 1991--September 30, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronauer, D.C.; Swanson, A.J.; Sajkowski, D.J.

Research under way in this project centers upon developing and evaluating catalysts and process improvements for coal liquefaction in the two-stage close-coupled catalytic process. As documented in the previous quarterly report there was little advantage for presoaking Black Thunder coal or Martin Lake lignite in a hydrogen-donor solvent, such as tetralin, at temperatures up to 600{degrees}F prior to liquefaction at higher temperatures. The amount of decarboxylation that occurred during the presoaking of Black Thunder coal or Martin Lake lignite in tetralin in the temperature range of 400 to 600{degrees}F was also relatively small. As indicated by both CO{sub 2} releasemore » and the change in oxygen-containing coal functionality, the level of decarboxylation in coal-derived solvent seems to correlate with the depth of coal dissolution. The feedstock liquefaction studies for the three feedstocks (Black Thunder subbituminous coal, Martin Lake lignite, and Illinois No. 6 coal) have been completed, and their results were compared in this report. Both Black Thunder coal and Martin Lake lignite gave lighter products than Illinois No. 6 coal at similar process conditions. Severe catalyst deactivation in the first stage was also observed with the Martin Lake lignite run. The first stage catalyst testing program was started. After a successful reference run with Illinois No. 6 coal, a high temperature run with AMOCAT{trademark} 1C was completed. In addition, a run was made with Illinois No. 6 coal using an oil-soluble catalyst, Molyvan L, in the first stage and AMOCAT{trademark} 1C in the second stage, where preliminary run results look promising.« less

Influence of the microwave irradiation dewatering on the combustion characteristics of Chinese brown coals

NASA Astrophysics Data System (ADS)

Ge, Lichao; Feng, Hongcui; Xu, Chang; Zhang, Yanwei; Wang, Zhihua

2018-02-01

This study investigates the influence of microwave irradiation on coal composition, pore structure, coal rank, and combustion characteristics of typical brown coals in China. Results show that the upgrading process significantly decreased the inherent moisture, and increased calorific value and fixed carbon content. After upgrading, pore distribution extended to micropore region, oxygen functional groups were reduced and destroyed, and the apparent aromaticity increased suggesting an improvement in the coal rank. Based on thermogravimetric analysis, the combustion processes of upgraded coals were delayed toward the high temperature region, and the temperatures of ignition, peak and burnout increased. Based on the average combustion rate and comprehensive combustion parameter, the upgraded coals performed better compared with raw brown coals and a high rank coal. In ignition and burnout segments, the activation energy increased but exhibited a decrease in the combustion stage.

Chemical and physical aspects of refining coal liquids

NASA Astrophysics Data System (ADS)

Shah, Y. T.; Stiegel, G. J.; Krishnamurthy, S.

1981-02-01

Increasing costs and declining reserves of petroleum are forcing oil importing countries to develop alternate energy sources. The direct liquefaction of coal is currently being investigated as a viable means of producing substitute liquid fuels. The coal liquids derived from such processes are typically high in nitrogen, oxygen and sulfur besides having a high aromatic and metals content. It is therefore envisaged that modifications to existing petroleum refining technology will be necessary in order to economically upgrade coal liquids. In this review, compositional data for various coal liquids are presented and compared with those for petroleum fuels. Studies reported on the stability of coal liquids are discussed. The feasibility of processing blends of coal liquids with petroleum feedstocks in existing refineries is evaluated. The chemistry of hydroprocessing is discussed through kinetic and mechanistic studies using compounds which are commonly detected in coal liquids. The pros and cons of using conventional petroleum refining catalysts for upgrading coal liquids are discussed.

NEW METABOLITES FROM THE MICROBIAL OXIDATION OF FLUORINATED AROMATIC COMPOUNDS. (R826113)

EPA Science Inventory

Abstract

m-Bromo-,,A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation.

PubMed

Dikic, I; Tokiwa, G; Lev, S; Courtneidge, S A; Schlessinger, J

1996-10-10

The mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA- or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link Gi- and Gq-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PC12 cells.

C-terminal Src kinase (Csk) regulates the tricellular junction protein Gliotactin independent of Src

PubMed Central

Samarasekera, G. D. N. Gayathri; Auld, Vanessa Jane

2018-01-01

Tricellular junctions (TCJs) are uniquely placed permeability barriers formed at the corners of polarized epithelia where tight junctions in vertebrates or septate junctions (SJ) in invertebrates from three cells converge. Gliotactin is a Drosophila TCJ protein, and loss of Gliotactin results in SJ and TCJ breakdown and permeability barrier loss. When overexpressed, Gliotactin spreads away from the TCJs, resulting in disrupted epithelial architecture, including overproliferation, cell delamination, and migration. Gliotactin levels are tightly controlled at the mRNA level and at the protein level through endocytosis and degradation triggered by tyrosine phosphorylation. We identified C-terminal Src kinase (Csk) as a tyrosine kinase responsible for regulating Gliotactin endocytosis. Increased Csk suppresses the Gliotactin overexpression phenotypes by increasing endocytosis. Loss of Csk causes Gliotactin to spread away from the TCJ. Although Csk is known as a negative regulator of Src kinases, the effects of Csk on Gliotactin are independent of Src and likely occur through an adherens junction associated complex. Overall, we identified a new Src-independent role for Csk in the control of Gliotactin, a key tricellular junction protein. PMID:29167383

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

PubMed Central

Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

1999-01-01

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

Anxiety and Mood Clinical Profile following Sport-related Concussion: From Risk Factors to Treatment.

PubMed

Sandel, Natalie; Reynolds, Erin; Cohen, Paul E; Gillie, Brandon L; Kontos, Anthony P

2017-08-01

Conceptual models for assessing and treating sport-related concussion (SRC) have evolved from a homogenous approach to include different clinical profiles that reflect the heterogeneous nature of this injury and its effects. There are six identified clinical profiles, or subtypes from SRC, and one such clinical profile is the anxiety/mood profile. Athletes with this profile experience predominant emotional disturbance and anxiety following SRC. The purpose of this targeted review was to present an overview of the empirical evidence to support factors contributing to the anxiety/mood profile, along with methods of evaluation and treatment of this clinical profile following SRC. We discuss the potential underlying mechanisms and risk factors for this clinical profile, describe comprehensive assessments to evaluate concussed athletes with an anxiety/mood clinical profile, and explore behavioral and other interventions for treating these athletes. Although there is limited, but growing empirical evidence for the anxiety/mood clinical profile following SRC, understanding this clinical profile is germane for clinicians who are treating athletes with emotional sequelae after SRC.

Process for improving soluble coal yield in a coal deashing process

DOEpatents

Rhodes, Donald E.

1980-01-01

Coal liquefaction products are contacted with a deashing solvent and introduced into a first separation zone. The first separation zone is maintained at an elevated temperature and pressure, determined to maximize the recovery of soluble coal products, to cause said coal liquefaction products to separate into a first light phase and a first heavy phase. Under these conditions the heavy phase while still fluid-like in character is substantially non-flowable. Flowability is returned to the fluid-like heavy phase by the introduction of an additional quantity of deashing solvent into the first separation zone at a location below the interface between the first light and heavy phases or into the heavy phase withdrawal conduit during withdrawal of the first heavy phase and prior to any substantial pressure reduction. The first heavy phase then is withdrawn from the first separation zone for additional downstream processing without plugging either the withdrawal conduit or the downstream apparatus. The first light phase comprising the soluble coal products is withdrawn and recovered in an increased yield to provide a more economical coal deashing process.

EXXON donor solvent coal liquefaction process

NASA Technical Reports Server (NTRS)

Epperly, W. R.; Swabb, L. E., Jr.; Tauton, J. W.

1978-01-01

A solvent coal liquefaction process to produce low-sulfur liquid products from a wide range of coals is described. An integrated program of laboratory and engineering research and development in conjunction with operation of a 250 T/D pilot plant is discussed.

Filtering coal-derived oil through a filter media precoated with particles partially solubilized by said oil

DOEpatents

Rodgers, Billy R.; Edwards, Michael S.

1977-01-01

Solids such as char, ash, and refractory organic compounds are removed from coal-derived liquids from coal liquefaction processes by the pressure precoat filtration method using particles of 85-350 mesh material selected from the group of bituminous coal, anthracite coal, lignite, and devolatilized coals as precoat materials and as body feed to the unfiltered coal-derived liquid.

Fired heater for coal liquefaction process

DOEpatents

Ying, David H. S.; McDermott, Wayne T.; Givens, Edwin N.

1985-01-01

A fired heater for a coal liquefaction process is operated under conditions to maximize the slurry slug frequency and thereby improve the heat transfer efficiency. The operating conditions controlled are (1) the pipe diameter and pipe arrangement, (2) the minimum coal/solvent slurry velocity, (3) the maximum gas superficial velocity, and (4) the range of the volumetric flow velocity ratio of gas to coal/solvent slurry.

Integrated coal liquefaction process

DOEpatents

Effron, Edward

1978-01-01

In a process for the liquefaction of coal in which coal liquids containing phenols and other oxygenated compounds are produced during the liquefaction step and later hydrogenated, oxygenated compounds are removed from at least part of the coal liquids in the naphtha and gas oil boiling range prior to the hydrogenation step and employed as a feed stream for the manufacture of a synthesis gas or for other purposes.

Coal liquefaction process using pretreatment with a binary solvent mixture

DOEpatents

Miller, R.N.

1986-10-14

An improved process for thermal solvent refining or hydroliquefaction of non-anthracitic coal at elevated temperatures under hydrogen pressure in a hydrogen donor solvent comprises pretreating the coal with a binary mixture of an aromatic hydrocarbon and an aliphatic alcohol at a temperature below 300 C before the hydroliquefaction step. This treatment generally increases both conversion of coal and yields of oil. 1 fig.

Coal liquefaction process using pretreatment with a binary solvent mixture

DOEpatents

Miller, Robert N.

1986-01-01

An improved process for thermal solvent refining or hydroliquefaction of non-anthracitic coal at elevated temperatures under hydrogen pressure in a hydrogen donor solvent comprises pretreating the coal with a binary mixture of an aromatic hydrocarbon and an aliphatic alcohol at a temperature below 300.degree. C. before the hydroliquefaction step. This treatment generally increases both conversion of coal and yields of oil.

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery.

PubMed

Knock, Greg A; Shaifta, Yasin; Snetkov, Vladimir A; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P T; Aaronson, Philip I

2008-02-01

We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.

Cell Signaling Associated with Na+/K+-ATPase: Activation of Phosphatidylinositide 3-Kinase IA/Akt by Ouabain Is Independent of Src

PubMed Central

2013-01-01

Exposure of intact cells to selective inhibitors of Na+/K+-ATPase such as ouabain activates several growth-related cell signaling pathways. It has been suggested that the initial event of these pathways is the binding of ouabain to a preexisting complex of Src with Na+/K+-ATPase of the plasma membrane. The aim of this work was to evaluate the role of Src in the ouabain-induced activation of phosphatidylinositide 3-kinase 1A (PI3K1A) and its downstream consequences. When fibroblasts devoid of Src (SYF cells) and controls (Src++ cells) were exposed to ouabain, PI3K1A, Akt, and proliferative growth were similarly stimulated in both cell lines. Ouabain-induced activation of Akt was not prevented by the Src inhibitor PP2. In contrast, ERK1/2 were not activated by ouabain in SYF cells but were stimulated in Src++ cells; this was prevented by PP2. In isolated adult mouse cardiac myocytes, where ouabain induces hypertrophic growth, PP2 also did not prevent ouabain-induced activation of Akt and the resulting hypertrophy. Ouabain-induced increases in the levels of co-immunoprecipitation of the α-subunit of Na+/K+-ATPase with the p85 subunit of PI3K1A were noted in SYF cells, Src++ cells, and adult cardiac myocytes. In conjunction with previous findings, the results presented here indicate that (a) if there is a preformed complex of Src and Na+/K+-ATPase, it is irrelevant to ouabain-induced activation of the PI3K1A/Akt pathway through Na+/K+-ATPase and (b) a more likely, but not established, mechanism of linkage of Na+/K+-ATPase to PI3K1A is the ouabain-induced interaction of a proline-rich domain of the α-subunit of Na+/K+-ATPase with the SH3 domain of the p85 subunit of PI3K1A. PMID:24266852

Src Drives Growth of Antiestrogen Resistant Breast Cancer Cell Lines and Is a Marker for Reduced Benefit of Tamoxifen Treatment

PubMed Central

Larsen, Sarah L.; Laenkholm, Anne-Vibeke; Duun-Henriksen, Anne Katrine; Bak, Martin; Lykkesfeldt, Anne E.; Kirkegaard, Tove

2015-01-01

The underlying mechanisms leading to antiestrogen resistance in estrogen-receptor α (ER)-positive breast cancer is still poorly understood. The aim of this study was therefore to identify biomarkers and novel treatments for antiestrogen resistant breast cancer. We performed a kinase inhibitor screen on antiestrogen responsive T47D breast cancer cells and T47D-derived tamoxifen and fulvestrant resistant cell lines. We found that dasatinib, a broad-spectrum kinase inhibitor, inhibited growth of the antiestrogen resistant cells compared to parental T47D cells. Furthermore western blot analysis showed increased expression and phosphorylation of Src in the resistant cells and that dasatinib inhibited phosphorylation of Src and also signaling via Akt and Erk in all cell lines. Immunoprecipitation revealed Src: ER complexes only in the parental T47D cells. In fulvestrant resistant cells, Src formed complexes with the Human Epidermal growth factor Receptor (HER)1 and HER2. Neither HER receptors nor ER were co-precipitated with Src in the tamoxifen resistant cell lines. Compared to treatment with dasatinib alone, combined treatment with dasatinib and fulvestrant had a stronger inhibitory effect on tamoxifen resistant cell growth, whereas dasatinib in combination with tamoxifen had no additive inhibitory effect on fulvestrant resistant growth. When performing immunohistochemical staining on 268 primary tumors from breast cancer patients who had received tamoxifen as first line endocrine treatment, we found that membrane expression of Src in the tumor cells was significant associated with reduced disease-free and overall survival. In conclusion, Src was identified as target for treatment of antiestrogen resistant T47D breast cancer cells. For tamoxifen resistant T47D cells, combined treatment with dasatinib and fulvestrant was superior to treatment with dasatinib alone. Src located at the membrane has potential as a new biomarker for reduced benefit of tamoxifen. PMID:25706943

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery

PubMed Central

Knock, Greg A.; Shaifta, Yasin; Snetkov, Vladimir A.; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Abstract Aims We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Methods and results Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F2α (PGF2α) in α-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF2α were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF2α enhanced phosphorylation of three srcFK proteins at tyr-416. In α-toxin-permeabilized IPAs, PGF2α enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF2α enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF2α-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF2α triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. Conclusions srcFK are activated by PGF2α in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1. PMID:18032393

Eddy correlation measurements of size-dependent cloud droplet turbulent fluxes to complex terrain

NASA Astrophysics Data System (ADS)

Vong, Richard J.; Kowalski, Andrew S.

1995-07-01

An eddy correlation technique was used to measure the turbulent flux of cloud droplets to complex, forested terrain near the coast of Washington State during the spring of 1993. Excellent agreement was achieved for cloud liquid water content measured by two instruments. Substantial downward liquid water fluxes of 1mm per 24 h were measured at night during "steady and continuous" cloud events, about twice the magnitude of those measured by Beswick etal. in Scotland. Cloud water chemical fluxes were estimated to represent up to 50% of the chemical deposition associated with precipitation at the site. An observed size-dependence in the turbulent liquid water fluxes suggested that both droplet impaction, which leads to downward fluxes, and phase change processes, which can lead to upward fluxes, consistently are important contributors to the eddy correlation results. The diameter below which phase change processes were important to observed fluxes was shown to depend upon σL, the relative standard deviation of the liquid water content (LWC) within a 30-min averaging period. The crossover from upward to downward LW flux occurs at 8µm for steady and continuous cloud events but at 13µm for events with a larger degree of LWC variability. This comparison of the two types of cloud events suggested that evaporation was the most likely cause of upward droplet fluxes for the smaller droplets (dia<13µm) during cloud with variable LWC (σL>0.3).

Southern Coal Corporation Clean Water Settlement

EPA Pesticide Factsheets

Southern Coal Corporation is a coal mining and processing company headquartered in Roanoke, VA. Southern Coal Corporation and the following 26 affiliated entities are located in Alabama, Kentucky, Tennessee, Virginia and West Virginia

Chronic traumatic encephalopathy in sports: a historical and narrative review.

PubMed

Solomon, Gary

2018-01-01

My objectives are to review: 1) a brief history of sport-related concussion (SRC) and chronic traumatic encephalopathy (CTE), 2) the evolution of CTE in American professional football, 3) the data regarding SRC/CTE as they relate to depression and suicide, 4) the data on the neurocognitive effects of subconcussion/repetitive head trauma (with emphases on heading the ball in soccer and early exposure to football), 5) the evidence related to SRC and neurodegenerative diseases, 6) the published studies of CTE, 7) the NINDS neuropathological criteria for CTE, 8) public beliefs about SRC/CTE, and 9) the scientific questions regarding CTE.

Status of H-Coal commercial activities. [Kentucky

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hicks, H.N. Jr.

1981-01-01

The H-Coal process is a development of Hydrocarbon Research, Inc. (HRI). It converts coal by catalytic hydrogenation to substitutes for petroleum ranging from a low sulfur fuel oil to an all distillate synthetic crude, the latter representing a potential source of raw material for the petrochemical industry. The process is a related application to HRI's H-Oil process which is used commercially for the desulfurization of residual oils from crude oil refining. A large scale pilot plant was constructed at Catlettsburg, Kentucky that is designed to process 200 to 600 TPD of coal. The paper includes an update on the keymore » activities associated with the Breckinridge Project: Pilot Plant H-Coal at Catlettsburg, Kentucky; commercial design activities in Houston; and permit and EIS activities for the Addison, Kentucky plant site.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elliott, G.R.B.; Vanderborgh, N.E.

Experimental and theoretical analyses show that uncontrolled water invasion during underground coal conversion (UCC) is harmful at all stages of UCC. By contrast, if water invasion is prevented, coal porosity can be created for further processing, pyrolysis can yield uniform hydrocarbon products, gasification can produce a uniform product, coal is fully consumed (not bypassed) during combustion, and environmental problems are minimized. In all cases the experimental results are supportive of the theory of underground coal processing presented. We see no insurmountable technical problems existing for a staged underground coal conversion process, but we emphasize that all concepts in underground coalmore » processing depend critically upon control of water influx. It is important that techniques for measuring and controlling water flow be developed if this technology is to make a contribution to the Nation's energy supply.« less

Coal fracturing and heteroatom removal. Annual report, fiscal year 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapienza, R.; Slegeir, W.; Butcher, T.

1983-09-01

Coal-water slurry fuels offer a practical, economical method to use coal, replacing the 3 million barrels of oil used per day to fuel utility boilers, industrial heaters, and furnaces in the US. The mineral matter and in some cases the costs of grinding are major impediments to the direct use of this fuel in existing fluid fuel combustors. A process for the simultaneous cleaning and fracturing of a variety of coals has been explored at Brookhaven National Laboratory. This process entails exposure of coal to a carbon dioxide-water solvent system under pressure. Substantial amounts of mineral matter are leached intomore » the liquid phase, significantly lowering the concentrations of alkaline, and alkaline earth metals, and of silica- and alumina-like minerals in the coal. Grindability studies have been conducted in a laboratory ball mill using processed coal. Grinding times for large-size feed coal (1-3/8 to 3/8 in.) are reduced by a factor up to 10 following exposure to CO/sub 2//water. With smaller-feed coal (4 x 8 mesh), however, improvements in grindability are much smaller. An integrated system has been constructed in which coal is ground while under CO/sub 2/ pressure. Significant improvements in grindability have been observed with this system, even with smaller-feed coal. 20 refs., 8 figs., 24 tabs.« less

Process for selective grinding of coal

DOEpatents

Venkatachari, Mukund K.; Benz, August D.; Huettenhain, Horst

1991-01-01

A process for preparing coal for use as a fuel. Forming a coal-water slurry having solid coal particles with a particle size not exceeding about 80 microns, transferring the coal-water slurry to a solid bowl centrifuge, and operating same to classify the ground coal-water slurry to provide a centrate containing solid particles with a particle size distribution of from about 5 microns to about 20 microns and a centrifuge cake of solids having a particle size distribution of from about 10 microns to about 80 microns. The classifer cake is reground and mixed with fresh feed to the solid bowl centrifuge for additional classification.

Characteristics of process oils from HTI coal/plastics co-liquefaction runs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, G.A.; Brandes, S.D.; Winschel, R.A.

1995-12-31

The objective of this project is to provide timely analytical support to DOE`s liquefaction development effort. Specific objectives of the work reported here are presented. During a few operating periods of Run POC-2, HTI co-liquefied mixed plastics with coal, and tire rubber with coal. Although steady-state operation was not achieved during these brief tests periods, the results indicated that a liquefaction plant could operate with these waste materials as feedstocks. CONSOL analyzed 65 process stream samples from coal-only and coal/waste portions of the run. Some results obtained from characterization of samples from Run POC-2 coal/plastics operation are presented.

Efficient volatile metal removal from low rank coal in gasification, combustion, and processing systems and methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bland, Alan E.; Sellakumar, Kumar Muthusami; Newcomer, Jesse D.

Efficient coal pre-processing systems (69) integrated with gasification, oxy-combustion, and power plant systems include a drying chamber (28), a volatile metal removal chamber (30), recirculated gases, including recycled carbon dioxide (21), nitrogen (6), and gaseous exhaust (60) for increasing the efficiencies and lowering emissions in various coal processing systems.

Assessment of coal geology, resources, and reserves in the northern Wyoming Powder River Basin

USGS Publications Warehouse

Scott, David C.; Haacke, Jon E.; Osmonson, Lee M.; Luppens, James A.; Pierce, Paul E.; Rohrbacher, Timothy J.

2010-01-01

The abundance of new borehole data from recent coal bed natural gas development in the Powder River Basin was utilized by the U.S. Geological Survey for the most comprehensive evaluation to date of coal resources and reserves in the Northern Wyoming Powder River Basin assessment area. It is the second area within the Powder River Basin to be assessed as part of a regional coal assessment program; the first was an evaluation of coal resources and reserves in the Gillette coal field, adjacent to and south of the Northern Wyoming Powder River Basin assessment area. There are no active coal mines in the Northern Wyoming Powder River Basin assessment area at present. However, more than 100 million short tons of coal were produced from the Sheridan coal field between the years 1887 and 2000, which represents most of the coal production within the northwestern part of the Northern Wyoming Powder River Basin assessment area. A total of 33 coal beds were identified during the present study, 24 of which were modeled and evaluated to determine in-place coal resources. Given current technology, economic factors, and restrictions to mining, seven of the beds were evaluated for potential reserves. The restrictions included railroads, a Federal interstate highway, urban areas, and alluvial valley floors. Other restrictions, such as depth, thickness of coal beds, mined-out areas, and areas of burned coal, were also considered. The total original coal resource in the Northern Wyoming Powder River Basin assessment area for all 24 coal beds assessed, with no restrictions applied, was calculated to be 285 billion short tons. Available coal resources, which are part of the original coal resource that is accessible for potential mine development after subtracting all restrictions, are about 263 billion short tons (92.3 percent of the original coal resource). Recoverable coal, which is that portion of available coal remaining after subtracting mining and processing losses, was determined for seven coal beds with a stripping ratio of 10:1 or less. After mining and processing losses were subtracted, a total of 50 billion short tons of recoverable coal was calculated. Coal reserves are the portion of the recoverable coal that can be mined, processed, and marketed at a profit at the time of the economic evaluation. With a discounted cash flow at 8 percent rate of return, the coal reserves estimate for the Northern Wyoming Powder River Basin assessment area is 1.5 billion short tons of coal (1 percent of the original resource total) for the seven coal beds evaluated.

Implementation of Paste Backfill Mining Technology in Chinese Coal Mines

PubMed Central

Chang, Qingliang; Zhou, Huaqiang; Bai, Jianbiao

2014-01-01

Implementation of clean mining technology at coal mines is crucial to protect the environment and maintain balance among energy resources, consumption, and ecology. After reviewing present coal clean mining technology, we introduce the technology principles and technological process of paste backfill mining in coal mines and discuss the components and features of backfill materials, the constitution of the backfill system, and the backfill process. Specific implementation of this technology and its application are analyzed for paste backfill mining in Daizhuang Coal Mine; a practical implementation shows that paste backfill mining can improve the safety and excavation rate of coal mining, which can effectively resolve surface subsidence problems caused by underground mining activities, by utilizing solid waste such as coal gangues as a resource. Therefore, paste backfill mining is an effective clean coal mining technology, which has widespread application. PMID:25258737

Implementation of paste backfill mining technology in Chinese coal mines.

PubMed

Chang, Qingliang; Chen, Jianhang; Zhou, Huaqiang; Bai, Jianbiao

2014-01-01

Implementation of clean mining technology at coal mines is crucial to protect the environment and maintain balance among energy resources, consumption, and ecology. After reviewing present coal clean mining technology, we introduce the technology principles and technological process of paste backfill mining in coal mines and discuss the components and features of backfill materials, the constitution of the backfill system, and the backfill process. Specific implementation of this technology and its application are analyzed for paste backfill mining in Daizhuang Coal Mine; a practical implementation shows that paste backfill mining can improve the safety and excavation rate of coal mining, which can effectively resolve surface subsidence problems caused by underground mining activities, by utilizing solid waste such as coal gangues as a resource. Therefore, paste backfill mining is an effective clean coal mining technology, which has widespread application.

Assessment of advanced coal gasification processes

NASA Technical Reports Server (NTRS)

Mccarthy, J.; Ferrall, J.; Charng, T.; Houseman, J.

1981-01-01

A technical assessment of the following advanced coal gasification processes is presented: high throughput gasification (HTG) process; single stage high mass flux (HMF) processes; (CS/R) hydrogasification process; and the catalytic coal gasification (CCG) process. Each process is evaluated for its potential to produce synthetic natural gas from a bituminous coal. Key similarities, differences, strengths, weaknesses, and potential improvements to each process are identified. The HTG and the HMF gasifiers share similarities with respect to: short residence time (SRT), high throughput rate, slagging, and syngas as the initial raw product gas. The CS/R hydrogasifier is also SRT, but is nonslagging and produces a raw gas high in methane content. The CCG gasifier is a long residence time, catalytic, fluidbed reactor producing all of the raw product methane in the gasifier.

Crack identification and evolution law in the vibration failure process of loaded coal

NASA Astrophysics Data System (ADS)

Li, Chengwu; Ai, Dihao; Sun, Xiaoyuan; Xie, Beijing

2017-08-01

To study the characteristics of coal cracks produced in the vibration failure process, we set up a static load and static and dynamic combination load failure test simulation system, prepared with different particle size, formation pressure, and firmness coefficient coal samples. Through static load damage testing of coal samples and then dynamic load (vibration exciter) and static (jack) combination destructive testing, the crack images of coal samples under the load condition were obtained. Combined with digital image processing technology, an algorithm of crack identification with high precision and in real-time is proposed. With the crack features of the coal samples under different load conditions as the research object, we analyzed the distribution of cracks on the surface of the coal samples and the factors influencing crack evolution using the proposed algorithm and a high-resolution industrial camera. Experimental results showed that the major portion of the crack after excitation is located in the rear of the coal sample where the vibration exciter cannot act. Under the same disturbance conditions, crack size and particle size exhibit a positive correlation, while crack size and formation pressure exhibit a negative correlation. Soft coal is more likely to lead to crack evolution than hard coal, and more easily causes instability failure. The experimental results and crack identification algorithm provide a solid basis for the prevention and control of instability and failure of coal and rock mass, and they are helpful in improving the monitoring method of coal and rock dynamic disasters.

Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss.

PubMed

Hiscox, Stephen; Barrett-Lee, Peter; Borley, Annabel C; Nicholson, Robert I

2010-08-01

Aromatase inhibitors have largely replaced tamoxifen as the first-line treatment for postmenopausal women with metastatic, hormone receptor-positive (HR+) breast cancer. However, many patients develop clinical resistance with prolonged treatment, and oestrogen deprivation following aromatase inhibition can result in loss of bone mineral density. Furthermore, most patients with metastatic breast cancer develop bone metastases, and the resulting adverse skeletal-related events are a significant cause of patient morbidity. Src, a non-receptor tyrosine kinase, is a component of signalling pathways that regulate breast cancer cell proliferation, invasion and metastasis as well as osteoclast-mediated bone turnover. Preclinical evidence also suggests a role for Src in acquired endocrine resistance. As such, Src inhibition represents a logical strategy for the treatment of metastatic breast cancer. In vitro, combination therapy with Src inhibitors and endocrine agents, including aromatase inhibitors, has been shown to inhibit the proliferation and metastasis of both endocrine-responsive and endocrine-resistant breast cancer cell lines more effectively than either of the therapy alone. Src inhibition has also been shown to suppress osteoclast formation and activity. Combination therapy with aromatase inhibitors and Src inhibitors therefore represents a novel approach through which the development of both acquired resistance and bone pathology could be delayed. Data from clinical trials utilising such combinations will reveal if this strategy has the potential to improve patient outcomes. Copyright 2010 Elsevier Ltd. All rights reserved.

Identification of N-Terminal Lobe Motifs that Determine the Kinase Activity of the Catalytic Domains and Regulatory Strategies of Src and Csk Protein Tyrosine Kinases†

PubMed Central

Huang, Kezhen; Wang, Yue-Hao; Brown, Alex; Sun, Gongqin

2009-01-01

Csk and Src protein tyrosine kinases are structurally homologous, but use opposite regulatory strategies. The isolated catalytic domain of Csk is intrinsically inactive and is activated by interactions with the regulatory SH3 and SH2 domains, while the isolated catalytic domain of Src is intrinsically active and is suppressed by interactions with the regulatory SH3 and SH2 domains. The structural basis for why one isolated catalytic domain is intrinsically active while the other is inactive is not clear. In this current study, we identify the structural elements in the N-terminal lobe of the catalytic domain that render the Src catalytic domain active. These structural elements include the α-helix C region, a β-turn between the β-4 and β-5 strands, and an Arg residue at the beginning of the catalytic domain. These three motifs interact with each other to activate the Src catalytic domain, but the equivalent motifs in Csk directly interact with the regulatory domains that are important for Csk activation. The Src motifs can be grafted to the Csk catalytic domain to obtain an active Csk catalytic domain. These results, together with available Src and Csk tertiary structures, reveal an important structural switch that determines the kinase activity of a catalytic domain and dictates the regulatory strategy of a kinase. PMID:19244618

A RNA Interference Screen Identifies the Protein Phosphatase 2A Subunit PR55γ as a Stress-Sensitive Inhibitor of c-SRC

PubMed Central

Eichhorn, Pieter J. A; Creyghton, Menno P; Wilhelmsen, Kevin; van Dam, Hans; Bernards, René

2007-01-01

Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogene-induced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH2-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ. PMID:18069897

Activities of the Institute of Chemical Processing of Coal at Zabrze

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dreszer, K.

1995-12-31

The Institute of Chemical Processing of Coal at Zabrze was established in 1955. The works on carbochemical technologies have been, therefore, carried out at the Institute for 40 years. The targets of the Institute`s activities are research, scientific and developing works regarding a sensible utilization of fuels via their processing into more refined forms, safe environment, highly efficient use of energy carriers and technological products of special quality. The Institute of Chemical Processing of Coal has been dealing with the following: optimized use of home hard coals; improvement of classic coal coking technologies, processing and utilization of volatile coking products;more » production technologies of low emission rate fuels for communal management; analyses of coal processing technologies; new technologies aimed at increasing the efficiency of coal utilization for energy-generating purposes, especially in industry and studies on the ecological aspects of these processes; production technologies of sorbents and carbon activating agents and technologies of the utilization; rationalization of water and wastes management in the metallurgical and chemical industries in connection with removal of pollution especially dangerous to the environment from wastes; utilization technologies of refined materials (electrode cokes, binders, impregnating agents) for making electrodes, refractories and new generation construction carbon materials; production technologies of high quality bituminous and bituminous and resin coating, anti-corrosive and insulation materials; environmentally friendly utilization technologies for power station, mine and other wastes, and dedusting processes in industrial gas streams.« less

Ash characterization in laboratory-scale oxy-coal combustor

EPA Science Inventory

Oxygen enriched coal (oxy-coal) combustion is a developing technology. During oxy-coal combustion, combustion air is separated and the coal is burned in a mixture of oxygen and recycled flue gas. The resulting effluent must be further processed before the C02 can be compressed, t...

Relationship between solvent retention capacity and protein molecular weight distribution, quality characteristics, and breadmaking functionality of hard red spring wheat flour

USDA-ARS?s Scientific Manuscript database

In order to investigate suitability of solvent retention capacity (SRC) test for quality assessment of hard red spring (HRS) wheat flour, ten HRS genotypes from six locations in North Dakota State were analyzed for SRC and flour and breadmaking quality characteristics. The SRC values were significa...

Research of a possibility of receiving sorbents for a sewage disposal from a wastage of coal preparation factory

NASA Astrophysics Data System (ADS)

Buyantuev, S. L.; Kondratenko, A. S.; Shishulkin, S. Y.; Stebenkova, Y. Y.; Khmelev, A. B.

2017-05-01

The paper presents the results of the studies of the structure and porosity of the coal cake processed by electric arc plasma. The main limiting factor in processing of coal cakes sorbents is their high water content. As a result of coal washing, the main share of water introduced into the cake falls on hard-hydrate and colloidal components. This makes impossible application of traditional processes of manufacturing from a cake of coal sorbents. Using the electric arc intensifies the processes of thermal activation of coal cakes associated with thermal shock, destruction and vapor-gas reactions occurring at the surfaces of the particles at an exposure temperature of up to 3000 °C, which increases the title product outlet (sorbent) and thereby reduces manufacturing costs and improves environmental performance. The investigation of the thermal activation zone is carried out in the plasma reactor chamber by thermal imaging method followed by mapping-and 3D-modeling of temperature fields. the most important physical and chemical properties of the sorbents from coal cake activated by plasma was studied. The obtained results showed the possibility of coal cake thermal activation by electric arc plasma to change its material composition, the appearance of porosity and associated sorption capacity applied for wastewater treatment.

Effect of a Dispersant Agent in Fine Coal Recovery from Washery Tailings by Oil Agglomeration (Preliminary Study)

NASA Astrophysics Data System (ADS)

Yasar, Özüm; Uslu, Tuncay

2017-12-01

Among the fine coal cleaning methods, the oil agglomeration process has important advantages such as high process recovery, more clean product, simple dewatering stage. Several coal agglomeration studies have been undertaken recently and effects of different variables on the process performance have been investigated. However, unlike flotation studies, most of the previous agglomeration studies have not used dispersing agents to minimize slime coating effects of clays. In this study, agglomeration process was applied for recovery of fine coals from coal washery tailings containing remarkable amount of fine coal. Negative effect of fine clays during recovery was tried to be eliminated by using dispersing agent instead of de-sliming. Although ash reductions over 90 % were achieved, performance remained below expectations in terms of combustible matter recovery. However, this study is a preliminary one. It is considered that more satisfied results will be obtained in the next studies by changing the variables such as solid ratio, oil dosage, dispersant type and dosage.

Multiple Sparse Representations Classification

PubMed Central

Plenge, Esben; Klein, Stefan S.; Niessen, Wiro J.; Meijering, Erik

2015-01-01

Sparse representations classification (SRC) is a powerful technique for pixelwise classification of images and it is increasingly being used for a wide variety of image analysis tasks. The method uses sparse representation and learned redundant dictionaries to classify image pixels. In this empirical study we propose to further leverage the redundancy of the learned dictionaries to achieve a more accurate classifier. In conventional SRC, each image pixel is associated with a small patch surrounding it. Using these patches, a dictionary is trained for each class in a supervised fashion. Commonly, redundant/overcomplete dictionaries are trained and image patches are sparsely represented by a linear combination of only a few of the dictionary elements. Given a set of trained dictionaries, a new patch is sparse coded using each of them, and subsequently assigned to the class whose dictionary yields the minimum residual energy. We propose a generalization of this scheme. The method, which we call multiple sparse representations classification (mSRC), is based on the observation that an overcomplete, class specific dictionary is capable of generating multiple accurate and independent estimates of a patch belonging to the class. So instead of finding a single sparse representation of a patch for each dictionary, we find multiple, and the corresponding residual energies provides an enhanced statistic which is used to improve classification. We demonstrate the efficacy of mSRC for three example applications: pixelwise classification of texture images, lumen segmentation in carotid artery magnetic resonance imaging (MRI), and bifurcation point detection in carotid artery MRI. We compare our method with conventional SRC, K-nearest neighbor, and support vector machine classifiers. The results show that mSRC outperforms SRC and the other reference methods. In addition, we present an extensive evaluation of the effect of the main mSRC parameters: patch size, dictionary size, and sparsity level. PMID:26177106

Steroid receptor coactivator-1 mediates letrozole induced downregulation of postsynaptic protein PSD-95 in the hippocampus of adult female rats.

PubMed

Liu, Mengying; Huangfu, Xuhong; Zhao, Yangang; Zhang, Dongmei; Zhang, Jiqiang

2015-11-01

Hippocampus local estrogen which is converted from androgen that catalyzed by aromatase has been shown to play important roles in the regulation of learning and memory as well as cognition through action on synaptic plasticity, but the underlying mechanisms are poorly understood. Steroid receptor coactivator-1 (SRC-1) is one of the coactivators of steroid nuclear receptors; it is widely distributed in brain areas that related to learning and memory, reproductive regulation, sensory and motor information integration. Previous studies have revealed high levels of SRC-1 immunoreactivities in the hippocampus; it is closely related to the levels of synaptic proteins such as PSD-95 under normal development or gonadectomy, but its exact roles in the regulation of these proteins remains unclear. In this study, we used aromatase inhibitor letrozole in vivo and SRC-1 RNA interference in vitro to investigate whether SRC-1 mediated endogenous estrogen regulation of hippocampal PSD-95. The results revealed that letrozole injection synchronously decreased hippocampal SRC-1 and PSD-95 in a dose-dependant manner. Furthermore, when SRC-1 specific shRNA pool was applied to block the expression of SRC-1 in the primary hippocampal neuron culture, both immunocytochemistry and Western blot revealed that levels of PSD-95 were also decreased significantly. Taking together, these results provided the first evidence that SRC-1 mediated endogenous estrogen regulation of hippocampal synaptic plasticity by targeting the expression of synaptic protein PSD-95. Additionally, since letrozole is frequently used to treat estrogen-sensitive breast cancer, the above results also indicate its potential side effects in clinical administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

All-trans-retinoic acid activates the pro-invasive Src-YAP-Interleukin 6 axis in triple-negative MDA-MB-231 breast cancer cells while cerivastatin reverses this action.

PubMed

Mezquita, Belén; Mezquita, Pau; Pau, Montserrat; Gasa, Laura; Navarro, Lourdes; Samitier, Mireia; Pons, Miquel; Mezquita, Cristóbal

2018-05-04

All-trans-retinoic acid (RA), the active metabolite of vitamin A, can reduce the malignant phenotype in some types of cancer and paradoxically also can promote cancer growth and invasion in others. For instance, it has been reported that RA induces tumor suppression in tumor xenografts of MDA-MB-468 breast cancer cells while increasing tumor growth and metastases in xenografts of MDA-MB-231 breast cancer cells. The signaling pathways involved in the pro-invasive action of retinoic acid remain mostly unknown. We show here that RA activates the pro-invasive axis Src-YAP-Interleukin 6 (Src-YAP-IL6) in triple negative MDA-MB-231 breast cancer cells, yielding to increased invasion of these cells. On the contrary, RA inhibits the Src-YAP-IL6 axis of triple-negative MDA-MB-468 cells, which results in decreased invasion phenotype. In both types of cells, inhibition of the Src-YAP-IL6 axis by the Src inhibitor PP2 drastically reduces migration and invasion. Src inhibition also downregulates the expression of a pro-invasive isoform of VEGFR1 in MDA-MB-231 breast cancer cells. Furthermore, interference of YAP nuclear translocation using the statin cerivastatin reverses the upregulation of Interleukin 6 (IL-6) and the pro-invasive effect of RA on MDA-MB-231 breast cancer cells and also decreases invasion and viability of MDA-MB-468 breast cancer cells. These results altogether suggest that RA induces pro-invasive or anti-invasive actions in two triple-negative breast cancer cell lines due to its ability to activate or inhibit the Src-YAP-IL6 axis in different cancer cells. The pro-invasive effect of RA can be reversed by the statin cerivastatin.

Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

PubMed

Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

2016-07-01

Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells.

PubMed

Filosto, Simone; Baston, David S; Chung, Samuel; Becker, Cathleen R; Goldkorn, Tzipora

2013-08-01

The EGF receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung carcinoma (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKI) such as erlotinib. However, despite the efficacy observed in patients with NSCLC harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in patients with NSCLC who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, we showed that NSCLC cells harboring either wild-type (WT) EGFR or oncogenic mutant (MT) L858R EGFR become resistant to the effects of TKIs when exposed to cigarette smoke, evidenced by their autophosphorylation and prolonged downstream signaling. Here, we present Src as a target mediating cigarette smoke-induced resistance to TKIs in both WT EGFR- and L858R MT EGFR-expressing NSCLC cells. First, we show that cigarette smoke exposure of A549 cells leads to time-dependent activation of Src, which then abnormally binds to the WT EGFR causing TKI resistance, contrasting previous observations of constitutive binding between inactive Src and TKI-sensitive L858R MT EGFR. Next, we show that Src inhibition restores TKI sensitivity in cigarette smoke-exposed NSCLC cells, preventing EGFR autophosphorylation in the presence of erlotinib. Furthermore, we show that overexpression of a dominant-negative Src (Y527F/K295R) restores TKI sensitivity to A549 exposed to cigarette smoke. Importantly, the TKI resistance that emerges even in cigarette smoke-exposed L858R EGFR-expressing NSCLC cells could be eliminated with Src inhibition. Together, these findings offer new rationale for using Src inhibitors for treating TKI-resistant NSCLC commonly observed in smokers.

Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells

PubMed Central

Filosto, Simone; Baston, David S.; Chung, Samuel; Becker, Cathleen R.; Goldkorn, Tzipora

2015-01-01

The EGF Receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung cancer (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKIs) such as Erlotinib. However, despite the efficacy observed in NSCLC patients harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in NSCLC patients who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, we showed that NSCLC cells harboring either wild-type (WT) EGFR or oncogenic mutant (MT) L858R EGFR become resistant to the effects of TKIs when exposed to cigarette smoke (CS), evidenced by their auto-phosphorylation and prolonged downstream signaling. Here, we present Src as a target mediating CS-induced resistance to TKIs in both WT EGFR and L858R MT EGFR expressing NSCLC cells. First, we show that CS exposure of A549 cells leads to time-dependent activation of Src which then abnormally binds to the WT EGFR causing TKI resistance, contrasting previous observations of constitutive binding between inactive Src and TKI-sensitive L858R MT EGFR. Next, we demonstrate that Src inhibition restores TKI sensitivity in CS-exposed NSCLC cells, preventing EGFR auto-phosphorylation in the presence of Erlotinib. Furthermore, we show that over-expression of a dominant-negative Src (Y527F/K295R) restores TKI sensitivity to A549 exposed to CS. Importantly, the TKI resistance that emerges even in CS-exposed L858R EGFR expressing NSCLC cells could be eliminated with Src inhibition. Together, these findings offer new rationale for using Src inhibitors for treating TKI-resistant NSCLC commonly observed in smokers. PMID:23686837

A cell-penetrating peptide based on the interaction between c-Src and connexin43 reverses glioma stem cell phenotype

PubMed Central

Gangoso, E; Thirant, C; Chneiweiss, H; Medina, J M; Tabernero, A

2014-01-01

Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is downregulated in malignant gliomas. These tumors are composed of a heterogeneous population of cells that include many with stem-cell-like properties, called glioma stem cells (GSCs), which are highly tumorigenic and lack Cx43 expression. Interestingly, restoring Cx43 reverses GSC phenotype and consequently reduces their tumorigenicity. In this study, we investigated the mechanism by which Cx43 exerts its antitumorigenic effects on GSCs. We have focused on the tyrosine kinase c-Src, which interacts with the intracellular carboxy tail of Cx43. We found that Cx43 regulates c-Src activity and proliferation in human GSCs expanded in adherent culture. Thus, restoring Cx43 in GSCs inhibited c-Src activity, which in turn promoted the downregulation of the inhibitor of differentiation Id1. Id1 sustains stem cell phenotype as it controls the expression of Sox2, responsible for stem cell self-renewal, and promotes cadherin switching, which has been associated to epithelial–mesenchymal transition. Our results show that both the ectopic expression of Cx43 and the inhibition of c-Src reduced Id1, Sox2 expression and promoted the switch from N- to E-cadherin, suggesting that Cx43, by inhibiting c-Src, downregulates Id1 with the subsequent changes in stem cell phenotype. On the basis of this mechanism, we found that a cell-penetrating peptide, containing the region of Cx43 that interacts with c-Src, mimics the effect of Cx43 on GSC phenotype, confirming the relevance of the interaction between Cx43 and c-Src in the regulation of the malignant phenotype and pinpointing this interaction as a promising therapeutic target. PMID:24457967

Increased risk of kidney damage among Chinese adults with simple renal cyst.

PubMed

Kong, Xianglei; Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Xu, Dongmei

2018-05-04

The presence of simple renal cyst (SRC) has been related to hypertension, the early and long-term allograft function, and aortic disease, but the relationship with kidney damage was still controversial. Accordingly, we conducted a large sample cross-sectional study to explore the association of SRC with indicators of kidney damage among Chinese adults. A total of 42,369 adults (aged 45.8 ± 13.67 years, 70.6% males) who visited the Health Checkup Clinic were consecutively enrolled. SRC was assessed by ultrasonography according to Bosniak category. Multiple regression models were applied to explore the relationships between SRC and indicators of kidney damage [proteinuria (dipstick urine protein ≥ 1+) and decreased estimated glomerular filtration rate (DeGFR) < 60 ml/min/1.73 m 2 ]. Among all participants in the study, the prevalence of SRC was 10.5%. As a categorical outcome, participants with more 1 cyst and with 1 cyst had higher percentage of proteinuria [53 (5.3%) and 93 (2.7%) vs. 596 (1.6%), p < 0.001] and DeGFR [57 (5.7%) and 85 (2.5%) vs. 278 (0.7%), p < 0.001] compared with participants with no cyst. SRC significantly correlated with proteinuria [OR 1.59 (95% CI 1.30-1.95)] and DeGFR [OR 1.97 (95% CI 1.56-2.47)] after adjusting for potential confounders. Furthermore, the results also demonstrated that maximum diameter (per 1 cm increase), bilateral location, and multiple cysts significantly correlated with DeGFR in the multiple logistic regression analysis. The study revealed that SRC significantly correlated with kidney damage and special attention should be paid among Chinese adults with SRC.

Effects of coal contamination on early life history processes of a reef-building coral, Acropora tenuis.

PubMed

Berry, Kathryn L E; Hoogenboom, Mia O; Brinkman, Diane L; Burns, Kathryn A; Negri, Andrew P

2017-01-15

Successful reproduction and larval dispersal are important for the persistence of marine invertebrate populations, and these early life history processes can be sensitive to marine pollution. Coal is emerging as a contaminant of interest due to the proximity of ports and shipping lanes to coral reefs. To assess the potential hazard of this contaminant, gametes, newly developed embryos, larvae and juveniles of the coral Acropora tenuis were exposed to a range of coal leachate, suspended coal, and coal smothering treatments. Fertilisation was the most sensitive reproductive process tested. Embryo survivorship decreased with increasing suspended coal concentrations and exposure duration, effects on larval settlement varied between treatments, while effects on juvenile survivorship were minimal. Leachate exposures had negligible effects on fertilisation and larval settlement. These results indicate that coral recruitment could be affected by spills that produce plumes of suspended coal particles which interact with gametes and embryos soon after spawning. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Low temperature aqueous desulfurization of coal

DOEpatents

Slegeir, W.A.; Healy, F.E.; Sapienza, R.S.

1985-04-18

This invention describes a chemical process for desulfurizing coal, especially adaptable to the treatment of coal-water slurries, at temperatures as low as ambient, comprising treating the coal with aqueous titanous chloride whereby hydrogen sulfide is liberated and the desulfurized coal is separated with the conversion of titanous chloride to titanium oxides.

A Course in Fundamentals of Coal Utilization and Conversion Processes.

ERIC Educational Resources Information Center

Radovic, Ljubisa R.

1985-01-01

Describes the content, objectives, and requirements for a one-semester (30 20-hour sessions) graduate engineering course at the University of Concepcion, Chile. Major course topics include: structure and properties of coal; coal pyrolysis and carbonization; coal liquefaction; coal combustion and gasification; and economic and environmental…

Low temperature aqueous desulfurization of coal

DOEpatents

Slegeir, William A.; Healy, Francis E.; Sapienza, Richard S.

1985-01-01

This invention describes a chemical process for desulfurizing coal, especially adaptable to the treatment of coal-water slurries, at temperatures as low as ambient, comprising treating the coal with aqueous titanous chloride whereby hydrogen sulfide is liberated and the desulfurized coal is separated with the conversion of titanous chloride to titanium oxides.

Aladdin: Transforming science at SRC

NASA Astrophysics Data System (ADS)

Bisognano, J.; Bissen, M.; Green, M.; Jacobs, K.; Moore, C.; Olson, E.; Severson, M.; Wehlitz, R.

2011-09-01

The Synchrotron Radiation Center (SRC) is dedicated to enabling of innovative research using IR, ultraviolet, and soft X-ray synchrotron radiation. It delivers beam time with high reliability (99%) and continues to improve the Aladdin storage ring complex. A lower emittance tuning has been commissioned to support a microfocus capability. SRC successfully installed an APPLE II undulator providing elliptically polarized light with lattice compensation for flexible scanning. Installation of a new IR beamline at SRC is providing synchrotron chemical imaging with unprecedented structural and chemical information, simultaneously. In addition, SRC has established a strong education and outreach program to bring the knowledge and power of light source science to a wider national community. It is moving forward into the future by developing a new micro focus beamline producing a diffraction-limited focus of about 500 nm at 22 eV, proposing an additional diffraction-limited chemical imaging beamline, and advancing the Wisconsin Free Electron Laser (WiFEL) concept.

CHLAMYDIA TRACHOMATIS TARP IS PHOSPHORYLATED BY SRC FAMILY TYROSINE KINASES

PubMed Central

Jewett, Travis J.; Dooley, Cheryl A.; Mead, David J.; Hackstadt, Ted

2008-01-01

The translocated actin recruiting phosphoprotein (Tarp) is injected into the cytosol shortly after Chlamydia trachomatis attachment to a target cell and subsequently phosphorylated by an unidentified tyrosine kinase. A role for Tarp phosphorylation in bacterial entry is unknown. In this study, recombinant C. trachomatis Tarp was employed to identify the host cell kinase(s) required for phosphorylation. Each tyrosine rich repeat of L2 Tarp harbors a sequence similar to a Src and Abl kinase consensus target. Furthermore, purified p60-src, Yes, Fyn, and Abl kinases were able to phosphorylate Tarp. Mutagenesis of potential tyrosines within a single tyrosine rich repeat peptide indicated that both Src and Abl kinases phosphorylate the same residues suggesting that C. trachomatis Tarp may serve as a substrate for multiple host cell kinases. Surprisingly, chemical inhibition of Src and Abl kinases prevented Tarp phosphorylation in culture and had no measurable effect on bacterial entry into host cells. PMID:18442471

Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angrist, M.; Chakravarti, A.; Wells, D.E.

1995-12-10

Molecules containing Src-homology 2 (SH2) and Src-homology 3 (SH3) domains are critical components of signal transduction pathways that serve to relay signals originating from the cell surface to the interior of the cell. Src-like adapter protein (SLAP) is a recently described adapter protein that binds activated the Eck receptor protein-tyrosine kinase. Although SLAP bears a striking homology to the SH3 and SH2 domains of the Src family of nonreceptor tyrosine kinases, it does not contain a tyrosine kinase catalytic domain. In this report, the Slap gene was mapped by linkage analysis to mouse chromosome 15, while its putative human homologmore » (SLA) was identified and mapped to human 8q22.3-qter using a panel of somatic cell hybrids. 10 refs., 2 figs.« less

The effects of finite-rate reactions at the gas/surface interface in support of thermal protection system design

NASA Astrophysics Data System (ADS)

Beerman, Adam Farrell

2011-12-01

Gas-surface modeling is dependent on material type and atmospheric reentry conditions. Lower molecular collisions at the low pressure trajectories make it more likely for occurrences of nonequilibrium, or finite-rate, reactions. Equilibrium is often assumed at the surface of a material as it is a subset of nonequilibrium and is easier to compute, though it can lead to overly conservative predictions. A case where a low density material experiences a low pressure trajectory and designed for equilibrium is the Stardust Return Capsule (SRC) with the Phenolic Impregnated Carbon Ablator (PICA) as its heatshield. Post-flight analysis of the recession on the SRC found that the prediction from the equilibrium model can be more than 50% larger than the measured recession. The Modified Park Model was chosen as the finite-rate model as it contains simple four reactions (oxidation, sublimation, and nitridation) and has been previously used to study individual points of the SRC trajectory. The Modified Park Model cannot model equilibrium so a model BFIAT was developed that allows finite-rate reactions to be applied to the surface for a certain length of time. Finite-rate sublimation was determined to be reaction of importance in the Park Model for SRC-like conditions. The predicted recession on the SRC heatshield experienced a reduction in its overprediction; the finite-rate predictions fall with the measurement error of the recession at three points on the heatshield. The recession reduction was driven by a significant reduction in char formation. There was little change in the pyrolysis gas rate. The finite-rate model was also applied to simulations of various arc-jet tests that covered a range of heating conditions on the surface of the PICA material. Comparison to this experimental data further showed the role of finite-rate reactions and sublimation in the Park Model and conditions that favor the nonequilibrium assumption (heating over 1000 W/cm2). For the emerging PICA material, used for the Mars Science Laboratory and one of two material choices for the Crew Exploration Vehicle, and SRC-like trajectories, a finite-rate model was developed such that the more robust nonequilibrium assumption can be applied to design processes to reduce heatshield mass.

The use of ethanol to remove sulfur from coal. Final report, September 1991--December 1992; Revision

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savage, R.L.; Lazarov, L.K.; Prudich, M.E.

1994-03-10

The initial technical goal in the project was to develop a chemical method for the cost effective removal of both inorganic and organic sulfur from Ohio coals. Verifying and using a process of reacting ethanol vapors with coal under conditions disclosed in U.S. Patent 4,888,029, the immediate technical objectives were to convert a small scale laborative batch process to a larger scale continuous process which can serve as the basis for commercial development of the technology. This involved getting as much information as possible from small scale batch autoclave or fluid bed laboratory reactors for use in pilot plant studies.more » The laboratory data included material balances on the coal and sulfur, temperature and pressure ranges for the reaction, minimum reaction times at different conditions, the effectiveness of different activators such as oxygen and nitric oxide, the amount and nature of by-products such as sulfur dioxide, hydrogen sulfide and acetaldehyde, the effect of coal particle size on the speed and completeness of the reaction, and the effectiveness of the reaction on different Ohio coals. Because the laboratory experiments using the method disclosed in U.S. 4,888,029 were not successful, the objective for the project was changed to develop a new laboratory process to use ethanol to remove sulfur from coal. Using copper as a catalyst and as an H{sub 2}S scavenger, a new laboratory procedure to use ethanol to remove sulfur from coal has been developed at Ohio University and a patent application covering this process was filed in March, 1993. The process is based on the use of copper as a catalyst for the dehydrogenation of ethanol to produce nascent hydrogen to remove sulfur from the coal and the use of copper as a scavenger to capture the hydrogen sulfide formed from the sulfur removed from coal.« less

Comprehensive evaluation on low-carbon development of coal enterprise groups.

PubMed

Wang, Bang-Jun; Wu, Yan-Fang; Zhao, Jia-Lu

2017-12-19

Scientifically evaluating the level of low-carbon development in terms of theoretical and practical significance is extremely important to coal enterprise groups for implementing national energy-related systems. This assessment can assist in building institutional mechanisms that are conducive for the economic development of coal business cycle and energy conservation as well as promoting the healthy development of coal enterprises to realize coal scientific development and resource utilization. First, by adopting systematic analysis method, this study builds low-carbon development evaluation index system for coal enterprise groups. Second, to determine the weight serving as guideline and criteria of the index, analytic hierarchy process (AHP) is applied using integrated linear weighted sum method to evaluate the level of low-carbon development of coal enterprise groups. Evaluation is also performed by coal enterprise groups, and the process comprises field analysis and evaluation. Finally, industrial policies are proposed regarding the development of low-carbon coal conglomerate strategies and measures. This study aims mainly to guide the low-carbon development of coal enterprise groups, solve the problem of coal mining and the destruction of ecological environment, support the conservation of raw materials and various resources, and achieve the sustainable development of the coal industry.

Process for converting heavy oil deposited on coal to distillable oil in a low severity process

DOEpatents

Ignasiak, Teresa; Strausz, Otto; Ignasiak, Boleslaw; Janiak, Jerzy; Pawlak, Wanda; Szymocha, Kazimierz; Turak, Ali A.

1994-01-01

A process for removing oil from coal fines that have been agglomerated or blended with heavy oil comprises the steps of heating the coal fines to temperatures over 350.degree. C. up to 450.degree. C. in an inert atmosphere, such as steam or nitrogen, to convert some of the heavy oil to lighter, and distilling and collecting the lighter oils. The pressure at which the process is carried out can be from atmospheric to 100 atmospheres. A hydrogen donor can be added to the oil prior to deposition on the coal surface to increase the yield of distillable oil.

Catalytic two-stage coal hydrogenation and hydroconversion process

DOEpatents

MacArthur, James B.; McLean, Joseph B.; Comolli, Alfred G.

1989-01-01

A process for two-stage catalytic hydrogenation and liquefaction of coal to produce increased yields of low-boiling hydrocarbon liquid and gas products. In the process, the particulate coal is slurried with a process-derived liquid solvent and fed at temperature below about 650.degree. F. into a first stage catalytic reaction zone operated at conditions which promote controlled rate liquefaction of the coal, while simultaneously hydrogenating the hydrocarbon recycle oils at conditions favoring hydrogenation reactions. The first stage reactor is maintained at 650.degree.-800.degree. F. temperature, 1000-4000 psig hydrogen partial pressure, and 10-60 lb coal/hr/ft.sup.3 reactor space velocity. The partially hydrogenated material from the first stage reaction zone is passed directly to the close-coupled second stage catalytic reaction zone maintained at a temperature at least about 25.degree. F. higher than for the first stage reactor and within a range of 750.degree.-875.degree. F. temperature for further hydrogenation and thermal hydroconversion reactions. By this process, the coal feed is successively catalytically hydrogenated and hydroconverted at selected conditions, which results in significantly increased yields of desirable low-boiling hydrocarbon liquid products and minimal production of undesirable residuum and unconverted coal and hydrocarbon gases, with use of less energy to obtain the low molecular weight products, while catalyst life is substantially increased.

Novel autophosphorylation sites of Src family kinases regulate kinase activity and SH2 domain-binding capacity.

PubMed

Weir, Marion E; Mann, Jacqueline E; Corwin, Thomas; Fulton, Zachary W; Hao, Jennifer M; Maniscalco, Jeanine F; Kenney, Marie C; Roman Roque, Kristal M; Chapdelaine, Elizabeth F; Stelzl, Ulrich; Deming, Paula B; Ballif, Bryan A; Hinkle, Karen L

2016-04-01

Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the C-terminal site to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. © 2016 Federation of European Biochemical Societies.

Damage evolution analysis of coal samples under cyclic loading based on single-link cluster method

NASA Astrophysics Data System (ADS)

Zhang, Zhibo; Wang, Enyuan; Li, Nan; Li, Xuelong; Wang, Xiaoran; Li, Zhonghui

2018-05-01

In this paper, the acoustic emission (AE) response of coal samples under cyclic loading is measured. The results show that there is good positive relation between AE parameters and stress. The AE signal of coal samples under cyclic loading exhibits an obvious Kaiser Effect. The single-link cluster (SLC) method is applied to analyze the spatial evolution characteristics of AE events and the damage evolution process of coal samples. It is found that a subset scale of the SLC structure becomes smaller and smaller when the number of cyclic loading increases, and there is a negative linear relationship between the subset scale and the degree of damage. The spatial correlation length ξ of an SLC structure is calculated. The results show that ξ fluctuates around a certain value from the second cyclic loading process to the fifth cyclic loading process, but spatial correlation length ξ clearly increases in the sixth loading process. Based on the criterion of microcrack density, the coal sample failure process is the transformation from small-scale damage to large-scale damage, which is the reason for changes in the spatial correlation length. Through a systematic analysis, the SLC method is an effective method to research the damage evolution process of coal samples under cyclic loading, and will provide important reference values for studying coal bursts.

Synthesis and analysis of jet fuel from shale oil and coal syncrudes

NASA Technical Reports Server (NTRS)

Gallagher, J. P.; Collins, T. A.; Nelson, T. J.; Pedersen, M. J.; Robison, M. G.; Wisinski, L. J.

1976-01-01

Thirty-two jet fuel samples of varying properties were produced from shale oil and coal syncrudes, and analyzed to assess their suitability for use. TOSCO II shale oil and H-COAL and COED syncrudes were used as starting materials. The processes used were among those commonly in use in petroleum processing-distillation, hydrogenation and catalytic hydrocracking. The processing conditions required to meet two levels of specifications regarding aromatic, hydrogen, sulfur and nitrogen contents at two yield levels were determined and found to be more demanding than normally required in petroleum processing. Analysis of the samples produced indicated that if the more stringent specifications of 13.5% hydrogen (min.) and 0.02% nitrogen (max.) were met, products similar in properties to conventional jet fuels were obtained. In general, shale oil was easier to process (catalyst deactivation was seen when processing coal syncrudes), consumed less hydrogen and yielded superior products. Based on these considerations, shale oil appears to be preferred to coal as a petroleum substitute for jet fuel production.

Hydration kinetics of cementitious materials composed of red mud and coal gangue

NASA Astrophysics Data System (ADS)

Zhang, Na; Li, Hong-xu; Liu, Xiao-ming

2016-10-01

To elucidate the intrinsic reaction mechanism of cementitious materials composed of red mud and coal gangue (RGC), the hydration kinetics of these cementitious materials at 20°C was investigated on the basis of the Krstulović-Dabić model. An isothermal calorimeter was used to characterize the hydration heat evolution. The results show that the hydration of RGC is controlled by the processes of nucleation and crystal growth (NG), interaction at phase boundaries (I), and diffusion (D) in order, and the pozzolanic reactions of slag and compound-activated red mud-coal gangue are mainly controlled by the I process. Slag accelerates the clinker hydration during NG process, whereas the compound-activated red mud-coal gangue retards the hydration of RGC and the time required for I process increases with increasing dosage of red mud-coal gangue in RGC.

Low-rank coal oil agglomeration

DOEpatents

Knudson, Curtis L.; Timpe, Ronald C.

1991-01-01

A low-rank coal oil agglomeration process. High mineral content, a high ash content subbituminous coals are effectively agglomerated with a bridging oil which is partially water soluble and capable of entering the pore structure, and usually coal derived.

Characteristics of coking coal burnout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, M.; Bailey, J.G.

An attempt was made to clarify the characteristics of coking coal burnout by the morphological analysis of char and fly ash samples. Laboratory-scale combustion testing, simulating an ignition process, was carried out for three kinds of coal (two coking coals and one non-coking coal for reference), and sampled chars were analyzed for size, shape and type by image analysis. The full combustion process was examined in industrial-scale combustion testing for the same kinds of coal. Char sampled at the burner outlet and fly ash at the furnace exit were also analyzed. The difference between the char type, swelling properties, agglomeration,more » anisotropy and carbon burnout were compared at laboratory scale and at industrial scale. As a result, it was found that coking coals produced chars with relatively thicker walls, which mainly impeded char burnout, especially for low volatile coals.« less

Energy and Resource-Saving Sources of Energy in Small Power Engineering of Siberia

NASA Astrophysics Data System (ADS)

Baranova, Marina

2017-11-01

The sustainable development of distant areas of Siberia is associated with the structures of energy demand and supply, the implementation and promotion of the process of environmentally safe restructuring of the energy supply system. It has been established that suspension coal fuels derived from brown coal, coal mining, coal processing wastes can be used as fuel. The results of experimental and industrial boilers on suspension water coal fuel are presented. The designs of vortex combustion chambers of various powers are developed and tested. The possibility of using coal-enrichment wastes and substandard coals for the production of manure-coal fuel briquettes was studied. It is shown that the strength and thermal power characteristics of briquettes depend on the moisture content and degree of metamorphism of the raw materials. The most effective percentage of the solid phase and manure, as a binder, was determined.

Surfactant-Assisted Coal Liquefaction

NASA Technical Reports Server (NTRS)

Hickey, Gregory S.; Sharma, Pramod K.

1993-01-01

Obtaining liquid fuels from coal which are economically competitive with those obtained from petroleum based sources is a significant challenge for the researcher as well as the chemical industry. Presently, the economics of coal liquefaction are not favorable because of relatively intense processing conditions (temperatures of 430 degrees C and pressures of 2200 psig), use of a costly catalyst, and a low quality product slate of relatively high boiling fractions. The economics could be made more favorable by achieving adequate coal conversions at less intense processing conditions and improving the product slate. A study has been carried out to examine the effect of a surfactant in reducing particle agglomeration and improving hydrodynamics in the coal liquefaction reactor to increase coal conversions...

Sulfur compounds in coal

NASA Technical Reports Server (NTRS)

Attar, A.; Corcoran, W. H.

1977-01-01

The literature on the chemical structure of the organic sulfur compounds (or functional groups) in coal is reviewed. Four methods were applied in the literature to study the sulfur compounds in coal: direct spectrometric and chemical analysis, depolymerization in drastic conditions, depolymerization in mild conditions, and studies on simulated coal. The data suggest that most of the organic sulfur in coal is in the form of thiophenic structures and aromatic and aliphatic sulfides. The relative abundance of the sulfur groups in bituminous coal is estimated as 50:30:20%, respectively. The ratio changes during processing and during the chemical analysis. The main effects are the transformation during processing of sulfides to the more stable thiophenic compounds and the elimination of hydrogen sulfide.

Process for blending coal with water immiscible liquid

DOEpatents

Heavin, Leonard J.; King, Edward E.; Milliron, Dennis L.

1982-10-26

A continuous process for blending coal with a water immiscible liquid produces a uniform, pumpable slurry. Pulverized raw feed coal and preferably a coal derived, water immiscible liquid are continuously fed to a blending zone (12 and 18) in which coal particles and liquid are intimately admixed and advanced in substantially plug flow to form a first slurry. The first slurry is withdrawn from the blending zone (12 and 18) and fed to a mixing zone (24) where it is mixed with a hot slurry to form the pumpable slurry. A portion of the pumpable slurry is continuously recycled to the blending zone (12 and 18) for mixing with the feed coal.

75 FR 65377 - Notice of Public Meeting for the National Park Service (NPS) Alaska Region's Subsistence Resource...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

... Resource Commission (SRC) program. SUMMARY: The Gates of the Arctic National Park SRC will meet to develop.... Gates of the Arctic National Park SRC Meeting Date and Location: The Gates of the Arctic National Park... meeting may end early if all business is completed. For Further Information On the Gates of the Arctic...

76 FR 1458 - Public Meeting for the National Park Service Alaska Region's Subsistence Resource Commission (SRC...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-10

... Plan Update. c. Subsistence Uses of Horns, Antlers, Bones and Plants EA Update. 13. New Business. 14... guarantee that we will be able to do so. Wrangell-St. Elias National Park SRC Meeting Date and Location: The... if all business is completed. For Further Information on the Gates of the Arctic National Park SRC...

ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion

PubMed Central

Long, Weiwen; Foulds, Charles E.; Qin, Jun; Liu, Jian; Ding, Chen; Lonard, David M.; Solis, Luisa M.; Wistuba, Ignacio I.; Qin, Jun; Tsai, Sophia Y.; Tsai, Ming-Jer; O’Malley, Bert W.

2012-01-01

In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the regulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progression. Here, we report that ERK3 interacted with and phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity in lung cancer cells. Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to invade and form tumors in the lung in a xenograft mouse model. In addition, ERK3 was found to be highly upregulated in human lung carcinomas. Our study identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylation. As such, ERK3 protein kinase may be an attractive target for therapeutic treatment of invasive lung cancer. PMID:22505454

Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer

PubMed Central

Montagner, Alexandra; Delgado, Maria B; Tallichet-Blanc, Corinne; Chan, Jeremy S K; Sng, Ming K; Mottaz, Hélène; Degueurce, Gwendoline; Lippi, Yannick; Moret, Catherine; Baruchet, Michael; Antsiferova, Maria; Werner, Sabine; Hohl, Daniel; Al Saati, Talal; Farmer, Pierre J; Tan, Nguan S; Michalik, Liliane; Wahli, Walter

2014-01-01

Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers. PMID:24203162

Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function

PubMed Central

Ammer, Amanda Gatesman; Kelley, Laura C.; Hayes, Karen E.; Evans, Jason V.; Lopez-Skinner, Lesly Ann; Martin, Karen H.; Frederick, Barbara; Rothschild, Brian L.; Raben, David; Elvin, Paul; Green, Tim P.; Weed, Scott A.

2010-01-01

Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in pre-clinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity. PMID:20505783

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

PubMed

Li, Wei; Xu, Ling; Che, Xiaofang; Li, Haizhou; Zhang, Ye; Song, Na; Wen, Ti; Hou, Kezuo; Yang, Yi; Zhou, Lu; Xin, Xing; Xu, Lu; Zeng, Xue; Shi, Sha; Liu, Yunpeng; Qu, Xiujuan; Teng, Yuee

2018-05-02

Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth. MTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression. Our results suggested that c-Cbl can reverse tamoxifen resistance in HER2-overexpressing breast cancer cells by inhibiting the formation of the ER-c-Src-HER2 complex.

Breaking the limits of structural and mechanical imaging of the heterogeneous structure of coal macerals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, L.; Tselev, A.; Jesse, S.

The correlation between local mechanical (elasto-plastic) and structural (composition) properties of coal presents significant fundamental and practical interest for coal processing and the development of rheological models of coal to coke transformations and for advancing novel approaches. Here, we explore the relationship between the local structural, chemical composition and mechanical properties of coal using a combination of confocal micro-Raman imaging and band excitation atomic force acoustic microscopy (BE-AFAM) for a bituminous coal. This allows high resolution imaging (10s of nm) of mechanical properties of the heterogeneous (banded) architecture of coal and correlating them to the optical gap, average crystallite size,more » the bond-bending disorder of sp2 aromatic double bonds and the defect density. This methodology hence allows the structural and mechanical properties of coal components (lithotypes, microlithotypes, and macerals) to be understood, and related to local chemical structure, potentially allowing for knowledge-based modelling and optimization of coal utilization processes.« less

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Experimental Study of the Influence of the Concentration of Organic Water-Coal Fuel Components on the Integral Ignition Characteristics

NASA Astrophysics Data System (ADS)

Vershinina, K. Yu.; Kuznetsov, G. V.; Strizhak, P. A.

2017-01-01

To enlarge the power raw material base, the processes of stable initiation of combustion of drops of organic watercoal fuels have been investigated. For the main components, we used filter cakes (coal processing waste), anthracite, bituminous and brown coals of brands D and B2, water, and spent machine, turbine, and transformer oils. We have established the influence of concentrations of components on the minimum (limiting) ignition temperatures of organic water-coal fuels and the ignition delay times of drops of fuel components with initial sizes of 0.25-1.5 mm. Investigations were carried out for oxidizer temperatures of 600-1100 K and its velocities of 0.5-5 m/s characteristic of units, aggregates, and large and small power plants. We have determined the characteristic differences of organic water-coal fuel from water-coal fuel and the close laws of the investigated processes for these fuels.

The experimental research on response characteristics of coal samples under the uniaxial loading process

NASA Astrophysics Data System (ADS)

Jia, Bing; Wei, Jian-Ping; Wen, Zhi-Hui; Wang, Yun-Gang; Jia, Lin-Xing

2017-11-01

In order to study the response characteristics of infrasound in coal samples under the uniaxial loading process, coal samples were collected from GengCun mine. Coal rock stress loading device, acoustic emission tested system and infrasound tested system were used to test the infrasonic signal and acoustic emission signal under uniaxial loading process. The tested results were analyzed by the methods of wavelet filter, threshold denoise, time-frequency analysis and so on. The results showed that in the loading process, the change of the infrasonic wave displayed the characteristics of stage, and it could be divided into three stages: initial stage with a certain amount infrasound events, middle stage with few infrasound events, and late stage gradual decrease. It had a good consistency with changing characteristics of acoustic emission. At the same time, the frequency of infrasound was very low. It can propagate over a very long distance with little attenuation, and the characteristics of the infrasound before the destruction of the coal samples were obvious. A method of using the infrasound characteristics to predict the destruction of coal samples was proposed. This is of great significance to guide the prediction of geological hazards in coal mines.

Method for processing coal-enrichment waste with solid and volatile fuel inclusions

NASA Astrophysics Data System (ADS)

Khasanova, A. V.; Zhirgalova, T. B.; Osintsev, K. V.

2017-10-01

The method relates to the field of industrial heat and power engineering. It can be used in coal preparation plants for processing coal waste. This new way is realized to produce a loose ash residue directed to the production of silicate products and fuel gas in rotary kilns. The proposed method is associated with industrial processing of brown coal beneficiation waste. Waste is obtained by flotation separation of rock particles up to 13 mm in size from coal particles. They have in their composition both solid and volatile fuel inclusions (components). Due to the high humidity and significant rock content, low heat of combustion, these wastes are not used on energy boilers, they are stored in dumps polluting the environment.

The direct liquefaction proof of concept program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comolli, A.G.; Lee, L.K.; Pradhan, V.R.

1995-12-31

The goal of the Proof of Concept (POC) Program is to develop Direct Coal Liquefaction and associated transitional technologies towards commercial readiness for economically producing premium liquid fuels from coal in an environmentally acceptable manner. The program focuses on developing the two-stage liquefaction (TSL) process by utilizing geographically strategic feedstocks, commercially feasible catalysts, new prototype equipment, and testing co-processing or alternate feedstocks and improved process configurations. Other high priority objectives include dispersed catalyst studies, demonstrating low rank coal liquefaction without solids deposition, improving distillate yields on a unit reactor volume basis, demonstrating ebullated bed operations while obtaining scale-up data, demonstratingmore » optimum catalyst consumption using new concepts (e.g. regeneration, cascading), producing premium products through on-line hydrotreating, demonstrating improved hydrogen utilization for low rank coals using novel heteroatom removal methods, defining and demonstrating two-stage product properties for upgrading; demonstrating efficient and economic solid separation methods, examining the merits of integrated coal cleaning, demonstrating co-processing, studying interactions between the preheater and first and second-stage reactors, improving process operability by testing and incorporating advanced equipment and instrumentation, and demonstrating operation with alternate coal feedstocks. During the past two years major PDU Proof of Concept runs were completed. POC-1 with Illinois No. 6 coal and POC-2 with Black Thunder sub-bituminous coal. Results from these operations are continuing under review and the products are being further refined and upgraded. This paper will update the results from these operations and discuss future plans for the POC program.« less

Similar simulation study on the characteristics of the electric potential response to coal mining

NASA Astrophysics Data System (ADS)

Niu, Yue; Li, Zhonghui; Kong, Biao; Wang, Enyuan; Lou, Quan; Qiu, Liming; Kong, Xiangguo; Wang, Jiali; Dong, Mingfu; Li, Baolin

2018-02-01

An electric potential (EP) can be generated during the failure process of coal and rock. In this article, a similar physical model of coal rock was built and the characteristics of the EP responding to the process of coal mining were studied. The results showed that, at the early mining stage, the structure of coal rock strata were stable in the simulation model, the support stress of overlying coal rock strata was low and the maximum subsidence was little, while the EP change was less. With the advancement of the working face, the support stress of the overlying coal rock strata in the mined-out area changed dramatically, the maximum subsidence increased constantly, the deformation and destruction were aggravated, and cracks expanded continuously. Meanwhile, the EP response was significant with fluctuation. When significant macro damage appeared in coal rock strata, the EP signal fluctuation was violent. The overlying coal rock strata were influenced by gravity and mining activity. During the mining process, the crack growth and the friction, together with slip between coal and rock particles, resulted in the response of EP. The change in EP was closely related to the damage state and stress distribution of the coal rock strata. EP monitoring has the advantages of accurate reflection and strong anti-interference in the field. Therefore, with further study, an EP monitoring method could be applied for monitoring and early warning of coal and rock dynamic disaster, and risk evaluation in the future. The strength of the EP and its fluctuation degree could serve as the key discrimination indexes.

An Investigation Of The Effect Of Particle Size On Oxidation Of Pyrites In Coal.

NASA Astrophysics Data System (ADS)

Chan, Paul K.; Frost, David C.

1986-08-01

We have used X-ray photoelectron spectroscopy (XPS) to study the variation of surface pyrite density with coal particle size (53 4m - 250 4μm). We also detect and monitor pyrite oxidation to sulfate, an important process influencing the surface-dependency of coal-cleansing methods such as flotation. It is very likely that as coal is crushed as part of the processes employed to rid it of prospective pollutants one eventually reaches a pyrite size which may be called "characteristic". It is this parameter that we examine here. Good correlations are established between (i) the liberation of pyrite and particle size, (ii) surface pyrite/sulfate ratio, and (iii) oxidized and non-oxidized sulfur in a typical Canadian coal. For "non-oxidized", or "fresh" coal, the dispersion of pyrite on the coal surface is inversely proportional to coal particle radius, and the tangents of this curve intersect at a particular particle size (106±5 4μm). Although, for the oxidized coal, the appearance of the curves depend on oxidation time intervals at low temperature with humid air, there is an "optimum" particle size which exhibits maximum surface pyrite. Notably, this "optimum" size corresponds to the tangent's intersection for the non-oxidized coal, and hence the "characteristic" size of constituent pyrite. This should allow prediction of pyrite occurrence, a parameter of paramount interest in coal processing and cleaning technology. Coal surface characterization obtained by XPS after various conditioning steps and during flotation, allow both a functional analysis via the study of chemical shifts and a semi-quantitative analysis based on relative intensity measurements.

Optimization of enhanced coal-bed methane recovery using numerical simulation

NASA Astrophysics Data System (ADS)

Perera, M. S. A.; Ranjith, P. G.; Ranathunga, A. S.; Koay, A. Y. J.; Zhao, J.; Choi, S. K.

2015-02-01

Although the enhanced coal-bed methane (ECBM) recovery process is one of the potential coal bed methane production enhancement techniques, the effectiveness of the process is greatly dependent on the seam and the injecting gas properties. This study has therefore aimed to obtain a comprehensive knowledge of all possible major ECBM process-enhancing techniques by developing a novel 3D numerical model by considering a typical coal seam using the COMET 3 reservoir simulator. Interestingly, according to the results of the model, the generally accepted concept that there is greater CBM (coal-bed methane) production enhancement from CO2 injection, compared to the traditional water removal technique, is true only for high CO2 injection pressures. Generally, the ECBM process can be accelerated by using increased CO2 injection pressures and reduced temperatures, which are mainly related to the coal seam pore space expansion and reduced CO2 adsorption capacity, respectively. The model shows the negative influences of increased coal seam depth and moisture content on ECBM process optimization due to the reduced pore space under these conditions. However, the injection pressure plays a dominant role in the process optimization. Although the addition of a small amount of N2 into the injecting CO2 can greatly enhance the methane production process, the safe N2 percentage in the injection gas should be carefully predetermined as it causes early breakthroughs in CO2 and N2 in the methane production well. An increased number of production wells may not have a significant influence on long-term CH4 production (50 years for the selected coal seam), although it significantly enhances short-term CH4 production (10 years for the selected coal seam). Interestingly, increasing the number of injection and production wells may have a negative influence on CBM production due to the coincidence of pressure contours created by each well and the mixing of injected CO2 with CH4.

Catalysts and process developments for two-stage liquefaction. First quarterly technical progress report No. 52, October 1, 1991--December 31, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronauer, D.C.; Swanson, A.J.; Sajkowski, D.J.

Research under way in this project centers upon developing and evaluating catalysts and process improvements for coal liquefaction in the two-stage, close-coupled catalytic process. As discussed in the previous quarterly report, the feedstock liquefaction studies for the three feedstocks (Black Thunder subbituminous coal, Martin Lake lignite, and Illinois No. 6 coal) were completed. Both Black Thunder coal and Martin Lake lignite gave lighter products than Illinois No. 6 coal at similar process conditions. Severe catalyst deactivation in the first stage was also observed with the Martin Lake lignite run. The first stage catalyst testing program was started (Task 3.2.1). Aftermore » a successful reference run with Illinois No. 6 coal, a high-temperature run with AMOCAT{trademark} 1C was completed, where the results showed that the first stage temperature should be no higher than 820{degrees}F. In addition, several runs were made both with Illinois No. 6 and Black Thunder coals using oil-soluble catalysts, Molyvan L, and molybdenum octoate in one or both stages. Overall, the results look very promising and show that dispersed molybdenum catalysts are good alternatives for Stage 1 or both 1 and 2, especially for Illinois No. 6 coal. In the case of Black Thunder coal, the conversion and yields were good, although the product quality was poorer, however, the use of slurry catalysts is still recommended.« less

Advanced technology applications for second and third generation coal gasification systems. Appendix

NASA Technical Reports Server (NTRS)

Bradford, R.; Hyde, J. D.; Mead, C. W.

1980-01-01

Sixteen coal conversion processes are described and their projected goals listed. Tables show the reactants used, products derived, typical operating data, and properties of the feed coal. A history of the development of each process is included along with a drawing of the chemical reactor used.

A Course in Coal Science and Technology.

ERIC Educational Resources Information Center

Wheelock, T. D.

1978-01-01

This course introduces graduate students and advanced undergraduates to coal science and technology. Topics include: (1) the nature and occurrence of coal, (2) its chemical and physical characteristics, (3) methods of cleaning and preparing coal, and (4) processes for converting coal into clean solid, liquid, and gaseous fuels, as well as coke.…

Organic matter in a coal ball: Peat or coal?

USGS Publications Warehouse

Hatcher, P.G.; Lyons, P.C.; Thompson, C.L.; Brown, F.W.; Maciel, G.E.

1982-01-01

Chemical analyses of morphologically preserved organic matter in a Carboniferous coal ball reveal that the material is coalified to a rank approximately equal to that of the surrounding coal. Hence, the plant tissues in the coal ball were chemically altered by coalification processes and were not preserved as peat. Copyright ?? 1982 AAAS.

Low-rank coal oil agglomeration

DOEpatents

Knudson, C.L.; Timpe, R.C.

1991-07-16

A low-rank coal oil agglomeration process is described. High mineral content, a high ash content subbituminous coals are effectively agglomerated with a bridging oil which is partially water soluble and capable of entering the pore structure, and is usually coal-derived.

Thermal effects from the release of selenium from a coal combustion during high-temperature processing: a review.

PubMed

Hu, Jianjun; Sun, Qiang; He, Huan

2018-05-01

The release of selenium (Se) during coal combustion can have serious impacts on the ecological environment and human health. Therefore, it is very important to study the factors that concern the release of Se from coal combustion. In this paper, the characteristics of the release of Se from coal combustion, pyrolysis, and gasification of different coal species under different conditions are studied. The results show that the amount of released Se increases at higher combustion temperatures. There are obvious increases in the amount of released Se especially in the temperature range of 300 to 800 °C. In addition, more Se is released from the coal gasification than coal combustion process, but more Se is released from coal combustion than pyrolysis. The type of coal, rate of heating, type of mineral ions, and combustion atmosphere have different effects on the released percentage of Se. Therefore, having a good understanding of the factors that surround the release of Se during coal combustion, and then establishing the combustion conditions can reduce the impacts of this toxic element to humans and the environment.

Longitudinal Brain Magnetic Resonance Imaging CO2 Stress Testing in Individual Adolescent Sports-Related Concussion Patients: A Pilot Study.

PubMed

Mutch, W Alan C; Ellis, Michael J; Ryner, Lawrence N; Morissette, Marc P; Pries, Philip J; Dufault, Brenden; Essig, Marco; Mikulis, David J; Duffin, James; Fisher, Joseph A

2016-01-01

Advanced neuroimaging studies in concussion have been limited to detecting group differences between concussion patients and healthy controls. In this small pilot study, we used brain magnetic resonance imaging (MRI) CO2 stress testing to longitudinally assess cerebrovascular responsiveness (CVR) in individual sports-related concussion (SRC) patients. Six SRC patients (three males and three females; mean age = 15.7, range = 15-17 years) underwent longitudinal brain MRI CO2 stress testing using blood oxygen level-dependent (BOLD) MRI and model-based prospective end-tidal CO2 targeting under isoxic conditions. First-level and second-level comparisons were undertaken using statistical parametric mapping (SPM) to score the scans and compare them to an atlas of 24 healthy control subjects. All tests were well tolerated and without any serious adverse events. Anatomical MRI was normal in all study participants. The CO2 stimulus was consistent between the SRC patients and control subjects and within SRC patients across the longitudinal study. Individual SRC patients demonstrated both quantitative and qualitative patient-specific alterations in CVR (p < 0.005) that correlated strongly with clinical findings, and that persisted beyond clinical recovery. Standardized brain MRI CO2 stress testing is capable of providing a longitudinal assessment of CVR in individual SRC patients. Consequently, larger prospective studies are needed to examine the utility of brain MRI CO2 stress testing as a clinical tool to help guide the evaluation, classification, and longitudinal management of SRC patients.

Accuracy of Monte Carlo photon transport simulation in characterizing brachytherapy dosimeter energy-response artefacts

NASA Astrophysics Data System (ADS)

Das, R. K.; Li, Z.; Perera, H.; Williamson, J. F.

1996-06-01

Practical dosimeters in brachytherapy, such as thermoluminescent dosimeters (TLD) and diodes, are usually calibrated against low-energy megavoltage beams. To measure absolute dose rate near a brachytherapy source, it is necessary to establish the energy response of the detector relative to that of the calibration energy. The purpose of this paper is to assess the accuracy of Monte Carlo photon transport (MCPT) simulation in modelling the absolute detector response as a function of detector geometry and photon energy. We have exposed two different sizes of TLD-100 (LiF chips) and p-type silicon diode detectors to calibrated , HDR source and superficial x-ray beams. For the Scanditronix electron-field diode, the relative detector response, defined as the measured detector readings per measured unit of air kerma, varied from (40 kVp beam) to ( beam). Similarly for the large and small chips the same quantity varied from and , respectively. Monte Carlo simulation was used to calculate the absorbed dose to the active volume of the detector per unit air kerma. If the Monte Carlo simulation is accurate, then the absolute detector response, which is defined as the measured detector reading per unit dose absorbed by the active detector volume, and is calculated by Monte Carlo simulation, should be a constant. For the diode, the absolute response is . For TLDs of size the absolute response is and for TLDs of it is . From the above results we can conclude that the absolute response function of detectors (TLDs and diodes) is directly proportional to absorbed dose by the active volume of the detector and is independent of beam quality.

The src-family protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation.

PubMed Central

Möhn, H; Le Cabec, V; Fischer, S; Maridonneau-Parini, I

1995-01-01

The src-family protein-tyrosine kinase p59hck is mainly expressed in neutrophils; however, its functional role in these cells is unknown. Several other src-family members are localized on secretory vesicles and have been proposed to regulate intracellular traffic. We have established here the subcellular localization of p59hck in human neutrophils. Immunoblotting of subcellular fractions showed that approx. 60% of the p59hck per cell is localized on the secretory granules; the other 40% is distributed equally between non-granular membranes and the cytosol. Immunofluorescence of neutrophils and HL60 cells suggests that the p59hck-positive granules are azurophil granules. Granular p59hck is highly susceptible to degradation by an azurophil-granule proteinase. Different forms of p59hck occur in the three subcellular compartments: a 61 kDa form is mainly found in the granules, a 59 kDa form is predominant in the non-granular membranes, whereas cytosolic p59hck migrates as a doublet at 63 kDa. During the process of phagocytosis-linked degranulation, induced by serum-opsonized zymosan in neutrophils or HL60 cells, granular p59hck translocates towards the phagosome. The subcellular localization of p59hck suggests that the enzyme could be involved in the regulation of the degranulation process. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7626033

Process for hydrogenating coal and coal solvents

DOEpatents

Tarrer, Arthur R.; Shridharani, Ketan G.

1983-01-01

A novel process is described for the hydrogenation of coal by the hydrogenation of a solvent for the coal in which the hydrogenation of the coal solvent is conducted in the presence of a solvent hydrogenation catalyst of increased activity, wherein the hydrogenation catalyst is produced by reacting ferric oxide with hydrogen sulfide at a temperature range of 260.degree. C. to 315.degree. C. in an inert atmosphere to produce an iron sulfide hydrogenation catalyst for the solvent. Optimally, the reaction temperature is 275.degree. C. Alternately, the reaction can be conducted in a hydrogen atmosphere at 350.degree. C.

Assessment of Advanced Coal Gasification Processes

NASA Technical Reports Server (NTRS)

McCarthy, John; Ferrall, Joseph; Charng, Thomas; Houseman, John

1981-01-01

This report represents a technical assessment of the following advanced coal gasification processes: AVCO High Throughput Gasification (HTG) Process; Bell Single-Stage High Mass Flux (HMF) Process; Cities Service/Rockwell (CS/R) Hydrogasification Process; Exxon Catalytic Coal Gasification (CCG) Process. Each process is evaluated for its potential to produce SNG from a bituminous coal. In addition to identifying the new technology these processes represent, key similarities/differences, strengths/weaknesses, and potential improvements to each process are identified. The AVCO HTG and the Bell HMF gasifiers share similarities with respect to: short residence time (SRT), high throughput rate, slagging and syngas as the initial raw product gas. The CS/R Hydrogasifier is also SRT but is non-slagging and produces a raw gas high in methane content. The Exxon CCG gasifier is a long residence time, catalytic, fluidbed reactor producing all of the raw product methane in the gasifier. The report makes the following assessments: 1) while each process has significant potential as coal gasifiers, the CS/R and Exxon processes are better suited for SNG production; 2) the Exxon process is the closest to a commercial level for near-term SNG production; and 3) the SRT processes require significant development including scale-up and turndown demonstration, char processing and/or utilization demonstration, and reactor control and safety features development.

Jet fuels from synthetic crudes

NASA Technical Reports Server (NTRS)

Antoine, A. C.; Gallagher, J. P.

1977-01-01

An investigation was conducted to determine the technical problems in the conversion of a significant portion of a barrel of either a shale oil or a coal synthetic crude oil into a suitable aviation turbine fuel. Three syncrudes were used, one from shale and two from coal, chosen as representative of typical crudes from future commercial production. The material was used to produce jet fuels of varying specifications by distillation, hydrotreating, and hydrocracking. Attention is given to process requirements, hydrotreating process conditions, the methods used to analyze the final products, the conditions for shale oil processing, and the coal liquid processing conditions. The results of the investigation show that jet fuels of defined specifications can be made from oil shale and coal syncrudes using readily available commercial processes.

Using coal inside California for electric power

NASA Technical Reports Server (NTRS)

Moore, J. B.

1978-01-01

In a detailed analysis performed at Southern California Edison on a wide variety of technologies, the direct combustion of coal and medium BTU gas from coal were ranked just below nuclear power for future nonpetroleum based electric power generation. As a result, engineering studies were performed for demonstration projects for the direct combustion of coal and medium BTU gas from coal. Graphs are presented for power demand, and power cost. Direct coal combustion and coal gasification processes are presented.

Competitiveness and potentials of UCG-CCS on the European energy market

NASA Astrophysics Data System (ADS)

Kempka, T.; Nakaten, N.; Schlüter, R.; Fernandez-Steeger, T.; Azzam, R.

2009-04-01

The world-wide coal reserves can satisfy the world's primary energy demand for several hundred years. However, deep coal deposits with seams of low thickness and structural complexity do currently not allow an economic exploitation of many deposits. Here, underground coal gasification (UCG) can offer an economical approach for coal extraction. The intended overall process relies on coal deposit exploitation using directed drillings located at the coal seam base and the subsequent in situ coal conversion into a synthesis gas. The resulting synthesis gas is used for electricity generation in a combined cycle plant at the surface. A reduction of the CO2 emissions resulting from the combined process is realized by subsequent CO2 capture and its injection into the previously gasified coal seams. The scope of the present study was the investigation of UCG-CCS competitiveness on the European energy market and the determination of the impacting factors. For that purpose, a modular model for calculation of UCG-CCS electricity generation costs was implemented and adapted to the most relevant process parameters. Furthermore, the range of energy supply coverage was estimated based on different German energy generation scenarios.

Free radical reaction characteristics of coal low-temperature oxidation and its inhibition method.

PubMed

Li, Zenghua; Kong, Biao; Wei, Aizhu; Yang, Yongliang; Zhou, Yinbo; Zhang, Lanzhun

2016-12-01

Study on the mechanism of coal spontaneous combustion is significant for controlling fire disasters due to coal spontaneous combustion. The free radical reactions can explain the chemical process of coal at low-temperature oxidation. Electron spin resonance (ESR) spectroscopy was used to measure the change rules of the different sorts and different granularity of coal directly; ESR spectroscopy chart of free radicals following the changes of temperatures was compared by the coal samples applying air and blowing nitrogen, original coal samples, dry coal samples, and demineralized coal samples. The fragmentation process was the key factor of producing and initiating free radical reactions. Oxygen, moisture, and mineral accelerated the free radical reactions. Combination of the free radical reaction mechanism, the mechanical fragmentation leaded to the elevated CO concentration, fracturing of coal pillar was more prone to spontaneous combustion, and spontaneous combustion in goaf accounted for a large proportion of the fire in the mine were explained. The method of added diphenylamine can inhibit the self-oxidation of coal effectively, the action mechanism of diphenylamine was analyzed by free radical chain reaction, and this research can offer new method for the development of new flame retardant.

Gas processing handbook

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1982-04-01

Brief details are given of processes including: BGC-Lurgi slagging gasification, COGAS, Exxon catalytic coal gasification, FW-Stoic 2-stage, GI two stage, HYGAS, Koppers-Totzek, Lurgi pressure gasification, Saarberg-Otto, Shell, Texaco, U-Gas, W-D.IGI, Wellman-Galusha, Westinghouse, and Winkler coal gasification processes; the Rectisol process; the Catacarb and the Benfield processes for removing CO/SUB/2, H/SUB/2s and COS from gases produced by the partial oxidation of coal; the selectamine DD, Selexol solvent, and Sulfinol gas cleaning processes; the sulphur-tolerant shift (SSK) process; and the Super-meth process for the production of high-Btu gas from synthesis gas.

Process for treating moisture laden coal fines

DOEpatents

Davis, Burl E.; Henry, Raymond M.; Trivett, Gordon S.; Albaugh, Edgar W.

1993-01-01

A process is provided for making a free flowing granular product from moisture laden caked coal fines, such as wet cake, by mixing a water immiscible substance, such as oil, with the caked coal, preferably under low shear forces for a period of time sufficient to produce a plurality of free flowing granules. Each granule is preferably comprised of a dry appearing admixture of one or more coal particle, 2-50% by weight water and the water immiscible substance.

The prostaglandin receptor EP2 activates multiple signaling pathways and β-arrestin1 complex formation during mouse skin papilloma development

PubMed Central

Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S.; Okada, Manabu; Langenbach, Robert

2009-01-01

Prostaglandin E2 (PGE2) is elevated in many tumor types, but PGE2's contributions to tumor growth are largely unknown. To investigate PGE2's roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors—cyclic adenosine 3′,5′-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2—were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE2 production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3′,5′-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2−/− mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR–β-arrestin–Src complex. Indeed, immunoprecipitation of β-arrestin1 or p-Src indicated the presence of an EP2–β-arrestin1–p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with β-arrestin1 and Src that contributed to signaling and/or EP2 desensitization. PMID:19587094

Magnetic fields from domestic appliances in the UK

NASA Astrophysics Data System (ADS)

Preece, A. W.; Kaune, W.; Grainger, P.; Preece, S.; Golding, J.

1997-01-01

In a survey of 50 UK homes the 50 Hz fundamental and harmonic magnetic fields generated by 806 domestic appliances found in the homes, and used regularly by mothers, were measured. Measurements were made in the direction of most likely access, and from the surface of the appliances. Mothers completed a questionnaire on the use of appliances and were monitored for 24 h so that acquired exposure could be compared with the measured ambient fields in the home. Appliances were measured at standard distances and an algorithm was used to calculate fields at 100 and 50 cm to remove room background contributions. A few appliances generated fields in excess of at 1 m: microwave cookers ; washing machines ; dishwashers ; some electric showers and can openers . Of continuously operating devices, only central heating pumps (), central heating boilers () and fish-tank air pumps () produced significant fields at 0.5 m. There were no obvious ways to group different types of appliances as high- or low-strength sources. Mothers spent on average about 4.5 h per day in the kitchen, where the strongest sources of magnetic field were located.

The auditory comprehension changes over time after sport-related concussion can indicate multisensory processing dysfunctions.

PubMed

Białuńska, Anita; Salvatore, Anthony P

2017-12-01

Although science findings and treatment approaches of a concussion have changed in recent years, there continue to be challenges in understanding the nature of the post-concussion behavior. There is growing a body of evidence that some deficits can be related to an impaired auditory processing. To assess auditory comprehension changes over time following sport-related concussion (SRC) in young athletes. A prospective, repeated measures mixed-design was used. A sample of concussed athletes ( n  = 137) and the control group consisted of age-matched, non-concussed athletes ( n  = 143) were administered Subtest VIII of the Computerized-Revised Token Test (C-RTT). The 88 concussed athletes selected for final analysis (neither previous history of brain injury, neurological, psychiatric problems, nor auditory deficits) were evaluated after injury during three sessions (PC1, PC2, and PC3); controls were tested once. Between- and within-group comparisons using RMANOVA were performed on the C-RTT Efficiency Score (ES). ES of the SRC athletes group improved over consecutive testing sessions ( F  =   14.7, p  <   .001), while post-hoc analysis showed that PC1 results differed from PC2 and PC3 ( ts  ≥ 4.0, ps  < .001), but PC2 and PC3 C-RTT ES did not change statistically ( t  =   0.6, p =  .557). The SRC athletes demonstrated lower ES for all test session when compared to the control group ( ts  > 2.0, Ps <.01). Dysfunctional auditory comprehension performance following a concussion improved over time, but after the second testing session improved performance slowed, especially in terms of its timing. Yet, not only auditory processing but also sensorimotor integration and/or motor execution can be compromised after a concussion.

Liquefaction of calcium-containing subbituminous coals and coals of lower rank

DOEpatents

Brunson, Roy J.

1979-01-01

An improved process for the treatment of a calcium-containing subbituminous coal and coals of lower rank to form insoluble, thermally stable calcium salts which remain within the solids portions of the residue on liquefaction of the coal, thereby suppressing the formation of scale, made up largely of calcium carbonate which normally forms within the coal liquefaction reactor (i.e., coal liquefaction zone), e.g., on reactor surfaces, lines, auxiliary equipment and the like. An oxide of sulfur, in liquid phase, is contacted with a coal feed sufficient to impregnate the pores of the coal. The impregnated coal, in particulate form, can thereafter be liquefied in a coal liquefaction reactor (reaction zone) at coal liquefaction conditions without significant formation of scale.

Fluidized-bed bioreactor system for the microbial solubilization of coal

DOEpatents

Scott, C.D.; Strandberg, G.W.

1987-09-14

A fluidized-bed bioreactor system for the conversion of coal into microbially solubilized coal products. The fluidized-bed bioreactor continuously or periodically receives coal and bio-reactants and provides for the production of microbially solubilized coal products in an economical and efficient manner. An oxidation pretreatment process for rendering coal uniformly and more readily susceptible to microbial solubilization may be employed with the fluidized-bed bioreactor. 2 figs.

Coal gasification systems engineering and analysis. Appendix B: Medium B+U gas design

NASA Technical Reports Server (NTRS)

1980-01-01

A four module, 20,000 TPD, based on KT coal gasification technology was designed. The plant processes Kentucky No. 9 coal with provisions for up to five percent North Alabama coal. Medium BTU gas with heat content of 305 BTU/SCF and not more than 200 ppm sulfur is the primary plant product. Sulfur is recovered for scale as prilled sulfur. Ash disposal is on site. The plant is designed for zero water discharge. Trade studies provided the basis for not using boiler produced steam to drive prime movers. Thus process derived steam in excess of process requirements in superheated for power use in prime movers. Electricity from the TVA grid is used to supply the balance of the plant prime mover power requirements. A study of the effect of mine mouth coal cleaning showed that coal cleaning is not an economically preferred route. The design procedure involved defining available processes to meet the requirements of each system, technical/economic trade studies to select the preferred processes, and engineering design and flow sheet development for each module. Cost studies assumed a staggered construction schedule for the four modules beginning spring 1981 and a 90% on stream factor.

Characterization of coal liquids derived from the H-coal process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, S.A.; Woodward, P.W.; Sturm, G.P. Jr.

1976-11-01

Compositional data of coal liquid products derived from the H-Coal process were obtained. Two overhead products (one from the fuel oil mode of operation and the other from the syncrude mode of operation) were prepared by Hydrocarbon Research, Inc. from Illinois No. 6 coal. The compositional data of these products are tabulated, and characteristics of the materials are discussed. Separation and characterization methods, with slight modification, as developed by the Bureau of Mines-API Research Project 60 for characterizing heavy ends of petroleum, were successfully used in analyzing coal liquid distillates within the boiling range 200/sup 0/ to 540/sup 0/C. Distillatesmore » boiling below 200/sup 0/C were separated and analyzed using chromatographic and spectral techniques.« less

Coal Research

NASA Technical Reports Server (NTRS)

1986-01-01

Coal slurries are "clean" pulverized coal mixed with oil or water. Significant fuel savings can be realized when using coal slurries. Advanced Fuels Technology (AFT) utilized a COSMIC program, (Calculation of Complex Chemical Equilibrium Compositions), which provides specific capabilities for determining combustion products. The company has developed a cleaning process that removes much of the mineral sulphur and ash from the coals.

JunD/AP-1 Antagonizes the Induction of DAPK1 To Promote the Survival of v-Src-Transformed Cells.

PubMed

Maślikowski, Bart M; Wang, Lizhen; Wu, Ying; Fielding, Ben; Bédard, Pierre-André

2017-01-01

The increase in AP-1 activity is a hallmark of cell transformation by tyrosine kinases. Previously, we reported that blocking AP-1 using the c-Jun dominant negative mutant TAM67 induced senescence, adipogenesis, or apoptosis in v-Src-transformed chicken embryo fibroblasts (CEFs) whereas inhibition of JunD by short hairpin RNA (shRNA) specifically induced apoptosis. To investigate the role of AP-1 in Src-mediated transformation, we undertook a gene profiling study to characterize the transcriptomes of v-Src-transformed CEFs expressing either TAM67 or the JunD shRNA. Our study revealed a cluster of 18 probe sets upregulated exclusively in response to AP-1/JunD impairment and v-Src transformation. Four of these probe sets correspond to genes involved in the interferon pathway. One gene in particular, death-associated protein kinase 1 (DAPK1), is a C/EBPβ-regulated mediator of apoptosis in gamma interferon (IFN-γ)-induced cell death. Here, we show that inhibition of DAPK1 abrogates cell death in v-Src-transformed cells expressing the JunD shRNA. Chromatin immunoprecipitation data indicated that C/EBPβ was recruited to the DAPK1 promoter while the expression of a dominant negative mutant of C/EBPβ abrogated the induction of DAPK1 in response to the inhibition of AP-1. In contrast, as determined by chromatin immunoprecipitation (ChIP) assays, JunD was not detected on the DAPK1 promoter under any conditions, suggesting that JunD promotes survival by indirectly antagonizing the expression of DAPK1 in v-Src transformed cells. Transformation by the v-Src oncoprotein causes extensive changes in gene expression in primary cells such as chicken embryo fibroblasts. These changes, determining the properties of transformed cells, are controlled in part at the transcriptional level. Much attention has been devoted to transcription factors such as AP-1 and NF-κB and the control of genes associated with a more aggressive phenotype. In this report, we describe a novel mechanism of action determined by the JunD component of AP-1, a factor enhancing cell survival in v-Src-transformed cells. We show that the loss of JunD results in the aberrant activation of a genetic program leading to cell death. This program requires the activation of the tumor suppressor death-associated protein kinase 1 (DAPK1). Since DAPK1 is phosphorylated and inhibited by v-Src, these results highlight the importance of this kinase and the multiple mechanisms controlled by v-Src to antagonize the tumor suppressor function of DAPK1. Copyright © 2016 American Society for Microbiology.

Monetization of Nigeria coal by conversion to hydrocarbon fuels through Fischer-Tropsch process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oguejiofor, G.C.

Given the instability of crude oil prices and the disruptions in crude oil supply chains, this article offers a complementing investment proposal through diversification of Nigeria's energy source and dependence. Therefore, the following issues were examined and reported: A comparative survey of coal and hydrocarbon reserve bases in Nigeria was undertaken and presented. An excursion into the economic, environmental, and technological justifications for the proposed diversification and roll-back to coal-based resource was also undertaken and presented. The technology available for coal beneficiation for environmental pollution control was reviewed and reported. The Fischer-Tropsch synthesis and its advances into Sasol's slurry phasemore » distillate process were reviewed. Specifically, the adoption of Sasol's advanced synthol process and the slurry phase distillate process were recommended as ways of processing the products of coal gasification. The article concludes by discussing all the above-mentioned issues with regard to value addition as a means of wealth creation and investment.« less

Meeting today's challenges to supply tomorrow's energy. Clean fossil energy technical and policy seminar

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2005-07-01

Papers discussed the coal policy of China, Russia, Indonesia and Vietnam; clean coal technology (small-scale coal power plants, carbon capture and sequestration, new coking process SCOPE21, coal gasification (HyPr-RING), CO{sub 2} reduction technology, Supercritical coal-fired units and CFB boilers, EAGLE project, coal liquefaction), the coal consumer's view of clean fossil energy policy, and natural gas policy and technology. Some of the papers only consist of the presentation overheads/viewgraphs.

Superacid Catalyzed Coal Conversion Chemistry. Final Technical Report, September 1, 1983-September 1, 1986

DOE R&D Accomplishments Database

Olah, G. A.

1986-01-01

This research project involved the study of a raw comparatively mild coal conversion process. The goal of the project was to study model systems to understand the basic chemistry involved and to provide a possible effective pretreatment of coal which significantly improves liquefaction-depolymerization under mild conditions. The conversion process operates at relatively low temperatures (170 degrees C) and pressures and uses an easily recyclable, stable superacid catalysts (HF-BF{sub 3}). It consequently offers an attractive alternative to currently available processes. From the present studies it appears that the modification of coal structure by electrophilic alkylation and subsequent reaction of alkylated coal with HF-BF{sub 3}-H{sub 2} system under mild conditions considerably improves the extractability of coal in pyridine and cyclohexane. On the other hand, nitration of coal and its subsequent reaction with HF-BF{sub 3}H{sub 2} decreases the pyridine and cyclohexane extractability. Study of model compounds under conditions identical with the superacidic HF/BF{sub 3}/H{sub 2} system provided significant information about the basic chemistry of the involved cleavage-hydrogenation reactions.

Coal liquefaction process

DOEpatents

Carr, Norman L.; Moon, William G.; Prudich, Michael E.

1983-01-01

A C.sub.5 -900.degree. F. (C.sub.5 -482.degree. C.) liquid yield greater than 50 weight percent MAF feed coal is obtained in a coal liquefaction process wherein a selected combination of higher hydrogen partial pressure, longer slurry residence time and increased recycle ash content of the feed slurry are controlled within defined ranges.

Progress in donor assisted coal liquefaction: Hydroaromatic compound formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kottenstette, R.J.; Stephens, H.P.

1993-12-31

The role of hydrogen donor compounds in coal liquefaction has been extensively investigated since the mid 1960`s using model compounds and process derived hydrogen donor solvents. Our recent research and that of other investigators have shown that two model compounds in particular have great efficacy in solvating low rank coals. 1,2,3,10b tetrahydrofluoranthene (H{sub 4}Fl) and 1,2,3,6,7,8 hexahydropyrene (H{sub 6}Py) have been used to dissolve Wyodak coal to > 95% soluble material as measured by tetrahydrofuran (THF). Although these hydrogen donors are very effective, they may not be found in any significant concentrations in actual liquefaction process recycle solvents. Therefore, studiesmore » with process derived recycle materials are necessary to understand donor solvent chemistry. The objective of this paper is to present results of solvent hydrogenation experiments using heavy distillate solvents produced during testing at the Wilsonville Advanced Coal Liquefaction Test Facility. We evaluated the impact of hydrogenation conditions upon hydrogen donor formation in process derived distillates and compared these process derived solvents with the highly effective H{sub 4}Fl and H{sub 6}Py donors in coal liquefaction tests. This paper presents data on reaction conditions used for distillate hydrotreating and subsequent coal liquefaction, with an aim toward understanding the relationship between reaction conditions and donor solvent quality in recycle distillates.« less

Coal liquefaction process

DOEpatents

Karr, Jr., Clarence

1977-04-19

An improved coal liquefaction process is provided which enables conversion of a coal-oil slurry to a synthetic crude refinable to produce larger yields of gasoline and diesel oil. The process is characterized by a two-step operation applied to the slurry prior to catalytic desulfurization and hydrogenation in which the slurry undergoes partial hydrogenation to crack and hydrogenate asphaltenes and the partially hydrogenated slurry is filtered to remove minerals prior to subsequent catalytic hydrogenation.

Two-stage coal liquefaction without gas-phase hydrogen

DOEpatents

Stephens, H.P.

1986-06-05

A process is provided for the production of a hydrogen-donor solvent useful in the liquefaction of coal, wherein the water-gas shift reaction is used to produce hydrogen while simultaneously hydrogenating a donor solvent. A process for the liquefaction of coal using said solvent is also provided. The process enables avoiding the use of a separate water-gas shift reactor as well as high pressure equipment for liquefaction. 3 tabs.

Model of environmental life cycle assessment for coal mining operations.

PubMed

Burchart-Korol, Dorota; Fugiel, Agata; Czaplicka-Kolarz, Krystyna; Turek, Marian

2016-08-15

This paper presents a novel approach to environmental assessment of coal mining operations, which enables assessment of the factors that are both directly and indirectly affecting the environment and are associated with the production of raw materials and energy used in processes. The primary novelty of the paper is the development of a computational environmental life cycle assessment (LCA) model for coal mining operations and the application of the model for coal mining operations in Poland. The LCA model enables the assessment of environmental indicators for all identified unit processes in hard coal mines with the life cycle approach. The proposed model enables the assessment of greenhouse gas emissions (GHGs) based on the IPCC method and the assessment of damage categories, such as human health, ecosystems and resources based on the ReCiPe method. The model enables the assessment of GHGs for hard coal mining operations in three time frames: 20, 100 and 500years. The model was used to evaluate the coal mines in Poland. It was demonstrated that the largest environmental impacts in damage categories were associated with the use of fossil fuels, methane emissions and the use of electricity, processing of wastes, heat, and steel supports. It was concluded that an environmental assessment of coal mining operations, apart from direct influence from processing waste, methane emissions and drainage water, should include the use of electricity, heat and steel, particularly for steel supports. Because the model allows the comparison of environmental impact assessment for various unit processes, it can be used for all hard coal mines, not only in Poland but also in the world. This development is an important step forward in the study of the impacts of fossil fuels on the environment with the potential to mitigate the impact of the coal industry on the environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct liquefaction proof-of-concept program. Topical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comolli, A.G.; Lee, L.K.; Pradhan, V.R.

This report presents the results of work conducted under the DOE Proof-of-Concept Program in direct coal liquefaction at Hydrocarbon Technologies, Inc. in Lawrenceville, New Jersey, from February 1994 through April 1995. The work includes modifications to HRI`s existing 3 ton per day Process Development Unit (PDU) and completion of the second PDU run (POC Run 2) under the Program. The 45-day POC Run 2 demonstrated scale up of the Catalytic Two-Stage Liquefaction (CTSL Process) for a subbituminous Wyoming Black Thunder Mine coal to produce distillate liquid products at a rate of up to 4 barrels per ton of moisture-ash-free coal.more » The combined processing of organic hydrocarbon wastes, such as waste plastics and used tire rubber, with coal was also successfully demonstrated during the last nine days of operations of Run POC-02. Prior to the first PDU run (POC-01) in this program, a major effort was made to modify the PDU to improve reliability and to provide the flexibility to operate in several alternative modes. The Kerr McGee Rose-SR{sup SM} unit from Wilsonville, Alabama, was redesigned and installed next to the U.S. Filter installation to allow a comparison of the two solids removal systems. The 45-day CTSL Wyoming Black Thunder Mine coal demonstration run achieved several milestones in the effort to further reduce the cost of liquid fuels from coal. The primary objective of PDU Run POC-02 was to scale-up the CTSL extinction recycle process for subbituminous coal to produce a total distillate product using an in-line fixed-bed hydrotreater. Of major concern was whether calcium-carbon deposits would occur in the system as has happened in other low rank coal conversion processes. An additional objective of major importance was to study the co-liquefaction of plastics with coal and waste tire rubber with coal.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The coal industry, the utilities, and the state government are planning for development of high-energy coal gasification in Illinois to convert its abundant high-sulfur coal supply to a substitute natural gas. Following a summary of the findings, the following topics are discussed briefly: Illinois coal and the push for coal gasification; coal gasification: a look at the process; potential sites for an Illinois coal gasification industry; the impact of coal gasification's water requirements; solid wastes from coal gasification; land losses: the impact on agriculture; potential human health problems with coal gasification; the energy efficiency of coal gasification; potential economic impactsmore » of coal gasification; the corporations behind high-energy coal gasification; state involvement: legalizing the losses of the people; the national energy picture: the impact of western coal developments on Illinois; action: what you can do now. 27 references. (MCW)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nabeel, A.; Khan, T.A.; Sharma, D.K.

The use of low-grade coal in thermal power stations is leading to environmental pollution due to the generation of large amounts of fly ash, bottom ash, and CO{sub 2} besides other pollutants. It is therefore important to clean the coal before using it in thermal power stations, steel plants, or cement industries etc. Physical beneficiation of coal results in only limited cleaning of coal. The increasing environmental pollution problems from the use of coal have led to the development of clean coal technologies. In fact, the clean use of coal requires the cleaning of coal to ultra low ash contents,more » keeping environmental norms and problems in view and the ever-growing need to increase the efficiency of coal-based power generation. Therefore this requires the adaptation of chemical cleaning techniques for cleaning the coal to obtain ultra clean coal having ultra low ash contents. Presently the reaction conditions for chemical demineralization of low-grade coal using 20% aq NaOH treatment followed by 10% H{sub 2}SO{sub 4} leaching under reflux conditions have been optimized. In order to reduce the concentration of alkali and acid used in this process of chemical demineralization of low-grade coals, stepwise, i.e., three step process of chemical demineralization of coal using 1% or 5% aq NaOH treatment followed by 1% or 5% H{sub 2}SO{sub 4} leaching has been developed, which has shown good results in demineralization of low-grade coals. In order to conserve energy, the alkali-acid leaching of coal was also carried out at room temperature, which gave good results.« less

An evolutionary switch in ND2 enables Src kinase regulation of NMDA receptors

NASA Astrophysics Data System (ADS)

Scanlon, David P.; Bah, Alaji; Krzeminski, Mickaël; Zhang, Wenbo; Leduc-Pessah, Heather L.; Dong, Yi Na; Forman-Kay, Julie D.; Salter, Michael W.

2017-05-01

The non-receptor tyrosine kinase Src is a key signalling hub for upregulating the function of N-methyl D-aspartate receptors (NMDARs). Src is anchored within the NMDAR complex via NADH dehydrogenase subunit 2 (ND2), a mitochondrially encoded adaptor protein. The interacting regions between Src and ND2 have been broadly identified, but the interaction between ND2 and the NMDAR has remained elusive. Here we generate a homology model of ND2 and dock it onto the NMDAR via the transmembrane domain of GluN1. This interaction is enabled by the evolutionary loss of three helices in bilaterian ND2 proteins compared to their ancestral homologues. We experimentally validate our model and demonstrate that blocking this interaction with an ND2 fragment identified in our experimental studies prevents Src-mediated upregulation of NMDAR currents in neurons. Our findings establish the mode of interaction between an NMDAR accessory protein with one of the core subunits of the receptor.

Presence of an SH2 domain in the actin-binding protein tensin.

PubMed

Davis, S; Lu, M L; Lo, S H; Lin, S; Butler, J A; Druker, B J; Roberts, T M; An, Q; Chen, L B

1991-05-03

The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

The tumor suppressor DAPK is reciprocally regulated by tyrosine kinase Src and phosphatase LAR.

PubMed

Wang, Won-Jing; Kuo, Jean-Cheng; Ku, Wei; Lee, Yu-Ru; Lin, Feng-Chi; Chang, Yih-Leong; Lin, Yu-Min; Chen, Chun-Hau; Huang, Yuan-Ping; Chiang, Meng-Jung; Yeh, Sheng-Wen; Wu, Pei-Rung; Shen, Che-Hung; Wu, Chen-Tu; Chen, Ruey-Hwa

2007-09-07

Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine kinase and elicits tumor suppression function through inhibiting cell adhesion/migration and promoting apoptosis. Despite these biological functions, the signaling mechanisms through which DAPK is regulated remain largely elusive. Here, we show that the leukocyte common antigen-related (LAR) tyrosine phosphatase dephosphorylates DAPK at pY491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of DAPK. Conversely, Src phosphorylates DAPK at Y491/492, which induces DAPK intra-/intermolecular interaction and inactivation. Upon EGF stimulation, a rapid Src activation leads to subsequent LAR downregulation, and these two events act in synergism to inactivate DAPK, thereby facilitating tumor cell migration and invasion toward EGF. Finally, DAPK Y491/492 hyperphosphorylation is found in human cancers in which Src activity is aberrantly elevated. These results identify LAR and Src as a DAPK regulator through their reciprocal modification of DAPK Y491/492 residues and establish a functional link of this DAPK-regulatory circuit to tumor progression.

Losartan Improves Palmitate-Induced Insulin Resistance in 3T3-L1 Adipocytes Through Upregulation of Src Phosphorylation.

PubMed

Tian, X; Ye, M; Cao, Y; Wang, C

2017-02-01

Angiotensin II type 1 receptor blocker losartan has shown strongly anti-insulin resistance properties in vivo and in vitro ; however, the underlying mechanisms are poorly understood. In this study, we demonstrate that losartan administration increased phosphorylation of Akt and its downstream Akt substrate of 160 kDa (AS160), enhanced plasma membrane translocation of glucose transporter type 4 (GLUT4), and increased glucose uptake, along with increased Src phosphorylation as well as reduced expression of docking protein 1(DOK1) in palmitate-treated 3T3-L1 adipocytes. The beneficial impacts of losartan on insulin signaling were diminished in Src-deficient 3T3-L1 adipocytes. In addition, suppressed expression of DOK1 by losartan was abolished by Src knockdown. Our results suggest that anti-insulin resistance ability of losartan is mediated by Src/DOK1/Akt pathway. © Georg Thieme Verlag KG Stuttgart · New York.