Sample records for aurin
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Davis, Angela L.; Qiao, Shuxi; Lesson, Jessica L.; Rojo de la Vega, Montserrat; Park, Sophia L.; Seanez, Carol M.; Gokhale, Vijay; Cabello, Christopher M.; Wondrak, Georg T.
2015-01-01
Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinderTM PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. PMID:25477506
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Davis, Angela L; Qiao, Shuxi; Lesson, Jessica L; Rojo de la Vega, Montserrat; Park, Sophia L; Seanez, Carol M; Gokhale, Vijay; Cabello, Christopher M; Wondrak, Georg T
2015-01-16
Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinder(TM) PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Use of triammonium salt of aurin tricarboxylic acid as risk mitigant for aluminum hydride
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cortes-Concepcion, Jose A.; Anton, Donald L.
2017-08-08
A process and a resulting product by process of an aluminum hydride which is modified with by physically combining in a ball milling process an aluminum hydride with a triammonium salt of aurin tricarboxylic acid. The resulting product is an aluminum hydride which is resistant to air, ambient moisture, and liquid water while maintaining useful hydrogen storage and release kinetics.
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Developing a research and practice tool to measure walkability: a demonstration project.
Giles-Corti, Billie; Macaulay, Gus; Middleton, Nick; Boruff, Bryan; Bull, Fiona; Butterworth, Iain; Badland, Hannah; Mavoa, Suzanne; Roberts, Rebecca; Christian, Hayley
2014-12-01
Growing evidence shows that higher-density, mixed-use, pedestrian-friendly neighbourhoods encourage active transport, including transport-related walking. Despite widespread recognition of the benefits of creating more walkable neighbourhoods, there remains a gap between the rhetoric of the need for walkability and the creation of walkable neighbourhoods. Moreover, there is little objective data to benchmark the walkability of neighbourhoods within and between Australian cities in order to monitor planning and design intervention progress and to assess built environment and urban policy interventions required to achieve increased walkability. This paper describes a demonstration project that aimed to develop, trial and validate a 'Walkability Index Tool' that could be used by policy makers and practitioners to assess the walkability of local areas; or by researchers to access geospatial data assessing walkability. The overall aim of the project was to develop an automated geospatial tool capable of creating walkability indices for neighbourhoods at user-specified scales. The tool is based on open-source software architecture, within the Australian Urban Research Infrastructure Network (AURIN) framework, and incorporates key sub-component spatial measures of walkability (street connectivity, density and land use mix). Using state-based data, we demonstrated it was possible to create an automated walkability index. However, due to the lack of availability of consistent of national data measuring land use mix, at this stage it has not been possible to create a national walkability measure. The next stage of the project is to increase useability of the tool within the AURIN portal and to explore options for alternative spatial data sources that will enable the development of a valid national walkability index. AURIN's open-source Walkability Index Tool is a first step in demonstrating the potential benefit of a tool that could measure walkability across Australia. It also demonstrates the value of making accurate spatial data available for research purposes. SO WHAT?: There remains a gap between urban policy and practice, in terms of creating walkable neighbourhoods. When fully implemented, AURIN's walkability tool could be used to benchmark Australian cities against which planning and urban design decisions could be assessed to monitor progress towards achieving policy goals. Making cleaned data readily available for research purposes through a common portal could also save time and financial resources.
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Karbasi, Mohamad-Hadi; Jahanparast, Babak; Shamsipur, Mojtaba; Hassan, Jalal
2009-10-15
Multielement simultaneous determination of 35 trace elements in environmental samples was carried out by inductively coupled plasma emission spectrometry (ICP-OES) after preconcentration with octadecyl silicagel, modified with aurin tricarboxylic acid (Aluminon). Optimal experimental conditions including pH of sample solution, sample volume, sample and eluent flow rate, type, concentration and volume of eluent and foreign ions effect were investigated and established. Trace element ions in aqueous solution were quantitatively adsorbed onto octadecyl silicagel modified with aurin tricarboxylic acid at pH 8.0 with a flow rate of 11.0 mL min(-1). The adsorbed element ions were eluted with 3-5 mL of 0.5 mol L(-1) HNO(3) at a flow rate of 10.0 mL min(-1) and analyzed by ICP-OES simultaneously. The proposed method has at least preconcentration factor of 100 in water samples, which results high sensitive detection of ultra-trace and trace analysis. The present methodology gave recoveries better than 70% and RSD less than 16%.
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Kaempfer, Raymond; Kaufman, Jennifer
1972-01-01
The continued recycling of ribosomes during protein synthesis in rabbit reticulocyte lysates at 37° requires an initiation factor whose activity is rapidly lost in the absence of added heme. Partially purified factor (i) fully maintains the polysomes; (ii) inhibits the association of 40S and 60S ribosomal subunits into single ribosomes; (iii) promotes the quantitative entry of added 60S subunits into polysomes; (iv) allows the accumulation of ribosomal subunits, instead of single ribosomes, when initiation is blocked with aurin tricarboxylate; and (v) is absolutely required for the binding of globin messenger RNA to ribosomes. These properties suggest that this mammalian initiation factor functions analogously to bacterial IF-3. In addition, the translational control of globin synthesis by heme is exerted, directly or indirectly, through this factor. PMID:4508325
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Chan, Leo L.; Pineda, Maria; Heeres, James T.; Hergenrother, Paul J.; Cunningham, Brian T.
2009-01-01
Protein–DNA interactions are essential for fundamental cellular processes such as transcription, DNA damage repair, and apoptosis. As such, small molecule disruptors of these interactions could be powerful tools for investigation of these biological processes, and such compounds would have great potential as therapeutics. Unfortunately, there are few methods available for the rapid identification of compounds that disrupt protein–DNA interactions. Here we show that photonic crystal (PC) technology can be utilized to detect protein–DNA interactions, and can be used in a high-throughput screening mode to identify compounds that prevent protein–DNA binding. The PC technology is used to detect binding between protein–DNA interactions that are DNA-sequence-dependent (the bacterial toxin–antitoxin system MazEF) and those that are DNA-sequence-independent (the human apoptosis inducing factor (AIF)). The PC technology was further utilized in a screen for inhibitors of the AIF–DNA interaction, and through this screen aurin tricarboxylic acid was identified as the first in vitro inhibitor of AIF. The generality and simplicity of the photonic crystal method should enable this technology to find broad utility for identification of compounds that inhibit protein–DNA binding. PMID:18582039
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Debnath, Tushar; Maity, Partha; Dana, Jayanta; Ghosh, Hirendra N
2016-03-03
Wide-band-gap ZnS nanocrystals (NCs) were synthesized, and after sensitizing the NCs with series of triphenyl methane (TPM) dyes, ultrafast charge-transfer dynamics was demonstrated. HRTEM images of ZnS NCs show the formation of aggregate crystals with a flower-like structure. Exciton absorption and lumimescence, due to quantum confinement of the ZnS NCs, appear at approximately 310 and 340 nm, respectively. Interestingly, all the TPM dyes (pyrogallol red, bromopyrogallol red, and aurin tricarboxylic acid) form charge-transfer complexes with the ZnS NCs, with the appearance of a red-shifted band. Electron injection from the photoexcited TPM dyes into the conduction band of the ZnS NCs is shown to be a thermodynamically viable process, as confirmed by steady-state and time-resolved emission studies. To unravel charge-transfer (both electron injection and charge recombination) dynamics and the effect of molecular coupling, femtosecond transient absorption studies were carried out in TPM-sensitized ZnS NCs. The electron-injection dynamics is pulse-width-limited in all the ZnS/TPM dye systems, however, the back electron transfer differs, depending on the molecular coupling of the sensitizers (TPM dyes). The detailed mechanisms for the above-mentioned processes are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Using Remote Sensing to Determine the Spatial Scales of Estuaries
NASA Astrophysics Data System (ADS)
Davis, C. O.; Tufillaro, N.; Nahorniak, J.
2016-02-01
One challenge facing Earth system science is to understand and quantify the complexity of rivers, estuaries, and coastal zone regions. Earlier studies using data from airborne hyperspectral imagers (Bissett et al., 2004, Davis et al., 2007) demonstrated from a very limited data set that the spatial scales of the coastal ocean could be resolved with spatial sampling of 100 m Ground Sample Distance (GSD) or better. To develop a much larger data set (Aurin et al., 2013) used MODIS 250 m data for a wide range of coastal regions. Their conclusion was that farther offshore 500 m GSD was adequate to resolve large river plume features while nearshore regions (a few kilometers from the coast) needed higher spatial resolution data not available from MODIS. Building on our airborne experience, the Hyperspectral Imager for the Coastal Ocean (HICO, Lucke et al., 2011) was designed to provide hyperspectral data for the coastal ocean at 100 m GSD. HICO operated on the International Space Station for 5 years and collected over 10,000 scenes of the coastal ocean and other regions around the world. Here we analyze HICO data from an example set of major river delta regions to assess the spatial scales of variability in those systems. In one system, the San Francisco Bay and Delta, we also analyze Landsat 8 OLI data at 30 m and 15 m to validate the 100 m GSD sampling scale for the Bay and assess spatial sampling needed as you move up river.
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Using simple agent-based modeling to inform and enhance neighborhood walkability.
Badland, Hannah; White, Marcus; Macaulay, Gus; Eagleson, Serryn; Mavoa, Suzanne; Pettit, Christopher; Giles-Corti, Billie
2013-12-11
Pedestrian-friendly neighborhoods with proximal destinations and services encourage walking and decrease car dependence, thereby contributing to more active and healthier communities. Proximity to key destinations and services is an important aspect of the urban design decision making process, particularly in areas adopting a transit-oriented development (TOD) approach to urban planning, whereby densification occurs within walking distance of transit nodes. Modeling destination access within neighborhoods has been limited to circular catchment buffers or more sophisticated network-buffers generated using geoprocessing routines within geographical information systems (GIS). Both circular and network-buffer catchment methods are problematic. Circular catchment models do not account for street networks, thus do not allow exploratory 'what-if' scenario modeling; and network-buffering functionality typically exists within proprietary GIS software, which can be costly and requires a high level of expertise to operate. This study sought to overcome these limitations by developing an open-source simple agent-based walkable catchment tool that can be used by researchers, urban designers, planners, and policy makers to test scenarios for improving neighborhood walkable catchments. A simplified version of an agent-based model was ported to a vector-based open source GIS web tool using data derived from the Australian Urban Research Infrastructure Network (AURIN). The tool was developed and tested with end-user stakeholder working group input. The resulting model has proven to be effective and flexible, allowing stakeholders to assess and optimize the walkability of neighborhood catchments around actual or potential nodes of interest (e.g., schools, public transport stops). Users can derive a range of metrics to compare different scenarios modeled. These include: catchment area versus circular buffer ratios; mean number of streets crossed; and modeling of different walking speeds and wait time at intersections. The tool has the capacity to influence planning and public health advocacy and practice, and by using open-access source software, it is available for use locally and internationally. There is also scope to extend this version of the tool from a simple to a complex model, which includes agents (i.e., simulated pedestrians) 'learning' and incorporating other environmental attributes that enhance walkability (e.g., residential density, mixed land use, traffic volume).
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Using simple agent-based modeling to inform and enhance neighborhood walkability
2013-01-01
Background Pedestrian-friendly neighborhoods with proximal destinations and services encourage walking and decrease car dependence, thereby contributing to more active and healthier communities. Proximity to key destinations and services is an important aspect of the urban design decision making process, particularly in areas adopting a transit-oriented development (TOD) approach to urban planning, whereby densification occurs within walking distance of transit nodes. Modeling destination access within neighborhoods has been limited to circular catchment buffers or more sophisticated network-buffers generated using geoprocessing routines within geographical information systems (GIS). Both circular and network-buffer catchment methods are problematic. Circular catchment models do not account for street networks, thus do not allow exploratory ‘what-if’ scenario modeling; and network-buffering functionality typically exists within proprietary GIS software, which can be costly and requires a high level of expertise to operate. Methods This study sought to overcome these limitations by developing an open-source simple agent-based walkable catchment tool that can be used by researchers, urban designers, planners, and policy makers to test scenarios for improving neighborhood walkable catchments. A simplified version of an agent-based model was ported to a vector-based open source GIS web tool using data derived from the Australian Urban Research Infrastructure Network (AURIN). The tool was developed and tested with end-user stakeholder working group input. Results The resulting model has proven to be effective and flexible, allowing stakeholders to assess and optimize the walkability of neighborhood catchments around actual or potential nodes of interest (e.g., schools, public transport stops). Users can derive a range of metrics to compare different scenarios modeled. These include: catchment area versus circular buffer ratios; mean number of streets crossed; and modeling of different walking speeds and wait time at intersections. Conclusions The tool has the capacity to influence planning and public health advocacy and practice, and by using open-access source software, it is available for use locally and internationally. There is also scope to extend this version of the tool from a simple to a complex model, which includes agents (i.e., simulated pedestrians) ‘learning’ and incorporating other environmental attributes that enhance walkability (e.g., residential density, mixed land use, traffic volume). PMID:24330721
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Nuclear factor kappa B: a potential target for anti-HIV chemotherapy.
Pande, V; Ramos, M J
2003-08-01
The Nuclear Factor Kappa B (NF-kappaB) is a lymphoid-specific transcription factor, which is sequestered in the cytoplasm by the protein IkappaB. NF-kappaB plays a major role in the regulation of HIV-1 gene expression. Upon activation, NF-kappaB is released from IkappaB, moves to the nucleus, and binds to its sites on the HIV long terminal repeat to start transcription of integrated HIV genome. The present review focuses on the NF-kappaB as a potential target for the development of chemotherapy against HIV-1. Beginning from the viral-binding to reverse transcription, integration, and gene expression, to the virion maturation, the life cycle of HIV presents drug-targets at all the stages. As a result, many drugs have been developed and have entered clinical trials. Some of the most important of these are reverse transcriptase and protease inhibitors, which have been used mostly in clinical studies in the form of combined therapy. But, this combined therapy has presented the problem of resistance, due to mutations in the virus. However, targeting NF-kappaB for the suppression of virus does not present the problem of resistance, as NF-kappaB is a normal part of the human T-4 cell, and is not subject to mutations, as is the virus. An overview of the NF-kappaB system and its role in HIV-1 is presented, followed by a critical review of its current and potential synthetic inhibitors. The drugs studied against NF-kappaB fall mainly into three categories: (1) Antioxidants, against oxidative stress conditions, which aid in NF-kappaB activation, (2) IkappaB phosphorylation and degradation inhibitors (the phosphorylation and degradation of IkappaB is necessary to make NF-kappaB free and move to the nucleus), and (3) NF-kappaB DNA binding inhibitors. The antioxidants include N-Acetyl-L-cysteine (NAC), alpha-Lipoic acid, glutathione monoester, pyrrolidine dithiocarbamate, and tepoxalin, of which NAC is the best studied. The IkappaB phosphorylation and degradation inhibitors, which have been studied in the context of HIV-1 include the salicylates (sodium salicylate, and acetylsalicylic acid (aspirin)). Finally, the NF-kappaB DNA binding inhibitors, which have received attention only recently, are reviewed. These include the most potential, aurine tricarboxylic acid (ATA), a chelating agent, which has been found to inhibit NF-kappaB DNA binding at a low concentration of 30 micro M. The probable mechanism of action of these drugs is discussed alongwith relevant suggestions and conclusions.
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NASA Astrophysics Data System (ADS)
Wyborn, L. A.; Woodcock, R.
2013-12-01
One of the greatest drivers for change in the way scientific research is undertaken in Australia was the development of the Australian eResearch Infrastructure which was coordinated by the then Australian Government Department of Innovation, Industry, Science and Research. There were two main tranches of funding: the 2007-2013 National Collaborative Research Infrastructure Strategy (NCRIS) and the 2009 Education and Investment Framework (EIF) Super Science Initiative. Investments were in two areas: the Australian e-Research Infrastructure and domain specific capabilities: combined investment in both is 1,452M with at least 456M being invested in eResearch infrastructure. NCRIS was specifically designed as a community-guided process to provide researchers, both academic and government, with major research facilities, supporting infrastructures and networks necessary for world-class research. Extensive community engagement was sought to inform decisions on where Australia could best make strategic infrastructure investments to further develop its research capacity and improve research outcomes over the next 5 to 10years. The current (2007-2014) Australian e-Research Infrastructure has 2 components: 1. The National eResearch physical infrastructure which includes two petascale HPC facilities (one in Canberra and one in Perth), a 10 Gbps national network (National Research Network), a national data storage infrastructure comprising 8 multi petabyte data stores and shared access methods (Australian Access Federation). 2. A second component is focused on research integration infrastructures and includes the Australian National Data Service, which is concerned with better management, description and access to distributed research data in Australia and the National eResearch Collaboration Tools and Resources (NeCTAR) project. NeCTAR is centred on developing problem oriented digital laboratories which provide better and coordinated access to research tools, data environments and workflows. The eResearch Infrastructure Stack is designed to support 12 individual domain-specific capabilities. Four are relevant to the Earth and Space Sciences: (1) AuScope (a national Earth Science Infrastructure Program), (2) the Integrated Marine Observing System (IMOS), (3) the Terrestrial Ecosystems Research Network (TERN) and (4) the Australian Urban Research Infrastructure Network (AURIN). The two main research integration infrastructures, ANDS and NeCTAR, are seen as pivotal to the success of the Australian eResearch Infrastructure. Without them, there was a risk that that the investments in new computers and data storage would provide physical infrastructure, but few would come to use it as the skills barriers to entry were too high. ANDS focused on transforming Australia's research data environment. Its flagship is Research Data Australia, an Internet-based discovery service designed to provide rich connections between data, projects, researchers and institutions, and promote visibility of Australian research data collections in search engines. NeCTAR focused on building eResearch infrastructure in four areas: virtual laboratories, tools, a federated research cloud and a hosting service. Combined, ANDS and NeCTAR are ensuring that people ARE coming and ARE using the physical infrastructures that were built.