d3 Pull Up and Start Drying with the Phoenix HD308 By www.randrmagonline.com Published On :: Tue, 03 Jan 2012 13:32:00 -0500 Designed and built for the rigors of the restoration industry, the Phoenix FireBird HD308 is the safest, most efficient, flexible, and durable heat system made. Full Article
d3 D3 fell and got up By rightmusicvideo.d3.ru Published On :: Wed, 13 Nov 2024 21:38:38 GMT https://youtu.be/43e74d1Xg6k?si=3nQEGOZjXxNjanEC Ну, d3... Ну, упал... Поднялся. И простое информационное сообщение @mudhoney однако же вызвало, хоть ленивое, но брожение говнов. И не стыдно, а? :)) Активные комментаторы d3, вы хоть на что–нибудь, кроме брожения говнов, способны? Я в этом сомневаюсь, и не без оснований... Написал yaila на rightmusicvideo.d3.ru / комментировать Full Article rising d3
d3 44. Return-path: <lwlui@guptacoal.com> Envelope-to: petgord34truew ... By www.similia.ca Published On :: 2009-01-26T01:46:28+00:00 Simply uk gadgets vendita casa annuncio immobiliare, download giochi ... Simply UK Gadgets will be back shortly.<br> This is not a ploy to get more hits. ... Full Article
d3 GD3 Sport - How many channels? By www.fitfreak.net Published On :: Tue, 12 Nov 2024 23:29:01 GMT Good Day, I am looking at upgrading the head unit on my 2008 Honda Fit Sport. Since I have the additional 2 tweeters in the door from the sport package does this mean I need to get a six channel... Full Article Fit I.C.E.
d3 World War Iphone Alliance Code 2S2D3T China By bryanong.blogspot.com Published On :: Fri, 13 Jan 2012 20:44:00 +1030 World War Iphone Alliance Code 2S2D3T China. My country is China and alliance code is 2S2D3T. I only will add Chinese Flag. Chinese Brothers and Sisters, please add me and let's form a powerful World War alliance. If you are not Chinese flag, will consider adding you into alliance as well but you must be of high level and a player with integrity and play fair. I don't like players who keep sanctioning other world war players and also those who keep farming especially farm on low level or inexperienced world war players. ATM is definitely welcome, please send me a link and I will definitely welcome your generosity. Once again, please add my World War Iphone Alliance Code 2S2D3T and flag is China. ------------------------------- World War Iphone Alliance Code 2S2D3T China. World War Iphone Alliance Code 2S2D3T China. World War Iphone Alliance Code 2S2D3T China. World War Iphone Alliance Code 2S2D3T China. World War Iphone Alliance Code 2S2D3T China. Full Article World War Iphone
d3 New Camera: Canon PowerShot SD30 By www.shuttermag.com Published On :: 2005-08-26 Sure it's a fashion statement, but the PowerShot SD30 Digital ELPH lives up to its looks with impressive features including a 5.0 Megapixel CCD, high quality optical zoom and a cool new Camera Station. Full Article
d3 AIS, ZTE complete D3-ELAA trial in Thailand By www.telecompaper.com Published On :: Wed, 13 Nov 2024 08:51:00 +0100 (Telecompaper) Thai operator AIS and ZTE have completed a Dynamic Distributed and Deterministic Extremely Large Antenna Array (D3-ELAA) trial on the local market... Full Article
d3 D3.1 Application software implementing remote sensing, distributional down- and biodiversity up-scaling By www.eubon.eu Published On :: Wed, 23 Sep 2015 15:55:12 +0300 Full Article Events
d3 D3.2 Report on integrated distributional modelling and associated software By www.eubon.eu Published On :: Wed, 23 Mar 2016 15:22:11 +0200 Full Article Events
d3 D3.3 Updated release and report on publication data-mining software By www.eubon.eu Published On :: Wed, 30 Nov 2016 11:29:46 +0200 Full Article Events
d3 The Urban Cyclist's Conundrum: Evaluating Bodywel T16 vs. DYU D3F for City Riding By www.24-7pressrelease.com Published On :: Sun, 26 May 2024 08:00:00 GMT A Detailed Comparison of Bodywel T16 and DYU D3F Electric Bikes for City Commuters Full Article
d3 The Brand New TuneFab Pandora Music Converter With Power-Packed Features: Select Format, ID3, Metadata & More By www.24-7pressrelease.com Published On :: Thu, 27 Apr 2023 08:00:00 GMT Suppose Pandora's music magic is a passion in your pastime. In that case, you must take advantage of the jaw-dropping opportunities to save online Pandora passion for your offline pleasure with the recently launched TuneFab Pandora Music Converter. Full Article
d3 Get Ready With the Latest Features & Trendy Function Of TuneFab YouTube Music Converter: Multi-Format, Batch Saving, ID3 Tags & More To Explore By www.24-7pressrelease.com Published On :: Fri, 19 May 2023 08:00:00 GMT To tap with friends, you have to grab the new trends in the TuneFab YouTube Music Converter. This brand-new music downloader will get you the entire YouTube music world in your offline library with ultimate customization & specifications. Full Article
d3 UkeySoft Spotify Music Converter & Apple Music Converter: Multi-Format, Batch Conversion, ID3 Tags & More To Explore By www.24-7pressrelease.com Published On :: Sun, 06 Aug 2023 08:00:00 GMT Do you want to convert Spotify Music and Apple Music to MP3 for listening offline? Try the professional UkeySoft Spotify Music Converter and Apple Music Converter, which can make all Apple Music tracks and Spotify songs playable on any devices. Full Article
d3 WikiLeaks: 2009-12-07: 09BAGHDAD3154: Compensation Finalized... By www.atour.com Published On :: Tue, 31 Dec 2013 10:09:00 UT WikiLeaks: 2009-12-07: 09BAGHDAD3154: Compensation Finalized to Repair Heart of Iraq's Christian Community Full Article WikiLeaks Information
d3 C0d3rs Champions, la serie de Amazon para impulsar la tecnología y la programación By www.spreaker.com Published On :: Sat, 23 Jul 2022 17:56:18 +0000 C0d3rs Champions, la serie de Amazon para impulsar la tecnología y la programación Full Article
d3 Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors [Metabolism, Transport, and Pharmacogenetics] By jpet.aspetjournals.org Published On :: 2024-10-18T07:04:15-07:00 Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited. SIGNIFICANCE STATEMENT This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors. Full Article
d3 SOLARIS Trial: High-Dose Vitamin D3 in Metastatic Colon Cancer By www.medindia.net Published On :: SOLARIS, a phase 3 clinical trial led by Dana-Farber Cancer Institute, tested the addition of high-dose medlinkvitamin D3/medlink to standard treatment Full Article
d3 A narrowband ultraviolet-B-emitting LiCaPO4:Gd3+ phosphor with super-long persistent luminescence for over 100 h By pubs.rsc.org Published On :: Inorg. Chem. Front., 2024, Advance ArticleDOI: 10.1039/D4QI02407A, Research ArticleXihui Shan, Xulong Lv, Dongxun Chen, Yi Zhang, Lixin Ning, Yanjie LiangIntense NB-UVB emission at 312 nm and super-long persistent luminescence for >100 h have been realized in a LiCaPO4:Gd3+ phosphor after ceasing X-ray excitation, accompanied by a remarkable white-to-brown photochromism phenomenon.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 Towards ultra-sensitive multimodal luminescent thermometers enabled by high crystal field strength of Lu2CaMg2Ge3O12:Yb3+,Nd3+,Er3+ phosphors By pubs.rsc.org Published On :: Inorg. Chem. Front., 2024, 11,7955-7965DOI: 10.1039/D4QI01767F, Research ArticleZhijiao Zhao, Mengmeng Dai, Kejie Li, Guiying Liang, Yanling Wei, Zuoling FuAn effective full-spectrum thermometer covering from the visible to NIR-II band was designed based on garnet Lu2CaMg2Ge3O12:Yb3+,Er3+/Nd3+ phosphors; meanwhile, Er3+ (4I13/2) split into four Stark sublevels due to high crystal field strength.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 Tunable luminescence via Cr3+–Yb3+/Nd3+ energy transfer in Cr3+ and Yb3+/Nd3+ coactivated NIR phosphors for non-destructive analysis By pubs.rsc.org Published On :: Inorg. Chem. Front., 2024, Advance ArticleDOI: 10.1039/D4QI02260B, Research Article Open Access   This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.Xiaowei Zhang, Dashuai Sun, Pengcheng Luo, Luhui Zhou, Zheng Lu, Jia Liu, Congcong Fan, Xinyu Ye, Hongpeng YouNovel high-efficiency near-infrared phosphors with tunable luminescence via Cr3+–Yb3+/Nd3+ energy transfer for non-destructive analysis.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 The structural, electronic and thermodynamic properties of the designed p-benzoquinone based dicationic ionic liquids: insight from DFT–GD3 and QTAIM By pubs.rsc.org Published On :: Mol. Syst. Des. Eng., 2024, Advance ArticleDOI: 10.1039/D4ME00119B, PaperHossein Roohi, Sajedeh Habibipour, Khatereh GhauriIn this work, physicochemical properties of the dicationic ionic liquids [BTAD][A1–8]2 ([BTAD]2+ = [p-C6O2(N3H2)2]2+ and A1–8 = [CH3CO2]−, [CF3CO2]−, [N(CN)2]−, [CF3SO3]−, [ClO4]−, [BF4]−, [NTf2]− and [PF6]−) were theoretically investigated.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 Review: Samsung Galaxy Z Flip3 and Fold3 By www.wired.com Published On :: Wed, 15 Sep 2021 16:00:00 +0000 The Galaxy Z Flip3 and Fold3 are Samsung's newest folding phones. Both have bright and colorful 120-Hz screens that are easy to read in daylight, and both have an IPX8 water-resistance rating. And while the Flip3 is wonderfully compact, the Fold3 has made multitasking even easier. Reviews Editor Julian Chokkattu takes us through both phones and why you don't necessarily need a folding phone, but you may want one. Full Article
d3 8802-11-2018/Amd3-2020 - Telecommunications and exchange between information technology systems--Requirements for local and metropolitan area networks--Part 11:Wireless LAN medium access control (MAC) [electronic journal]. By encore.st-andrews.ac.uk Published On :: Full Article
d3 Synthesis and characterization of a CsPbCl3 perovskite doped with Nd3+: structural, optical, and energy transfer properties By pubs.rsc.org Published On :: Inorg. Chem. Front., 2024, Advance ArticleDOI: 10.1039/D4QI00171K, Research ArticleMariusz Stefanski, Bartosz Bondzior, Adam Basinski, Maciej Ptak, Bibo Lou, Chong-Geng MaThe levels of Nd3+ in CsPbCl3 lie below the top of the host's VB. Consequently, Nd3+ luminescence is not observed.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights By pubs.rsc.org Published On :: Biomater. Sci., 2024, 12,2108-2120DOI: 10.1039/D3BM02107F, PaperOscar Ceballos-Sanchez, Diego E. Navarro-López, Jorge L. Mejía-Méndez, Gildardo Sanchez-Ante, Vicente Rodríguez-González, Angélica Lizeth Sánchez-López, Araceli Sanchez-Martinez, Sergio M. Duron-Torres, Karla Juarez-Moreno, Naveen Tiwari, Edgar R. López-MenaThe antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition.The content of this RSS Feed (c) The Royal Society of Chemistry Full Article
d3 ultra-d3.zip By packetstormsecurity.com Published On :: Tue, 17 Aug 1999 00:14:22 GMT No information is available for this file. Full Article
d3 Fighting Illicit Financial Flows - FfD3 Side Event By www.oecd.org Published On :: Mon, 06 Jul 2015 17:57:00 GMT Fighting Illicit Financial Flows: Are Partnerships and Policy Coherence the keys to success? Full Article
d3 Crystal structure and chemistry of tricadmium digermanium tetraarsenide, Cd3Ge2As4 By scripts.iucr.org Published On :: 2019-08-02 A cadmium germanium arsenide compound, Cd3Ge2As4, was synthesized using a double-containment fused quartz ampoule method within a rocking furnace and a melt-quench technique. The crystal structure was determined from single-crystal X-ray diffraction (SC-XRD), scanning and transmission electron microscopies (i.e. SEM, STEM, and TEM), and selected area diffraction (SAD) and confirmed with electron backscatter diffraction (EBSD). The chemistry was verified with electron energy loss spectroscopy (EELS). Full Article text
d3 Crystal structures of two charge–transfer complexes of benzo[1,2-c:3,4-c':5,6-c'']trithiophene (D3h-BTT) By scripts.iucr.org Published On :: 2019-09-30 Benzo[1,2-c:3,4-c':5,6-c'']trithiophene (D3h-BTT) is an easily prepared electron donor that readily forms charge–transfer complexes with organic acceptors. We report here two crystal structures of its charge–transfer complexes with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and buckminsterfullerene (C60). The D3h-BTT·TCNQ complex, C12H6S3·C12H4N4, crystallizes with mixed layers of donors and acceptors, with an estimated degree of charge transfer at 0.09 e. In the D3h-BTT·C60·toluene complex, C12H6S3·C60·C7H8, the central ring of BTT is `squeezed' by the C60 molecules from both faces. However, the degree of charge transfer is low. The C60 unit is disordered over two sites in a 0.766 (3):0.234 (3) ratio and was refined as a two-component inversion twin. Full Article text
d3 ID30A-3 (MASSIF-3) – a beamline for macromolecular crystallography at the ESRF with a small intense beam By scripts.iucr.org Published On :: 2020-04-29 ID30A-3 (or MASSIF-3) is a mini-focus (beam size 18 µm × 14 µm) highly intense (2.0 × 1013 photons s−1), fixed-energy (12.81 keV) beamline for macromolecular crystallography (MX) experiments at the European Synchrotron Radiation Facility (ESRF). MASSIF-3 is one of two fixed-energy beamlines sited on the first branch of the canted undulator setup on the ESRF ID30 port and is equipped with a MD2 micro-diffractometer, a Flex HCD sample changer, and an Eiger X 4M fast hybrid photon-counting detector. MASSIF-3 is recommended for collecting diffraction data from single small crystals (≤15 µm in one dimension) or for experiments using serial methods. The end-station has been in full user operation since December 2014, and here its current characteristics and capabilities are described. Full Article text
d3 Socialfix Media Launches Amplified3 Podcast By www.24-7pressrelease.com Published On :: Thu, 21 Nov 2019 07:00:00 GMT A Show of Emerging Tech, Media & Entrepreneurship Full Article
d3 Woman Owned Startup Tackles Microsoft D365 Finance and Operations Online Training By www.24-7pressrelease.com Published On :: Thu, 03 May 2018 07:00:00 GMT This week Item by Item, a woman owned company based in Texas announced the release of the IBI Learning Platform which provides convenient and cost effective online and mobile training to Microsoft Dynamics 365 (D365) Finance and Operations end users. Full Article
d3 IBI (Item by Item) Announces the Release of Courses and Learning Paths for Microsoft D365 F&O Advanced Warehouse By www.24-7pressrelease.com Published On :: Tue, 11 Jun 2019 07:00:00 GMT Item by Item (IBI) announced today the expansion of its Microsoft Dynamics 365 Finance and Operations online training curriculum with a new set of online courses focusing on Advanced Warehouse module. Full Article
d3 Triple ISPO Awards Success for D3O Protection By www.24-7pressrelease.com Published On :: Wed, 30 Jan 2019 07:00:00 GMT Market-leading impact protection brand D3O is a common denominator in three ISPO 2019 award-winning products Full Article
d3 Crystallization of (20R) and (20S) analogs of 2-methylene-19-nor-24-dimethyl-1α,25-dihydroxyvitamin D3 By www.freepatentsonline.com Published On :: Tue, 11 Nov 2014 08:00:00 EST Disclosed are methods of purifying (20R) and (20S) analogs of 2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D3 to obtain the (20R) and (20S) analogs in crystalline form. The method includes the steps of preparing a solvent of either diethyl ether or a mixture of 2-propanol and hexane, dissolving a product containing the (20R) and (20S) analog to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. Full Article
d3 Low-calcemic 16,23-diene 25-oxime analogs of 1α,25-dihydroxy vitamin D3 By www.freepatentsonline.com Published On :: Tue, 09 Dec 2014 08:00:00 EST The present invention provides novel 16,23-diene 25-oxime ether analogs of 1,25-dihydroxy vitamin D3, compositions comprising these compounds and methods of using these compounds as inhibitors of CYP24. In particular, the novel compound of the invention are useful for treating diseases which benefit from a modulation of the levels of 1,25-dihydroxy vitamin D3, for example, cell-proliferative disorders. Full Article
d3 Crystallization of (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 By www.freepatentsonline.com Published On :: Tue, 27 Jan 2015 08:00:00 EST Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. Full Article
d3 23-yne-vitamin D3 derivative By www.freepatentsonline.com Published On :: Tue, 14 Apr 2015 08:00:00 EDT To provide a novel vitamin D3 derivative useful as a therapeutic agent for osteoporosis. Provided is a vitamin D3 derivative represented by the following formula (1) or a medicinally acceptable solvate thereof: wherein R1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkylcarbonyloxyalkyl group with each alkyl having 1 to 6 carbon atoms, or an arylcarbonyloxyalkyl group with the aryl having 6 to 10 carbon atoms and the alkyl having 1 to 6 carbon atoms; R2 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or, together with the other R2 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; R3 represents an alkyl group having 1 to 6 carbon atoms or, together with the other R3 and the carbon atom to which they are bound to, may form a cyclic alkyl group having 3 to 6 carbon atoms; X represents an oxygen atom or a methylene group; and n represents an integer of 1 or 2. Full Article
d3 Crystallization of (20R) 19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 By www.freepatentsonline.com Published On :: Tue, 26 May 2015 08:00:00 EDT Disclosed are methods of purifying the compound (20R)-19-nor-24-difluoro-1α,25-dihydroxyvitamin D3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. Full Article
d3 Variety corn line HID3483 By www.freepatentsonline.com Published On :: Tue, 19 May 2015 08:00:00 EDT The present invention provides an inbred corn line designated HID3483, methods for producing a corn plant by crossing plants of the inbred line HID3483 with plants of another corn plant. The invention further encompasses all parts of inbred corn line HID3483, including culturable cells. Additionally provided herein are methods for introducing transgenes into inbred corn line HID3483, and plants produced according to these methods. Full Article
d3 Maize hybrid X08D387 By www.freepatentsonline.com Published On :: Tue, 19 May 2015 08:00:00 EDT A novel maize variety designated X08D387 and seed, plants and plant parts thereof, produced by crossing Pioneer Hi-Bred International, Inc. proprietary inbred maize varieties. Methods for producing a maize plant that comprises crossing hybrid maize variety X08D387 with another maize plant. Methods for producing a maize plant containing in its genetic material one or more traits introgressed into X08D387 through backcross conversion and/or transformation, and to the maize seed, plant and plant part produced thereby. This invention relates to the maize variety X08D387, the seed, the plant produced from the seed, and variants, mutants, and minor modifications of maize variety X08D387. This invention further relates to methods for producing maize varieties derived from maize variety X08D387. Full Article
d3 SD3 II v. Black & Decker Inc. By feeds.findlaw.com Published On :: 2018-04-19T08:00:00+00:00 (United States Fourth Circuit) - Affirming the grant of summary judgment to a group of table saw manufacturers sued under antitrust laws because the acts upon which the complaint was based occurred prior to 2002, the claims expired in 2006, and the suit was not filed until 2014, refusing to apply the equitable doctrine of fraudulent concealment because the plaintiff was found to have had notice, at latest, by 2003. Full Article Consumer Protection Law Civil Procedure Antitrust & Trade Regulation
d3 SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement. Full Article
d3 Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
d3 212Pb Alpha-Radioimmunotherapy targeting CD38 in Multiple Myeloma: a preclinical study. By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Multiple myeloma (MM) is a plasma cell cancer and represents the second most frequent hematological malignancy. Despite new treatments and protocols including high doses chemotherapy associated with autologous stem cell transplantation, the prognosis of MM patients is still poor. Alpha-radioimmunotherapy (alpha-RIT) represents an attractive treatment strategy due to the high linear energy transfer and short path length of alpha-radiation in tissues, resulting in high tumor cell killing and low toxicity to surrounding tissues. In this study, we investigated the potential of alpha-RIT with 212Pb-Daratumumab (anti-CD38), in both in vitro and in vivo models, as well as an anti-mouse CD38 antibody using in vivo models. Methods: Inhibition of cell proliferation after incubation of RPMI8226 cell line with increasing activities (0.185-3.7 kBq/ml) of 212Pb-isotypic control or 212Pb-Daratumumab was evaluated. Biodistribution was performed in vivo by SPECT-CT imaging and post-mortem. Dose range finding (DRF) and acute toxicity studies were conducted. As Daratumumab does not bind the murine CD38, biodistribution and DRF were also determined using an anti-murine CD38 antibody. To evaluate in vivo efficacy of 212Pb-Daratumumab, mice were engrafted subcutaneously with 5.106 RPMI8226 cells. Mice were treated 13 days post-engraftment with an intravenous injection of 212Pb-Daratumumab or control solutions. Therapeutic efficacy was monitored by tumor volume measurements and overall survival. Results: Significant inhibition of proliferation of the human myeloma RPMI8226 cell line was observed after three days of incubation with 212Pb-Daratumumab compared to 212Pb-Isotypic Control or cold antibodies. Biodistribution studies showed a specific tumoral accumulation of Daratumumab. No toxicity was observed with 212Pb-Daratumumab up to 370 kBq due to the lack of cross-reactivity. Nevertheless, acute toxicity experiments with 212Pb-anti-mCD38 established a toxic activity of 277.5 kBq. To remain within realistically safe treatment activities for efficacy studies, mice were treated with 185 kBq or 277.5 kBq of 212Pb-Daratumumab. Marked tumor growth inhibition compared to controls was observed, with a median survival of 55 days for 277.5 kBq of 212Pb-Daratumumab instead of 11 for PBS control groups. Conclusion: These results showed 212Pb-Daratumumab efficacy on xenografted mice with significant tumor regression and increased survival. This study highlights alpha-RIT potency in MM treatment. Full Article
d3 Biodistribution of a CD3/EpCAM bispecific T-cell engager is driven by the CD3 arm By jnm.snmjournals.org Published On :: 2020-04-13T14:09:24-07:00 BiTE® (Bispecific T-cell engager) molecules are designed to engage and activate cytotoxic T-cells to kill tumor cells. Little is known about their biodistribution in immunocompetent settings. To explore their pharmacokinetics and the role of the immune cells, BiTE molecules were radiolabeled with positron emission tomography (PET) isotope zirconium-89 (89Zr) and studied in immunocompetent and immunodeficient mouse models. PET images and ex-vivo biodistribution in immunocompetent mice with 89Zr-muS110, targeting mouse CD3 (Kd = 2.9 nM) and mouse EpCAM (Kd = 21 nM), and 89Zr-hyS110, targeting only mouse CD3 (Kd = 2.9 nM), showed uptake in tumor, spleen and other lymphoid organs, while the human-specific control BiTE 89Zr-AMG 110 showed similar tumor uptake but lacked spleen uptake. 89Zr-muS110 spleen uptake was lower in immunodeficient than in immunocompetent mice. After repeated administration of non-radiolabeled muS110 to immunocompetent mice 89Zr-muS110 uptake in spleen, and other lymphoid tissues, decreased and was comparable to uptake in immunodeficient mice, indicating saturation of CD3 binding sites. Autoradiography and immunohistochemistry demonstrated colocalization of 89Zr-muS110 and 89Zr-hyS110 with CD3-positive T-cells in the tumor and spleen but not with EpCAM expression. Also, uptake in the duodenum correlated with a high incidence of T-cells. This study shows that in immunocompetent mice the BiTE 89Zr-muS110 distribution is predominantly based on its high affinity CD3 binding arm. Significance: 89Zr-muS110 biodistribution is mainly dependent on the T-cell targeting arm with limited contribution of its second arm, targeting EpCAM. These findings highlight the need for extensive biodistribution studies of novel bispecific constructs as results might have implications for their respective drug development and clinical translation. Full Article
d3 Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation By feedproxy.google.com Published On :: 2020-05-01 Henry J. PownallMay 1, 2020; 61:595-597Commentary Full Article
d3 SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement. Full Article
d3 Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article