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1

Schetky, L. McD. "Miscellaneous Applications of Intermetallic Compounds." MRS Bulletin 21, no. 5 (May 1996): 50–55. http://dx.doi.org/10.1557/s088376940003551x.

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So ubiquitous are intermetallic compounds (IMCs) in all areas of materials application that examples of their use in industrial, medical, consumer, and military products are almost limitless. We will in this brief discussion attempt to identify some of the more important of these applications, which we categorize as miscellaneous. These include shape-memory alloys (SMAs), gold alloys used in jewelry, dental amalgams, tribology applications, diffusion barriers in electronic devices, elevated-heat storage systems, nuclear applications, metal-matrix composites, and high damping alloys. In some cases, the IMC is present as a precipitate or dispersed particle that provides strengthening or other property modification while in other examples, the IMC is employed in bulk form.
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2

Latif, Noor Syafiqah Habdul, Sheikh Ahmad Izaddin Sheikh Mohd Ghazali, Erna Normaya Abdullah, Azizul Hakim Lahuri, Mohammad Fadzlee Ngatiman, and Nur Nadia Dzulkifli. "Synthesis, Structural, Density Functional Theory, and X-Ray Diffraction Study of Zn(II) N-Isopropylbenzyldithiocarbamate: Anti-Corrosion Screening in Acid Media." Indonesian Journal of Chemistry 18, no. 4 (November 12, 2018): 755. http://dx.doi.org/10.22146/ijc.34703.

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Corrosion of metal is a serious issue across many industries and is considered costly. Acids used during the cleaning process in industries may contribute to metal erosion. Dithiocarbamate is a ligand that can act as a corrosion inhibitor due to the presence of sulfur and nitrogen as electronegative atoms. Zn(II) N-isopropylbenzyldithiocarbamate (Zn[N-isopbenzdtc]2) complex was synthesized through direct synthetic method of < 4 °C and characterized using Fourier Transform Infrared-Attenuated Total Reflectance (FTIR-ATR), Ultraviolet-Visible (UV-Vis), Nuclear Magnetic Resonance (NMR), X-ray crystallography study, molar conductivity, melting point, and gravimetric analysis. Corrosion inhibition of mild steel was studied for different corrosive media (1 M HCl and 1 M H2SO4). The synthesized inhibitor was studied at different concentrations of 1, 2, 3, 4, and 5 mM at 40 °C. As a conclusion, as the inhibitor concentration decreased, the efficiency of the corrosion inhibitor also decreased at a constant temperature. In this study, it showed that the corrosion activity of mild steel in 1 M H2SO4 was higher compared to 1 M HCl due to the higher concentration of H+, which makes H2SO4 more corrosive than HCl.
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3

Alkhalaf, Maha I., and Wafa S. Alansari. "Ameliorative Effects of Indole-3-Carbinol and/or Sulforaphane Against Gold Nanoparticle-Induced Cytotoxicity in Rats." Science of Advanced Materials 13, no. 2 (February 1, 2021): 222–34. http://dx.doi.org/10.1166/sam.2021.3891.

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Gold nanoparticles (GNPs) are the most commonly used metal nanoparticles due to their promising characteristics. However, application of GNs in medical and biological fields has resulted in toxicity to several organs. Indole-3-carbinol (I3C) and sulforaphane (SF) are the two well-known natural compounds, largely present in cruciferous vegetables. This study aimed to explore the therapeutic efficacy of I3C and SF alone or in combination against GN-induced renal and cardiac toxicities. Fifty male Albino rats were randomly segregated into five groups with each group containing 10 rats; G1, control; G2, intraperitoneally administered with a suspension of GNPs (10 nm in size; 20 µg/kg body weight (b.w.) for 7 days; G3, GN-injected rats, supplemented with SF (5 mg/kg b.w) daily for 7 days; G4, GN-injected rats, supplemented orally with I3C (150 mg/kg b.w.) for 7 days and G5, GN-injected rats supplemented orally with SF and I3C daily for 7 days. GN treatment significantly disturbed kidney functional markers, as evidenced by significantly increased levels of urea, creatinine and creatine kinase. Additionally, GNs significantly increased renal and cardiac levels of malondialdehyde, 8-hydroxydeoxyguanosine and interleukin-6, and depleted, glutathione S-transferase, glutathione reductase, superoxide dismutase, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2. In contrast, treatment with I3C and SF alone or in combination significantly restored all the parameters to their near normal levels. GN induced histological abnormalities were also significantly attenuated. Taken together, the data indicate that the SF and I3C are more effective when given separately than when given together in lowering GN-induced toxicity by their ability to alleviate oxidative stress and inflammation.
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Wise, Robert K., Sherry M. Waldhausen, Van T. Nguyen, David A. Palanzo, and Larry D. Baer. "Unique static discharge events on two CentriMag® (2nd Gen) ECMO patients causing console failure." Perfusion 33, no. 8 (June 29, 2018): 707–10. http://dx.doi.org/10.1177/0267659118779671.

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The use of ECMO for cardiovascular support continues to increase in the United States and around the world. It is not a benign endeavor as serious complications may occur. We present our experience of two second generation CentriMag® (Abbott formerly Thoratec Inc.) console failures that occurred while transporting the patients to other areas of the hospital. In each incident, the patients were immediately placed on back-up units and the transport continued. No patient complications could be attributed to the failures. An investigation by Abbott engineers traced the failure to a static build-up and discharge caused by a non-manufacturer-approved metal rod that was utilized to mount the external monitor. The static discharge caused a disruption of electrical continuity between the control system and the motor, stopping the motor as well as the monitoring system. Removal of the mounting rod prevented replication of the situation in the lab. We have removed the rod from our clinical units and have not experienced any other pump failures.
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5

Lamb, C. A., J. Doyle, G. Hulme, K. Cooke, A. Au-Yeung, J. Ojeda-Garcia, A. Fuller, et al. "P002 Methodological development of single-cell phenotyping and spatial analysis of intestinal leukocyte, stromal and epithelial cell populations in inflammatory bowel disease formalin fixed paraffin embedded tissue by Hyperion imaging mass cytometry." Journal of Crohn's and Colitis 15, Supplement_1 (May 1, 2021): S123—S125. http://dx.doi.org/10.1093/ecco-jcc/jjab076.131.

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Abstract Background Conventional cellular phenotyping of intestinal cell populations by multi-parameter fluorescence cytometry is reliant on collection of fresh tissue for immediate enzymatic or mechanical disaggregation, or cryopreservation of samples. These factors limit widescale use of tissue for research, increase cost, and time for sample collection or preparation. Due to tissue disaggregation suspension cytometry does not provide data regarding spatial localisation of cells in tissue. Formalin fixed paraffin embedded (FFPE) tissue is widely collected at endoscopy and surgery for clinical histopathological assessment, and can be stored and transported at room temperature. Methods We aimed to develop a method for analysing FFPE intestinal tissue using Imaging Mass Cytometry (IMC) in combination with an analysis pipeline for cellular phenotyping and spatial characterisation that preserved multi-parameter, high dimensional phenotyping capabilities normally only afforded by suspension methodologies. FFPE blocks were accessed following written informed consent in accordance with research and ethics committee approval. Carrier-free antibodies specific to cell subsets of interest were selected based on conventional suspension fluorescence cytometry and immunohistochemistry data. Results Antibodies were conjugated to metal isotopes. Antigen retrieval and antibody dilution was optimised on 4µm tissue sections using Tris-EDTA pH 9 initially by immunofluorescence then in multiple assays by Hyperion (Fluidigm) IMC (Figure 1A). An analysis pipeline was developed based on the “Bodenmiller approach” using a combination of R, Python and MATLAB packages: CellProfiler and ilastik to segment single cells, and ImaCyte to explore the resident phenotypes and cellular neighbourhoods in diseased and healthy tissues. A staining panel with 25 antibodies was optimised to identify stromal, epithelial and leukocyte populations. Training algorithms allowed computational segmentation of nuclear, cytoplasmic and non-cellular regions (Figure 1B), cell mask, segmentation and spatial analysis (Figure 1C), and t-SNE (Figure 1D). Representative three parameter images created in MCD viewer (Fluidigm) are shown in Figure 1E to demonstrate cell populations and spatial localisation. Conclusion Quantifiable, multiparameter cellular phenotyping with spatial visualisation can be undertaken with FFPE intestinal tissue using IMC. Due to the existence of archival healthcare samples, the ease of tissue acquisition, processing and storage of FFPE specimens this provides a valuable resource for investigation, including mechanisms of disease pathogenesis, molecular biomarker discovery, and longitudinal pharmacodynamic analysis in clinical trials.
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6

Coelho-Silva, Fernanda, Luciano Augusto Cano Martins, Daniela Azeredo Braga, Eliana Zandonade, Francisco Haiter-Neto, and Sergio Lins de-Azevedo-Vaz. "Influence of windowing and metal artefact reduction algorithms on the volumetric dimensions of five different high-density materials: a cone-beam CT study." Dentomaxillofacial Radiology 49, no. 8 (December 1, 2020): 20200039. http://dx.doi.org/10.1259/dmfr.20200039.

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Objective: To assess the influence of windowing and metal artefact reduction (MAR) algorithms on the volumetric dimensions of high-density materials using two CBCT systems. Methods: Four cylinders of amalgam, cobalt-chromium, gutta-percha, titanium and zirconium, were manufactured and their physical volumes (PV) were measured. A polymethyl methacrylate phantom containing the cylinders was submitted to CBCT acquisitions with Picasso Trio and OP300 units with their MAR enabled and disabled. The tomographic volume (TV) of all the cylinders was obtained by semi-automatic segmentation using two windowing adjustments: W1—large window width and upper window level; W2—narrow window width and low window level. Volumetric distortion was expressed as the difference between TV and PV. Statistics comprised intraclass correlation coefficient (ICC) and analysis of variance (ANOVA) for repeated measures with Tukey post hoc test (α = 5%). Results: The ICC values ​​indicated excellent reproducibility of TV. Gutta-percha and titanium resulted in the smallest volumetric distortion. Using W1 provided less volumetric distortion for almost all experimental conditions (p < 0.05). Activating MAR algorithm of Picasso Trio underestimated gutta-percha and titanium TV (p < 0.05) and was inefficient in significantly reducing the volumetric distortion of the other materials (p > 0.05). Disabling MAR algorithm of OP300 resulted in smaller volumetric distortion for almost all experimental conditions (p < 0.05). Conclusions: The TV of gutta-percha and titanium were closer to the PV. In general, the MAR algorithms of both systems were inefficient in significantly reducing the volumetric distortion of high-density materials. We encourage the use of large window width and upper window level to evaluate high-density materials.
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7

Richards, Paul G., Douglas A. Anderson, and David W. Simpson. "A survey of blasting activity in the United States." Bulletin of the Seismological Society of America 82, no. 3 (June 1, 1992): 1416–33. http://dx.doi.org/10.1785/bssa0820031416.

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Abstract Statistical information on chemical explosions is needed in seismology, to evaluate the practical difficulties in identifying this very common type of seismic source from other seismic sources such as small earthquakes and small nuclear explosions. We have obtained data on blasting activity from three different sources: (1) overview information from the U.S. Bureau of Mines (USBM) on the total amount of chemical explosives used in the United States during 1987, with breakdowns into different explosive types, and usage by different states; (2) overview information from the Mine Safety and Health Administration (MSHA) on the numbers of mines, of different types, in the United States; and (3) detailed information from a private company (Vibra-Tech Engineers, Inc.) on total shot size and size of charge per delay for 20,813 blasts carried out in 1987 at 532 locations. Our procedure has been to extrapolate the detailed information contained in the 1987 Vibra-Tech data for a limited number of states and thus to obtain estimates for the whole country on numbers of shots and their size distribution. The extrapolation is constrained by the data from USBM (numbers of shots, sizes) and the MSHA (locations). Blasting activity does not fluctuate greatly from year to year and 1987 was representative of current practice. We find that about 2.2 million metric tons of chemical explosive are used annually in the continental U.S., principally in mining for coal and metal ores. On a typical work day, there are roughly 30 explosions greater than 50 tons, including about one greater than 200 tons. There was one industrial explosion in 1987 at about 1400 tons. For shots between 1 ton and 100 tons, the cumulative distribution has a b-value near unity; that is, if N is the number of shots (per year) greater than or equal to W tons, N ∝ 10 − b log ⁡ W = W − b with b roughly equal to 1. This result is similar to the size distribution of earthquakes greater than magnitude mb, N ∝ 10 − b m b . Almost all chemical explosions above 1 ton are ripple-fired. The typical shot uses 20 to 50 separate delays.
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Oetjen, Karolyn A., Diane E. Bender, Marianna B. Ruzinova, Stephen T. Oh, and Daniel C. Link. "Interrogating the Spatial Architecture of Human Bone Marrow Via Imaging Mass Cytometry." Blood 134, Supplement_1 (November 13, 2019): 3728. http://dx.doi.org/10.1182/blood-2019-127460.

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Hematopoietic stem cell (HSC) proliferation, self-renewal, differentiation, and trafficking are dependent, in part, upon signals generated by stromal cells in the bone marrow. Stromal cells are organized into niches that support specific subsets of hematopoietic progenitors. Intimate interactions between HSCs and neighboring stromal cells coordinate hematopoietic responses during periods of physiologic stress, while also maintaining the lifelong integrity of the hematopoietic stem cell pool. Hematopoietic niches are comprised of a heterogeneous population of stromal and hematopoietic cells. The identity and function of the known stromal cell subsets have primarily been gleaned through genetic manipulation of mouse models. In humans, the spatial organization of these stromal cells in bone marrow and the signals they generate to regulate hematopoiesis are poorly understood. Current methods to characterize bone marrow mesenchymal stromal cells in humans include: 1) immunostaining of bone sections; 2) analysis of flow sorted stromal cells; and 3) analysis of ex vivoexpanded mesenchymal stem/progenitors. Major limitations to all of these approaches exist that relate to the heterogeneity of bone marrow stromal cells, the lack of markers that reliably distinguish different stromal cell populations, and inherent technical limitations of the assays, such as the number of markers that can be analyzed at one time. Here we report our efforts to use imaging mass cytometry imaging (IMC) to interrogate the complex cellular architecture of human bone marrow. IMC allows for the simultaneous detection of up to 40 markers through the use of antibodies conjugated to elemental metal tags acquired by time-of-flight mass spectrometry. We first used standard immunostaining techniques to develop a panel of antibodies compatible with archived formalin-fixed paraffin-embedded (FFPE) human bone marrow specimens using a heat-induced epitope retrieval method. Hematopoietic lineages have been successfully identified using CD11b, CD68, CD15, CD14, CD16, CD11c, CD20, CD3, CD4, CD8a, CD38, CD45RA, CD45RO, CD235a, CD71, CD34, CD31; stromal cells and structures with CXCL12, alpha-smooth muscle actin, collagen I, vimentin; and nuclear staining using Ki67, Histone H3, and DNA intercalator. We used panels consisting of up to 18 of these antibodies each to test IMC on FFPE human bone marrow specimens. Imaging was performed using the Hyperion Imaging System (Fluidigm), which consists of a UV laser scanning module to capture regions of more than 10,000 cells with 1-micron resolution coupled with a Helios Mass Cytometer. Image analysis was performed by creation of a cell segmentation mask using CellProfiler software and high dimensional analysis in histoCAT. Representative images and corresponding dimensional reduction with t-SNE are shown in Figure 1A-H, demonstrating successful discrimination of distinct hematopoietic lineages. Gating on subpopulations within the t-SNE clusters can be projected on to the original image to illustrate spatial distribution and marker co-expression, as an example CD3+ and CD8+ cells are shown in Figure 1I. These data indicate that IMC allows for highly multiplexed analysis of bone marrow cell populations. Developing imaging techniques for analysis of tissue-banked FFPE bone marrow samples would have broad applications for translational research on hematologic diseases. In particular, this technology has tremendous potential to advance understanding of the spatial architecture of human bone marrow and to investigate alterations in the bone marrow environment in malignant hematopoiesis. Disclosures Oh: Incyte: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy.
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Metais, Jean-Yves, Phillip A. Doerfler, Thiyagaraj Mayuranathan, Daniel E. Bauer, Stephanie Fowler, Matthew Hsieh, Varun Katta, et al. "CRISPR-Cas9 Genome Editing of γ-Globin Promoters in Human Hematopoietic Stem Cells to Induce Erythrocyte Fetal Hemoglobin for Treatment of β-Hemoglobinopathies." Blood 134, Supplement_1 (November 13, 2019): 2066. http://dx.doi.org/10.1182/blood-2019-131318.

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Induction of fetal hemoglobin (HbF, α2γ2) via genome editing-mediated disruption of DNA regulatory elements that repress expression of γ-globin genes (HBG1 and HBG2) is a promising therapeutic strategy for b-hemoglobinopathies including sickle cell disease (SCD) and β-thalassemia. Optimal technical approaches and safety profiles are yet to be fully defined. We used CRISPR/Cas9 to target a DNA repressor element near the distal CCAAT box of the HBG1/HBG2 promoters. This region contains a "TGACC" motif recognized by BCL11A, a transcriptional repressor protein that regulates γ-to-β globin switch after birth. Rare germline variants at or near this motif are associated with hereditary persistence of fetal hemoglobin, a benign genetic condition that alleviates the clinical manifestations of co-inherited b-hemoglobinopathies. Previously, we showed that transduction of human CD34+ cells with lentiviral vector encoding Cas9 and guideRNA (gRNA) targeting the HBG1/HBG2 promoter caused induction of HbF in red blood cell (RBC) progeny generated in vitro (Traxler et. al, Nature Medicine v22,2016). Here we present a clinically tractable approach for disrupting the HBG1/HBG2 BCL11A binding site in human hematopoietic stem cells (HSCs). Electroporation of Cas9:gRNA ribonucleoprotein (RNP) complex into healthy or SCD donor CD34+ cells resulted in up to 80% on-target insertion-deletion (indel) mutations and 35% HbF in erythroid progeny generated in vitro. Sixteen to 17 weeks after transplantation of gene edited CD34+ cells into immunodeficient NBSGW mice, up to 75% of donor CD34+ cells in recipient bone marrow contained on-target indels, demonstrating efficient modification of repopulating human HSCs. No differences in CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages were observed between edited and control cells. Moreover, up to 78% of gene edited erythroid cells stained with anti-HbF antibody ("F-cells") compared to 15% in control erythroid cells, suggesting a "pan-cellular" pattern of HbF expression after editing. Strikingly, human donor-derived erythroid cells in recipient bone marrow expressed up to 40% HbF compared to 3% HbF in controls. Although the editing frequencies of HBG1 and HBG2 promoters varied between different donor CD34+ cells, an engineered variant of Cas9 containing 3 nuclear localization sequences (Wu et. al,Nature Medicine v25, 2019) edited repopulating HSCs more efficiently and consistently than conventional Cas9 with two nuclear localization signals. Simultaneous on-target RNP-induced DSBs at both HBG1 and HBG2 can result in the deletion of the intervening 4.9-kb region, leaving a single hybrid gene with HBG2 promoter sequences fused to the downstream HBG1 gene. We detected this deletion in approximately 30% of edited cells, with no associated decline in HbF expression determined by clonal analysis of erythroid colonies. No off-target mutations were detected by targeted sequencing of the 26 top candidate sites identified by CIRCLE-seq, an in vitro genome-scale method for detecting Cas9 activity. Analysis of gene edited human donor cells purified from mouse bone marrow showed no chromosomal rearrangements by G-banding (n=20) or fluorescence in situ hybridization with a probe located distal to the HBG1/HBG2 loci (n=225). Taken together, our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a CRISPR-Cas9 genome editing approach to induce HbF for treating hemoglobinopathies. Figure. Gene editing of the HBG1/HBG2 promoters in HSCs and HbF induction of erythroid progeny in vivo. Plerixafor-mobilized CD34+ cells from an individual with SCD were edited with RNP and transplanted into NBSGW mice, which were analyzed 16-17 weeks later. A. On-target indel frequency before (Pre) and after bone marrow transplantation (BM). The black bars represent a 13-nucleotide deletion associated with human hereditary persistence of fetal hemoglobin. B. Human erythroblasts and reticulocytes derived from RNP-edited and non-edited Control CD34+ donor cells. Scale bar = 10 mm. C. HbF immunostaining control and RNP edited erythroid cells in recipient bone marrow assessed by flow cytometry. D. %HbF protein in hemolysates of control (C) and RNP edited erythroid cells assessed by ion-exchange HPLC. n= 3 biological replicates. **** P < 0.0001. Figure Disclosures Metais: MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Sharma:Doris Duke Foundation: Research Funding; Vertex Pharmaceuticals: Other: Study PI. Weiss:Beam Therapeutics: Consultancy; Rubius INC: Consultancy; GlaxoSmithKline: Consultancy; Cellarity INC: Consultancy; Esperian: Consultancy.
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Schöneborn, M., W. Hoffbauer, J. Schmedt auf der Günne, and R. Glaum. "Beiträge zur Kristallchemie und zum thermischen Verhalten von wasserfreien Phosphaten, XXXVII [1]. Synthese, Kristallstruktur und kernresonanzspektroskopische Untersuchung von In2Ti6(PO4)6[Si2O(PO4)6] – Eine Hybride aus den NASICON und M4[Si2O(PO4)6] Strukturtypen / Contributions on Crystal Chemistry and Thermal Behaviour of Anhydrous Phospates, XXXVII [1]. Synthesis, Crystal Structure and Nuclear Magnetic Resonance Investigation of In2Ti6(PO4)6- [Si2O(PO4)6] – A Hybride Built from Layers with NASICON and M4[Si2O(PO4)6] Structures." Zeitschrift für Naturforschung B 61, no. 6 (June 1, 2006): 741–48. http://dx.doi.org/10.1515/znb-2006-0614.

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In2Ti6(PO4)6[Si2O(PO4)6] has been obtained by heating (1100 °C) stoichiometric amounts of In2O3, SiP2O7, TiP2O7, and TiO2 in air. Colourless crystals of the phosphate-silicophosphate suitable for a single crystal structure investigation have been grown by chemical vapour transport (1000°C → 900°C, mixture of 70 mg PtCl2 and 3.5 mg TiP as transport agent). In2Ti6(PO4)6[Si2O(PO4)6] adopts its own structure type (R3̅ (No. 148), Z = 3, a = 8.4380(10) Å , c = 44.295(1) Å , 1809 independent reflections, 109 variables, R1 = 0.044, wR2 = 0.112). The crystal structure represents a hybride built up from alternating layers (⟂ to the c-axis) of the NASICON structure-type and those showing the structure of silicophosphates M4[Si2O(PO4)6]. Isolated heteropolyanions [Si2O(PO4)6]12− and double-octahedra [InIIITiIVO9] occur as coordination polyhedra besides isolated octahedra [TiIVO6] and tetrahedral phosphate groups. The results of 29Si and 31P-MAS-NMR studies are in agreement with one crystallographically independent site for silicon and two sites for phosphorus. The phosphorus resonances can be related to the two sites by 2-dimensional cross-polarisation experiments, by the anisotropies of their chemical shifts, and by the observed line widths. All criteria lead to the same assignment. Substitution of In3+ by several trivalent transition metal ions leads to phosphate-silicophosphates M2Ti6(PO4)6[Si2O(PO4)6] (M = Ti3+, V3+, Cr3+, Fe3+)
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Papanikolaou, Xenofon, Sarah K. Johnson, Tarun K. Garg, Erming Tian, Ruslana Tytarenko, Bart Barlogie, Joshua Epstein, and Christoph Heuck. "The Antimalarial Agent Artesunate Exerts Its Antimyeloma Activity By Affecting The Mitochondria and The Reactive Oxygen Status Of The Myeloma Cells and Its Efficacy Depends On Intracellular Bivalent Iron Levels." Blood 122, no. 21 (November 15, 2013): 4444. http://dx.doi.org/10.1182/blood.v122.21.4444.4444.

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Therapeutic advances have resulted in a 5 year life expectancy for patients diagnosed with multiple myeloma (MM) of 70% compared to 15% two decades ago. However MM remains incurable for a majority of patients and ultimately resistance to the most effective antimyeloma agents develops in the clinical setting of a late MM relapse. The antimalarial artesunate (ART) exerts potent antimyeloma activity in vitro by inducing a non-caspase mediated apoptosis without cross-resistance to other antimyeloma agents (Blood, Nov 2012; 120:4015). Non caspase mediated apoptosis is driven by the nuclear translocation of the mitochondrial factors AIF and EndoG which occurs in myeloma cells after ART treatment, as we have previously shown. Hence, we hypothesized that mitochondria constitute a primary target of ART in MM cells. Therefore we examined the effect of ART on the mitochondria by examining the mitochondrial membrane potential (ΔΨm) of the JJN3, RPMI and INA-6 myeloma cell lines, using the JC-1 dye as an indicator of the change in ΔΨm. ART produced a small but statistically significant change in the ΔΨm as early as 30 minutes after drug exposure (ΔΨm=0.222 vs. ΔΨm=0.327 p=0.021). This change held constant for 12 hours when a brisk and continuous increase in the ΔΨm was noticed. Mitochondria play a pivotal role in the cellular ROS equilibrium and high levels of ROS are linked to the induction of apoptosis. We therefore proceeded with examining the effects of ART on the ROS status of the cells and on mitochondrial derived superoxide production. ART at 125 μΜ (IC90) caused an initial ROS increase within 30 minutes (829 vs. 701 fluorence units (FU) mean value, p=0.043); however, the ROS level decreased with continued drug exposure, reaching subnormal levels at 12 hours and afterwards (701 vs. 433 FU mean value, p<0.001). In contrast, bortezomib (BZ) at comparable effective dosage (10nM, IC90) produced ROS levels around normal at the 12h timepoint (701 vs 750 FU mean value, p=0.176). This decrease cannot be explained by the reduced number of viable cells, since early apoptosis, as measured by annexin V expression using flow cytometry, could only be detected after 12 hours. While subnormal ROS levels were detected by the general ROS stain H2DCFDA, staining with the mitochondria specific dye MitoSOX™ revealed high levels of mitochondrial derived superoxide as measured by flow cytometry. An iron dependent mechanism has been proposed for the antimalarial action of ART. We therefore examined the effect of iron on ART’s anti-MM efficacy. Supplementation of growth medium with 0.8 mg/L bivalent iron in the form of Iron (II) sulfate heptahydrate (a concentration resembling the normal iron concentration in human blood ) drastically increased ART efficacy as evidenced by a marked decrease in the IC50 of ART in the JJN3, INA-6, RPMI-8286, cell lines. The protein bound form of iron, holotransferrin, was not as effective in reducing the IC50, which did not achieve statistical significance when the trivalent form of iron was used (Table 1). Deferoxamine, a cell membrane permeating metal chelator with a specific affinity for iron, exerted clear antagonism to ART since IC50 could not be reached. However when the non cell membrane permeating metal chelator EDTA was used there was not a statistical significant effect ART’s IC50 in JJN3 and RPMI-8226 cells, suggesting that it is the intracellular bivalent form of iron that potentiates ART’s efficacy.Table 1IC50 (72h) on different forms of iron in three different MM cell linesMM cell lineIC50 μΜ (RPMI-1640)IC50 μΜ (RPMI+Fe+2)IC50 μΜ (RPMI+Fe+3)IC50 μΜ (RPMI+holotransferin)JJN316.42.7***14.6∼7.9***INA-618.94.1***17.5∼12.8**RPMI-82266.72.3***5.1*3.9*Fe+2 : iron sulfate heptahydrate, [Fe+2]= 0.8mg/L, Fe+3 :iron citrate, [Fe+3]=0.8mg/L, [holotransferin]: 1 μΜ.***p<0.001, **p<0.01, *p<0.05, ∼p<0.1. Based on the different characteristics of apoptosis induced by ART, we next examined the combined effect of ART with known antimyeloma agents bortezomib, doxorubicin and dexamethasone, that do not share the mechanism of action or the effects of ART on ROS level in the JJN3 cells. ART exhibited an additive or synergistic effect with all agents (Interaction Index≤1.0) implying that low ROS is the aftermath of ART’s molecular action and that through its effect on the mitochondria cannot only act independently but also complement and augment the action of other anti myeloma agents. Disclosures: Barlogie: Celgene: Consultancy, Honoraria, Research Funding; Internation Myeloma Foundation: Consultancy, Honoraria; Millennium: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; National Cancer Institute: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding; Myeloma Health, LLC: Patents & Royalties.
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"MOLYBDENUM 44-48 RHENIUM." Alloy Digest 48, no. 4 (April 1, 1999). http://dx.doi.org/10.31399/asm.ad.mo0017.

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Abstract Molybdenum-rhenium alloy is available in wire, tubing, and sheet products for the electronics, nuclear, and space industries. This datasheet provides information on composition and physical properties. It also includes information on heat treating. Filing Code: MO-17. Producer or source: Rhenium Metals Inc. (Rhenium Alloys Inc.). Originally published January 1999, corrected April 1999.
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"BERALCAST 363, 191, and 310." Alloy Digest 46, no. 9 (September 1, 1997). http://dx.doi.org/10.31399/asm.ad.be0009.

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Abstract Beralcast 363, 191, and 310 are lightweight beryllium-aluminum (Be-Al) alloys for producing near net shapes by investment casting. Beralcast 363 is used primarily for structural applications, Beralcast 191 is used primarily for electronic packaging and Beralcast 310 for wrought products (from cast input material). This datasheet provides information on composition, physical properties, elasticity, and tensile properties. Filing Code: BE-9. Producer or source: Nuclear Metals Inc.
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Nakayama, Junpei, and Kiyoshi Kiuchi. "Developments of Extra-High Purity Stainless Steels for Nuclear Corrosive Environments." MRS Proceedings 1298 (2011). http://dx.doi.org/10.1557/opl.2011.586.

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Abstract:
ABSTRACTThe austenitic stainless steels so-called, the EHP steels with the extra high purity, are developed for improving the reliability of nuclear equipments materials used in the heavily corrosive irradiation environments. By considering the impurities segregation mechanism, the major impurities included in the EHP steels is controlled less than 100ppm by the new melting technology. It is two-step refining process composed of CCIM and EB for effectively removing both non-volatile and volatile harmful elements. The risk to cracking on melting and welding processes is also effectively minimized by enhancing both the eutectic point and the metallic bonding at grain-boundaries. In the EHP steels, it is possible to select the appropriate composition of Ni and Cr for stabilizing austenitic phase and enhancing corrosion resistance. The characteristics of the welding joints are as good as those of the base metal because the same filler metal is sed without the formation of residual delta ferrite. The resistance to IGC and SCC of the EHP steels is markedly improved by minimizing the refining effects, except for type 316 steels with Mo. The welding technique and the chemical composition range are selected for standardizing the EHP.
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15

De Luca, Francesca, Martin Bolin, Lennart Blomqvist, Cecilia Wassberg, Heather Martin, and Anna Falk Delgado. "Validation of PET/MRI attenuation correction methodology in the study of brain tumours." BMC Medical Imaging 20, no. 1 (November 25, 2020). http://dx.doi.org/10.1186/s12880-020-00526-8.

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Abstract Background This study aims to compare proton density weighted magnetic resonance imaging (MRI) zero echo time (ZTE) and head atlas attenuation correction (AC) to the reference standard computed tomography (CT) based AC for 11C-methionine positron emission tomography (PET)/MRI. Methods A retrospective cohort of 14 patients with suspected or confirmed brain tumour and 11C-Methionine PET/MRI was included in the study. For each scan, three AC maps were generated: ZTE–AC, atlas-AC and reference standard CT-AC. Maximum and mean standardised uptake values (SUV) were measured in the hotspot, mirror region and frontal cortex. In postoperative patients (n = 8), SUV values were additionally obtained adjacent to the metal implant and mirror region. Standardised uptake ratios (SUR) hotspot/mirror, hotspot/cortex and metal/mirror were then calculated and analysed with Bland–Altman, Pearson correlation and intraclass correlation reliability in the overall group and subgroups. Results ZTE–AC demonstrated narrower SD and 95% CI (Bland–Altman) than atlas-AC in the hotspot analysis for all groups (ZTE overall ≤ 2.84, − 1.41 to 1.70; metal ≤ 1.67, − 3.00 to 2.20; non-metal ≤ 3.04, − 0.96 to 3.38; Atlas overall ≤ 4.56, − 1.05 to 3.83; metal ≤ 3.87, − 3.81 to 4.64; non-metal ≤ 4.90, − 1.68 to 5.86). The mean bias for both ZTE–AC and atlas-AC was ≤ 2.4% compared to CT-AC. In the metal region analysis, ZTE–AC demonstrated a narrower mean bias range—closer to zero—and narrower SD and 95% CI (ZTE 0.21–0.48, ≤ 2.50, − 1.70 to 2.57; Atlas 0.56–1.54, ≤ 4.01, − 1.81 to 4.89). The mean bias for both ZTE–AC and atlas-AC was within 1.6%. A perfect correlation (Pearson correlation) was found for both ZTE–AC and atlas-AC compared to CT-AC in the hotspot and metal analysis (ZTE ρ 1.00, p < 0.0001; atlas ρ 1.00, p < 0.0001). An almost perfect intraclass correlation coefficient for absolute agreement was found between Atlas-, ZTE and CT maps for maxSUR and meanSUR values in all the analyses (ICC > 0.99). Conclusions Both ZTE and atlas-AC showed a good performance against CT-AC in patients with brain tumour.
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