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Background: In phase I/II clinical trials, the tamoxifen metabolite Z-endoxifen (ENDX) demonstrated substantial oral bioavailability and promising antitumor activity in endocrine-refractory estrogen-receptor positive breast cancer (ER+ BC) and other solid tumors, with ENDX plasma concentrations reaching as high as 5 µM, a concentration that far exceeds the ERα-targeting nanomolar concentrations. We previously identified protein kinase C beta 1 (PKCβ1), an oncogenic signaling kinase which regulates cell proliferation and tumorigenic transformation, as a novel ENDX receptor. ENDX-bound PKCβ1 (KD: 100 nM) and inhibited PKCβ1 kinase activity (IC50: 357 nM) in vitro, at concentrations achieved in phase I/II ENDX studies. Given the observations that ENDX induces antitumor activity in breast cancers resistant to endocrine therapies, including AIs, tamoxifen and fulvestrant, we postulated that ENDX may impact additional signaling pathways. Therefore, in this study we performed unbiased mass spectrometry to analyze the effects of ENDX on the phosphoproteome and total proteome. Methods: In estrogen unstimulated aromatase-expressing ER+/human epidermal growth factor 2 receptor negative (HER2-) MCF7AC1 breast cancer cells, the effects of ENDX on the phosphoproteome and total proteome were analyzed using ENDX concentrations achieved in tamoxifen treated patients (0.01 and 0.1 µM) and concentrations observed in the ENDX phase I/II trials (5 µM). NetWorKIN and RoKAI prediction tools were utilized to identify the upstream kinases of ENDX downregulated phosphoproteins. In estrogen unstimulated MCF7AC1 as well as in the ER+/HER2- T47D breast cancer cells, the ability of ENDX, tamoxifen, fulvestrant and PKC kinase inhibitor enzastaurin to block insulin or PKC agonist phorbol 12-myristate 13-acetate (PMA)-stimulated AKTSer473 phosphorylation was analyzed by immunoblot (IB) assay. Additionally, ENDX effects on AKTSer473 phosphorylation in the MCF7AC1 xenograft model in vivo was analyzed by IB assay. Further, the effects of PKCβ1 silencing in MCF7AC1 cells and the effects of AKT inhibitor MK-2206 treatment on growth and AKTSer473 phosphorylation in the MCF7AC1 as well as long-term estrogen deprived T47D (T47D-LTED) cell lines were analyzed by cell proliferation and IB assays. Results: In MCF7AC1 cells unstimulated with estrogen, ENDX at 5 µM but not at 0.01 and 0.1 µM concentrations inhibited growth, and induced apoptosis, suggesting an ERα-independent effect. Further, ENDX at 5 µM displayed three-fold greater effects in downregulating the phosphoproteome compared to the other concentrations, with minimal impact on the total proteome. Protein kinase C beta (PKCβ) and AKT1 were identified as the prevalent upstream kinases for ENDX downregulated protein phosphorylations. Notably, in estrogen unstimulated MCF7AC1 and T47D cells, ENDX at 5 µM attenuated phosphorylation of AKTSer473 and AKT substrates in vitro in the presence of insulin and in vivo. In MCF7AC1 cells, PMA-induced phosphorylation of PKCβ1 as well as AKTSer473 and AKT substrate phosphorylations were blocked by ENDX at 5 µM, with ENDX inducing PKCβ1 protein degradation both in the presence of insulin and PMA. Further, ENDX effects on growth and AKTSer473 phosphorylation were phenocopied by siRNA-mediated PKCβ1 knockdown as well as treatment with the pan-AKT inhibitor, MK-2206. Notably, the potent PKCβ1 kinase inhibitor, enzastaurin, had no effects either on PKCβ1 protein degradation nor on downstream AKT signaling. Conclusion: Taken together, these findings suggest that ENDX may exert anticancer activity via dual effects on blocking ERα as well as by targeting PKCβ1 for degradation, thus suppressing AKT signaling and induction of apoptosis. These preclinical findings will be studied in a planned neoadjuvant trial comparing ENDX with exemestane and ovarian function suppression (EVANGELINE) that will activate in the Fall of 2022. Citation Format: Swaathi Jayaraman, Xinyan Wu, Krishna R. Kalari, Xiaojia Tang, Mary Kuffel, Elizabeth S. Bruinsma, Santosh Renuse, James N. Ingle, Joel Reid, Matthew Schellenberg, John Hawse, Akhilesh Pandey, Matthew P. Goetz. Endoxifen Downregulates AKT Phosphorylation Through Protein Kinase C Beta 1 in ER+/HER2- Breast Cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-04.

Supplementary Figure S4. Dose dependent increase in cytotoxic effects of veliparib, TMZ or their combination in multiple PDX GBM models of differential TMZ sensitivity

Background Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. Procedure The Children’s Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug reinduction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m /dose) was administered orally once daily for 21 consecutive days, first as a single agent (days 1-3) and subsequently combined with reinduction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) followed by an expansion pharmacokinetic (PK) cohort. Results Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose-limiting hematologic toxicity (DLT) occurred at the starting dose of 50 mg/m /dose orally for 21 days. No additional DLTs were observed in the dose determination or PK expansion cohorts and overall rates of grade 3/4 non-hematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. Conclusions Palbociclib in combination with reinduction chemotherapy was well tolerated with a RP2D of 50 mg/m /day for 21 days. Complete responses were observed among heavily pretreated patients.

The determination of fractionation factors associated with important biogeochemical processes controlling Ni availability in the environment is necessary to confidently use Ni isotope signatures as tracers in environmental studies. In this paper we present experimental results on Ni isotope fractionation during the precipitation of Ni secondary minerals (Ni hydroxide, Ni hydroxycarbonate and Ni sulfide minerals) that can control Ni fate and mobility in settings where high dissolved Ni(II) concentrations may pose a serious threat to the environment. Results show a preferential partition of lighter isotopes into the solid phase with associated fractionation factors e of −0.40‰ ± 0.04‰, −0.50‰ ± 0.02‰, and −0.73‰ ± 0.08‰ relative to the hydroxide, carbonate and sulfide systems, respectively. Early kinetically induced isotope fractionation, followed by possible re-equilibration with the reacting solutions was suggested for the three investigated systems. Distortions of Ni-O bonds in the octahedra constituting the structures of Ni hydroxide and hydroxycarbonate minerals could have also contributed to the isotopic fractionation measured in these systems. In contrast, for Ni sulfide system, the magnitude of Ni isotope fractionation seemed to be determined by water and sulfide ligands exchange in solution prior to mineral nucleation. Although there is insufficient evidence to determine whether complete equilibrium occurred in the three studied systems, the fractionation factors reported in this study can provide useful indicators of Ni isotope fractionation associated with fast precipitation of secondary minerals involved in the sequestration of Ni from contaminated environments. These findings also contribute to the characterization of Ni isotope systematics which is still in the early stages of development.

The crystal structure of donepezil hydrochloride, form III, has been solved with FOX using laboratory powder diffraction data previously submitted to and published in the Powder Diffraction File. Rietveld refinement with GSAS yielded monoclinic lattice parameters of a = 14.3662(9) Å, b = 11.8384(6) Å, c = 13.5572(7) Å, and β = 107.7560(26)° (C24H30ClNO3, Z = 4, space group P21/c). The Rietveld-refined structure was compared to a density functional theory (DFT)-optimized structure, and the structures exhibit excellent agreement. Layers of donepezil molecules parallel to the (101) planes are maintained by columns of chloride anions along the b-axis, where each chloride anion hydrogen bonds to three donepezil molecules each.

Synchrotron powder diffraction data is presented for the monoclinic polymorph of dimethylarsinic acid, (CH3)2AsO(OH) (DMAV). Rietveld refinement with GSASII yielded lattice parameters of a = 15.9264(15) Å, b = 6.53999(8) Å, c = 11.3401(9) Å, and β = 125.8546(17)° (Z = 8, space group C2/c). The Rietveld-refined structure was compared with both a density functional theory (DFT)-optimized structure and the published, low-temperature single-crystal structure, and all three structures exhibited excellent agreement. The triclinic polymorph of DMAV was also DFT optimized with CRYSTAL17 to determine the positions of the hydrogen atoms. Monoclinic DMAV forms zigzag chains parallel to the b-axis with adjacent DMAV molecules connected by an O–H⋯O bond, whereas triclinic DMAV forms dimers connected by two O–H⋯O bonds.

A new diffraction beamline for materials science has been built at the Canadian Light Source synchrotron. The X-ray source is an in-vacuum wiggler with a 2.5 T peak magnetic field at 5.2 mm gap. The optical configuration includes a toroidal mirror, a single side-bounce Bragg monochromator, and a cylindrical mirror, producing a sub-150 µm vertical × 500 µm horizontal focused beam with a photon energy range of 7–22 keV and a flux of 1012 photons per second at the sample position. Three endstations are currently open to general users, and the techniques available include high-resolution powder diffraction, small molecule crystallography, X-ray reflectivity, in situ rapid thermal annealing, and SAXS/WAXS. The beamline design parameters, calculated and measured performance, and initial experimental results are presented to demonstrate the capabilities for materials science.

Sveite [KAl7(NO3)4(OH)16Cl2·8H2O] first described from Venezuela and material recently collected from northern California have similar X-ray diffraction patterns and chemical compositions. The main difference in the chemical composition is the absence of significant chlorine and sulfate in the sveite from California. The changes observed by X-ray diffraction upon hydration and the SEM images of the crystals suggest a layered atomic structure. Water-extractable NO3 in the Venezuelan sveite sample is isotopically enriched in δ15N and δ18O and likely was affected by the microbial process of denitrification. In contrast, the extractable nitrate from the California sveite is less isotopically enriched than the Venezuelan mineral and there is only modest evidence that denitrification had affected its isotopic composition. Overall, the nitrate in the California sveite is isotopically similar to nitrate present in acidic soils overlying the mineral occurrence, suggesting a general biogenic source of uric acid from bird feces for the mineral-bound nitrogen.

Introduction There are currently no approved targeted therapies for lung squamous-cell carcinoma (LSCC) and KRAS-mutant lung adenocarcinoma (LUAD). About 30% of LSCC and 25% of KRAS-mutant LUAD exhibit hyperactive NRF2 pathway activation through mutations in NFE2L2 (the gene encoding NRF2) or its negative regulator, KEAP1. Preclinical data demonstrate that these tumors are uniquely sensitive to dual inhibition of glycolysis and glutaminolysis via mammalian target of rapamycin (mTOR) and glutaminase inhibitors. This phase 1 study was designed to assess safety and preliminary activity of the mTOR inhibitor MLN0128 (sapanisertib) in combination with the glutaminase inhibitor CB-839 HCl. Methods Phase 1 dose finding will use the queue-based variation of the 3 + 3 dose escalation scheme with the primary endpoint of identifying the recommended expansion dose. To confirm the acceptable tolerability of the recommended expansion dose, patients will subsequently enroll onto 1 of 4 expansion cohorts (n = 14 per cohort): (1) LSCC harboring NFE2L2 or (2) KEAP1 mutations, or (3) LUAD harboring KRAS/(KEAP1 or NFE2L2) coalterations, or (4) LSCC wild type for NFE2L2 and KEAP1. The primary endpoint of the dose expansion is to determine the preliminary efficacy of MLN0128/CB-839 combination therapy. Conclusion This phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non–small-cell lung cancer with a focus on subsets of LSCC and KRAS-mutant LUAD harboring NFE2L2 or KEAP1 mutations.

Cadwaladerite, described in 1941 as Al(OH)2Cl·4H2O, and lesukite, described in 1997 as Al2(OH)5Cl·2H2O, are very closely related chemically and structurally, but are found in very different environments. Cadwaladerite was found at the edge of a salar in Chile. Lesukite has been described from a volcanic fumarole and from burning coal seams. Both materials have cubic symmetry with a = 19.788 to 19.859Å. The crystal structure, common to both, consists of a rigid three-dimensional framework of edge- and corner-sharing Al(OH,H2O)6 octahedra that contains large interconnected cavities where loosely held Cl, OH, and H2O are located. The fact that Cl is loosely held within the structure is demonstrated by a dramatic reduction in Cl content after washing the material in distilled water, while the structural integrity is maintained. Herein, cadwaladerite is confirmed as a valid mineral species and lesukite is discredited because the only difference between the two materials is the loosely held extra-framework Cl, OH, and H2O. Cadwaladerite, Al2(H2O)(OH)4·n(Cl,OH,H2O) (Z = 48) takes precedence over lesukite based on the date of description. Material similar to cadwaladerite is found as a corrosion product on some types of nuclear fuel elements and is also closely related to the molecular species used in antiperspirant and water filtration.

IDH mutant gliomas depend on glutaminase for glutamate/glutathione generation from glutamine because R-2-hydroxyglutarate inhibits branched chain amino acid transaminase mediated glutamate biosynthesis. Telaglenastat (CB-839 HCl) is a potent glutaminase-1 specific inhibitor which depletes tumor glutamate in orthotopic IDH mutant glioma PDX models and extends survival in these orthotopic models when added to radiation/temozolomide. NCI-10218 (NCT03528642) is a phase I clinical trial investigating the safety and tolerability of telaglenastat administered orally concurrently with standard doses of radiation (50.4 Gy, grade 2; 59.4 Gy, grade 3) and temozolomide (75 mg/m2 orally daily) in patients (age 16+) with previously untreated IDH mutant grade 2/3 astrocytoma. Telaglenastat dose was escalated in cohorts (400-800 mg twice daily) based on a standard 3 + 3 design to determine the recommended phase 2 dose (RP2D). Toxicities were graded per CTCAE v5.0. An expansion cohort additionally incorporated a seven-day run-in of telaglenastat monotherapy at RP2D prior to radiation to evaluate the pharmacodynamic impact of telaglenastat on plasma and tumor metabolites. 23 patients with IDH mutant astrocytoma (WHO grade 2, n = 5; WHO grade 3, n = 18) were accrued between December 2018 and January 2022 (Dose Escalation: 16; Dose Expansion: 7). Median age was 32 years (range 23-69 years). 61% were male and 70% were ECOG 0. No dose-limiting toxicities were observed. Grade 3/4 adverse events (independent of attribution) included: lymphopenia (3), neutropenia (2), leukocytosis (2), alanine transaminase elevation (2), thrombocytopenia (1), leukopenia (1), maculopapular rash (1), hyperglycemia (1), hyponatremia (1). The RP2D of concurrent telaglenastat was defined as 800 mg twice daily. Following peak absorption on Day 15 at RP2D, the mean (%CV) terminal elimination half-life in the plasma was 4.2 (53.5%) hours (range 2.1-7.1 hours). The Cmax, Tmax, oral clearance, and AUC were 1496 ng/mL, 4.0 hr, 93.6 L/hr/m2, and 7430 ng/mL*hr, respectively.

The crystal structure of MoO2(O2)(H2O)·H2O has been solved using parallel tempering with the FOX software package and refined using synchrotron powder diffraction data obtained from beamline 08B1-1 at the Canadian Light Source. Rietveld refinement, performed with the software package GSAS, yielded monoclinic lattice parameters of a = 17.3355(5) Å, b = 3.83342(10) Å, c = 6.55760(18) Å, and β = 91.2114(27)° (Z = 4, space group I2/m). The structure is composed of double zigzag molybdate chains running parallel to the b-axis. The Rietveld refined structure was compared with density functional theory (DFT) calculations performed with CRYSTAL14, and shows comparable agreement with two DFT optimized structures of similar energy, which differ by the location of the molybdate coordinated water molecule. The true structure is likely a disordered combination of the two DFT optimized structures.

Synchrotron Laue microdiffraction imaging (MDI) is a well-used technique in material science research and environmental research to determine the strain/stress and orientation of quartz and calcite crystallites. However, Laue MDI has unrealized potential to provide spatially resolved mineralogical information for geochemical and contaminated site samples. In this manuscript, three constructed mineral mixtures and two environmental samples were analyzed with Laue MDI to illustrate the strengths, limitations/challenges, and applicability of the technique for environmental research. Mixture 1 (quartz, calcite, and magnetite), mixture 2 (quartz, calcite, magnetite, and clinochlore), and mixture 3 (calcite, hematite, sphalerite, and arupite) were constructed to highlight the potential limitations of the technique. The mixtures illustrate the potential of Laue MDI and X-ray fluorescence imaging for clearly identifying environmentally relevant contaminant and sorbent minerals while demonstrating that minerals sm...

The properties and applications of metal–organic frameworks (MOFs) are strongly dependent on the nature of the metals and linkers, along with the specific conditions employed during synthesis. Al-fumarate, trademarked as Basolite A520, is a porous MOF that incorporates aluminum centers along with fumarate linkers and is a promising material for applications involving adsorption of gases such as CO2. In this work, the solvothermal synthesis and detailed characterization of the gallium- and indium-fumarate MOFs (Ga-fumarate, In-fumarate) are described. Using a combination of powder X-ray diffraction, Rietveld refinements, solid-state NMR spectroscopy, IR spectroscopy, and thermogravimetric analysis, the topologies of Ga-fumarate and In-fumarate are revealed to be analogous to Al-fumarate. Ultra-wideline 69Ga, 71Ga, and 115In NMR experiments at 21.1 T strongly support our refined structure. Adsorption isotherms show that the Al-, Ga-, and In-fumarate MOFs all exhibit an affinity for CO2, with Al-fumarate bei...

Summary To form any porous solid requires payment of an energetic penalty to create voids through either strong bonds or many weak interactions working in concert. Here, we present a porous solid that is composed, after pore activation, of 27 wt % water and sustained by charge-assisted hydrogen bonds between hexaaquachromium(III) cations and organophosphonate anions. The network forms a pillared layered motif including guest solvents, as confirmed crystallographically. Although aquo ligands are an integral part of the hydrogen-bonding network that sustains the pores, activation under high vacuum is possible, and the network demonstrates reversible CO 2 sorption. The stability of the network is attributed to the inertness of the octahedral d 3 Cr(III) center in combination with high degrees of complementarity and cooperativity of hydrogen bonds. The sub-nanometer pores are guest selective on the basis of size, shape, and chemical functionality.

AREVA Resources Canada operates the McClean Lake Operation (MLO), a uranium mine and processing facility located in northern Saskatchewan. Uranium-containing ores processed at the MLO contain high concentrations of arsenic that is oxidized to soluble arsenite and arsenate species when leaching and recovering uranium. To reduce the environmental impact of AREVA's mining operations, AREVA has developed a tailings preparation process designed to trap arsenic in a mineral form before the tailings are permanently deposited in the JEB Tailings Management Facility (TMF). Scorodite (FeAsO 4 ·2H 2 O) is predicted to be the primary arsenic species produced from the tailings preparation process. However, scorodite has never been observed in aged tailings samples. Confirming the presence of scorodite in the tailings is important in verifying that the tailings preparation process at the MLO can isolate high concentrations of arsenic from the environment in the form of stable minerals. Herein, X-ray Absorption Near-Edge Structure (XANES) spectroscopy was used to investigate arsenic speciation in a series of samples collected from the JEB TMF in 2013. Arsenic K-edge XANES analysis confirmed that most (86 wt%) of the arsenic content in the tailings samples consisted of iron-containing arsenates. Of these, crystalline scorodite was the most abundant arsenate species followed by poorly crystalline arsenates in the form of poorly crystalline ferric arsenate (FeAsO 4 ·xH 2 O) and arsenate adsorbed on ferrihydrite (AsO 4 –FeOOH). Arsenite adsorbed on ferrihydrite (AsO 3 –FeOOH), and gersdorffite (NiAsS) were also identified as minor arsenic species in the tailings samples. The abundance and distribution of scorodite in the TMF suggests that it is the major arsenic species produced in the tailings preparation process.

The crystal structure of Na(NH4)Mo3O10·H2O has been solved by parallel tempering using the FOX software package with synchrotron powder diffraction data obtained from beamline 08B1-1 at the Canadian Light Source. Rietveld refinement, performed with the software package GSAS, yielded orthorhombic lattice parameters of a = 13.549 82(10), b = 7.618 50(6), and c = 9.302 74(7) Å (Z = 4, space group Pnma). The structure is composed of molybdate chains running parallel to the b-axis. The Rietveld refinement results were compared with density functional theory calculations performed with CRYSTAL14, and show excellent agreement with the calculated structure.

Nanoscale Li 4 Ti 5 O 12 (LTO) is considered a promising anode material for Li-ion batteries because of its outstanding safety. However, cointercalation-induced structural relaxation adversely affects its Li-ion storage properties. Therefore, there is a need to elucidate the connection between electrochemistry and LTO structural relaxation of nano-LTO. Herein, various LTO nanosheet crystals with designated degrees of residual strain were prepared by varying the annealing temperature. The cyclability and rate capability of the prepared 2D LTO nanocrystals were evaluated. During annealing, dehydration of layered lithium titanate hydrate precursors (LTH, (Li 2−x H x )Ti 2 O 5 ·yH 2 O), leads to topotactic transformation from a C -centered orthorhombic to a body-centered orthorhombic system. Dehydrated LTH is then converted into spinel LTO nanosheets. Residual strain induced during transformation causes LTO structure distortion rendering Li-O bonding more covalent. Strongly covalent Li-O bonds screen the Li-Li Coulomb repulsion when 8 a −16 c cointercalation occurs, leading to large irreversible capacity loss and deteriorated cyclability. Meanwhile, rich irreversible Li intercalation degrade the power capability of LTO nanocrystals despite their high surface area. In addition to mechanism elucidation, conditions are identified to eliminate residual strain-induced structural relaxation giving rise to nanosheet anodes with superior power and highly reversible cycling performance.

Summary The versatility of synchrotron techniques for the solution of oilfield questions is illustrated by the application of powder X-ray diffraction (PXRD) and X-ray absorption near-edge structure (XANES) spectroscopy to a toluene-insoluble oilfield-residue sample from an alkaline/surfactant/polymer (ASP) -flood site in Taber, Alberta, Canada. The primary questions regarding the sample were the sources of the barium and nitrogen (both at levels of approximately 0.8 wt%). Synchrotron PXRD provided better signal–noise and detection limits than previously obtained laboratory PXRD data, enabling the identification of four additional crystalline minerals including heulandite, (Ba, Ca, Sr, K, Na)5 Al9 Si27 O72 (H2O)22, a tecto-silicate zeolite known for accommodation of a wide variety of cations. Heulandite provides a plausible location for barium (and strontium) observed with chemical analysis. Synchrotron XANES spectra at the nitrogen K-edge suggested that the source of the nitrogen content was a corrosion inhibitor, rather than a polyacrylamide (PAM) -based compound, as originally assumed.

Anthropogenic activities at the HudBay Minerals, Inc., Flin Flon (Manitoba, Canada) mining and processing facility have severely affected the surrounding boreal forest ecosystem. Soil contamination occurred via a combination of metal and sulfuric acid deposition and has resulted in forest dieback and ineffective natural recovery. A community-led effort to revegetate areas of the landscape through the application of a dolomitic limestone has been met with varied success. Zinc (Zn) speciation has shown to be closely linked to the presence or absence of an invasive metal-tolerant grass species, with soils being broadly classed into two revegetation response groups. Group I, characterized by the absence of metal-tolerant grasses, and group II, characterized by the presence of metal-tolerant grasses. The systematic approach used to lime areas of the landscape produced a liming chronosequence for each group. This study used a combination of X-ray absorption spectroscopy, X-ray fluorescence mapping, and X-ray diffraction techniques to determine the effect of liming on Zn speciation in these chronosequences. Liming group I soils resulted in the formation of a neo-phase Zn-Al-hydroxy interlayer coprecipitate and subsequent rapid boreal forest revegetation. The effect of liming on Zn speciation on the group II soils resulted in a gradual transition of increasingly stable adsorption species, culminating with a stable Zn-Al-layered double hydroxide precipitate. Boreal forest vegetation has failed to recolonize group II soils during the study. However, the formation of the layered double hydroxide species resulted in a significant reduction in CaCl-extractable Zn. Further research is required to determine how to promote the revegetation of these soils.

The valence electron topologies of Mg 2 Si thermoelectric materials multi-doped with Al, Zn and Sb have been determined by the Maximum Entropy Method (MEM) using synchrotron X-ray powder diffraction data. In spite of the very low concentrations, expansion was observed in the cubic unit cells of the doped samples. Using pure Mg 2 Si as a reference, charge density difference maps revealed qualitative features on the distributions of the electrons contributed by the doped atoms. The presence of excess electrons shows all doped samples are n -type semiconductors and they are shared among the atomic sites. We evaluated the reliability of the MEM calculated charge density by considering the effect of successively increasing the number of high angle Bragg reflections used in the analysis on the diffraction pattern of a single doped Al–Mg 2 Si sample.

The crystal structure of trandolapril has been solved by parallel tempering using the FOX software package with laboratory powder diffraction data submitted to and published in the Powder Diffraction File. Rietveld refinement was performed with the software package GSAS yielding orthorhombic lattice parameters of a = 19.7685(4), b = 15.0697(4), and c = 7.6704(2) Å (C24H34N2O5, Z = 4, space group P212121). The Rietveld refinement results were compared with density functional theory (DFT) calculations performed with CRYSTAL14. While the structures are similar, discrepancies are observed in the configuration of the octahydroindole ring between the Rietveld and DFT structures, suggesting the refined and calculated molecules are diastereomers.

Synchrotron powder diffraction data have been obtained and indexed for ferrous gluconate, a common supplement used for the treatment and prevention of iron-deficiency anemia. Ferrous gluconate (Fe(C6H11O7)2 · x H2O, Z = 4) crystallizes in a monoclinic cell (space group I2, #5) with lattice parameters a = 19.953 16(9) Å, b = 5.513 92(3) Å, c = 18.470 58(9) Å, and β = 111.3826(3)°. The pattern shows no evidence of impurity reflections.

Synchrotron powder X-ray diffraction, X-ray absorption spectroscopy (XAS), and proton nuclear magnetic resonance (1H-NMR) data have been used to examine the structure of hypoxanthine, 1,7-dihydro-6H-purin-6-one (C5H4N4O), a purine base that participates in numerous metabolic processes. XAS and 1H-NMR spectroscopy were used to determine that hypoxanthine was present in its keto form (both in solid state and dissolved in an organic solvent). Rigid body refinement was performed with the Rietveld software package GSAS yielding triclinic lattice parameters of a = 7.1179 (2) Å, b = 9.7830 (3) Å, c = 10.4009 (3) Å, α = 58.876 (1)°, β = 67.609 (1)°, and γ = 71.937 (2)° (C5H4N4O, Z = 4, space group P$\bar 1$).

The crystal structure of solifenacin hydrogen succinate [C23H27N2O2(HC4H4O4)] has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Solifenacin hydrogen succinate crystallizes in space groupP21(#4) witha= 6.477 03(2),b= 7.830 95(2),c= 23.848 72(7) Å,β= 90.2373(3)°,V= 1209.63(1) Å3, andZ= 2. The hydrogen succinate anions form a chain linked by strong hydrogen bonds parallel to thea-axis. Discrete N–H···O hydrogen bonds lie on the sides of this chain, resulting in a layer parallel to theab-plane rich in hydrogen bonds. Halfway between these layers the molecules meet in a herringbone packing of aromatic rings. The powder pattern has been submitted to ICDD for inclusion in future releases of the Powder Diffraction File™.

Enhanced thermoelectric and electrical transport properties of Mg2Si-based thermoelectric materials have been achieved by multi-doping with Sb, Al and Zn. Results on the investigation of the electrical transport and thermoelectric properties of multi-doped samples prepared using the spark plasma sintering technique are reported. Synchrotron radiation powder X-ray diffraction was used to characterize the structures of the doped samples. The electrical transport properties were determined from mid-infrared reflectivities, Hall effect and conventional quasi-four probe conductivity measurements. Using the electron concentrations (N) determined from the Hall coefficients, the effective masses (m*) were calculated from the frequency of the plasma edge (ωP) of the infrared reflectivities. The thermoelectric performance and thermoelectric figure of merits (ZT) in the temperature range of 300 K to 900 K of the doped Mg2Si compounds were calculated from the measured temperature dependent electrical conductivity (σ), Seebeck coefficient (S), and thermal conductivity (κ). A maximum ZT of 0.964 was found for Sb0.5%Zn0.5% doped Mg2Si at 880 K. This value is comparable to those of PbTe based thermoelectric materials.

Synchrotron powder diffraction data from beamline 08B1-1 at the Canadian Light Source have been used to examine the structure of curcumin, a prime component of the Asian spice turmeric. Rigid body refinement, with the application of restraints on distances and angles, was performed with the Rietveld software package GSAS yielding monoclinic lattice parameters ofa= 12.6967(1) Å,b= 7.198 52(3) Å,c= 19.9533(2) Å, andβ= 95.1241(6)° (C21H20O6,Z= 4, and space groupP2/n). The refinement was compared with a recent single-crystal structure andab initioresults obtained with density functional theory calculations.

The JEB Tailings Management Facility (TMF) is central to reducing the environmental impact of the uranium ore processing operation located at the McClean Lake facility and operated by AREVA Resources Canada (AREVA). The geochemical controls of this facility are largely designed around the idea that elements of concern, such as Mo, will be controlled in the very long term through equilibrium with supporting minerals. However, these systems are far from equilibrium when the tailings are first placed in the TMF, and it can take years, decades, or centuries to reach equilibrium. Therefore, it is necessary to understand how these reactions evolve toward an equilibrium state to understand the very long-term behavior of the TMF and to ensure that the elements of concern will be adequately contained. To this end, the Mo speciation in a series of samples taken from the JEB TMF during the 2008 sampling campaign has been analyzed. This analysis was performed using powder X-ray diffraction (XRD), X-ray fluorescence mapping (μ-XRF), and X-ray absorption near-edge spectroscopy (XANES). These results show that only XANES was effective in speciating Mo in the tailings samples, because it was both element-specific and sensitive enough to detect the low concentrations of Mo present. These results show that the predominant Mo-bearing phases present in the TMF are powellite, ferrimolybdite, and molybdate adsorbed on ferrihydrite.

An experimental X-ray powder diffraction pattern was produced and analyzed for imipenem monohydrate, an antimicrobial pharmaceutical agent. Although there are no experimental powder patterns in the ICDD PDF-4/Organics Database, there is one powder pattern calculated with single-crystal X-ray diffraction data from the Cambridge Structural Database. Here, we report the refined experimental powder diffraction data for imipenem monohydrate. These data for imipenem monohydrate are consistent with an orthorhombic crystal system having reduced unit-cell parameters of a = 8.2534(3) Å, b = 11.1293(4) Å, and c = 15.4609(6) Å. The resulting unit-cell volume, 1420.15(15) Å3, indicates four formula units per unit cell. Observed peaks are consistent with the P212121 space group.

GSAS instrument parameters are tabulated for a variety of laboratory and synchrotron diffractometers to give users an idea of the typical ranges of profile parameters when they generate their own instrument parameter files. For modern high-resolution laboratory diffractometers, the parameters fall in the ranges 0

Since the creation of the Joint Committee on Powder Diffraction Standards (JCPDS) over sixty years ago, the Powder Diffraction File (PDF) has been the key source of standard powder diffraction data for identification and analysis of materials of all types, from natural minerals and high-tech ceramics to metals and alloys and pharmaceuticals. Although this editorially reviewed database has been the mainstay for diffraction pattern reference for the x-ray powder diffraction community, recent developments provide information and tools for electron diffraction. In recent years, the International Centre for Diffraction Data (ICDD, formerly JCPDS) has transformed the flat-file format of the PDF to a more flexible relational database (RDB) format. The PDF has been greatly expanded to include calculated patterns from multiple collaborating databases, including the Inorganic Crystal Structure Database (FIZ Karlsruhe, Germany), the Linus Pauling File (MPDS, Vitznau, Switzerland), and the Cambridge Structural Database (CCDC, Cambridge, United Kingdom). A significant portion of its entries include atomic coordinates and a specific database dedicated to organic phases exists. All new entries for the ICDD databases undergo over 100 quality checks before inclusion, and a quality mark is assigned for each entry that passes.

Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP) ceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) generates materials with superior biological performance to stoichiometric counterparts. Si, an essential trace element required for healthy bone and connective tissues, influences the biological activity of CaP materials by modifying material properties and by direct effects on the physiological processes in skeletal tissue. The synthesis of Si substituted HA (Si-HA), Si substituted alpha-TCP (Si-alpha-TCP), and multiphase systems are reviewed. The biological performance of these Si substituted CaP materials in comparison to stoichiometric counterparts is discussed. Si substitution promotes biological activity by the transformation of the material surface to a biologically equivalent apatite by increasing the solubility of the material, by generating a more electronegative surface and by creating a finer microstructure. When Si is included in the TCP structure, recrystallization to a carbonated HA is mediated by serum proteins and osteoblast-like cells. Release of Si complexes to the extracellular media and the presence of Si at the material surface may induce additional dose-dependent stimulatory effects on cells of the bone and cartilage tissue systems.

Ultrasonically accelerated dissolution of multiphase silicon stabilized tricalcium phosphate powders in water or Earle's balanced salt solution transforms the powders into needle-like calcium deficient apatite crystals with the c-axis (001) oriented along the needle. Ion exchange with the solution occurs primarily in the first hours of immersion. The transformation is driven by an interaction between the crystal surface and adsorbed water leading to the growth of crystallites which have the most stable surface configuration. First principles calculations of the surface energies of various hydroxyapatite surfaces with and without adsorbed water shows that depending on the ion concentrations in the fluid that determine the chemical potential of tricalcium phosphate, either Ca-rich (010) or stoichiometric (001) layers are the dominant surfaces. The higher the chemical potential, the more elongated in the (001) direction the crystallites become to minimize the total surface energy. The loss of a calcium Ca(2+) compensated by the addition of two H(+) is strongly favoured energetically on the (001) and Ca-rich (010) surfaces. A high concentration of excess Si at grain boundaries may be partly responsible for the rapid transformation of multiphase Si-TCP.

A novel silicon-stabilized calcium phosphate phase mixture possesses a characteristic phase composition of ∼ 75 wt.% silicon-stabilized α-tricalcium phosphate (Si-α-TCP) with the balance being calcium hydroxyapatite (HA) and traces of β-tricalcium phosphate (β-TCP). Variability in the phase composition has been shown to be caused by trace magnesium (Mg) contained in the calcium nitrate tetrahydrate used to prepare the sol gel. Mg contents between 250 and 300 ppm are sufficient to form significant quantities of β-TCP at the expense of the Si-α-TCP phase.

Rietveld refinement has been employed to estimate the crystalline phase compositions of multiphase calcium phosphate mixtures containing calcium hydroxyapatite [Ca5(PO4)3OH], and alpha and beta tricalcium phosphate [Ca3(PO4)2]. Two methods were employed using fixed structural models for all three phases and refining the zero offset, scale factors, lattice parameters and one peak breadth parameter using either a constant background (method A) or a background with two refined parameters (method B). Analysis of a matrix of quantitative standards across a broad spectrum of phase compositions indicates that method A results in small systematic deviations of the Rietveld phase compositions (< 1 wt%) from the nominal values, but the systematic deviations are eliminated by refining the background (method B). The methods require approximately 10 min to complete, and are suitable for quality control of calcium phosphate production (and potentially other multiphase systems) when accuracy, precision and time are all significant considerations.

Silicon-substituted calcium phosphate (CaP) powders with a Ca/(P+Si) ratio of 1.50 have been prepared by a wet chemical method, with silicon contents up to 2.16 weight percent (wt%). Sintering for 2 h at 1250 °C yields single-phase silicon-substituted alpha tricalcium phosphate (Si- α -TCP) for compositions between 0.59 and 1.14 wt% silicon. The sintered powders have been characterized with X-ray fluorescence (XRF) spectrometry, X-ray diffraction (XRD), attenuated total reflection infrared spectroscopy (ATR-IR) and transmission electron microscopy (TEM). Compositions with less than 0.59 wt% silicon result in mixtures of Si- α -TCP, β -TCP, and calcium hydroxyapatite (HA), while compositions with more than 1.14 wt% silicon result in mixtures of Si- α -TCP and HA. The lattice parameters of single-phase Si- α -TCP prepared with 0.87 wt% silicon are a = 1 2.8 7 4 ( 1 ) A , b = 2 7.3 7 2 ( 2 ) A , c = 1 5.2 2 5 ( 1 ) A , and β = 1 2 6.3 8 ( 1 ) ° .

The sintering of silicon doped calcium phosphate ceramics prepared from a basic colloidal hydroxyapatite (Ca5(PO4)3OH or HA) precipitate mixed with silica over 800 degrees C yields a phase mixture of tricalcium phosphate phases (TCP) designated Si-TCP, beta-TCP and a silicon substituted dehydrated apatite (Si-Ap). The Si-TCP phase is defined as a combination of a silicon stabilized TCP in which the silicon content attains a saturated value (Ca3(P0.9Si0.1O3.95)2 or Si-TCP(sat)) and alpha-TCP (Ca3(PO4)2). Si-TCP(sat) has the same crystalline space group (P2(1)/a) as alpha-TCP, but with characteristically different lattice parameters due to the substitution of silicon in tetrahedral phosphorus sites. The nucleation and growth kinetics of Si-TCP in samples of composition 0.2 mol SiO2:mol HA (0.2:1) and 1 mol SiO2:mol HA (1:1) can be understood in terms of the initial growth of alpha-TCP at a silica-HA interface followed by a transformation to Si-TCP(sat) or beta-TCP. A thermodynamic model for the formation of Si-TCP(sat) predicts a nucleation temperature of 795 degrees C, in close agreement with experiment. If sufficient silicon is available, the alpha-TCP transforms to Si-TCP(sat) during extended sintering. In the absence of sufficient silicon, the alpha-TCP transforms to beta-TCP.

Impurity centers associated with silicon have been observed in the phase mixture of silicon substituted apatite (Si-Ap) and silicon stabilized tricalcium phosphate (Si-TCP) using electron spin resonance (ESR). Two unique centers occur upon addition of SiO2 to the calcium phosphate system: an orthorhombic center with g-values 2.0072+/-0.0001, 2.0024+/-0.0001 and 2.0003+/-0.0001 (Si-h1) and a center with tetrahedral symmetry having g-values components 2.0054+/-0.0001 and 1.9992+/-0.0003 (Si-h2). Both centers are hypothesized to be characteristic of defects associated with silicon in the Si-Ap phase. Through comparison of the intensity of F-OH centers in undoped calcium hydroxyapatite (HA) prepared with various levels of OH occupancy, a relationship is demonstrated between the ESR intensity of an F-center signal with g = 2.0019+0.0004 (F-OH) and the OH occupation of HA. Relative changes in the intensity of ESR signals Si-h1 and F-OH are consistent with a chemical model describing the substitution of SiO4(4-) for PO4(3-) in HA with the creation of OH- vacancies as charge compensation, resulting in a mixed phase composition of Si-Ap and Si-TCP that results when a hydroxyapatite precipitate (HA) is heated in the presence of added SiO2.

Silicon stabilized tricalcium phosphate [Si-TCP] is formed within the calcium hydroxyapatite (HA)-tricalcium phosphate (TCP) system when a stoichiometric precipitate of hydroxyapatite is fired at 1,000 degrees in the presence of SiO(2). This paper proposes a composition range and crystallographic structure for Si-TCP. Reitveld XRD powder diffraction, transmission electron microscopy, infrared and proton nuclear magnetic resonance measurements show that crystalline Si-TCP is associated with the displacement of OH from an initial hydroxyapatite structure. The resulting calcium phosphate is modified by the incorporation of silicon into its structure with excess silica contributing to an amorphous component. Si-TCP has a monoclinic structure with a space group P2(1)/a akin to alpha-TCP with estimated lattice constants of a=12.863+/-0.004 A, b=9.119 +/-0.003 A, c=15.232+/-0.004 A, beta=126.3+/-0.1 degrees. It is proposed that Si(4+) substitutes for P(5+)in the TCP lattice with the average chemical composition of Si-TCP set primarily by the mechanisms available for charge compensation. While the formation of OH vacancies in HA initiates the transformation to Si-TCP, two mechanisms of charge compensation in the Si-TCP structure are plausible. If O(2-) vacancies provide charge compensation, the composition of Si-TCP is Ca(3)(P(0.9)Si(0.1)O(3.95))(2) derived for the addition of 0.33 mol SiO(2):mol HA. If excess Ca(2+) compensates, the composition is Ca(3.08)(P(0.92)Si(0.08)O(4))(2) derived for the addition of 0.25 mol SiO(2):mol HA. The reaction occurs most effectively when SiO(2) is added as a colloidal suspension rather than by the in-situ thermal decomposition of a silicon metallorganic compound. The material is a bioceramic of major biological interest because of its osteoconductivity and unique influence on skeletal tissue repair and remodeling.

Zero-strain and long-term stability of nanoscale lithium titanate (LTO) anode materials make possible the fabrication of exceptionally stable lithium ion batteries. But one issue must be considered that of nanostructure-induced relaxation in 2D LTO nanosheets which profoundly modifies their Li storage properties and structural stability. Excessively intercalated Li ions at both 8a and 16c sites trigger nucleation of the relaxed LTO structure in the near-surface region, which impedes Li-ion diffusion and causes the increasing polarization of LTO nanosheet electrodes. Nuclei of relaxed LTO then undergo isotropic growth along the 3D Li-ion pathways in LTO to completely convert near-surface regions into relaxed LTO. With increasing population of trapped Li ions, the enhanced conductivity due to Ti4+/Ti3+ reduction gradually eliminates the raised polarization. In the meantime, spontaneous electrolyte/LTO reduction to form the solid electrolyte interphase starts playing a major role in capacity loss once the transformation of near-surface region into relaxed LTO becomes saturated. Elucidation of these fundamental intercalation-induced surface structure transformations contribute greatly into the design of highly performing 2D nanoscaled LTO and other electrode materials.

Synchrotron techniques, including synchrotron X-ray diffraction (SR-XRD) and X-ray absorption spectroscopy (XAS), have been widely used over the past twenty years to investigate the chemical and physical behavior of batteries. The uniquely high brilliance and coherence of synchrotron light has made it especially well-suited for in-situ analysis of batteries, as data can be acquired very quickly with excellent spectral and spatial resolution [1] . Generally in-situ studies of batteries employ a custom-made research cell that is designed with “windows” in the casing that are x-ray transparent. Such cells typically employ a simple coin-cell-type design where two discs of electrode material are pressed together in an air-tight assembly [2, 3] . While these types of cells are very useful and convenient for most materials research, they cannot exactly replicate the conditions present in many common commercial cells, and they are not generally suitable for long-term studies on ageing and degradation. The work presented here demonstrates several examples of how synchrotron techniques can be used to analyze unmodified commercial pouch cells. With high brilliance and tunability of incident wavelength, synchrotron light can be used to penetrate commercial cell casings and analyze active electrode material in-operando. At the Canadian Light Source, SR-XRD was used to analyze the crystal structure and phase changes in an operating commercial nickel-manganese-cobalt-oxide/graphite pouch cell. Transmission SR-XRD was also used to map structural inhomogeneities in cell components with high spatial resolution. In-operando XAS was also successfully carried out on an unmodified commercial pouch cell, which will provide a simple means of monitoring changes in structure and redox chemistry as commercial batteries undergo long-term ageing, cycling, and stress testing. [1] Yoon W-S, Grey CP, Balasubramanian M, Yang X-Q, Fischer DA, McBreen J. Electrochem Solid-State Lett., 2014, 13, 1051-1061. [2] De Marco R, Veder JP. Trends in Analytical Chem., 2010, 29, 6. [3] Herklotz M, Scheiba F, Hinterstein M, Nikolowski K, Knapp M, Dippel AC, Giebeler L, Eckert J, Ehrenberg H. J. Appl. Cryst., 2013, 46, 1117-1127.