bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial Tissue Hyperplasia Induced by the RAF Inhibitor PF-04880594 Is Attenuated by a Clinically Well-Tolerated Dose of the MEK Inhibitor PD-0325901
Authors: Torti Vince R. , Wojciechowicz Donald , Hu Wenyue , John-Baptiste Annette , Evering Winston , Troche Gabriel , Marroquin Lisa D. , Smeal Tod , Yamazaki Shinji , Palmer Cynthia L. , Burns-Naas Leigh Ann , Bagrodia Shubha 
Published: July 2012

Abstract
Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal–regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor–induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. Mol Cancer Ther; 11(10); 2274–83. ©2012 AACR.
The Gamma Secretase Inhibitor MRK-003 Attenuates Pancreatic Cancer Growth in Preclinical Models
Authors: Mizuma Masamichi , Rasheed Zeshaan A. , Yabuuchi Shinichi , Omura Noriyuki , Campbell Nathaniel R. , de Wilde Roeland F. , De Oliveira Elizabeth , Zhang Qing , Puig Oscar , Matsui William , Hidalgo Manuel , Maitra Anirban , Rajeshkumar N.V. 
Published: July 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, with most patients facing an adverse clinical outcome. Aberrant Notch pathway activation has been implicated in the initiation and progression of PDAC, specifically the aggressive phenotype of the disease. We used a panel of human PDAC cell lines as well as patient-derived PDAC xenografts to determine whether pharmacologic targeting of Notch pathway could inhibit PDAC growth and potentiate gemcitabine sensitivity. MRK-003, a potent and selective γ-secretase inhibitor, treatment resulted in the downregulation of nuclear Notch1 intracellular domain, inhibition of anchorage-independent growth, and reduction of tumor-initiating cells capable of extensive self-renewal. Pretreatment of PDAC cells with MRK-003 in cell culture significantly inhibited the subsequent engraftment in immunocompromised mice. MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) PDAC xenografts. A combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared with gemcitabine in 4 of 9 (44%) PDAC xenografts, reduced tumor cell proliferation, and induced both apoptosis and intratumoral necrosis. Gene expression analysis of untreated tumors indicated that upregulation of NF-κB pathway components was predictive of sensitivity to MRK-003, whereas upregulation in B-cell receptor signaling and nuclear factor erythroid-derived 2-like 2 pathway correlated with response to the combination of MRK-003 with gemcitabine. Our findings strengthen the rationale for small-molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. Mol Cancer Ther; 11(9); 1999–2009. ©2012 AACR.
Targeted Expression of BikDD Eliminates Breast Cancer with Virtually No Toxicity in Noninvasive Imaging Models
Authors: Xie Xinhua , Li Laisheng , Xiao Xiangsheng , Guo Jiaoli , Kong Yanan , Wu Minqing , Liu Wanli , Gao Guoquan , Hsu Jennifer L. , Wei Weidong , Hung Mien-Chie , Xie Xiaoming 
Published: July 2012

Abstract
Breast cancer is a major public health problem all over the world, and the current treatment strategies are not potent enough for some patients, especially those with triple-negative breast cancer. Therefore, novel and more effective treatments are critically needed. Of the current methods, targeted therapy, which not only retains cancer-specific expression but also limits toxicity, is a new strategy for treating cancers. In this study, we found that the human telomerase reverse transcriptase (hTERT; T) promoter also possesses high target specificity in breast cancer. Moreover, we developed a versatile T-based breast cancer–specific promoter VISA (VP16-Gal4-WPRE integrated systemic amplifier) composite (T-VISA) to target transgene expression in breast tumors, which has stronger activity comparable or higher than that of the cytomegalovirus promoter in cancer cells. Thereafter, targeted expression of BikDD (a mutant form of proapoptotic gene Bik) through the T-VISA platform in breast cancer initiated robust antitumor effects and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of breast tumors with virtually no toxicity in intact mice. Thus, these findings show that our T-VISA-BikDD nanoparticles effectively and safely eradicate breast cancer in vitro and in vivo and are worthy of development in clinical trials treating breast cancer. Mol Cancer Ther; 11(9); 1915–24. ©2012 AACR.
Essential Factors for the Development of a Residency Global Health Track
Authors: Campagna Ann M. , St. Clair Nicole E. , Gladding Sophia P. , Wagner Sabrina M. , John Chandy C. 
Published: July 2012

Objective There is increasing awareness of the importance of global health (GH) residency education but little guidance on what departmental, financial, and human resource support is required to develop a GH track. The authors aimed to identify essential factors and major obstacles to the development of a GH track. Methods A survey assessing curriculum, support, and factors considered essential to or obstacles to successful development of a GH track was sent to 24 GH education directors within pediatric residencies. Results In all, 19 programs (79%) completed the survey, and 6 factors were identified as essential for developing and sustaining a GH track by ≥95% of all GH education directors: supportive residency program director, resident commitment, supportive department chair, protected resident elective time, dedicated budget, and GH faculty with protected time. Conclusions Residency programs aiming to start a GH track should start by assessing the availability and sustainability of these identified essential factors within their program.
Impact of Blue Force Tracking on Combat Identification Judgments
Authors: Bryant David J. , Smith David G. 
Published: July 2012

Objective: We examined the effectiveness of blue force tracking (BFT) decision support for dismounted infantry soldiers. Background: Technologies to support combat identification (CID) are rapidly evolving and may be deployable to dismounted soldiers in the future. BFT systems are designed to mitigate the risk of fratricide by supplying positional information regarding friendly units to enhance situation awareness. Method: Participants played the role of a dismounted infantry soldier in a first-person perspective gaming environment and made engagement decisions for a series of simulated targets, half of which were enemies and half of which were friends. Results: Participants performed better overall when they were able to use a BFT system than when they performed the task without assistance. When a 10-s latency was added to the updating of position information in the BFT, participants made significantly more false alarms (engaged a friendly target) regardless of whether they knew about the latency. Conclusion: The results indicate the promise of a personal BFT device to reduce the likelihood of fratricide by dismounted infantry soldiers. The results, however, also indicate that the effectiveness of such a device can be dramatically reduced when it does not provide real-time data. Application: Potential applications of this research include development of performance standards for BFT devices and assessment of decision support for dismounted soldiers.
Molybdophyllite: crystal chemistry, crystal structure, OD character and modular relationships with britvinite
Authors: Kolitsch U. , Merlino S. , Holtstam D. 
Published: July 2012

AbstractA detailed crystal-chemical study of the complex layered silicate molybdophyllite was conducted using single-crystal X-ray diffraction (XRD) methods, supplemented by powder XRD, infrared (IR) and Raman spectroscopic studies, chemical analyses by energy-dispersive spectrometry (EDS) on a scanning electron microscope (SEM), and electron probe microanalysis (EPMA). The results, based on several samples from both Långban and Harstigen, Filipstad, Sweden, show that the crystal structure of molybdophyllite has an order-disorder (OD) character. The latter is especially evident in specimens from Långban which display a complex diffraction pattern characterized by the simultaneous presence of sharp spots, diffuse reflections and continuous streaks. The sharp reflections define the unit cell of the family structure (a = 3.124, c = 41.832 Å, space group R32). Two main polytypes (maximum degree of order structures) are indicated by the OD approach: a trigonal one and a monoclinic one; the latter polytype is the most common in the samples that were studied and has space group C2, with a = 16.232(6), b = 9.373(2), c = 14.060(3) Å, b = 97.36(4)º and V = 2121.5(10) Å3.The crystal structure determination [R1= 0.096], together with the EPMA, IR and Raman data, reveal that molybdophyllite is built up by a regular alternation of complex layers with a composition {Mg9[Si10O28(OH)8][OPb4]2}6+and simple layers with a composition [(CO3)3·H2O]6–, leading to the ideal crystal-chemical formula Pb8Mg9[Si10O28(OH)8|O2|(CO3)3]·H2O (Z = 2).This contribution is mainly devoted to the results obtained for molybdophyllite sensu stricto, but new data for britvinite [i.e. 'molybdophyllite-18 Å'] are also presented and its modular relationship with molybdophyllite is discussed.
The crystal structure determination and redefinition of matulaite, Fe3+Al7(PO4)4(PO3OH)2(OH)8(H2O)8·8H2O
Authors: Kampf A. R. , Mills S. J. , Rumsey M. S. , Spratt J. , Favreau G. 
Published: July 2012

AbstractMatulaite was first described by Moore and Ito (1980) from the Bachman mine, Hellertown, Northampton County, Pennsylvania, USA. Its ideal formula was reported as CaAl18(PO4)12(OH)20·28H2O, based on wet-chemical analysis. Re-examination of both existing cotype specimens of matulaite revealed no material matching the powder or single-crystal X-ray diffraction data reported for the species. Other samples examined from the type locality, as well as from the LCA pegmatite in North Carolina, USA, and Fumade, Tarn, France, provided material crystallographically consistent with matulaite: P21/n, a = 10.604(2), b = 16.608(4), c = 20.647(5) Å , b = 98.848(7)° and Z = 4. Electron microprobe and crystal structure analysis of newly studied material from the type locality showed the ideal formula of matulaite to be Fe3+ Al7(PO4)4(PO3OH)2(OH)8(H2O)8˙8H2O. The chemical composition reported by Moore and Ito (1980) was most probably determined on a mixture of mostly kobokoboite and afmite, with lesser amounts of crandallite. As there is no matulaite on any of the existing cotype specimens of the species, the two specimens used to obtain the new chemical analyses, powder and single-crystal X-ray diffraction data and the structure determination are designated as neotypes. The neotypes have also been used to obtain crystal morphology and new measurements of the physical and optical properties of the species. The neotypes and new data have been approved by the CNMNC, proposal 11-F. The crystal structure of matulaite contains seven-member chain segments of AlO6 octahedra decorated by PO4 tetrahedra. The PO4 tetrahedra also link to isolated FeO6 octahedra, resulting in a 'pinwheel' Fe(PO4)6 group. The linkage of octahedra and tetrahedra defines a thick layer parallel to {001}. The only linkage between layers is via hydrogen bonding to interlayer water molecules.
A chemical and structural re-examination of fettelite samples from the type locality, Odenwald, southwest Germany
Authors: Bindi L. , Downs R. T. , Spry P. G. , Pinch W. W. , Menchetti S. 
Published: July 2012

AbstractThe crystal structure and chemical composition of two samples of fettelite from the type locality, including a portion of the holotype material, was investigated to verify if a previously proposed revision of the chemical formula was applicable, and to study the role of cation substitution for Hg that would suggest new members of the fettelite family. The crystal structure of fettelite from the type locality was found to be equivalent to that reported previously for the Chilean occurrence, and consists of an alternation of two kinds of layers along c: layer A with general composition [Ag6As2S7]2–and layer B with general composition [Ag10HgAs2S8]2+. In this structure, the Ag atoms occur in various coordination configurations, varying from quasi-linear to quasi-tetrahedral, the AsS3 groups form pyramids as are typically observed in sulfosalts, and Hg links two sulfur atoms in a linear coordination. The refined compositions for the crystals in this study, [Ag6As2S7][Ag10(Fe0.53Hg0.47)As2S8] (R100124) and [Ag6As2S7][Ag10(Hg0.79Cu0.21)As2S8] (R110042), clearly indicate that new mineral species related to fettelite are likely to be found in nature.
Pb2(AsO2OH)Cl2, a new phase from the Lavrion ancient slags, Greece: occurrence and characterization
Authors: Siidra O. I. , Chukanov N. V. , Pekov I. V. , Krivovichev S. V. , Magganas A. , Katerinopoulos A. , Voudouris P. 
Published: July 2012

AbstractTransparent prismatic crystals of Pb2(AsO2OH)Cl2were collected in black metallurgical slag on the coast in the Punta Zeza area, 3 km south of the town of Lavrion, Greece. Analyses by energy-dispersive X-ray spectrometry (EDS) provided the following chemical composition: PbO 73.04, As2O315.97, Cl 11.42, O=Cl –2.58, total 97.85 wt.%. The empirical formula calculated on the basis of As = 1 is HxPb2.03(AsO3)1.00Cl1.995(x = 0.96). The infrared spectrum of Pb2(AsO2OH)Cl2has characteristic AsO33–bands at 707 and 594 cm–1, O–H stretching vibrations at 3310 and 2900 cm–1and a band at 1107 cm–1which is assigned to As–O–H bending vibrations. The structure, which is monoclinic P21/m, a = 6.4235(8), b = 5.5399(7), c = 9.321(1) Å, β = 90.767(2)°, V = 331.67(7) Å3, R1= 0.035, is identical to that of synthetic Pb2(AsO2OH)Cl2and contains two symmetrically unique Pb sites and one As site. The crystal structure is based on [Pb2AsO2OH]2+double chains interconnected via weak Pb–Cl bonds to produce a three-dimensional framework which is closely related to that of Pb oxysalt minerals containing [O2Pb3]2+chains of oxocentred [OPb4]6+tetrahedra including mendipite, damaraite, rickturnerite and plumboselite.
Arsenohopeite, a new zinc arsenate mineral from the Tsumeb mine, Namibia
Authors: Neuhold F. , Kolitsch U. , Bernhardt H.-J. , Lengauer C. L. 
Published: July 2012

AbstractArsenohopeite, ideally Zn3(AsO4)2·4H2O, is the arsenate analogue of hopeite, Zn3(PO4)2·4H2O (it is isostructural with α-hopeite). It was found as a single colourless to blue crystalline grain from the Tsumeb mine, Namibia. The holotype specimen is ∼1 × 1 × 1 mm in size. Arsenohopeite is associated with tiny white fibres of an unidentified Zn- and As-bearing phase. It is orthorhombic, space group Pnma, with a = 10.804(2), b = 19.003(4), c = 5.112(1) Å, V = 1049.5(4) Å3 and Z = 4. Electron microprobe analysis yielded: ZnO 44.92, Fe2O3 0.92, MnO 0.51, MgO 0.20, CuO 0.02, As2O5 45.84 (wt.%). The empirical formula is (Zn2.80Fe0.06Mn0.04Mg0.03)Σ2.93(As1.01O4)2·4H2O, based on 12 oxygen atoms. Optically, the mineral is biaxial negative, with α = 1.598(2), β = 1.606(2), γ = 1.613(2) (white light) and 2Vcalc = 86°. It is not pleochroic or fluorescent. Arsenohopeite is translucent with a vitreous lustre. It is brittle, has an uneven fracture and (by analogy with hopeite) a cleavage that is perfect on {010}, good on {100} and poor on {001}. The calculated density is 3.420 g cm–3. The five strongest calculated powder diffraction lines are [d in Å (I)(hkl)]: 9.502 (100)(020), 2.926 (95)(241), 4.937 (50)(011), 4.110 (48)(230) and 3.567 (31)(240). The crystal structure of arsenohopeite has been solved by direct methods and refined in space group Pnma to R1 = 0.0353. Raman spectroscopy confirms the crystal-structure data and indicates the presence of weak hydrogen bonds.
Krásnoite, the fluorophosphate analogue of perhamite, from the Huber open pit, Czech Republic and the Silver Coin mine, Nevada, USA
Authors: Mills S. J. , Sejkora J. , Kampf A. R. , Grey I. E. , Bastow T. J. , Ball N. A. , Adams P. M. , Raudsepp M. , Cooper M. A. 
Published: July 2012

AbstractKrásnoite is a new mineral (IMA2011-040) from the Huber open pit, Krásno ore district, Czech Republic and the Silver Coin mine, Nevada, USA. Krásnoite is the fluorophosphate analogue of perhamite. Krásnoite occurs as compact to finely crystalline aggregates, balls and rosette-like clusters up to 1 mm across. Individual crystals are platy, show a hexagonal outline and can reach 0.1 mm on edge at Krásno and 0.4 mm at Silver Coin. At both localities, krásnoite occurs very late in phosphaterich paragenetic sequences. Krásnoite crystals are partly transparent with a typically pearly lustre, but can also appear greasy (Krásno) or dull (Silver Coin). The streak is white and the hardness is 5 on the Mohs scale. Crystals are brittle, have an irregular fracture, one imperfect cleavage on {001} and are not fluorescent under SW and LW ultraviolet light. Penetration twinning ⊥ {001} is common. The density for both Krásno and Silver Coin material is 2.48(4) g cm–3, measured by the sink–float method in an aqueous solution of sodium polytungstate. The calculated density is 2.476 g cm–3 (Krásno). Krásnoite crystals are uniaxial (+), with ω = 1.548(2) and ε = 1.549(2) (Krásno) and ω = 1.541(1) and ε = 1.543(1) (Silver Coin). The simplified formula of krásnoite is: Ca3Al7.7Si3P4O23.5(OH)12.1F2·8H2O. Krásnoite is trigonal, space group Pm1, with a = 6.9956(4), c = 20.200(2) Å, V = 856.09(9) Å3 and Z = 3. Raman and infrared spectroscopy, coupled with magic-angle spinning nuclear magnetic resonance (MAS–NMR) spectrometry, confirmed the presence of PO3F, PO4, SiO4, H2O and OH in the crystal structure of krásnoite.
A reinvestigation of mayenite from the type locality, the Ettringer Bellerberg volcano near Mayen, Eifel district, Germany
Authors: Galuskin E. V. , Kusz J. , Armbruster T. , Bailau R. , Galuskina I. O. , Ternes B. , Murashko M. 
Published: July 2012

AbstractNew electron-microprobe analyses of mayenite from the Ettringer Bellerberg volcano near Mayen in the Eifel district, Germany have high Cl contents and Raman spectroscopy indicates the presence of OH groups. Neither of these components is included in the generally accepted chemical formula, Ca12Al14O33. A refinement of the crystal structure by single-crystal X-ray methods reveals a previously unrecognized partial substitution. The O2 site which forms one of the apices of an AlO4tetrahedron (with 3 × O1 sites) is replaced by 3 × O2a sites, which change the coordination of the central Al atom from tetrahedral to octahedral. This substitution is related to partial hydration of Ca12Al14O32Cl2according to the isomorphic scheme (O2–+ Cl–) ↔ 3(OH)–. The revised composition of Eifel mayenite is best described by the formula Ca12Al14O32–xCl2–x(OH)3x(x ∼0.75); the original formula, Ca12Al14O33, is inadequate. The analysed mineral can be considered to consist of endmember Ca12Al14O32Cl2 (62.5 mol.%) and endmember Ca12Al14O30(OH)6(37.5 mol.%).
Metavivianite, Fe2+Fe3+2(PO4)2(OH)2·6H2O: new data and formula revision
Authors: Chukanov N. V. , Scholz R. , Aksenov S. M. , Rastsvetaeva R. K. , Pekov I. V. , Belakovskiy D. I. , Krambrock K. , Paniago R. M. , Righi A. , Martins R. F. , Belotti F. M. , Bermanec V. 
Published: July 2012

AbstractThe composition, structure, X-ray powder diffraction pattern, optical properties, density, infrared, Raman and Mössbauer spectra, and thermal properties of a homogeneous sample of metavivianite from the Boa Vista pegmatite, near Galiléia, Minas Gerais, Brazil are reported for the first time. Metavivianite is biaxial (+) with α = 1.600(3), β = 1.640(3), γ = 1.685(3) and 2Vmeas = 85(5)°. The measured and calculated densities are Dmeas = 2.56(2) and Dcalc = 2.579 g cm–3. The chemical composition, based on electronmicroprobe analyses, Mössbauer spectroscopy (to determine the Fe2+:Fe3+ ratio) and gas chromatography (to determine H2O) is MgO 0.70, MnO 0.92, FeO 17.98, Fe2O3 26.60, P2O5 28.62, H2O 26.5; total 101.32 wt.%. The empirical formula is (Fe3+1.64Fe2+1.23Mg0.085Mn0.06)Σ3.015(PO4)1.98(OH)1.72·6.36H2O. Metavivianite is triclinic, P, a = 7.989(1), b = 9.321(2), c = 4.629(1) Å, α = 97.34(1), β = 95.96(1), γ = 108.59(2)°, V = 320.18(11) Å3 and Z = 1. The crystal structure was solved using a single-crystal techniques to an agreement index R = 6.0%. The dominant cations in the independent sites are Fe2+ and Fe3+, with multiplicities of 1 and 2, respectively. The simplified crystal-chemical formula for metavivianite is Fe2+ (Fe3+, Fe2+)2(PO4)2(OH,H2O)2·6H2O; the endmember formula is Fe2+Fe3+2(PO4)2(OH)2·6H2O, which is dimorphous with ferrostrunzite.
Debattistiite, Ag9Hg0.5As6S12Te2, a new Te-bearing sulfosalt from Lengenbach quarry, Binn valley, Switzerland: description and crystal structure
Authors: Guastoni A. , Bindi L. , Nestola F. 
Published: July 2012

AbstractDebattistiite, ideally Ag9Hg0.5As6S12Te2, is a new mineral (IMA-CNMNC 2011-098) from the Lengenbach quarry in the Binn Valley, Valais, Switzerland. It occurs as very rare tabular euhedral crystals up to 150 μm across in cavities in dolomitic marble, associated with realgar, rutile, trechmannite and hutchinsonite. Debattistiite is opaque with a metallic lustre and a grey streak. It is brittle; the Vickers hardness (VHN25) is 80 kg mm–2 (range: 65–94), corresponding to a Mohs hardness of 2–2½. In reflected light debattistiite is dark grey, highly bireflectant and weakly pleochroic from dark grey to a slightly greenish grey. Between crossed polars it is highly anisotropic with brownish to blue rotation tints. Internal reflections are absent. Reflectance percentages for the four COM wavelengths (Rmin and Rmax) are 27.2, 34.5 (471.1 nm), 25.5, 31.0 (548.3 nm), 22.9, 28.4 (586.6 nm), and 20.1, 25.2 (652.3 nm), respectively.Debattistiite is triclinic, space group P1, with a = 7.832(5), b = 8.606(4), c = 10.755(5) Å, α = 95.563(9), β = 95.880(5), γ = 116.79(4)°, V = 635.3(6) Å3 and Z = 1. The crystal structure [R1 = 0.0826 for 795 reflections with I > 2σ(I)] consists of corner-sharing AsS3 pyramids forming three-membered distorted rings linked by Ag atoms in triangular or tetrahedral coordination.The five strongest powder-diffraction lines [d in Å (I/I0) (hkl)] are as follows: 10.56 (6) (001); 3.301 (5) (12); 2.991 (4) (22); 2.742 (1) and 2.733 (10) (30). A mean of nine electron microprobe analyses gave: Ag 44.88, Hg 4.49, As 20.77, S 17.72, Te 11.82; total 99.68 wt.%, which corresponds to Ag9.02Hg0.49As6.012S11.98Te2.01, on the basis of 29.5 atoms. The new mineral is named for Luca De Battisti, a systematic mineralogist and expert on the minerals of Lengenbach quarry.