bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of Paleoproterozoic granitoid magmatism along the northwestern Superior Province margin: implications for the tectonic evolution of the Thompson Nickel BeltThis article is one of a series of papers published in this Special Issue on the theme of Geochronology in honour of Tom Krogh.
Authors: Machado N. , Heaman L. M. , Krogh T. E. , Weber W. , Corkery M. T. 
Published: February 2011

The U–Pb geochronology of three granitoid plutons and three granitic pegmatite dykes, largely from the Thompson Nickel Belt located along the northwestern Superior craton margin, was investigated to place constraints on the timing of felsic magmatism associated with closure of the Manikewan Ocean and final continent–continent collision to form the Trans-Hudson Orogen. These data indicate that 1840–1820 Ma granite magmatism along the Superior margin was more active than previously thought and that some magmatism extended beyond the Thompson Nickel Belt sensu stricto, including the 1836 ± 3 Ma Mystery Lake granodiorite, 1822 ± 5 Ma Wintering Lake granodiorite, and the 1825 ± 8 Ma Fox Lake granite located in the Split Lake Block. Granitic pegmatites within the Thompson Nickel Belt were emplaced late in the collisional history in the period 1.79–1.75 Ga and include a 1770 ± 2 Ma dyke exposed at the Thompson pit, a 1767 ± 6 Ma dyke at the Pipe Pit, and a 1786 ± 2 Ma dyke located at Paint Lake. The final stage of crustal amalgamation in the eastern Trans-Hudson Orogen involved Superior Province crustal thickening and partial melting forming 1.84–1.82 Ga granite magmas and then final collision at ∼1.8 Ga between the Superior Province and a continental block to the west consisting of the previously amalgamated Sask and Hearne cratons. Heating of the Superior craton margin and granitic magmatism continued past peak metamorphism (1790–1750 Ma); this thermal event is represented by the emplacement of numerous late pegmatite dykes and evidenced by cooling dates recorded by metamorphic minerals (e.g., titanite) in reworked Archean gneisses and Proterozoic intrusions.
The Krogh revolution: advances in the measurement of timeThis article is the Introduction to a series of papers published in this Special Issue on the theme of Geochronology in honour of Tom Krogh.
Authors: Kamo Sandra L. , Corfu Fernando , Heaman Larry M. , Moser Desmond E. 
Published: February 2011

Tom Krogh revolutionized the field of precise U–Pb geochronology through a series of ground-breaking technical advances in the 1970s and 1980s that changed our investigative approach to understanding geologic processes. Earth scientists around the world have used his dating methods for more than 30 years to produce high-precision ages that have advanced our knowledge of Earth’s evolution through time. Tom applied these techniques to investigate the formation of ancient crust in the Superior and Grenville provinces, and other orogens, and the timing of terrestrial impacts. His legacy is built upon these scientific contributions, the many people he trained and inspired, and the global distribution of laboratories that use his methods.
New zircon shock phenomena and their use for dating and reconstruction of large impact structures revealed by electron nanobeam (EBSD, CL, EDS) and isotopic U–Pb and (U–Th)/He analysis of the Vredefort domeThis article is one of a series of papers published in this Special Issue on the theme of Geochronology in honour of Tom Krogh.
Authors: Moser D. E. , Cupelli C. L. , Barker I. R. , Flowers R. M. , Bowman J. R. , Wooden J. , Hart J.R. 
Published: February 2011

Integrated electron nanobeam (EBSD, CL, EDS) and isotopic measurements (U–Pb, (U–Th)/He) of zircon from the collar and centre of the 80 km wide central uplift of the 2020 ± 3 Ma Vredefort impact structure reveal new shock features in a microstructural progression related to impact basin formation and degree of U–Pb age resetting: (1) planar fractures in {1K0} and {1K2} orientation during initial shock wave compression; (2) curviplanar fractures in {1K1} orientation, now annealed, which host glassy inclusions of partial melt of the host rock; (3) microtwin lamellae in an orientation of 65° about [110], attributed to shock wave rarefaction; (4) nucleation of impact-age crystallites, possibly on microtwins, during post-shock heating by impact melt; and (5) crystal-plastic deformation linked to crater modification of the core of the central uplift. Planar fracturing and microtwinning ≥20 GPa in “cold shock” zircon in granitoid at a radial distance of 25 km failed to reset zircon age. Single-grain ID–TIMS data extend between pre-impact age of 2077 ± 11 Ma and a secondary Pb-loss event at ca. 1.0 Ga — the latter reflecting Kibaran igneous activity between 1.110 and 1.021 Ga. Age resetting by the impact event operated in an ∼15 km wide “hot shock” zone of impact-elevated temperatures ≥700 °C at the core of the central uplift. Mechanisms include internal recrystallization, defect-accelerated Pb diffusion via shock microstructures and melt films, and late crystal-plastic deformation. Igneous zircons from a 2019 ± 2 Ma foliated norite impact melt yield a mean (U–Th)/He date of 923 ± 61 Ma, indicating exposure of the present surface after this time.
Experimental investigation on the effect of longitudinal reinforcement on shear strength of fibre reinforced polymer reinforced concrete beams
Authors: Alam M.S. , Hussein A. 
Published: February 2011

The shear design equation of CSA S806-02 does not consider the effect of the axial stiffness of the reinforcing bars for beams with effective depth greater than 300 mm. This paper examines the shear strength of such beams without stirrups. A total of 16 beams reinforced with GFRP, CFRP, and steel bars were tested under four-point monotonic loading. The test results were analyzed and compared with the predictions of CSA S806-02 shear design equation. It was observed that the conservatism of CSA S806-02 prediction, for beams with effective depth greater than 300 mm, increased with the increase in the axial stiffness of the reinforcing bars. Based on the test results, a modification to the CSA S806-02 shear design equation is proposed. The proposed modification was found to be consistent for predicting the shear strength of beams with different axial stiffness of the reinforcing bars.
Effect of a temperature gradient on Sphagnum fallax and its associated living microbial communities: a study under controlled conditions
Authors: Jassey Vincent E.J. , Gilbert Daniel , Binet Philippe , Toussaint Marie-Laure , Chiapusio Geneviève 
Published: February 2011

Microbial communities living in Sphagnum are known to constitute early indicators of ecosystem disturbances, but little is known about their response (including their trophic relationships) to climate change. A microcosm experiment was designed to test the effects of a temperature gradient (15, 20, and 25 °C) on microbial communities including different trophic groups (primary producers, decomposers, and unicellular predators) in Sphagnum segments (0–3 cm and 3–6 cm of the capitulum). Relationships between microbial communities and abiotic factors (pH, conductivity, temperature, and polyphenols) were also studied. The density and the biomass of testate amoebae in Sphagnum upper segments increased and their community structure changed in heated treatments. The biomass of testate amoebae was linked to the biomass of bacteria and to the total biomass of other groups added and, thus, suggests that indirect effects on the food web structure occurred. Redundancy analysis revealed that microbial assemblages differed strongly in Sphagnum upper segments along a temperature gradient in relation to abiotic factors. The sensitivity of these assemblages made them interesting indicators of climate change. Phenolic compounds represented an important explicative factor in microbial assemblages and outlined the potential direct and (or) indirect effects of phenolics on microbial communities.
Swarming motility by Photorhabdus temperata is influenced by environmental conditions and uses the same flagella as that used in swimming motilityThis is scientific contribution No. 2431 from the New Hampshire Agricultural Experiment Station.
Authors: Michaels Brandye , Tisa Louis S. 
Published: February 2011

Photorhabdus temperata , an insect pathogen and nematode symbiont, is motile in liquid medium by swimming. We found that P. temperata was capable of surface movement, termed swarming behavior. Several lines of evidence indicate that P. temperata use the same flagella for both swimming and swarming motility. Both motility types required additional NaCl or KCl in the medium and had peritrichous flagella, which were composed of the same flagellin as detected by immunoblotting experiments. Mutants defective in flagellar structural proteins were nonmotile for both motility types. Unlike swimming, we observed swarming behavior to be a social form of movement in which the cells coordinately formed intricate channels covering a surface. The constituents of the swarm media affected motility. Swarming was optimal on low agar concentrations; as agar concentrations increased, swarm ring diameters decreased.
Taxol Resistance in Breast Cancer Cells Is Mediated by the Hippo Pathway Component TAZ and Its Downstream Transcriptional TargetsCyr61andCTGF
Authors: Lai Dulcie , Ho King Ching , Hao Yawei , Yang Xiaolong 
Published: February 2011

AbstractTaxol (paclitaxel) resistance represents a major challenge in breast cancer treatment. The TAZ (transcriptional co-activator with PDZ-binding motif) oncogene is a major component of the novel Hippo–LATS signaling pathway and a transcriptional coactivator that interacts with and activates multiple transcription factors to regulate various biological processes. Here, we report that elevated levels of TAZ found in human breast cancer cells are responsible for their resistance to Taxol. DNA microarray analysis identified the oncogenes Cyr61 and CTGF as downstream transcriptional targets of TAZ. Short hairpin RNA–mediated knockdown of both Cyr61 and CTGF reversed TAZ-induced Taxol resistance in breast cancer cells. Interaction of TAZ with the TEAD family of transcription factors was essential for TAZ to activate the Cyr61/CTGF promoters and to induce Taxol resistance. Our findings define the TAZ-TEAD-Cyr61/CTGF signaling pathway as an important modifier of the Taxol response in breast cancer cells, as well as highlighting it as a novel therapeutic target to treat drug-resistant breast cancers that arise commonly at advanced stages of disease. Cancer Res; 71(7); 2728–38. ©2011 AACR.
Vandetanib Restores Head and Neck Squamous Cell Carcinoma Cells' Sensitivity to Cisplatin and Radiation In Vivo and In Vitro
Authors: Sano Daisuke , Matsumoto Fumihiko , Valdecanas David R. , Zhao Mei , Molkentine David P. , Takahashi Yoko , Hanna Ehab Y. , Papadimitrakopoulou Vali , Heymach John , Milas Luka , Myers Jeffrey N. 
Published: February 2011

Abstract
Purpose: We investigated whether vandetanib, an inhibitor of the tyrosine kinase activities of vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET), could augment the antitumor activity of radiation with or without cisplatin in preclinical in vitro and in vivo models of human head and neck squamous cell carcinoma (HNSCC).
Experimental Design: OSC-19 and HN5 HNSCC cells that were cisplatin and radioresistant were treated with vandetanib, cisplatin, and radiation alone or in combination in vitro and in vivo using an orthotopic nude mouse model. Treatment effects were assessed using clonogenic survival assay, tumor volume, bioluminescence imaging, tumor growth delay, survival, microvessel density, tumor and endothelial cell apoptosis, and EGFR and Akt phosphorylation data.
Results: Vandetanib plus cisplatin radiosensitized HNSCC cells in vitro and in vivo. The combination treatment with vandetanib, cisplatin, and radiation was superior to the rest of treatments (including the double combinations) in antitumoral effects, prolonging survival, decreasing cervical lymph node metastases in vivo. It also increased both tumor and tumor-associated endothelial cell apoptosis and decreased microvessel density in vivo. An analysis of tumor growth delay data revealed that vandetanib plus cisplatin enhanced radioresponse in vivo. All vandetanib-containing treatments inhibited EGFR and Akt phosphorylation in vitro and in vivo.
Conclusion: The addition of vandetanib to combination therapy with cisplatin and radiation was able to effectively overcome cisplatin and radioresistance in in vitro and in vivo models of HNSCC. Further study of this regimen in clinical trials may be warranted. Clin Cancer Res; 17(7); 1815–27. ©2011 AACR.
DNA Repair Biomarker Profiling of Head and Neck Cancer: Ku80 Expression Predicts Locoregional Failure and Death following Radiotherapy
Authors: Moeller Benjamin J. , Yordy John S. , Williams Michelle D. , Giri Uma , Raju Uma , Molkentine David P. , Byers Lauren A. , Heymach John V. , Story Michael D. , Lee J. Jack , Sturgis Erich M , Weber Randal S. , Garden Adam S. , Ang K. Kian , Schwartz David L. 
Published: February 2011

Abstract
Purpose: Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes.
Experimental Design: Archival HNSCC tumor specimens (n = 89) were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort (n = 34).
Results: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy (P &lt; 0.01). The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years.
Conclusions: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. Clin Cancer Res; 17(7); 2035–43. ©2011 AACR.
Differential Response of Human and Mouse Dendritic Cells to VEGF Determines Interspecies Discrepancies in Tumor-Mediated Th1/Th2 Polarity Shift
Authors: Block Matthew S. , Nevala Wendy K. , Leontovich Alexey A. , Markovic Svetomir N. 
Published: February 2011

Abstract
Purpose: Metastatic cancer patients exhibit systemic dysregulation of immune polarity and are biased toward Th-2 immune responses. This is due, at least in part, to effects of VEGF on antigen presenting cell (APC) function. We therefore compared immune polarity changes in mouse models of cancer with those seen in human patients.
Experimental Design: We measured plasma levels of vascular growth factors and multiple cytokines via ELISA and multiplex analysis in mice with transplantable and spontaneous tumors. We compared immune cell subsets in naive and vaccinated mice with and without tumors. We assessed cytokine immune responses by multiplex analysis. Finally, we assessed gene expression and receptor surface expression in response to VEGF in mouse and human APCs.
Results: Although human patients have elevated plasma cytokines and altered immune polarity in response to antigen, mice have minimal immune abnormalities. Mouse VEGF does not mediate immune repolarization in vitro. Human but not mouse APCs upregulate VEGFR2 and downregulate interleukin (IL)-12β in response to VEGF.
Conclusions: Whereas humans with metastatic cancer demonstrate dysregulated immune polarity in response to excess plasma VEGF, tumor mice do not. This appears to be due to differences in APC responses to VEGF stimulation. Differential immune effects of VEGF may represent a key species difference in the context of translation of preclinical cancer immunotherapeutics into early clinical testing. Clin Cancer Res; 17(7); 1776–83. ©2011 AACR.
Abstract 100: Preclinical and clinical studies data consolidation and federation using an integrative data analysis system: SIMUSITETM
Authors: Vora Meena I. 
Published: February 2011

Abstract
One of the biggest challenges of the drug development process is to secure, access the experimental work and critical communications amongst the persons involved. These are the primary assets of any organization. These challenges stem from, (i) the data generated are collected mostly over a long period of time. (ii) the fast pace of development of new laboratory technologies requires the project management and underlying data structure constantly changing. (iii) outsourcing of the project work. (iv) multiple modes of communications among the peers.
Here we describe the data consolidation and federation module of BioPhase Systems’ SIMUSITETM (http://www.biophasesystems.com/simusite), a commercial software platform that allows users to integrate and analyze biological data from multiple experimental sources to uncover potentially valuable targets and guide the further drug development of therapeutic compounds. In order to ensure the accessibility to disparate knowledge bases, SIMUSITE has been architected using caBIGTM compatibility guidelines (http://cabig.nci.nih.gov). Though the software is built for the present needs of the industry, it is also designed to address the future challenges.
A case study depicting the migration of various types of data generated from multiple third party data analysis applications is presented spanning from pre-clinical to clinical level studies. It also demonstrates the analysis of the consolidated data further in the context of the public domain knowledge on the fly, thus providing the environment to consolidate data, updating the projects dynamically and allowing the communications amongst the peers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 100.
Abstract 1005: Mesenchymal stem cells in breast cancer dormancy: Role of regulatory T cell induction
Authors: Patel Shyam A. , Rameshwar Pranela 
Published: February 2011

Abstract
Mesenchymal stem cells (MSCs) have been shown to support breast cancer growth. Since MSCs also increase the expansion of regulatory T cells (Tregs), we hypothesize that human MSCs protect breast cancer cells (BCCs) from immune clearance by recruitment and expansion of Tregs. MSCs suppressed the proliferation of PBMCs when the latter were exposed to γ-irradiated BCCs. Similarly, MSCs showed significant inhibition in the migration of PBMCs towards BCCs, despite the production of chemokines. MSCs also inhibited functional NK and CTL functions, which correlated with reduced numbers of CD8 and CD56 cells as compared to parallel cultures without MSCs. The reduced NK and CTL activities correlated with decrease in the total number of granzyme B-producing cells. To explain these findings, we compared Tregs in the presence or absence of MSCs and found increases with MSCs. The expansion of Tregs correlated with decreases in Th1 cytokines and increases in Th2 cytokines. MSC-derived TGF-β was mostly responsible for the increase in Tregs, based on knockdown studies. Together, these studies show increase in Tregs in co-cultures of PBMCs, BCCs and MSCs. The results could be partly explained by increase in Th2 type cytokines and MSC-generated TGF-β. These findings demonstrate immune protection by MSCs to BCCs. The reduced immune cell proliferation and recruitment mediated by MSCs has implications for treatment with chemotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1005.
Abstract 102: Mathematical models for growth of metastatic tumors
Authors: El-Kareh Ardith W. , Secomb Timothy W. 
Published: February 2011

Abstract
The mathematical form best describing the growth of a single tumor mass has been found to be any of several models including the power law, logistic or Gompertzian, depending on the particular clinical or experimental tumor considered. All these models exhibit monotonically decreasing growth rate over time; some plateau at some finite volume. However, the kinetics of growth of the total mass of a metastatic tumor remains a separate question with relevance for understanding survival time, optimal treatment, and the development of symptoms that arise from total tumor burden. Here, exact analytical solutions for total tumor burden are derived under the assumption that both the primary tumor and each individual metastatic lesion grow with power law kinetics. Solutions are also derived for the case of metastatic growth after removal of the primary tumor. Two cases are considered: one where the rate of metastasis formation from an individual lesion grows with power law kinetics, and one where this rate is independent of size. Surprisingly, the latter assumption, which is consistent with only a small subpopulation of cells having metastatic potential, proves entirely adequate to describe data of Iwata et al on the cumulative distribution of metastases of a human hepatocellular carcinoma. For both cases, as time progresses, the growth ultimately becomes exponential, regardless of whether or not the primary tumor has been excised. However, it is shown that for the range of parameters describing observed tumors, this exponential limit is not reached before the tumor burden becomes lethal. The growth does not, however, show the trend of decreasing rate with increasing volume exhibited by single lesions, and appears in fact approximately exponential over the range of clinical detectability. This provides an explanation for experimental data showing near exponential growth of plasma tumor markers such as carcinoembryonic antigen in patients followed for metastatic colorectal or medullary thyroid carcinoma. Using the model, it can be seen that neither the growth rate of individual lesions, nor the rate of metastasis formation by itself causes tumor lethality; rather it is the ratio of these two rates that determines whether a large number of metastases form before the primary tumor reaches detectable size. The models derived here are expected to have application to mathematical modeling of optimal treatment and tumor-immune system interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 102.