bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of cetuximab‐related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: Results from a randomized trial of the GERMAN AIO CRC Study Group
Authors: Stintzing Sebastian , Kapaun Christine , Laubender Rüdiger Paul , Jung Andreas , Neumann Jens , Modest Dominik Paul , Giessen Clemens , Moosmann Nicolas , Wollenberg Andreas , Kirchner Thomas , Heinemann Volker 
Published: May 2012

AbstractSkin toxicity is a frequent adverse event of epidermal growth factor receptor (EGFR) targeting agents. Occurrence of cetuximab‐induced skin toxicity (Cet‐ST) correlates with better treatment response and longer survival times. Molecular markers predicting Cet‐ST are still missing. This investigation analyzed the value of Cet‐ST for treatment efficacy in a randomized trial comparing cetuximab plus capecitabine/irinotecan to cetuximab plus capecitabine/oxaliplatin as first‐line treatment of metastatic colorectal cancer. Patient characteristics and molecular parameters (KRAS mutation, EGFR‐FISH, EGFR‐IHC and EGFR intron‐1 polymorphism) of the tumour were correlated with response and Cet‐ST. Cet‐ST grade 0–1 was observed in 31%, grade 2–3 in 69% of patients. Outcome favoured patients with grade 2–3 Cet‐ST with regard to overall response rate (62 vs. 41%), PFS (7.8 vs. 5.2 months) and overall survival (OS) (30.3 vs. 18.0 months). First‐cycle rash was observed in 66% of patients and corresponded with longer survival (30.7 vs. 20.2 months, p = 0.007). Patients without Cet‐ST had a poor outcome (PFS, 1.9 months; OS, 11 months). The correlation of Cet‐ST with survival was specifically evident in patients with KRAS codon‐12‐mutated tumours assumed to be cetuximab resistant. In multivariate analysis of patient characteristics, male gender and younger age were significantly correlated with Cet‐ST. Among molecular parameters, no significant correlation with Cet‐ST was found. Cet‐ST is an early predictor of treatment efficacy in cetuximab‐treated patients. This effect of Cet‐ST is independent of the KRAS mutation status, suggesting that Cet‐ST rather relates to constitutional factors of the patient than alterations of the EGFR pathway in the tumour.
Mitochondrial alteration in malignantly transformed human small airway epithelial cells induced by α‐particles
Authors: Zhang Suping , Wen Gengyun , Huang Sarah XL , Wang Jianrong , Tong Jian , Hei Tom K. 
Published: May 2012

AbstractHuman small airway epithelial cells (SAECs) immortalized with human telomerase reverse transcriptase were exposed to either a single or multiple doses of α‐particles. Irradiated cells showed a dose‐dependent cytotoxicity and progressive neoplastic transformation phenotype. These included an increase in saturation density of growth, a greater resistance to N‐phosphonoacetyl‐L‐aspartate, faster anchorage‐independent growth, reinforced cell invasion and c‐Myc expression. In addition, the transformed cells formed progressively growing tumors upon inoculation into athymic nude mice. Specifically, α‐irradiation induced damage to both mitochondrial DNA (mtDNA) and mitochondrial functions in transformed cells as evidenced by increased mtDNA copy number and common deletion, decreased oxidative phosphorylation activity as measured by cytochrome C oxidase (COX) activity and oxygen consumption. There was a linear correlation between mtDNA copy number, common deletion, COX activity and cellular transformation represented by soft agar colony formation and c‐Myc expression. These results suggest that mitochondria are associated with neoplastic transformation of SAEC cells induced by α‐particles, and that the oncogenesis process may depend not only on the genomes inside the nucleus, but also on the mitochondrial DNA outside the nucleus.
Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70
Authors: Garbe Annette I , Roscher Anne , Schüler Christiane , Lutter Anne-Helen , Glösmann Martin , Bernhardt Ricardo , Chopin Michael , Hempel Ute , Hofbauer Lorenz C , Rammelt Stefan , Egerbacher Monika , Erben Reinhold G , Jessberger Rolf 
Published: May 2012

Abstract
Bone remodeling involves tightly regulated bone-resorbing osteoclasts and bone-forming osteoblasts. Determining osteoclast function is central to understanding bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel function of the F-actin binding and regulatory protein SWAP-70 in osteoclast biology. F-actin ring formation, cell morphology, and bone resorption are impaired in Swap-70−/− osteoclasts, whereas the expression of osteoclast differentiation markers induced in vitro by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) remains unaffected. Swap-70−/− mice develop osteopetrosis with increased bone mass, abnormally dense bone, and impaired osteoclast function. Ectopic expression of SWAP-70 in Swap-70−/− osteoclasts in vitro rescues their deficiencies in bone resorption and F-actin ring formation. Rescue requires a functional pleckstrin homology (PH) domain, known to support membrane localization of SWAP-70, and the F-actin binding domain. Transplantation of SWAP-70–proficient bone marrow into Swap-70−/− mice restores osteoclast resorption capacity in vivo. The identification of the role of SWAP-70 in promoting osteoclast function through modulating membrane-proximal F-actin rearrangements reveals a new pathway to control osteoclasts and bone homeostasis. © 2012 American Society for Bone and Mineral Research.
Thrombotic thrombocytopenic purpura precipitated by thyrotoxicosis
Authors: Chhabra Saurabh , Tenorio Grace 
Published: May 2012

AbstractThrombotic thrombocytopenic purpura (TTP) may be seen in association with autoimmune disorders such as immune hemolytic anemia and systemic lupus erythematosus, but rarely has it been associated with Graves' disease. We report one such case of a woman with new‐onset thyrotoxicosis caused by Graves' disease, who abruptly developed TTP, confirmed by low serum ADAMTS‐13 value. She had a dramatic response to plasma exchange, with remission of TTP. Definitive treatment with radioactive iodine resulted in euthyroidism and has prevented recurrence of TTP. J. Clin. Apheresis 27:265–266, 2012. © 2012 Wiley Periodicals, Inc.
Reoptimized interaction parameters for the peptide‐backbone model compound N‐methylacetamide in the GROMOS force field: Influence on the folding properties of two beta‐peptides in methanol
Authors: Horta Bruno A. C. , Lin Zhixiong , Huang Wei , Riniker Sereina , van Gunsteren Wilfred F. , Hünenberger Philippe H. 
Published: May 2012

AbstractConsidering N‐methylacetamide (NMA) as a model compound, new interaction parameters are developed for the amide function in the GROMOS force field that are compatible with the recently derived 53A6OXY parameter set for oxygen‐containing chemical functions. The resulting set, referred to as 53A6OXY+A, represents an improvement over earlier GROMOS force‐field versions in the context of the pure‐liquid properties of NMA, including the density, heat of vaporization, dielectric permittivity, self‐diffusion constant and viscosity, as well as in terms of the Gibbs hydration free energy of this molecule. Assuming that NMA represents an adequate model compound for the backbone of peptides, 53A6OXY+A may be expected to also provide an improved description of polypeptide chains. As an initial test, simulations are reported for two β‐peptides characterized by very different folding properties in methanol. For these systems, earlier force‐field versions provided good agreement with experimental NMR data, and the test shows that the improved description achieved in the context of NMA is not accompanied by any deterioration in the representation of the conformational properties of these peptides. © 2012 Wiley Periodicals, Inc.
The Generation of Variation and the Developmental Basis for Evolutionary Novelty
Authors: HALLGRÍMSSON BENEDIKT , JAMNICZKY HEATHER A. , YOUNG NATHAN M. , ROLIAN CAMPBELL , SCHMIDT‐OTT URS , MARCUCIO RALPH S. 
Published: May 2012

ABSTRACTOrganisms exhibit an incredible diversity of form, a fact that makes the evolution of novelty seemingly self‐evident. However, despite the “obvious” case for novelty, defining this concept in evolutionary terms is highly problematic, so much so that some have suggested discarding it altogether. Approaches to this problem tend to take either an adaptation‐ or development‐based perspective, but we argue here that an exclusive focus on either of these misses the original intent of the novelty concept and undermines its practical utility. We propose instead that for a feature to be novel, it must have evolved both by a transition between adaptive peaks on the fitness landscape and that this transition must have overcome a previous developmental constraint. This definition focuses novelty on the explanation of apparently difficult or low‐probability evolutionary transitions and highlights how the integration of developmental and functional considerations are necessary to evolutionary explanation. It further reinforces that novelty is a central concern not just of evolutionary developmental biology (i.e., “evo‐devo”) but of evolutionary biology more generally. We explore this definition of novelty in light of four examples that range from the obvious to subtle. J. Exp. Zool. (Mol. Dev. Evol.) 318B:501–517, 2012. © 2012 Wiley Periodicals, Inc.
Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral‐mediated atrial natriuretic peptide delivery
Authors: Larifla Laurent , Déprez Isabelle , Pham Isabelle , Rideau Dominique , Louzier Vanessa , Adam Micheline , Eloit Marc , Foucan Lydia , Adnot Serge , Teiger Emmanuel 
Published: May 2012

AbstractBackgroundVascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury.MethodsANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad‐RSV‐ANP). A recombinant adenovirus expressing the RSV‐controlled β‐galactosidase gene (Ad‐RSV‐β‐gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution.ResultsVSMCs transfected by Ad‐RSV‐ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad‐RSV‐ANP‐treated group compared to the control group.ConclusionsThe present study demonstrates the efficacy of recombinant adenovirus Ad‐RSV‐ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of nontechnical leadership practices on it project success
Authors: Kaminsky Jason B. 
Published: May 2012

AbstractThis article examines the leadership practices utilized by information technology (IT) project managers that contribute to project success. Specifically, technical and nontechnical leadership practices are contrasted. The importance of nontechnical leadership practices in IT project management has been largely ignored in research until recently. The article identifies key nontechnical leadership practices that are important for the success of IT projects. The article is based on a qualitative study that gathered data from actual IT projects conducted at U.S. companies across several different industry segments. Study results are analyzed to determine the relevance and value of Heifetz's adaptive leadership framework to the area of IT project management. Study findings indicate that nontechnical leadership practices are important to the success of IT projects. Findings also indicate that Heifetz's adaptive leadership framework is consistent with the key nontechnical leadership practices that are important for the success of IT projects. A framework for the development of IT project managers is also proposed.
The intercultural communication cultural immersion experience: Preparing leaders for a global future
Authors: Caputo John S. , Crandall Heather M. 
Published: May 2012

AbstractThe dynamics of globalization mean we face a reality wherein leaders are called upon to communicate effectively in cultural situations unfamiliar to them. This situation brings new challenges for communication and leadership educators. Our article describes a cultural immersion experience called The Cagli Project, where communication and leadership students learn effective intercultural communication skills for leadership formation while studying in Italy. The philosophical and experiential aspects of the program are described along with leadership outcomes. The article ends with a discussion of the transferability of this model to alternative programs.Perhaps nothing has had a more profound effect on human communication and hence leadership in the past half century than the movement of people around the globe and the growing diversity of world society. Globalization is the mantra that seems to be driving much that is new in higher education today. It has its roots in the “global economy” and seems most relevant to the business disciplines, but there is a sub‐text to globalization that resonates throughout all our institutions, and that is diversity (Caputo, 2011).
Learning about hardiness and servant leadership by accompanying refugees at a united nations resettlement camp
Authors: Popa Adrian B. 
Published: May 2012

AbstractThe internationalization of curriculum has contributed to a number of models for study abroad programs, service learning, and global engagement. Some frameworks are intentionally grounded in program theories and objectives shared by multiple stakeholders and the mission of the sponsoring academic institution. This article describes an international program inspired by a partnership between a Jesuit University and the United Nations agency charged with the purpose of safeguarding the rights and well‐being of refugees. The international program was grounded in the practice of accompaniment and theoretical frameworks of hardiness and servant leadership. These principles are described in the context of the curriculum, objectives, activities, and outcomes. The article concludes with lessons learned and future direction for design and delivery.
Evolutionary leadership theory
Authors: Kenney Matthew T. 
Published: May 2012

AbstractThis article reviews an important new monograph on evolutionary leadership theory by Mark van Vugt and Anjana Ahuja (Naturally Selected: The Evolutionary Science of Leadership. New York: HarperBusiness, 2011, 272 pp. ISBN 978‐0‐06196‐383‐4, $25.99, Hardcover). I summarize the main arguments of this work, which draws on evolutionary psychology and Charles Darwin's theory of natural selection to explain why and under what circumstances leadership and followership traits emerged in human societies. In so doing, I assess the extent to which it succeeds, as intended, in providing a scientifically rigorous framework for our understanding of leadership in the 21st century.
Significance of the “Delayed hyperintense portal vein sign” in the hepatobiliary phase MRI obtained with Gd‐EOB‐DTPA
Authors: Lee Nam Kyung , Kim Suk , Kim Gwang Ha , Heo Jeong , Seo Hyung Il , Kim Tae Un , Kang Dae Hwan 
Published: May 2012

AbstractPurpose:To determine the significance of the delayed hyperintense portal vein sign in Gd‐EOB‐DTPA‐enhanced magnetic resonance imaging (MRI).Materials and Methods:This retrospective study was approved by the Institutional Review Board and the requirement for informed patient consent was obtained. Six‐hundred and seventy patients who underwent Gd‐EOB‐DTPA‐enhanced MRI were included in the study. Two readers who were blinded to clinical records reviewed MR images in consensus. The delayed hyperintense portal vein sign was defined if the portal vein appeared more hyperintense than surrounding liver parenchyma on the 30‐minute delayed hepatobiliary phase. The frequency of the delayed hyperintense portal vein sign and the association between the sign and serum biochemical tests were assessed. Multivariate analysis was performed to identify which variables were associated with the sign. Optimal cutoff values of variables for reflecting the sign were obtained with ROC analysis.Results:The delayed hyperintense portal vein sign was observed in 13.0%. In multivariate analysis, a direct bilirubin level was associated with the delayed hyperintense portal vein sign. Optimum cutoff value for reflecting the delayed hyperintense portal vein sign was 2.18 mg/dL (sensitivity, 89%; specificity, 96%).Conclusion:The delayed hyperintense portal vein sign in Gd‐EOB‐DTPA‐enhanced MRI can potentially be used to reflect hepatobiliary function. J. Magn. Reson. Imaging 2012;36:678–685. © 2012 Wiley Periodicals, Inc.
Signal polarity restoration in a 3D inversion recovery sequence used with delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC)
Authors: Szumowski Jerzy , Durkan Michael G. , Foss Erik W. , Brown Dawson S. , Schwarz Erwin , Crawford Dennis C. 
Published: May 2012

AbstractPurpose:To develop an image reconstruction algorithm that restores the signal polarity in a three‐dimensional inversion‐recovery (3D‐IR) sequence used in delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC). This approach effectively doubles the dynamic range of data used for T1 curve fitting.Materials and Methods:We applied this reconstruction algorithm to a 3D‐IR TFE sequence used for T1 mapping, validated the technique in a phantom study, and performed T1‐map calculations in postosteochondral allograft transplant (OAT) patients. In addition, we performed a signal simulation study to assess the algorithm's capability to reduce the number of inversion times used in the 3D‐IR TFE sequence.Results:In comparison to a standard T1‐mapping algorithm that uses the magnitude of the MRI signal, the proposed algorithm improves the reliability of T1 relaxation fits to the inversion‐recovery three‐parameter function. The signal simulation study shows that the number of TI inversion times can be reduced to as few as four, without compromising the accuracy of T1 calculations.Conclusion:This algorithm can be applied to any 2D‐ or 3D‐IR acquisition sequence used in conjunction with dGEMRIC. Application of the algorithm improves the reliability of T1 calculations and allows the number of TIs to be reduced, leading to shorter scan times in dGEMRIC. J. Magn. Reson. Imaging 2012;36:1248–1255. © 2012 Wiley Periodicals, Inc.
Observer reactions to interpersonal injustice: The roles of perpetrator intent and victim perception
Authors: Umphress Elizabeth E. , Simmons Aneika L. , Folger Robert , Ren Run , Bobocel Ramona 
Published: May 2012

SummaryThe present research contributes to a growing literature on observer reactions to injustice experienced by others. In particular, we separated two variables that have previously been confounded in prior research, namely perpetrator intent to cause harm and victim perception of harm. We expected that injustice intent and injustice perceptions would have both unique and joint effects on observer reactions. The results of three experiments in which we manipulated perpetrator injustice intent and victim injustice perceptions supported our predictions. First, we found that observers had more negative reactions toward superiors who intended to inflict high versus low levels of interpersonal injustice toward a subordinate. Second, the injustice intent of the superior influenced observers' reactions more than did victim perceptions of injustice. Third, most novel, we found that the mere intent to cause injustice generated negative reactions in observers, even in the absence of a “true” victim—that is, when the subordinate perceptions of injustice were low. Together, our results emphasize the importance of examining observers' reactions to injustice and incorporating perpetrator intentions into the study of organizational justice. Copyright © 2012 John Wiley & Sons, Ltd.
Bias correction of daily precipitation simulated by a regional climate model: a comparison of methods
Authors: Lafon Thomas , Dadson Simon , Buys Gwen , Prudhomme Christel 
Published: May 2012

AbstractQuantifying the effects of future changes in the frequency of precipitation extremes is a key challenge in assessing the vulnerability of hydrological systems to climate change but is difficult as climate models do not always accurately simulate daily precipitation. This article compares the performance of four published techniques used to reduce the bias in a regional climate model precipitation output: (1) linear, (2) nonlinear, (3) γ‐based quantile mapping and (4) empirical quantile mapping. Overall performance and sensitivity to the choice of calibration period were tested by calculating the errors in the first four statistical moments of generated daily precipitation time series and using a cross‐validation technique. The study compared the 1961–2005 precipitation time series from the regional climate model HadRM3.0‐PPE‐UK (unperturbed version) with gridded daily precipitation time series derived from rain gauges for seven catchments spread throughout Great Britain. We found that while the first and second moments of the precipitation frequency distribution can be corrected robustly, correction of the third and fourth moments of the distribution is much more sensitive to the choice of bias correction procedure and to the selection of a particular calibration period. Overall, our results demonstrate that, if both precipitation data sets can be approximated by a γ‐distribution, the γ‐based quantile‐mapping technique offers the best combination of accuracy and robustness. In circumstances where precipitation data sets cannot adequately be approximated using a γ‐distribution, the nonlinear method is more effective at reducing the bias, but the linear method is least sensitive to the choice of calibration period. The empirical quantile mapping method can be highly accurate, but results were very sensitive to the choice of calibration time period. However, it should be borne in mind that bias correction introduces additional uncertainties, which are greater for higher order moments. Copyright © 2012 Royal Meteorological Society
A method to estimate sky view factors from digital elevation models
Authors: Kastendeuch Pierre P. 
Published: May 2012

AbstractSky view factor (SVF) is a commonly used parameter in atmospheric sciences. A method how to obtain an approximate value of SVF from digital elevation models (DEM) is described. The method takes into account slopes and transmittance of objects and is able to compute SVF for complex geometries (e.g. urban environments, natural landscapes, etc.). It is based on the concept of view factor, sometimes called ‘form factor’ or ‘shape factor’ in the literature. The view factors are computed between the calculation point and numeric sky dome to obtain an estimate of the final SVF value. A special procedure is applied to take limitation of sky visibility by obstacles into account. Accuracy of the method is checked by comparison with theoretical SVF values and tested on examples of complex geometries. Copyright © 2012 Royal Meteorological Society