bluuebunny/crossref_metadata_2025_split huggingface dataset:
Service Provision for the Global Economy: The Evolving Indian Experience
Authors: Dossani Rafiq , Kenney Martin 
Published: March 2009

AbstractSince 1995, the offshoring of services to India has rapidly evolved from a curiosity only studied by a few scholars to a phenomenon portending a major shift in the geography of global economic activity. The article examines the evolution of Indian global services provision quantitatively and qualitatively through the use of four case studies. The first case study examines the challenge that the Indian information technology systems integrators (ITSIs) pose to the formerly larger—but now roughly comparable in terms of employment—incumbent developed‐nation ITSIs. Because IT systems have become central to nearly every enterprise, the second case study illustrates the wide variety of enterprises that now have significant Indian offshore operations. The third case study describes the rapid growth of offshore integrated circuit design in India, a nation with now commercial‐scale integrated circuit production. The final case study describes the emergence of high‐opportunity entrepreneurial startups in India and the increasing number of Silicon Valley startups that very early in their lives or even as part of their business model have significant operations in India. The concluding discussion situates India within the global economy and speculates upon its future evolution.
The Services Transformation and Network Policy: The New Logic of Value Creation1
Authors: Kushida Kenji E. , Zysman John 
Published: March 2009

AbstractThere is currently a fundamental transformation of services, a transformation central to the growth of productivity and competition in the global economy. This transformation, a response to commodification generated by decomposition of production and intensified competition in global markets, is driven by developments in IT tools, the uses they are being put to, and the networks they run on. The service transformation is changing how firms add value, affecting the underlying economic activity in countries around the world.This article introduces the notion of the services transformation, placing it in the historical context of production and competition, noting the advent of the Internet as a critical building block. Second, we consider national strategies for capturing value in this new era. The experiences of Japan and Korea, successful in deploying high‐speed IT networks, but facing unexpected challenges in using them to capture value, highlight several features of the services transformation.
Heterogeneity of systemic inflammatory responses to periodontal therapy
Authors: Behle Jan H. , Sedaghatfar Michael H. , Demmer Ryan T. , Wolf Dana L. , Celenti Romanita , Kebschull Moritz , Belusko Paul B. , Herrera‐Abreu Miriam , Lalla Evanthia , Papapanou Panos N. 
Published: March 2009

AbstractAims: We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers.Material and Methods: Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6‐week period. Blood samples were obtained at: 1‐week pre‐therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations.Results: At T3, PAI‐1, sE‐selectin, sVCAM‐1, MMP‐9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE‐selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis.Conclusions: Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.
OPTIMIZATION OF NEW FLOUR IMPROVER MIXING FORMULA BY SURFACE RESPONSE METHODOLOGY
Authors: GHORBEL RAOUDHA ELLOUZE , KAMOUN AMEL , NEIFAR MOHAMED , CHAABOUNI SEMIA ELLOUZE 
Published: March 2009

ABSTRACT In the present study, we search to improve the viscoelastic properties of wheat flour characterized by a low bread‐making quality. Six regulators were tested: broad bean flour, gluten, monodiglyceride (MDG), ascorbic acid, sodium alginate and a mixture of amylase and xylanase. A hybrid design was carried out in order to study the effect of these regulators on the alveographic properties of wheat flour dough. Two alveographic responses (W: deformation energy and P/L: elasticity‐to‐extensibility ratio) were studied and simultaneously optimized via the desirability functions. An optimal mixture, containing 13.17 g/kg of broad bean flour, 15.13 g/kg of gluten, 0.155 g/kg of ascorbic acid, 3.875 g/kg of MDG, 2.75 g/kg of sodium alginate and 0.3 g/kg of enzyme mixture, was obtained and tested in a Tunisian flour. It led to a dough characterized by a W = 274 × 10−4 J and P/L = 0.74 versus 191 × 10−4 J and 0.40, respectively, for the Tunisian flour without improvers.PRACTICAL APPLICATIONSIn this work, we developed a new flour improver mixing formula intended to be used with wheat flour characterized by a low bread‐making quality. This improver mixture is in powder form and contains 13.17 g of broad bean flour, 15.13 g of gluten, 0.155 g of ascorbic acid, 3.875 g of monodiglyceride, 2.75 g of sodium alginate and 0.3 g of enzyme mixture per kilogram of wheat flour. The incorporation of this improver mixture in low bread‐making quality wheatflour leads to an increase of its deformation energy (W) of about 43% and produces large volume bread.
Devices and Desires: How Useful Is the ‘New’ New Economic Sociology for Understanding Market Attachment?
Authors: Mcfall Liz 
Published: March 2009

AbstractThis article explores the usefulness of recent economic sociology literature for understanding processes of market attachment. It focuses particularly on concepts like agencement and market devices proposed by authors like Michel Callon, Fabian Muniesa and Franck Cochoy and their application to mass consumer markets. The article addresses critical responses which have been levelled at this literature to argue that despite what some regard as an overly descriptive and apolitical banality, this may in fact be a prime and necessary virtue.
GraphClust: A Method for Clustering Database of Graphs
Authors: Reforgiato Diego , Gutierrez Rodrigo , Shasha Dennis 
Published: March 2009

Any application that represents data as sets of graphs may benefit from the discovery of relationships among those graphs. To do this in an unsupervised fashion requires the ability to find graphs that are similar to one another. That is the purpose of GraphClust. The GraphClust algorithm proceeds in three phases, often building on other tools:(1) it finds highly connected substructures in each graph;(2) it uses those substructures to represent each graph as a feature vector; and(3) it clusters these feature vectors using a standard distance measure. We validate the cluster quality by using the Silhouette method. In addition to clustering graphs, GraphClust uses SVD decomposition to find frequently co-occurring connected substructures. The main novelty of GraphClust compared to previous methods is that it is application-independent and scalable to many large graphs.
RasV12-Mediated Down-regulation of CCAAT/Enhancer Binding Protein β in Immortalized Fibroblasts Requires Loss of p19Arf and Facilitates Bypass of Oncogene-Induced Senescence
Authors: Sebastian Thomas , Johnson Peter F. 
Published: March 2009

Abstract
The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) is involved in cellular responses to oncogenic and physiologic Ras signals. C/EBPβ is required for premature senescence of primary mouse fibroblasts induced by expression of H-RasV12, demonstrating its role in oncogene-induced senescence. Here, we have investigated the mechanisms by which Ras inhibits proliferation of normal cells but transforms immortalized cells. We show that oncogenic Ras down-regulates C/EBPβ expression in NIH 3T3 cells, which are immortalized by a deletion of the CDKN2A locus and, therefore, lack the p16Ink4a and p19Arf tumor suppressors. RasV12-induced silencing of C/EBPβ occurred at the mRNA level and involved both the Raf–mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase–ERK and phosphatidylinositol 3-kinase signaling pathways. Oncogenic Ras decreased C/EBPβ expression in Ink4a/Arf−/− mouse embryo fibroblasts (MEF) but increased C/EBPβ levels in wild-type MEFs. C/EBPβ down-regulation in NIH 3T3 cells was reversed by expression of p19Arf, but not of p53 or p16Ink4a, highlighting a critical role for p19Arf in sustaining C/EBPβ levels. Ectopic expression of p34 C/EBPβ (LAP) inhibited RasV12-mediated transformation of NIH 3T3 cells, suppressed their tumorigenicity in nude mice, and reactivated expression of the proapoptotic Fas receptor, which is also down-regulated by Ras. Our findings indicate that Cebpb gene silencing eliminates a growth inhibitory transcription factor that would otherwise restrain oncogenesis. We propose that C/EBPβ is part of a p53-independent, p19Arf-mediated network that enforces Ras-induced cell cycle arrest and tumor suppression in primary fibroblasts. [Cancer Res 2009;69(6):2588–98]
The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Acid-Mediated Invasion
Authors: Silva Ariosto S. , Yunes Jose A. , Gillies Robert J. , Gatenby Robert A. 
Published: March 2009

AbstractA number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral and peritumoral acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH buffers to increase the acidic pHe of tumors in vivo and investigate the chemical specifications of an optimal buffer for such purpose. We show that increased serum concentrations of the sodium bicarbonate (NaHCO3) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of tumor acid concentrations significantly reduces tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing buffer effectiveness is its pKa. This indicates that NaHCO3, with a pKa of 6.1, is not an ideal intratumoral buffer and that greater intratumoral pHe changes could be obtained using a buffer with a pKa of ∼7. The simulations support the hypothesis that systemic pH buffers can be used to increase the tumor pHe and inhibit tumor invasion. [Cancer Res 2009;69(6):2677–84]
CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection
Authors: Pavelko Kevin D. , Hansen Michael J. , Pease Larry R. 
Published: March 2009

AbstractVaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1). Cytotoxic T-cell responses are induced against TRP1222-229 by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1222 CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1222-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high-affinity MHC ligands. We propose that when administered appropriately, native low-affinity MHC ligands are optimal inducers of immunotherapeutic CTL. [Cancer Res 2009;69(7):3114–20]
Engineered Knottin Peptides: A New Class of Agents for Imaging Integrin Expression in Living Subjects
Authors: Kimura Richard H. , Cheng Zhen , Gambhir Sanjiv Sam , Cochran Jennifer R. 
Published: March 2009

AbstractThere is a critical need for molecular imaging agents to detect cell surface integrin receptors that are present in human cancers. Previously, we used directed evolution to engineer knottin peptides that bind with high affinity (∼10 to 30 nmol/L) to integrin receptors that are overexpressed on the surface of tumor cells and the tumor neovasculature. To evaluate these peptides as molecular imaging agents, we site-specifically conjugated Cy5.5 or 64Cu-1,4,7,10-tetra-azacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) to their N termini, and used optical and positron emission tomography (PET) imaging to measure their uptake and biodistribution in U87MG glioblastoma murine xenograft models. NIR fluorescence and microPET imaging both showed that integrin binding affinity plays a strong role in the tumor uptake of knottin peptides. Tumor uptake at 1 hour postinjection for two high-affinity (IC50, ∼20 nmol/L) 64Cu-DOTA–conjugated knottin peptides was 4.47% ± 1.21% and 4.56% ± 0.64% injected dose/gram (%ID/g), compared with a low-affinity knottin peptide (IC50, ∼0.4 μmol/L; 1.48 ± 0.53%ID/g) and c(RGDyK) (IC50, ∼1 μmol/L; 2.32 ± 0.55%ID/g), a low-affinity cyclic pentapeptide under clinical development. Furthermore, 64Cu-DOTA–conjugated knottin peptides generated lower levels of nonspecific liver uptake (∼2%ID/g) compared with c(RGDyK) (∼4%ID/g) 1 hour postinjection. MicroPET imaging results were confirmed by in vivo biodistribution studies. 64Cu-DOTA–conjugated knottin peptides were stable in mouse serum, and in vivo metabolite analysis showed minimal degradation in the blood or tumor upon injection. Thus, engineered integrin-binding knottin peptides show great potential as clinical diagnostics for a variety of cancers. [Cancer Res 2009;69(6):2435–42]
TWIST-1 Is Overexpressed in Neoplastic Choroid Plexus Epithelial Cells and Promotes Proliferation and Invasion
Authors: Hasselblatt Martin , Mertsch Sonja , Koos Björn , Riesmeier Barbara , Stegemann Heike , Jeibmann Astrid , Tomm Manuel , Schmitz Nicole , Wrede Brigitte , Wolff Johannes E. , Zheng Wei , Paulus Werner 
Published: March 2009

Abstract
The pathogenesis of choroid plexus papillomas, intraventricular papillary neoplasms most often occurring sporadically in children and young adults, remains poorly understood. To identify pathways operative in the development of choroid plexus papillomas, gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells (n = 7) were compared with that of normal choroid plexus epithelial cells laser microdissected from autopsy tissue (n = 8). On DNA microarray data analysis, 53 probe sets were differentially expressed in choroid plexus papilloma tumor cells (&gt;7-fold). Up-regulation of TWIST1, WIF1, TRPM3, BCLAF1, and AJAP1, as well as down-regulation of IL6ST was confirmed using quantitative reverse transcription-PCR. Knockdown of Twist1 gene expression in the rat choroid plexus epithelial cell line Z310 significantly reduced proliferation as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell invasion in a Matrigel assay, whereas cell migration was not affected. Screening for expressional changes of cancer-related genes upon Twist1 knockdown revealed up-regulation of Cdkn1a, Cflar, and Serpinb2 and down-regulation of Figf. To conclude, using gene expression profiling, several genes differentially expressed in human choroid plexus papillomas could be identified. Among those, TWIST1 is highly expressed in choroid plexus papillomas and promotes proliferation and invasion. [Cancer Res 2009;69(6):2219–23]
Diaphanous-Related Formins Are Required for Invadopodia Formation and Invasion of Breast Tumor Cells
Authors: Lizárraga Floria , Poincloux Renaud , Romao Maryse , Montagnac Guillaume , Le Dez Gaëlle , Bonne Isabelle , Rigaill Guillem , Raposo Graça , Chavrier Philippe 
Published: March 2009

Abstract
Proteolytic degradation of the extracellular matrix by metastatic tumor cells is initiated by the formation of invadopodia, i.e., actin-driven filopodia-like membrane protrusions endowed with matrix-degradative activity. A signaling cascade involving neural Wiskott-Aldrich syndrome protein and the Arp2/3 actin nucleating complex is involved in actin assembly at invadopodia. Yet, the mechanism of invadopodia formation is poorly understood. Based on their role as actin nucleators in cytoskeletal rearrangements, including filopodia formation, we examined the function of Diaphanous-related formins (DRF) in invadopodia formation and invasion by breast tumor cells. Using small interfering RNA silencing of protein expression in highly invasive MDA-MB-231 breast adenocarcinoma cells, we show that three members of the DRF family (DRF1–DRF3) are required for invadopodia formation and two-dimensional matrix proteolysis. We also report that invasion of a three-dimensional Matrigel matrix involves filopodia-like protrusions enriched for invadopodial proteins, including membrane type 1 matrix metalloproteinase, which depend on DRFs for their formation. These data identify DRFs as critical components of the invasive apparatus of tumor cells in two-dimensional and three-dimensional matrices and suggest that different types of actin nucleators cooperate during the formation of invadopodia. [Cancer Res 2009;69(7):2792–800]
A Role for CXCR2 in Senescence, but What about in Cancer?
Authors: Acosta Juan C. , Gil Jesús 
Published: March 2009

Abstract
Senescence is an irreversible arrest triggered by stresses such as telomere shortening, DNA damage, or oncogenic signaling. Oncogene-induced senescence occurs in preneoplastic lesions, but it is absent from full-blown malignancies suggesting a tumor suppressor function. We recently found that depletion of the receptor CXCR2 [which binds to chemokines such as interleukin (IL)-8 or GROα] delays both replicative senescence and impairs the senescence response to oncogenic signals. Our findings suggest that signaling by IL-8 and GROα might limit tumor growth by reinforcing senescence early in tumorigenesis. The challenge remains in how to integrate this with the well-known tumor promoting effects of IL-8 and GROα. [Cancer Res 2009;69(6):2167–70]
Critical Role of Smad2 in Tumor Suppression and Transforming Growth Factor-β–Induced Apoptosis of Prostate Epithelial Cells
Authors: Yang Jiayi , Wahdan-Alaswad Reema , Danielpour David 
Published: March 2009

Abstract
Transforming growth factor-β (TGF-β) functions as a tumor suppressor of the prostate through mechanisms that remain unresolved. Although TGF-β receptors directly activate both Smads 2 and 3, to date, Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-β responses, including control of gene expression, cell growth, apoptosis, and tumor suppression. Using a robust lentiviral short hairpin RNA system to silence Smads 2 and/or 3 in the NRP-152 nontumorigenic rat prostate basal epithelial cell line, we provide the first evidence for Smad2 as a critical mediator of TGF-β–induced apoptosis and gene expression. Parallel analyses revealed that Smad3 is the major mediator of TGF-β–induced transcriptional and apoptotic responses in the NRP-154 rat prostate carcinoma cell line. Remarkably, silencing Smad2 alone caused malignant transformation of NRP-152 cells, as assayed by s.c. tumor growth in athymic mice, whereas silencing Smad3 alone did not induce tumors. Nevertheless, tumors induced by silencing both Smads 2 and 3 were larger than those from silencing Smad2 alone. Given previous reports that NRP-152 cells have a stem cell phenotype, we speculate a critical role for Smad2 as a tumor suppressor in the basal epithelial or stem cell compartment of the prostate. [Cancer Res 2009;69(6):2185–90]
Impaired Turnover of Prolactin Receptor Contributes to Transformation of Human Breast Cells
Authors: Plotnikov Alexandr , Varghese Bentley , Tran Thai H. , Liu Chengbao , Rui Hallgeir , Fuchs Serge Y. 
Published: March 2009

Abstract
Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the βTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed. [Cancer Res 2009;69(7):3165–72]
Molecular Dosimetry of 1,2,3,4-Diepoxybutane–Induced DNA-DNA Cross-Links in B6C3F1 Mice and F344 Rats Exposed to 1,3-Butadiene by Inhalation
Authors: Goggin Melissa , Swenberg James A. , Walker Vernon E. , Tretyakova Natalia 
Published: March 2009

Abstract
1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a human carcinogen based on epidemiologic studies in occupationally exposed workers and animal studies in laboratory rats and mice. BD is metabolically activated to three epoxides that can react with nucleophilic sites in biomolecules. Among these, 1,2,3,4-diepoxybutane (DEB) is considered the ultimate carcinogen due to its high genotoxicity and mutagenicity attributed to its ability to form DNA-DNA cross-links. Our laboratory has developed quantitative high-performance liquid chromatography–μESI+–tandem mass spectrometry methods for two DEB-specific DNA-DNA cross-links, 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) and 1-(guan-7-yl)-4-(aden-1-yl)-2,3-butanediol (N7G-N1A-BD). This report describes molecular dosimetry analysis of these adducts in tissues of B6C3F1 mice and F344 rats exposed to a range of BD concentrations (0–625 ppm). Much higher (4- to 10-fold) levels of DEB-DNA cross-links were observed in mice compared with rats exposed to the same BD concentrations. In both species, bis-N7G-BD levels were 1.5- to 4-fold higher in the liver than in other tissues examined. Interestingly, tissues of female animals exposed to BD contained higher concentrations of bis-N7G-BD adducts than tissues of male animals, which is in accord with previously reported differences in tumor incidence. The molecular dosimetry data presented herein suggest that species and gender differences observed in BD-induced cancer are directly related to differences in the extent of BD metabolism to DEB. Furthermore, a rat model of sensitivity to BD may be more appropriate than a mouse model for assessing human risk associated with BD exposure, because rats and humans seem to be similar with respect to DEB formation. [Cancer Res 2009;69(6):2479–8]