bluuebunny/crossref_metadata_2025_split huggingface dataset:
CO-CONSTRUCTING THE BRAND AND THE PRODUCT
Authors: CHRISTIANSEN JOHN K. , VARNES CLAUS J. , HOLLENSEN BIRGITTE , BLOMBERG BIRGITTE C. 
Published: October 2009

How do brand and product development processes interact? How do brands and branding strategies influence product development? Moreover, does a branding strategy facilitate or impede the development process? So far, research on product development has focused on the development of new products and services, whereas research on marketing and especially branding has emphasized what types of line extensions to create rather than on how to integrate brands and product development processes.The present models of the product development process mostly distinguish between the process of innovation and that which follows, and also distinguish between the company as a sender and the user as a receiver of the communicated values. In the present study we suggest an alternative understanding of the innovation process: A network process perspective (NPP) as derived from the actor network theory (ANT), is used to explore the co-created relationship between the new product development process and branding.The network process perspective is used to analyse and understand the innovation process and represents a constructivist theory that departs from an ontological assumption that the 'world' is the relations and networks among heterogeneous human and non-human actors and that these networks are not per se stable, but are created, negotiated and dynamic. This theory is especially suitable for comprehending 'branding' where the 'ing' underscores the dynamic nature of this concept and to explore the dynamics in innovation.The empirical analysis identified four incidents as critical to the co-construction of the product and the brand in two companies. The effects are measured using the framework provided by Kapferer. The present analysis indicates that branding and innovation processes are interrelated in more subtle and complex ways than indicated in prior research on the subject. It further shows that even with well-organized marketing departments, consistent branding strategies and skilled project managers, the product development process is not easily managed. The brand and the branding strategies are non-human actors among other actors in the process, and it requires skill, persistence and energy if the 'brand' wants to become an influential 'actor'. Sometimes, the processes may even be reversed.
INTER-ORGANIZATIONAL INNOVATION PROMOTERS IN SMALL, KNOWLEDGE-INTENSIVE FIRMS
Authors: JENSSEN JAN INGE , NYBAKK ERLEND 
Published: October 2009

This paper examines the relationship between external relations and innovation in small, knowledge-intensive Norwegian firms. Our findings indicate that external relations are beneficial for innovation. The analysis shows that it is necessary to treat innovation as more than a concept. Our independent variables related differently to product innovation, process innovation, and market innovation.We found that market participation in product development has a positive impact on product, process and market innovation. We also found that top management interaction with other firms had a positive effect on market innovation and that top management interaction with external R&D had a positive effect on product innovation. This finding probably indicates that access to R&D resources is vital for product development in the context of knowledge-intensive products. The results also show that participation in conferences and courses positively influences process and market innovation and that systematic environmental scanning positively influences product innovation.
A case study of lateral spreading: the Precambrian Svecofennian Orogen
Authors: Korja Annakaisa , Kosunen Paula , Heikkinen Pekka 
Published: October 2009

Abstract

We have studied the crustal structures of the Palaeoproterozoic Svecofennian (
c.
1.9 Ga) Orogeny with the help of large scale seismic reflection surveys (FIRE 1–3), preliminary structural field work and geological and geophysical databases. The central part of the orogen is occupied by the Central Finland Granitoid Complex, which comprises two suites of granitoid rocks and associated mafic and volcanic rocks. The complex and the surrounding supracrustal belts are cut and deformed by numerous shear zones and faults; here divided into six groups. The most prominent reflections are usually shear zones or faults on outcrops. The granitoid complex is interpreted as a deep, lower-level section of an old core complex, where the younger granitoid intrusions form the basins and older granitoid intrusions and associated volcanic rocks form the horsts. The upper–middle crust detachment zone is exposed at the northeastern edge of the complex and middle crust is exposed in the migmatitic domes at northern and western margins.

The seismic reflection sections display a frozen image of orogenic thickening and lateral spreading. The decoupling of the upper, middle and lower crust during spreading resulted in the formation of layered superstructure–infrastructure of the crust.
Upper and lower crustal evolution during lithospheric extension: numerical modelling and natural footprints from the European Alps
Authors: Marotta Anna Maria , Spalla Maria Iole , Gosso Guido 
Published: October 2009

Abstract
When continental rifting does not develop on a stable continental lithosphere, geodynamic interpretation of igneous and metamorphic records, as well as structural and sedimentary imprints of rifting-related lithospheric extension, can be highly ambiguous since different mechanisms can be responsible for regional HT–LP metamorphism. This is the case of the European Alps, where the exposure of Variscan structural and metamorphic imprints within the present-day Alpine structural domains indicates that before the Pangaea break-up, the continental lithosphere was thermally and mechanically perturbed by Variscan subduction and collision. To reduce this ambiguity, we use finite-element techniques to implement numerical geodynamic models for analysing the effects of active extension during the Permian–Triassic period (from 300 to 220 Ma), overprinting a previous history of Variscan subduction-collision up to 300 Ma. The lithosphere is compositionally stratified in crust and mantle and its rheological behaviour is that of an incompressible viscous fluid controlled by a power law. Model predictions of lithospheric thermal state and strain localization are compared with metamorphic data, time interval of plutonic and volcanic activity and coeval onset of sedimentary environments. Our analysis confirms that the integrated use of geological data and numerical modelling is a valuable key for inferring the pre-orogenic rifting evolution of a fossil passive margin. In the specific case of the European Alps, we show that a relative high rate of active extension is required, associated for example with a far extensional field, to achieve the fit with the maximal number of tectonic units. Furthermore, in this case only, thermal conditions allowing partial melting of the crust accompanying gabbroic intrusions and HT–LP metamorphism are generated. The concordant set of geological events that took place from Permian to Triassic times in the natural Alpine case is justified by the model and is coherent with the progression of lithospheric thinning, later evolving into the appearance of oceanic crust.
Structure and evolution of the western Corinth Rift, through new field data from the Northern Peloponnesus
Authors: Skourtsos Emmanuel , Kranis Haralambos 
Published: October 2009

Abstract
Extensional structures with geometrical and kinematic features analogous to the known Gulf of Corinth faults, are found further to the south of what is considered to be the southern margin of the of Proto-Corinth Gulf, reaching south to the northern flanks of Mt Mainalon. This mountain front is marked by the North Mainalon Fault Zone, which comprises a series of normal fault segments with NNE dips. Assuming a listric or ramp-flat geometry for the North Mainalon Fault Zone, it could flatten at a depth of 6–8 km, underneath Mt Khelmos. Its southern, shallow part has been truncated by NNE- and NNW-trending faults, which may be linked to northward propagation of the east–west extension in the Southern Peloponnesus, causing further uplift in the central and northern Peloponnesus, while its deeper part is still active and may reach further north and sole onto the hypothesized detachment zone beneath the Gulf of Corinth.
Timing of the Amorgos detachment system and implications for detachment faulting in the southern Aegean Sea, Greece
Authors: Ring Uwe , Thomson Stuart N. , Rosenbaum Gideon 
Published: October 2009

Abstract

We present apatite and zircon fission-track (AFT and ZFT) ages from the Amorgos detachment system in the Aegean Sea, Greece. The Amorgos detachment system consists of a basal and an upper detachment. The lower Amorgos detachment occupies the same tectonic position as the regionally important large-magnitude Cretan detachment and therefore can provide improved constraints on the evolution of the latter. AFT ages from the footwalls of both detachments show that detachment-related cooling occurred in the early Miocene, coeval with an important phase of cooling in the footwall of the Cretan detachment on Crete. We interpret the footwall AFT ages to indicate an early Miocene age of movement on the Amorgos detachments, essentially simultaneously with slip on the Cretan detachment. ZFT ages from rocks above the lower Amorgos detachment are not reset indicating that metamorphic temperatures during the Tertiary Hellenic orogeny did not exceed
c.
300 °C significantly. We discuss a model in which top‐to-the-north movement on the Cretan/Amorgos detachment commenced in the early Miocene. Soon after the inception of the Cretan/Amorgos detachment, top‐to-the-south movement on the South Cyclades shear zone deformed the latter and brought the Amorgos detachment into a higher crustal position.
Senescence-Associated Oxidative DNA Damage Promotes the Generation of Neoplastic Cells
Authors: Gosselin Karo , Martien Sébastien , Pourtier Albin , Vercamer Chantal , Ostoich Peter , Morat Luc , Sabatier Laure , Duprez Laurence , T'Kint de Roodenbeke Claire , Gilson Eric , Malaquin Nicolas , Wernert Nicolas , Slijepcevic Predrag , Ashtari Marjan , Chelli Fazia , Deruy Emeric , Vandenbunder Bernard , De Launoit Yvan , Abbadie Corinne 
Published: October 2009

Abstract
Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age. [Cancer Res 2009;69(20):7917–24]
Combination of Sulindac and Antimicrobial Eradication ofHelicobacter pyloriPrevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice
Authors: Lee Chung-Wei , Rickman Barry , Rogers Arlin B. , Muthupalani Sureshkumar , Takaishi Shigeo , Yang Peiying , Wang Timothy C. , Fox James G. 
Published: October 2009

AbstractHelicobacter pylori infection causes severe dysplasia manifested as gastrointestinal intraepithelial neoplasia (GIN) after 28 weeks post–H. pylori infection (WPI) in cancer-prone, hypergastrinemic male INS-GAS mice. We examined the efficacy of the nonsteroidal anti-inflammatory drug sulindac (400 ppm in drinking water) alone, the CCK2/gastrin receptor antagonist YM022 (45 mg/kg/wk) alone, and sulindac or YM022 combined with H. pylori eradication therapy to prevent H. pylori–associated gastric cancer in male INS-GAS mice. Treatments started at 22 WPI, and mice were euthanized at 28 WPI. In uninfected mice, all treatments significantly delayed development of spontaneous GIN (P &lt; 0.05). In H. pylori–infected mice, sulindac alone or YM022 alone had no protective effect on H. pylori–associated GIN. Importantly, sulindac exacerbated the severity of H. pylori–associated gastritis despite decreased gastric prostaglandin E2 levels. However, sulindac combined with H. pylori antimicrobial eradication reduced the incidence of GIN (P &lt; 0.05), whereas YM022 combined with antimicrobial eradication did not reduce GIN. In infected mice, sulindac or YM022 treatment did not alter gastric expression of the proinflammatory cytokines Ifn-γ and Tnf-α and mucosal cell proliferation. Sulindac or YM022 combined with antimicrobial eradication down-regulated mRNA levels of Ifn-γ and Tnf-α and mucosal cell proliferation (P &lt; 0.05). We conclude that sulindac enhances H. pylori gastritis and may promote inflammation-mediated gastric carcinogenesis. The combination of sulindac and antimicrobial H. pylori eradication was beneficial for reducing proinflammatory cytokine mRNA in the stomach and preventing progression from severe dysplasia to gastric cancer in H. pylori–infected INS-GAS mice. [Cancer Res 2009;69(20):8166–74]
In vivo, Noninvasive, Label-Free Detection and Eradication of Circulating Metastatic Melanoma Cells Using Two-Color Photoacoustic Flow Cytometry with a Diode Laser
Authors: Galanzha Ekaterina I. , Shashkov Evgeny V. , Spring Paul M. , Suen James Y. , Zharov Vladimir P. 
Published: October 2009

Abstract
The circulating tumor cell (CTC) count has been shown as a prognostic marker for metastasis development. However, its clinical utility for metastasis prevention remains unclear, because metastases may already be present at the time of initial diagnosis with existing assays. Their sensitivity ex vivo is limited by a small blood sample volume, whereas in vivo examination of larger blood volumes may be clinically restricted by the toxicity of labels used for targeting of CTCs. We introduce a method for in vivo photoacoustic blood cancer testing with a high-pulse-repetition-rate diode laser that, when applied to melanoma, is free of this limitation. It uses the overexpression of melanin clusters as intrinsic, spectrally-specific cancer markers and signal amplifiers, thus providing higher photoacoustic contrast of melanoma cells compared with a blood background. In tumor-bearing mouse models and melanoma-spiked human blood samples, we showed a sensitivity level of 1 CTC/mL with the potential to improve this sensitivity 103-fold in humans in vivo, which is impossible with existing assays. Additional advances of this platform include decreased background signals from blood through changes in its oxygenation, osmolarity, and hematocrit within physiologic norms, assessment of CTCs in deep vessels, in vivo CTC enrichment, and photoacoustic-guided photothermal ablation of CTCs in the bloodstream. These advances make feasible the early diagnosis of melanoma during the initial parallel progression of primary tumor and CTCs, and laser blood purging using noninvasive or hemodialysis-like schematics for the prevention of metastasis. [Cancer Res 2009;69(20):7926–34]
The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia
Authors: McElligott Anthony M. , Maginn Elaina N. , Greene Lisa M. , McGuckin Siobhan , Hayat Amjad , Browne Paul V. , Butini Stefania , Campiani Giuseppe , Catherwood Mark A. , Vandenberghe Elisabeth , Williams D. Clive , Zisterer Daniela M. , Lawler Mark 
Published: October 2009

AbstractPyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity of PBOX-15 in samples taken from a cohort of CLL patients (n = 55) representing both high-risk and low-risk disease. PBOX-15 exhibited cytotoxicity in CLL cells (n = 19) in a dose-dependent manner, with mean IC50 of 0.55 μmol/L. PBOX-15 significantly induced apoptosis in CLL cells (n = 46) including cells with poor prognostic markers: unmutated IgVH genes, CD38 and zeta-associated protein 70 (ZAP-70) expression, and fludarabine-resistant cells with chromosomal deletions in 17p. In addition, PBOX-15 was more potent than fludarabine in inducing apoptosis in fludarabine-sensitive cells. Pharmacologic inhibition and small interfering RNA knockdown of caspase-8 significantly inhibited PBOX-15–induced apoptosis. Pharmacologic inhibition of c-jun NH2-terminal kinase inhibited PBOX-15–induced apoptosis in mutated IgVH and ZAP-70− CLL cells but not in unmutated IgVH and ZAP-70+ cells. PBOX-15 exhibited selective cytotoxicity in CLL cells compared with normal hematopoietic cells. Our data suggest that PBOX-15 represents a novel class of agents that are toxic toward both high-risk and low-risk CLL cells. The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential. [Cancer Res 2009;69(21):8366–75]
The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release
Authors: Seo Young-Woo , Woo Ha-Na , Piya Sujan , Moon Ae Ran , Oh Jae-Wook , Yun Cheol-Won , Kim Kyung-Keun , Min Ji-Young , Jeong Seon-Yong , Chung Seyung , Song Peter I. , Jeong Seong-Yun , Choi Eun Kyung , Seol Dai-Wu , Kim Tae-Hyoung 
Published: October 2009

Abstract
DNA damage stabilizes the p53 tumor suppressor protein that determines the cell fate by either cell cycle arrest or cell death induction. Noxa, the BH3-only Bcl-2 family protein, was shown to be a key player in p53-induced cell death through the mitochondrial dysfunction; however, the molecular mechanism by which Noxa induces the mitochondrial dysfunction to cause cell death in response to genotoxic agents is largely unknown. Here, we show that the mitochondrial-targeting domain (MTD) of Noxa is a prodeath domain. Peptide containing MTD causes massive necrosis in vitro through cytosolic calcium increase; it is released from the mitochondria by opening the mitochondrial permeability transition pore. MTD peptide–induced cell death can be inhibited by calcium chelator BAPTA-AM. Moreover, MTD peptide shows the potent tumor-killing activities in mice by joining with tumor-homing motifs. [Cancer Res 2009;69(21):8356–65]
Intravital Imaging Reveals Transient Changes in Pigment Production and Brn2 Expression during Metastatic Melanoma Dissemination
Authors: Pinner Sophie , Jordan Peter , Sharrock Kirsty , Bazley Laura , Collinson Lucy , Marais Richard , Bonvin Elise , Goding Colin , Sahai Erik 
Published: October 2009

Abstract
How melanoma acquire a metastatic phenotype is a key issue. One possible mechanism is that metastasis is driven by microenvironment-induced switching between noninvasive and invasive states. However, whether switching is a reversible or hierarchical process is not known and is difficult to assess by comparison of primary and metastatic tumors. We address this issue in a model of melanoma metastasis using a novel intravital imaging method for melanosomes combined with a reporter construct in which the Brn-2 promoter drives green fluorescent protein (GFP) expression. A subpopulation of cells containing little or no pigment and high levels of Brn2::GFP expression are motile in the primary tumor and enter the vasculature. Significantly, the less differentiated state of motile and intravasated cells is not maintained at secondary sites, implying switching between states as melanoma cells metastasize. We show that melanoma cells can switch in both directions between high- and low-pigment states. However, switching from Brn2::GFP high to low was greatly favored over the reverse direction. Microarray analysis of high- and low-pigment populations revealed that transforming growth factor (TGF)β2 was up-regulated in the poorly pigmented cells. Furthermore, TGFβ signaling induced hypopigmentation and increased cell motility. Thus, a subset of less differentiated cells exits the primary tumor but subsequently give rise to metastases that include a range of more differentiated and pigment-producing cells. These data show reversible phenotype switching during melanoma metastasis. [Cancer Res 2009;69(20):7969–77]
Kupffer Cell Suppression of CD8+ T Cells in Human Hepatocellular Carcinoma Is Mediated by B7-H1/Programmed Death-1 Interactions
Authors: Wu Ke , Kryczek Ilona , Chen Lieping , Zou Weiping , Welling Theodore H. 
Published: October 2009

Abstract
B7-H1 is a recently identified B7 family member that, along with one of its receptors, programmed death-1 (PD-1), has been involved in multiple immunopathologic scenarios. However, the nature of B7-H1 and PD-1 in human hepatocellular carcinoma (HCC) remains poorly defined. We investigated the expression and functional relevance of this pathway in patients with HCC. We showed that B7-H1 expression on Kupffer cells (KC) was increased in tumor tissues compared with surrounding nontumor liver tissues in patients with HCC and this correlated with poorer survival. Coculture of HCC cells with monocytes showed that tumor-associated interleukin-10 contributed to the induction of B7-H1 in the HCC environment. We further observed that the levels of PD-1+CD8+ T cells were higher in tumor tissues than in nontumor tissues. B7-H1+ KCs and PD-1+ T cells were colocalized in the HCC stroma. PD-1+CD8+ T cells had decreased proliferative ability and effector function as shown by reduced granule and cytokine expression compared with PD-1− T cells. Importantly, blocking KC B7-H1 interaction with PD-1+CD8+ cells using neutralizing antibodies recovered effector T-cell function. Our data indicate that the B7-H1/PD-1 axis contributes to immune suppression in human HCC, with blockade of this pathway carrying important therapeutic implications. [Cancer Res 2009;69(20):8067–75]