bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Targeted Promotions
Authors: Fruchter Gila E. , Zhang Z. John
Published: July 2004

This research analyzes the strategic use of targeted promotions for customer retention and acquisition in a dynamic and competitive environment. The normative analysis shows that a firm’s optimal targeting strategies, both offensive and defensive, depend on its actual market share, the relevant redemption rate of its targeted promotions, customer profitability, and the effectiveness of its targeted promotions. These strategies have the attractive feature of being an adaptive control rule. A firm can operationalize these strategies by adjusting its planned promotional incentives on the basis of the observed differences between actual and planned market shares and between actual and planned redemption rates. In the long run, a focus on customer retention is not an optimal strategy for all firms.
Whither Services Marketing?
Authors: Lovelock Christopher , Gummesson Evert
Published: July 2004

This article examines the received wisdom of services marketing and challenges the validity and continued usefulness of its core paradigm, namely, the assertion that four specific characteristics—intangibility, heterogeneity, inseparability, and perishability—make services uniquely different from goods. An alternative paradigm is proposed, based on the premise that marketing exchanges that do not result in a transfer of ownership from seller to buyer are fundamentally different from those that do. It posits that services offer benefits through access or temporary possession, instead of ownership, with payments taking the form of rentals or access fees. This rental/access perspective offers a different lens through which to view services. Important implications include opportunities to market goods in a service format; the need for more research into how time is perceived, valued, and consumed; and the notion of services as a means of sharing resources.
Service Encounters as a Sequence of Events
Authors: Verhoef Peter C. , Antonides Gerrit , de Hoog Arnoud N.
Published: July 2004

A service encounter can be considered as a sequence of events. In the early service literature, it was assumed that firms should deliver a consistent performance during a service encounter. However, research in psychology states that this is not necessarily true. In addition to the average performance, the peaks in the performance are important. Likewise, some service researchers have stressed the importance of a happy ending. The authors test a model on how events contribute to the overall evaluation of a sequence of events. They show that the average performance during the encounter is important. However, their results also stress the importance of peak experiences for satisfaction formation. Thus, managers of service encounters should not only manage the overall performance of a service encounter. To further elevate satisfaction, they could also provide some positive peak experiences.
The Critical Incident Technique in Service Research
Authors: Gremler Dwayne D.
Published: July 2004

The Critical Incident Technique (CIT) has been used in a variety of service contexts in recent years to explore service research issues and has been instrumental in advancing our understanding of these issues. Despite the popularity of this methodology, no published research synthesis systematically examines this research. The primary purpose of this study is to review the use of the CIT method in service research to (a) help current and future researchers employing the CIT method to examine their methodological decisions closely and (b) suggest guidelines for the proper application and reporting of the procedures involved when using this method. The study provides an overview of the CIT method, reports the results of a research synthesis conducted of 141 CIT studies appearing in service marketing and management publications, discusses implications for service research, and suggests guidelines for researchers employing this method.
Preconceptions about Service
Authors: Iglesias Víctor
Published: July 2004

Recent research has suggested that customer evaluation of service encounters depends not only on the attributes of the particular service rendered but also on other cognitive and affective factors. This article sets out to investigate the effects that preconceptions about service types have on customers’ perceptions and on their overall evaluation of service encounters. The study is founded on Categorization Theory and Perception Distortion Theories and poses and tests three hypotheses on a customer sample taken from the Spanish retail banking sector. The results show a strong effect of preconceptions about the service category on the perceptions of quality during the service encounter; however, their direct effect on the overall evaluation of the service is unsubstantiated in our study.
The anomalies of being Faye (Wong)
Authors: Fung Anthony , Curtin Michael
Published: July 2004

• Building on previous research regarding popular music and the culture industries, this article examines the intersection between gender politics in Chinese societies and the musical success of Faye Wong, the reigning diva of the Hong Kong-based pop music industry. Influential among adolescents and young women, she has not only become a figure for textual identification but also a polysemic icon for cultural aspirations and feminist projects throughout Greater China. Unlike earlier female singing stars, Faye's music and public persona explicitly defy standard market practices and conventional representations of femininity. Yet, paradoxically, these unconventional qualities have contributed to her sustained success over the past 10 years. Thus, Faye's star persona operates both as a marketable commodity and as a site of significant cultural work in the realm of gender politics. Using Bourdieu's distinction between economic and cultural capital, our analysis shows how music companies enriched Faye's cultural capital as part of their promotional efforts and how she in turn exploited that very capital in unconventional ways. •
The substance of consumption
Authors: Cronin Anne
Published: July 2004

•This article reconsiders the category of `commodity' by exploring its historical and contemporary articulation with the category of `drug' and the way in which both have been figured as transformative. I argue that ideas of substance, substance-dependency, willpower, structures of feeling and social struggles over power amass or materialize at particular moments in their cultural circulation. They coalesce temporarily into a structure conventionally apprehended as a commodity. Thus, values, norms, ideals and feelings substantialize in the form of the commodity. In turn, our relationship to commodities is called on to substantiate or legitimize a particular framing of our social order and control of social groups structured around `good commoditydrugs', `bad drugs' and so-called addictive consumption practices. Through such a framework, I analyse the category of `commodity' as transformational prism which tracks its complex discursive trajectories through pathology, social order, materiality, willpower and feeling. •
Federal Association Health Plans: Will this Proposal Remedy the Health Insurance Crisis?
Authors: Kofman Mila , Polzer Karl
Published: July 2004

For many years, some business groups have advocated that the federal government should begin licensing health plans offered by trade associations that would be subject to less stringent regulation than state-licensed insurance products. In recent years, legislation that would make this concept a reality has gained momentum on Capitol Hill. Supporters argue that association health plans (AHPs) are one way to expand access to health insurance and address the rising costs of coverage. President Bush promoted the concept in his 2004 State of the Union address. In May of 2004, the U.S. House of Representatives passed a bill that would encourage the growth of AHPs nationally—legislation almost identical to what the House passed in 2003. In this article, we examine the AHP legislation’s key elements including consumer protection standards and oversight. We discuss arguments for and against the legislation and conclude that it is unlikely that it would remedy the problems of rising health insurance costs and the growing number of people without health insurance coverage in the United States.
Cultivating Effective Leadership Skills for Nurses: A Commentary
Authors: Dickenson-Hazard Nancy
Published: July 2004

Opportunities abound for nurses to lead, but few are born leaders: Most must learn effective leadership skills. Paying attention to and developing four simple things—having followers, moving in the right direction, setting examples, and having authenticity—enable nurses to be effective leaders. The challenge lies in continually acting and questioning what can be done to make a difference.
The Coming Gerontocracy: Social and Ethical Ramifications
Authors: Curtin Leah L.
Published: July 2004

Today we face an aging population, increasing poverty among younger generations, massive federal budget deficits, and a burgeoning array of entitlement programs for the old, programs that are paid for by the young. For more than 2 decades, some of America’s best minds have been working on solutions to the coming crises in Social Security and Medicare. However, for every action, there is an equal and opposite reaction. This article explores the extent of the fiscal crises, some of the proposed solutions, and the impact that these proposals are likely to have on hospitals and health systems.
Down to the Wire: Bush and Kerry on Health Care
Authors: Jennings Carole P. , Ford-Roegner Pat
Published: July 2004

The presumed candidates are moving toward the starting gate for the 2004 presidential election. President Bush and Senator Kerry have each laid out their plans for health care change. In this Political Update, the authors discuss the candidate’s approaches for meeting the health care needs of Americans for the next four years.
Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology
Authors: Chandrashekran Anil , Gordon Myrtle Y. , Casimir Colin
Published: July 2004

Gene therapy for a wide variety of disorders would be greatly enhanced by the development of vectors that could be targeted for gene delivery to specific populations of cells. We describe here high-efficiency targeted transduction based on a novel targeting strategy that exploits the ability of retroviruses to incorporate host cell proteins into the surface of the viral particle as they bud through the plasma membrane. Ecotropic retroviral particles produced in cells engineered to express the membrane-bound form of stem cell factor (mbSCF) transduce both human cell lines and primary cells with high efficiency in a strictly c-kit (SCF receptor)-dependent fashion. The availability of efficient targeted vectors provides a platform for the development of a new generation of therapies using in vivo gene delivery. (Blood. 2004;104: 2697-2703)
Combination of retinoic acid and tumor necrosis factor overcomes the maturation block in a variety of retinoic acid-resistant acute promyelocytic leukemia cells
Authors: Witcher Michael , Shiu Hoi Ying , Guo Qi , Miller Wilson H.
Published: July 2004

Retinoic acid (RA) overcomes the maturation block in t(15:17) acute promyelocytic leukemia (APL), leading to granulocytic differentiation. Patients receiving RA alone invariably develop RA resistance. RA-resistant cells can serve as useful models for the development of treatments for both APL and other leukemias. Previously, we showed that RA and tumor necrosis factor (TNF) promote monocytic differentiation of the APL cell line NB4 and U937 monoblastic cells. Here, we report that combining TNF with RA leads to maturation of several RA-resistant APL cells along a monocytic pathway, whereas UF-1, a patient-derived RA-resistant cell line, showed characteristics of granulocytic differentiation. We found distinct differences in gene regulation between UF-1 cells and cells showing monocytic differentiation. Although IRF-7 was up-regulated by TNF and RA in all cells tested, expression of c-jun and PU.1 correlated with monocytic differentiation. Furthermore, synergistic induction of PU.1 DNA binding and macrophage colony-stimulating factor receptor (m-CSF-1R) mRNA was observed only in cells differentiating into monocytes. Using neutralizing antibodies against m-CSF-1R or its ligand, we found that inhibiting this pathway strongly reduced CD14 expression in response to RA and TNF, suggesting that this pathway is essential for their synergy in RA-resistant leukemia cells. (Blood. 2004;104:3335-3342)
Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance
Authors: St. Pierre Timothy G. , Clark Paul R. , Chua-anusorn Wanida , Fleming Adam J. , Jeffrey Gary P. , Olynyk John K. , Pootrakul Pensri , Robins Erin , Lindeman Robert
Published: July 2004

Measurement of liver iron concentration (LIC) is necessary for a range of iron-loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of needle biopsy specimens is the most common accepted method of measurement. This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver proton transverse relaxation rates (R2) were measured for 105 humans. A value for the LIC for each subject was obtained by chemical assay of a needle biopsy specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue. Proton transverse relaxation rates in aqueous paramagnetic solutions were also measured on each magnetic resonance imaging unit to ensure instrument-independent results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms on 13 different magnetic resonance imaging units using the method yielded a coefficient of variation of 2.1%.
Atypical marginal zone hyperplasia of mucosa-associated lymphoid tissue: a reactive condition of childhood showing immunoglobulin lambda light-chain restriction
Authors: Attygalle Ayoma D. , Liu Hongxiang , Shirali Sima , Diss Timothy C. , Loddenkemper Christoph , Stein Harald , Dogan Ahmet , Du Ming-Qing , Isaacson Peter G.
Published: July 2004

Mucosa-associated lymphoid tissue (MALT) lymphomas usually arise at sites of acquired MALT and are uncommon in native MALT (eg, Peyer patches and tonsil). Malignancy in these low-grade lymphomas is often inferred by immunoglobulin light-chain restriction and expression of CD43; molecular genetic evidence is sought only if these are in doubt. We report 6 cases (4 tonsils, 2 appendixes) of marginal zone (MZ) hyperplasia in children aged 3 to 11 years that, despite histologic and immunophenotypic features indicative of lymphoma, were polyclonal by molecular analysis. No lymphoma-directed therapy was given and patients remain alive and well (5 cases, median follow-up 35.3 months). The involved tonsil and appendix showed florid MZ hyperplasia with prominent intraepithelial B cells (IEBCs). The MZ B cells and IEBCs showed a high-proliferation fraction and a CD20+, CD21+, CD27-, immunoglobulin (Ig) superfamily receptor translocation-associated 1-positive (IRTA-1+), CD43+, multiple myeloma oncogene 1 (MUM-1), IgM+D+ phenotype. Polymerase chain reaction (PCR), cloning, and sequencing of rearranged IgH and Igλ genes (whole tissue sections [6 cases]; microdissected cells [2 cases]) showed that the MZ B cells and IEBCs were polyclonal and the IgH genes nonmutated. In contrast, MZ (intraepithelial) B cells of 6 control tonsils had a similar immunophenotype, except for expression of CD27 and polytypic light chains, whereas molecular studies showed that they were polyclonal with mutated Ig genes. (Blood. 2004;104:3343-3348)
Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
Authors: O'Hare Thomas , Pollock Roy , Stoffregen Eric P. , Keats Jeffrey A. , Abdullah Omar M. , Moseson Erika M. , Rivera Victor M. , Tang Hao , Metcalf Chester A. , Bohacek Regine S. , Wang Yihan , Sundaramoorthi Raji , Shakespeare William C. , Dalgarno David , Clackson Tim , Sawyer Tomi K. , Deininger Michael W. , Druker Brian J.
Published: July 2004

The deregulated, oncogenic tyrosine kinase Bcr-Abl causes chronic myeloid leukemia (CML). Imatinib mesylate (Gleevec, STI571), a Bcr-Abl kinase inhibitor, selectively inhibits proliferation and promotes apoptosis of CML cells. Despite the success of imatinib mesylate in the treatment of CML, resistance is observed, particularly in advanced disease. The most common imatinib mesylate resistance mechanism involves Bcr-Abl kinase domain mutations that impart varying degrees of drug insensitivity. AP23464, a potent adenosine 5′-triphosphate (ATP)–based inhibitor of Src and Abl kinases, displays antiproliferative activity against a human CML cell line and Bcr-Abl–transduced Ba/F3 cells (IC50 = 14 nM; imatinib mesylate IC50 = 350 nM). AP23464 ablates Bcr-Abl tyrosine phosphorylation, blocks cell cycle progression, and promotes apoptosis of Bcr-Abl–expressing cells. Biochemical assays with purified glutathione S transferase (GST)–Abl kinase domain confirmed that AP23464 directly inhibits Abl activity. Importantly, the low nanomolar cellular and biochemical inhibitory properties of AP23464 extend to frequently observed imatinib mesylate–resistant Bcr-Abl mutants, including nucleotide binding P-loop mutants Q252H, Y253F, E255K, C-terminal loop mutant M351T, and activation loop mutant H396P. AP23464 was ineffective against mutant T315I, an imatinib mesylate contact residue. The potency of AP23464 against imatinib mesylate–refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP23464 for the treatment of CML.
Effects of positive end-expiratory pressure on gastric mucosal perfusion in acute respiratory distress syndrome
Authors: Bruhn Alejandro , Hernandez Glenn , Bugedo Guillermo , Castillo Luis
Published: July 2004

Introduction

Positive end-expiratory pressure (PEEP) improves oxygenation and can prevent ventilator-induced lung injury in patients with acute respiratory distress syndrome (ARDS). Nevertheless, PEEP can also induce detrimental effects by its influence on the cardiovascular system. The purpose of this study was to assess the effects of PEEP on gastric mucosal perfusion while applying a protective ventilatory strategy in patients with ARDS.

Methods

Eight patients were included. A pressure–volume curve was traced and ideal PEEP, defined as lower inflection point + 2 cmH2O, was determined. Gastric tonometry was measured continuously (Tonocap). After baseline measurements, 10, 15 and 20 cmH2O PEEP and ideal PEEP were applied for 30 min each. By the end of each period, hemodynamic, CO2 gap (gastric minus arterial partial pressures), and ventilatory measurements were performed.

Results

PEEP had no effect on CO2 gap (median [range], baseline: 19 [2–30] mmHg; PEEP 10: 19 [0–40] mmHg; PEEP 15: 18 [0–39] mmHg; PEEP 20: 17 [4–39] mmHg; ideal PEEP: 19 [9–39] mmHg; P = 0.18). Cardiac index also remained unchanged (baseline: 4.6 [2.5–6.3] l min-1 m-2; PEEP 10: 4.5 [2.5–6.9] l min-1 m-2; PEEP 15: 4.3 [2–6.8] l min-1 m-2; PEEP 20: 4.7 [2.4–6.2] l min-1 m-2; ideal PEEP: 5.1 [2.1–6.3] l min-1 m-2; P = 0.08). One patient did not complete the protocol because of hypotension.

Conclusion

PEEP of 10–20 cmH2O does not affect gastric mucosal perfusion and is hemodynamically well tolerated in most patients with ARDS, including those receiving adrenergic drugs.
Genetic Targeting of Relaxin and Insulin-Like Factor 3 Receptors in Mice
Authors: Kamat Aparna A. , Feng Shu , Bogatcheva Natalia V. , Truong Anne , Bishop Colin E. , Agoulnik Alexander I.
Published: July 2004

Relaxin (RLN) is a small peptide hormone that affects a variety of biological processes. Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, agerelated pulmonary fibrosis, and abnormalities in the testes and prostate. We describe here RLN receptor Lgr7-deficient mice. Mutant females have grossly underdeveloped nipples and are unable to feed their progeny. Some Lgr7−/− females were unable to deliver their pups. Histological analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and fibrosis surrounding the bronchioles and the vascular bundles, absent in wild-type animals. However, Lgr7-deficient males do not exhibit abnormalities in the testes or prostate as seen in Rln1 knockout mice. Lgr7-deficient females with additional deletion of Lgr8 (Great), another putative receptor for RLN, are fertile and have normal-sized litters. Double mutant males have normal-sized prostate and testes, suggesting that Lgr8 does not account for differences in Rln1−/− and Lgr7−/− phenotypes. Transgenic overexpression of Insl3, the cognate ligand for Lgr8, does not rescue the mutant phenotype of Lgr7-deficient female mice indicating nonoverlapping functions of the two receptors. Our data indicate that neither Insl3 nor Lgr8 contribute to the RLN signaling pathway. We conclude that the Insl3/Lgr8 and Rln1/Lgr7 actions do not overlap in vivo.
Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor β
Authors: Baker Ann E. , Brautigam Vielska M. , Watters Jyoti J.
Published: July 2004

Estrogens are well known to exert antiinflammatory effects outside the central nervous system (CNS). They have also been shown to exert neuroprotective effects in the CNS after several types of injury, including neurodegeneration. However, the molecular mechanisms by which these effects occur remain unclear. Because microglial hyperactivation and their production of neurotoxins is associated with many types of brain injury for which estrogens are beneficial, we sought to investigate the ability of estrogen to modulate microglial function. Furthermore, because little is known regarding the role of each of the two known estrogen receptors (ERs) in microglia, our studies were designed to test the hypothesis that 17β-estradiol (E2) exerts antiinflammatory effects in microglia, specifically via interactions with ERβ. We tested this hypothesis using the murine microglial cell line BV-2, which naturally expresses only ERβ. Our results indicate that not only does E2 decrease lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, it also reduces the expression of cyclooxygenase-2, a target for estrogen that has not previously been reported for ERβ. We also observed that LPS-stimulated TNFα mRNA was increased by estrogen. E2 exerts these effects within 30 min compared with typical estrogen transcriptional responses. Tamoxifen and ICI 182,780 differentially blocked the inhibitory effects of E2 on LPS-stimulated iNOS and cyclooxygenase-2. In addition, we show that E2 alters LPS-stimulated MAPK pathway activation, supporting the idea that alterations in the MAPKs may be a potential mechanism by which ERβ mediates decreased microglial activation.
Identification of a Novel Apolipoprotein, ApoN, in Ovarian Follicular Fluid
Authors: O’Bryan Moira K. , Foulds Lynda M. , Cannon James F. , Winnall Wendy R. , Muir Julie A. , Sebire Kim , Smith A. Ian , Keah Hooi-Hong , Hearn Milton T. W. , de Kretser David M. , Hedger Mark P.
Published: July 2004

A novel apolipoprotein, designated ApoN, has been identified in bovine ovarian follicular fluid using chromatographic purification methods, amino acid sequence analysis, molecular biology, and bioinformatics. The apolipoprotein is a hydrophobic 12-kDa protein processed from the C terminus of a 29-kDa precursor expressed in a number of tissues, including the ovary, testis, the anterior chamber of the eye, skeletal muscle, uterus, and liver. Bovine, porcine, and murine ApoN display significant homology at the amino acid level across the entire precursor sequence. Surprisingly, there appears to be no orthologous protein in the human, although an APON-like pseudogene is found on chromosome 12. The N-terminal fragment of the ApoN precursor shows significant homology with the N-terminal sequence of the precursor of the cholesterol transport regulatory protein ApoF, but the corresponding C-terminal sequences of ApoN and ApoF possess no homology. ApoN is present in the high-density lipoprotein fraction of bovine serum and both the high-density lipoprotein and low-density lipoprotein fractions of bovine follicular fluid and is found in several tissues that are associated with local immunological privilege. These data suggest that ApoN may play a role in steroidogenesis and/or immunoregulation in the gonads of nonhuman species, as well as similar roles in other tissues.
Recruitment of β-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells
Authors: Masiello David , Chen Shao-Yong , Xu Youyuan , Verhoeven Manon C. , Choi Eunis , Hollenberg Anthony N. , Balk Steven P.
Published: July 2004

Prostate cancers respond to treatments that suppress androgen receptor (AR) function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR antagonists in clinical use. As CPA has substantial agonist activity, it was examined to identify AR coactivator/corepressor interactions that may mediate androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal interactions or recruit β-catenin, indicating a nonagonist conformation. Nonetheless, CPA did not enhance AR interaction with nuclear receptor corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated AR-nuclear receptor corepressor binding. The role of coactivators was further assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by β-catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and not β-catenin. In contrast, β-catenin coactivated a bicalutamide-responsive mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further implicating β-catenin recruitment in AR-stimulated growth. Androgen-stimulated prostate-specific antigen gene expression in LNCaP cells could be modulated by β-catenin, and endogenous c-myc expression was repressed by dihydrotestosterone, but not CPA. These results indicate that interactions between AR and β-catenin contribute to prostate cell growth in vivo, although specific growth promoting genes positively regulated by AR recruitment of β-catenin remain to be identified.
Sonic hedgehog, secreted by amacrine cells, acts as a short-range signal to direct differentiation and lamination in the zebrafish retina
Authors: Shkumatava Alena , Fischer Sabine , Müller Ferenc , Strahle Uwe , Neumann Carl J.
Published: July 2004

Neurogenesis in the zebrafish retina occurs in several waves of differentiation. The first neurogenic wave generates ganglion cells and depends on hedgehog (hh) signaling activity. Using transgenic zebrafish embryos that express GFP under the control of the sonic hedgehog (shh) promoter, we imaged the differentiation wave in the retina and show that, in addition to the wave in the ganglion cell layer, shh expression also spreads in the inner nuclear layer. This second wave generates amacrine cells expressing shh, and although it overlaps temporally with the first wave, it does not depend on it, as it occurs in the absence of ganglion cells. We also show that differentiation of cell types found in the inner and outer nuclear layers, as well as lamination of the retina, depends on shh. By performing mosaic analysis, we demonstrate that Shh directs these events as a short-range signal within the neural retina.
Mef2cis a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development
Authors: Dodou Evdokia , Verzi Michael P. , Anderson Joshua P. , Xu Shan-Mei , Black Brian L.
Published: July 2004

The vertebrate heart forms initially as a linear tube derived from a primary heart field in the lateral mesoderm. Recent studies in mouse and chick have demonstrated that the outflow tract and right ventricle originate from a separate source of mesoderm that is anterior to the primary heart field. The discovery of this anterior, or secondary, heart field has led to a greater understanding of the morphogenetic events involved in heart formation;however, many of the underlying molecular events controlling these processes remain to be determined. The MADS domain transcription factor MEF2C is required for proper formation of the cardiac outflow tract and right ventricle, suggesting a key role in anterior heart field development. Therefore, as a first step toward identifying the transcriptional pathways upstream of MEF2C, we introduced a lacZ reporter gene into a bacterial artificial chromosome (BAC) encompassing the murine Mef2clocus and used this recombinant to generate transgenic mice. This BAC transgene was sufficient to recapitulate endogenous Mef2c expression,and comparative sequence analyses revealed multiple regions of significant conservation in the noncoding regions of the BAC. We show that one of these conserved noncoding regions represents a transcriptional enhancer that is sufficient to direct expression of lacZ exclusively to the anterior heart field throughout embryonic development. This conserved enhancer contains two consensus GATA binding sites that are efficiently bound by the zinc finger transcription factor GATA4 and are completely required for enhancer function in vivo. This enhancer also contains two perfect consensus sites for the LIM-homeodomain protein ISL1. We show that these elements are specifically bound by ISL1 and are essential for enhancer function in transgenic embryos. Thus, these findings establish Mef2c as the first direct transcriptional target of ISL1 in the anterior heart field and support a model in which GATA factors and ISL1 serve as the earliest transcriptional regulators controlling outflow tract and right ventricle development.
Conditional β1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system
Authors: Pietri Thomas , Eder Olivier , Breau Marie Anne , Topilko Piotr , Blanche Martine , Brakebusch Cord , Fässler Reinhard , Thiery Jean-Paul , Dufour Sylvie
Published: July 2004

Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation,differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the β1-integrin gene to analyse the role ofβ1-integrins in neural crest cell migration and differentiation. This targeted mutation caused death within a month of birth. The loss ofβ1-integrins from the embryo delayed the migration of Schwann cells along axons and induced multiple defects in spinal nerve arborisation and morphology. There was an almost complete absence of Schwann cells and sensory axon segregation and defective maturation in neuromuscular synaptogenesis. Thus, β1-integrins are important for the control of embryonic and postnatal peripheral nervous system development.
FGF acts directly on the somitic tendon progenitors through the Ets transcription factorsPea3andErmto regulate scleraxis expression
Authors: Brent Ava E. , Tabin Clifford J.
Published: July 2004

During somite development, a fibroblast growth factor (FGF) signal secreted from the myotome induces formation of a scleraxis (Scx)-expressing tendon progenitor population in the sclerotome, at the juncture between the future lineages of muscle and cartilage. While overexpression studies show that the entire sclerotome is competent to express Scx in response to FGF signaling, the normal Scx expression domain includes only the anterior and posterior dorsal sclerotome. To understand the molecular basis for this restriction, we examined the expression of a set of genes involved in FGF signaling and found that several members of the Fgf8synexpression group are co-expressed with Scx in the dorsal sclerotome. Of particular interest were the Ets transcription factors Pea3 and Erm, which function as transcriptional effectors of FGF signaling. We show here that transcriptional activation by Pea3and Erm in response to FGF signaling is both necessary and sufficient for Scx expression in the somite, and propose that the domain of the somitic tendon progenitors is regulated both by the restricted expression of Pea3 and Erm, and by the precise spatial relationship between these Ets transcription factors and the FGF signal originating in the myotome.
On The Politics of Property Rights by Haber, Razo, and Maurer
Authors: Bates Robert H
Published: July 2004

Stephen Haber et al. explore economic growth in key sectors of the Mexican economy, 1876–1929, an era of political instability and (1914–17) civil war. The authors demonstrate that economic growth continued amidst political instability and offer an explanation for their conunterintuitive finding. Reviewing the evidence advanced by the authors, Robert Bates summarizes and comments on their argument, and applies it to “out of sample” data from Africa.
Success and Failure of Reform: Insights from the Transition of Agriculture
Authors: Rozelle Scott , Swinnen Johan F. M
Published: July 2004

The paper analyzes the linkages between the reform strategies in transition countries and economic performance. We focus on agriculture because of the sharpness of the policy changes, fundamental differences among countries, and relative simplicity of agricultural relationships. We document post reform performance in the transition countries of Asia and Europe. We show how: a.) pricing reform and subsidy reductions; b.) land rights reform and policies that affect farm restructuring; and c.) the presence institutions that facilitate exchange (either markets or market substitutes) affect output and productivity. The paper ends with general lessons on reforms and transition.
Modeling Knowledge in Economic Analysis
Authors: Samuelson Larry
Published: July 2004

This paper provides an introduction to how knowledge is modeled in economic contexts and the role played by the concepts of knowledge and common knowledge in economic analysis.
Whose Line Is It? Plagiarism in Economics
Authors: Enders Walter , Hoover Gary A
Published: July 2004

This paper reports the results of a survey regarding the instances of plagiarism reported by journal editors in the economics profession. The survey finds that nearly 24% of responding editors encounter one case of plagiarism in a typical year. In addition, the survey reveals that less than 19% of responding journals have a formal policy regarding plagiarism. Moreover, there is a great deal of variance in what is considered plagiarism and what an appropriate response to plagiarism should be. A majority of editors believe that the economics profession would benefit from a professional code of ethics.
A Rapid Method for Assessing the Distribution of Gold Labeling on Thin Sections
Authors: Lucocq John Milton , Habermann Anja , Watt Stephen , Backer Jonathan M. , Mayhew Terry M. , Griffiths Gareth
Published: July 2004

Particulate gold labeling on ultrathin sections is in widespread use for antigen localization at the EM level. To extend the usefulness of gold labeling technology, we are evaluating different methods for sampling and estimating quantities of gold labeling. Here we present a simple, rapid, and unbiased method for assessing the relative pool sizes of immunogold labeling distributed over different cell compartments. The method uses a sampling approach developed for stereology in which a regular array of microscopic fields or linear scans is positioned randomly on labeled sections. From these readouts, gold particles are counted and assigned to identifiable cell structures to construct a gold labeling frequency distribution of those labeled compartments. Here we use ultrathin cryosections labeled for a range of different proteins and for a signaling lipid. We show by scanning labeled sections at the electron microscope that counting 100–200 particles on each of two grids is sufficient to obtain a reproducible and rapid assessment of the pattern of labeling proportions over 10–16 compartments. If more precise estimates of labeling proportions over individual compartments are required (e.g., to achieve coefficients of error of 10–20%), then 100–200 particles need to be counted over each compartment of interest.
Rapid Analysis of Mitochondrial DNA Depletion by Fluorescence In Situ Hybridization and Immunocytochemistry: Potential Strategies for HIV Therapeutic Monitoring
Authors: Janes Michael S. , Hanson Bonnie J. , Hill Dani M. , Buller Gayle M. , Agnew Jakyoung Y. , Sherwood Steven W. , Cox W. Gregory , Yamagata Kunihiro , Capaldi Roderick A.
Published: July 2004

Nucleoside reverse transcriptase inhibitors (NRTIs) have been a mainstay in the treatment of human immunodeficiency virus since the introduction of azidothymidine (AZT) in 1987. However, none of the current therapies can completely eradicate the virus, necessitating long-term use of anti-retroviral drugs to prevent viral re-growth. One of the side effects associated with long-term use of NRTIs is mitochondrial toxicity stemming from inhibition of the mitochondrial DNA (mtDNA) polymerase γ, which leads to mtDNA depletion and consequently to mitochondrial dysfunction. Here we report the use of fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) to monitor mtDNA depletion in cultured fibroblasts treated with the NRTI 2',3'-dideoxycytidine (ddC). These techniques are amenable to both microscopy and flow cytometry, allowing analysis of populations of cells on a single-cell basis. We show that, as mtDNA depletion progresses, a mosaic population develops, with some cells being depleted of and others retaining mtDNA. These techniques could be useful as potential therapeutic monitors to indicate when NRTI therapy should be interrupted to prevent mitochondrial toxicity and could aid in the development of less toxic NRTIs by providing an assay suitable for pharmacodynamic evaluation of candidate molecules.
Tight Junction Proteins ZO-1, Occludin, and Claudins in Developing and Adult Human Perineurium
Authors: Pummi Kati P. , Heape Anthony M. , Grénman Reidar A. , Peltonen Juha T.K. , Peltonen Sirkku A.
Published: July 2004

In peripheral nerves, groups of Schwann cell–axon units are isolated from the adjacent tissues by the perineurium, which creates a diffusion barrier responsible for the maintenance of endoneurial homeostasis. The perineurium is formed by concentric layers of overlapping, polygonal perineurial cells that form tight junctions at their interdigitating cell borders. In this study, employing indirect immunofluorescence and immunoelectron microscopy, we demonstrate that claudin-1 and -3, ZO-1, and occludin, but not claudin-2, -4, and -5, are expressed in the perineurium of adult human peripheral nerve. We also describe the expression of occludin, ZO-1, claudin-1, -3, and -5 in the developing human perineurium, showing that the expressions of claudin-1 and -3, ZO-1, and occludin follow similar spatial developmental expression patterns but follow different timetables in achieving their respective adult distributions. Specifically, claudin-1 is already largely restricted to perineurium-derived structures at 11 fetal weeks, whereas claudin-3 and occludin are weakly expressed in the perineurial structures at this age and acquire a well-defined perineurial distribution only between 22 and 35 fetal weeks. ZO-1 appears to acquire its mature profile even later during the third trimester. The results of the present and previous studies show that the perineurial diffusion barrier matures relatively late during human peripheral nerve development.
Destiny and Intracellular Survival of Leishmania amazonensis in Control and Dexamethasone-treated Glial Cultures: Protozoa-specific Glycoconjugate Tagging and TUNEL Staining
Authors: Baetas-da-Cruz Wagner , Macedo-Silva Roger M. , Santos-Silva Alessandra , Henriques-Pons Andrea , Madeira Maria F. , Corte-Real Suzana , Cavalcante Leny A.
Published: July 2004

Leishmania amazonensis, an obligatory intracellular parasite, survives internalization by macrophages, but no information is available on the involvement of microglia. We have investigated microglia-protozoa interactions in mixed glial cultures infected with promastigote forms of L. amazonensis after lipopolysaccharide (LPS) or dexamethasone (DM) treatment. After 2 hr of exposure to parasites in control cultures, there was a small number of infected microglia (1%). Preincubation with LPS or DM led to 14% or 60% of microglial cells with attached parasites, respectively. DM treatment resulted in 39% of microglial cells with internalized parasites (controls or LPS-treated cells had ≤1%). Scanning electron micrographs showed numerous filopodia in DM-treated cells, whereas these projections were rarely observed in LPS-treated or control cells. DM treatment also affected the intramicroglial survival of Leishmania. In control cultures, internalized parasites, tagged with an anti-lipophosphoglycan (anti-LPG) antibody, showed fragmented DNA [terminal deoxyribonucleotide transferase-mediated dUTP-X nick end labeling (TUNEL+)] after 4 hr of interaction, but changes seemed slightly delayed in DM-treated cultures. After 12 hr, there were no LPG+/TUNEL+ profiles in controls, whereas rare LPG+ profiles still persisted in DM-treated cells. Our results suggest that microglia are highly effective in the elimination of Leishmania and that the process can be effectively studied by LPG/TUNEL double labeling.
Immunohistochemical Identification of an Extracellular Matrix Scaffold that Microguides Capillary Sprouting In Vivo
Authors: Anderson Christopher R. , Ponce Ana M. , Price Richard J.
Published: July 2004

To gain insight into how a naturally occurring scaffold composed of extracellular matrix (ECM) proteins provides directional guidance for capillary sprouting, we examined angiogenesis in whole-mount specimens of rat mesentery. Angiogenesis was studied in response to normal maturation, the injection of a mast cell degranulating substance (compound 48/80), and mild wounding. Confocal microscopy of specimens immunolabeled for elastin revealed a network of crosslinked elastic fibers with a density of 140.8 ± 37 mm of fiber/mm2 tissue. Fiber diameters ranged from 180 to 1400 nm, with a mean value of 710 ± 330 nm. Capillary sprouts contained CD31- and OX-43-positive endothelial cells as well as desmin-positive pericytes. During normal maturation, leading endothelial cells and pericytes were in contact and aligned with an elastic fiber in ≃80–90% of all sprouts. In wounding and compound 48/80-treated specimens, in which angiogenesis was markedly increased, leading endothelial cells remained in contact and aligned with elastic fibers in ≃60–80% of all sprouts. These observations indicate that elastic fibers are used for endothelial and pericyte migration during capillary sprouting in rat mesentery. The composition of this elastic fiber matrix may provide important clues for the development of tissue-engineered scaffolds that support and directionally guide angiogenesis.
Carbonic Anhydrase in Mammalian Vascular Smooth Muscle
Authors: Berg John T. , Ramanathan S. , Gabrielli M. Gabriella , Swenson Erik R.
Published: July 2004

Carbonic anhydrase (CA) is ubiquitously expressed and plays a pivotal role in acid-base balance, ion transport, and gas exchange. Limited observations by others, derived from functional, pharmacological, and histochemical studies, suggest that CA is present in vascular smooth muscle and is involved in vasoregulation. The present study, using measurements of bioactivity, inhibition characteristics, and immunohistochemical analysis, was undertaken to more fully evaluate CA in vascular smooth muscle. In isolated bovine aortic smooth muscle, which is devoid of erythrocytes, CA is present in low concentrations with a CO2 hydration activity (at 0C) of 3.5 ± 2.7 U/g. The I50 for acetazolamide inhibition is 0.07 ± 0.01 μM. Results with dorzolamide and bromopyruvate, selective inhibitors of the CA II and I isozymes, respectively, show that roughly 75% of the CA activity is accounted for by CA I, with 20% due to CA II. These results accord qualitatively with immunocytochemical staining with specific CA I and II antibodies, showing that both isozymes are present and that their staining co-localizes with cells positive for smooth muscle α-actin. These data establish the activity, inhibition, and isozyme pattern of carbonic anhydrase expression in mammalian vascular smooth muscle.
Alternative Models for Capturing the Compromise Effect
Authors: Kivetz Ran , Netzer Oded , Srinivasan V.
Published: July 2004

The compromise effect denotes the finding that brands gain share when they become the intermediate rather than extreme option in a choice set. Despite the robustness and importance of this phenomenon, choice modelers have neglected to incorporate the compromise effect in formal choice models and to test whether such models outperform the standard value maximization model. In this article, the authors suggest four context-dependent choice models that can conceptually capture the compromise effect. Although the models are motivated by theory from economics and behavioral decision research, they differ with respect to the particular mechanism that underlies the compromise effect (e.g., contextual concavity versus loss aversion). Using two empirical applications, the authors (1) contrast the alternative models and show that incorporating the compromise effect by modeling the local choice context leads to superior predictions and fit compared with the traditional value maximization model and a stronger (naive) model that adjusts for possible biases in utility measurement, (2) generalize the compromise effect by demonstrating that it systematically affects choice in larger sets of products and attributes than has been previously shown, (3) show the theoretical and empirical equivalence of loss aversion and local (contextual) concavity and (4) demonstrate the superiority of models that use a single reference point over “tournament models” in which each option serves as a reference point. They discuss the theoretical and practical implications of this research as well as the ability of the proposed models to predict other behavioral context effects.
Longitudinal Shifts in the Drivers of Satisfaction with Product Quality: The Role of Attribute Resolvability
Authors: Slotegraaf Rebecca J. , Inman J. Jeffrey
Published: July 2004

Research on customer equity has reemphasized the value of understanding the factors that influence satisfaction and quality. Although research has shown that many factors influence perceptions of satisfaction and quality, it has failed to consider the potential for asymmetric effects that shift over time and are based on the attributes used to form such perceptions. Using automobile ownership experiences during the manufacturer warranty period, the authors show that as consumers approach the end of their product's warranty period, satisfaction with attributes that can be remedied (“resolvable” attributes) declines at a greater rate, yet its effect on satisfaction with product quality intensifies. In contrast, satisfaction with attributes that cannot be remedied (“irresolvable” attributes) declines at a lesser rate, and its effect on satisfaction with product quality weakens over time. The authors also discuss implications for research and customer relationship management programs.