bluuebunny/crossref_metadata_2025 huggingface dataset:
The Promoter of the Rat Gonadotropin-Releasing Hormone Receptor Gene Directs the Expression of the Human Placental Alkaline Phosphatase Reporter Gene in Gonadotrope Cells in the Anterior Pituitary Gland as well as in Multiple Extrapituitary Tissues
Authors: Granger Anne , Ngô-Muller Valérie , Bleux Christian , Guigon Céline , Pincas Hanna , Magre Solange , Daegelen Dominique , Tixier-Vidal Andrée , Counis Raymond , Laverrière Jean-Noël
Published: November 2003

Previous studies dealing with the mechanisms underlying the tissue-specific and regulated expression of the GnRH receptor (GnRH-R) gene led us to define several cis-acting regulatory sequences in the rat GnRH-R gene promoter. These include functional sites for steroidogenic factor 1, activator protein 1, and motifs related to GATA and LIM homeodomain response elements as demonstrated primarily in transient transfection assays in mouse gonadotrope-derived cell lines. To understand these mechanisms in more depth, we generated transgenic mice bearing the 3.3-kb rat GnRH-R promoter linked to the human placental alkaline phosphatase reporter gene. Here we show that the rat GnRH-R promoter drives the expression of the reporter gene in pituitary cells expressing the LHβ and/or FSHβ subunit but not in TSHβ- or GH-positive cells. Furthermore, the spatial and temporal pattern of the transgene expression during the development of the pituitary was compatible with that characterizing the emergence of the gonadotrope lineage. In particular, transgene expression is colocalized with the expression of the glycoprotein hormone α-subunit at embryonic day 13.5 and with that of steroidogenic factor 1 at later stages of pituitary development. Transgene expression was also found in specific brain areas, such as the lateral septum and the hippocampus. A single promoter is thus capable of directing transcription in highly diverse tissues, raising the question of the different combinations of transcription factors that lead to such a multiple, but nevertheless cell-specific, expressions of the GnRH-R gene.
Novel Action of Activin and Bone Morphogenetic Protein in Regulating Aldosterone Production by Human Adrenocortical Cells
Authors: Suzuki Jiro , Otsuka Fumio , Inagaki Kenichi , Takeda Masaya , Ogura Toshio , Makino Hirofumi
Published: November 2003

We have uncovered a functional bone morphogenetic protein (BMP) and activin system complete with ligands (BMP-6 and activin βA/βB), receptors (activin receptor-like kinase receptors 2, 3, and 4; activin type-II receptor; and BMP type-II receptor), and the binding protein follistatin in the human adrenocortical cell line H295R. Administration of activin and BMP-6 to cultures of H295R cells caused concentration-responsive increases in aldosterone production. The mRNA levels of steroidogenic acute regulatory protein or P450 steroid side-chain cleavage enzyme, the rate-limiting steps of adrenocortical steroidogenesis, were enhanced by activin and BMP-6. Activin and BMP-6 also activated the transcription of steroidogenic acute regulatory protein as well as the late-step steriodogenic enzyme CYP11B2. Activin enhanced ACTH-, forskolin-, or dibutyryl-cAMP- but not angiotensin II (Ang II)-induced aldosterone production, whereas BMP-6 specifically augmented Ang II-induced aldosterone production. Activin and ACTH but not BMP-6 increased cAMP production. Follistatin, which inhibits activin actions by binding, suppressed basal and ACTH-induced aldosterone secretion but failed to affect the Ang II-induced aldosterone level. Furthermore, MAPK signaling appeared to be involved in aldosterone production induced by Ang II and BMP-6 because an inhibitor of MAPK activation, U0126, reduced the level of aldosterone synthesis stimulated by Ang II and BMP-6 but not activin. In addition, Ang II reduced the expression levels of BMP-6 but increased that of activin βB, whereas ACTH had no effect on these levels. Collectively, the present data suggest that activin acts to regulate adrenal aldosterone synthesis predominantly by modulating the ACTH-cAMP-protein kinase A signaling cascade, whereas BMP-6 works primarily by modulating the Ang II-MAPK cascade in human adrenal cortex in an autocrine/paracrine fashion.
Regulation of the Human Cholesterol 7α-Hydroxylase Gene (CYP7A1) by Thyroid Hormone in Transgenic Mice
Authors: Drover Victor A. B. , Agellon Luis B.
Published: November 2003

Thyroid hormones exert significant changes in the metabolism of bile acids. However, in humans, the effect of thyroid hormone on cholesterol 7α-hydroxylase (cyp7a), the rate- controlling enzyme in the classical bile acid biosynthetic pathway, remains poorly understood and has been difficult to study directly in vivo. Previous studies from our laboratory have shown that the activity of the human cholesterol 7α-hydroxylase gene promoter is repressed by T3 in cultured cells. Accordingly, we hypothesized that T3 would negatively regulate human CYP7A1 gene expression in vivo. We tested this hypothesis by inducing hypo- and hyperthyroidism in transgenic mice expressing the human CYP7A1 gene. Hypothyroidism did not affect the abundance of human cyp7a mRNA in transgenic mice. In hyperthyroid male mice, human cyp7a mRNA abundance was decreased. No significant change in cyp7a mRNA abundance was observed in hyperthyroid female mice. Gender differences in the amount of cholesterol and bile acids in gallbladder bile were also observed. The data indicate that thyroid hormone can repress the human CYP7A1 gene in transgenic mice, but this effect is dependent on gender in this in vivo model.
Urocortin II Is Expressed in Human Pregnant Myometrial Cells and Regulates Myosin Light Chain Phosphorylation: Potential Role of the Type-2 Corticotropin-Releasing Hormone Receptor in the Control of Myometrial Contractility
Authors: Karteris Emmanouil , Hillhouse Edward W. , Grammatopoulos Dimitris
Published: November 2003

The family of CRH-related peptides are suggested to play important roles in the control of myometrial contractility during pregnancy and labor. In this study we investigated the expression of urocortin II (UCN II) in human myometrium and its ability to phosphorylate intracellular components that can be involved in modulating myometrial contractility. Using RT-PCR and fluorescent in situ hybridization, we demonstrated that UCN II and type-2 CRH receptor (CRH-R2) mRNAs were expressed in human nonpregnant and pregnant myometrium. Immunofluorescent studies confirmed protein expression of UCN II in human pregnant myometrial cells, whereas chemical cross-linking studies with radiolabeled UCN II confirmed the presence of CRH-R2 sites with an apparent molecular mass of 50 kDa. Treatment of primary human myometrial cells with UCN II to specifically activate CRH-R2 resulted in a dose-dependent increase of myosin light chain (MLC20) phosphorylation. Activation of protein kinase C (PKC) and ERK1/2 was required for the UCN II-induced activation of MLC20, because treatment of myometrial cells with inhibitors of MAPK kinase 1 (U0126) and PKC (bisindolylmaleimide) inhibited the UCN II-induced phosphorylation of MLC20. Furthermore, the UCN II effect on MLC20 was dependent on RhoA translocation to the membrane and subsequent activation of RhoA-associated kinase, as shown by the use of the specific inhibitors exoenzyme C3 and Y27632. Collectively, our data suggest a distinctive role for CRH-R2- specific agonists like UCN II in the control of myometrial contractility during human pregnancy involving sequential activation of PKC, MAPK kinase 1, ERK1/2, RhoA, and RhoA-associated kinase, leading to the MLC20 phosphorylation.
Msx2andTwistcooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault
Authors: Ishii Mamoru , Merrill Amy E. , Chan Yan-Shun , Gitelman Inna , Rice David P. C. , Sucov Henry M. , Maxson Robert E.
Published: November 2003

The flat bones of the vertebrate skull vault develop from two migratory mesenchymal cell populations, the cranial neural crest and paraxial mesoderm. At the onset of skull vault development, these mesenchymal cells emigrate from their sites of origin to positions between the ectoderm and the developing cerebral hemispheres. There they combine, proliferate and differentiate along an osteogenic pathway. Anomalies in skull vault development are relatively common in humans. One such anomaly is familial calvarial foramina, persistent unossified areas within the skull vault. Mutations in MSX2 and TWIST are known to cause calvarial foramina in humans. Little is known of the cellular and developmental processes underlying this defect. Neither is it known whether MSX2 and TWIST function in the same or distinct pathways. We trace the origin of the calvarial foramen defect in Msx2 mutant mice to a group of skeletogenic mesenchyme cells that compose the frontal bone rudiment. We show that this cell population is reduced not because of apoptosis or deficient migration of neural crest-derived precursor cells, but because of defects in its differentiation and proliferation. We demonstrate, in addition, that heterozygous loss of Twist function causes a foramen in the skull vault similar to that caused by loss of Msx2 function. Both the quantity and proliferation of the frontal bone skeletogenic mesenchyme are reduced in Msx2-Twist double mutants compared with individual mutants. Thus Msx2 and Twist cooperate in the control of the differentiation and proliferation of skeletogenic mesenchyme. Molecular epistasis analysis suggests that Msx2 and Twist do not act in tandem to control osteoblast differentiation, but function at the same epistatic level.
Regulation of storage protein gene expression inArabidopsis
Authors: Kroj Thomas , Savino Gil , Valon Christiane , Giraudat Jérôme , Parcy François
Published: November 2003

The expression of seed storage proteins is under tight developmental regulation and represents a powerful model system to study the regulation of gene expression during plant development. In this study, we show that three homologous B3 type transcription factors regulate the model storage protein gene, At2S3, via two distinct mechanisms: FUSCA3 (FUS3) and LEAFY COTYLEDON2 (LEC2) activate the At2S3 promoter in yeast suggesting that they regulate At2S3 by directly binding its promoter; ABSCISIC ACID INSENSITIVE3 (ABI3), however, appears to act more indirectly on At2S3, possibly as a cofactor in an activation complex. In accordance with this, FUS3 and LEC2 were found to act in a partially redundant manner and differently from ABI3 in planta: At2S3expression is reduced to variable and sometimes only moderate extent in fus3 and lec2 single mutants but is completely abolished in the lec2 fus3 double mutant. In addition, we found that FUS3and LEC2 expression patterns, together with an unsuspected regulation of FUS3 by LEC2, enable us to explain the intriguing expression pattern of At2S3 in lec2 or fus3 single mutants. Based on these results, we present a model of At2S3regulation and discuss its implications for other aspects of seed maturation.
Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
Authors: Li Wenmei , Qiao Wenhui , Chen Lin , Xu Xiaoling , Yang Xiao , Li Dan , Li Cuiling , Brodie Steven G. , Meguid Michael M. , Hennighausen Lothar , Deng Chu-Xia
Published: November 2003

Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.
Uncoordinated regulation of stress fibers and focal adhesions by DAP kinase
Authors: Kuo Jean-Cheng , Lin Jia-Ren , Staddon James M. , Hosoya Hiroshi , Chen Ruey-Hwa
Published: November 2003

Death-associated protein kinase (DAP kinase) is a proapoptotic, calcium/calmodulin-dependent serine/threonine kinase. Here, we report that DAP kinase phosphorylates the regulatory light chain of myosin II (MLC) both in vitro and in vivo, and that this phosphorylation occurs preferentially at residue Ser19. In quiescent fibroblasts, DAP kinase stabilizes stress fibers through phosphorylation of MLC, but it is dispensable for the formation of peripheral microfilament bundles. This cytoskeletal effect of DAP kinase occurs before the onset of apoptosis and does not require an intact death domain. In addition, DAP kinase is required for serum-induced stress-fiber formation, which is associated with the upregulation of its catalytic activity. Despite being both sufficient and necessary for the assembly or maintenance of stress fibers, DAP kinase is incapable of stimulating the formation of focal adhesions in quiescent cells. Moreover, it promotes the disassembly of focal adhesions but not stress fibers in cells receiving serum factors. Together, our results identify a novel and unique function of DAP kinase in the uncoupling of stress fibers and focal adhesions. Such uncoupling would lead to a perturbation of the balance between contractile and adhesion forces and subsequent cell detachment, which might contribute to its pro-apoptotic activity.
Residues within the myristoylation motif determine intracellular targeting of the neuronal Ca2+ sensor protein KChIP1 to post-ER transport vesicles and traffic of Kv4 K+ channels
Authors: O'Callaghan Dermott W. , Hasdemir Burcu , Leighton Mark , Burgoyne Robert D.
Published: November 2003

KChIPs (K+ channel interacting proteins) regulate the function of A-type Kv4 potassium channels by modifying channel properties and by increasing their cell surface expression. We have explored factors affecting the localisation of Kv4.2 and the targeting of KChIP1 and other NCS proteins by using GFP-variant fusion proteins expressed in HeLa cells. ECFP-Kv4.2 expressed alone was not retained in the ER but reached the Golgi complex. In cells co-expressing ECFP-Kv4.2 and KChIP1-EYFP, the two proteins were co-localised and were mainly present on the plasma membrane. When KChIP1-EYFP was expressed alone it was instead targeted to punctate structures. This was distinct from the localisation of the NCS proteins NCS-1 and hippocalcin, which were targeted to the trans-Golgi network (TGN) and plasma membrane. The membrane localisation of each NCS protein required myristoylation and minimal myristoylation motifs of hippocalcin or KChIP1 were sufficient to target fusion proteins to either TGN/plasma membrane or to punctate structures. The existence of targeting information within the N-terminal motifs was confirmed by mutagenesis of residues corresponding to three conserved basic amino acids in hippocalcin and NCS-1 at positions 3, 7 and 9. Residues at these positions determined intracellular targeting to the different organelles. Myristoylation and correct targeting of KChIP1 was required for the efficient traffic of ECFP-Kv4.2 to the plasma membrane. Expression of KChIP1(1-11)-EYFP resulted in the formation of enlarged structures that were positive for ERGIC-53 and β-COP. ECFP-Kv4.2 was also accumulated in these structures suggesting that KChIP1(1-11)-EYFP inhibited traffic out of the ERGIC. We suggest that KChIP1 is targeted by its myristoylation motif to post-ER transport vesicles where it could interact with and regulate the traffic of Kv4 channels to the plasma membrane under the influence of localised Ca2+ signals.
A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts Src localization and activity and induces apoptosis in skeletal myotubes
Authors: Smythe Gayle M. , Eby Joshua C. , Disatnik Marie-Helene , Rando Thomas A.
Published: November 2003

Caveolins are membrane proteins that are the major coat proteins of caveolae, specialized lipid rafts in the plasma membrane that serve as scaffolding sites for many signaling complexes. Among the many signaling molecules associated with caveolins are the Src tyrosine kinases, whose activation regulates numerous cellular functions including the balance between cell survival and cell death. Several mutations in the muscle-specific caveolin, caveolin-3, lead to a form of autosomal dominant muscular dystrophy referred to as limb girdle muscular dystrophy type 1C (LGMD-1C). One of these mutations (here termed the `TFT mutation') results in a deletion of a tripeptide (ΔTFT(63-65)) that affects the scaffolding and oligomerization domains of caveolin-3. This mutation causes a 90-95% loss of caveolin-3 protein levels and reduced formation of caveolae in skeletal muscle fibers. However, the effects of this mutation on the specific biochemical processes and cellular functions associated with caveolae have not been elucidated. We demonstrate that the TFT caveolin-3 mutation in post-mitotic skeletal myotubes causes severely reduced localization of caveolin-3 to the plasma membrane and to lipid rafts, and significantly inhibits caveolar function. The TFT mutation reduced the binding of Src to caveolin-3, diminished targeting of Src to lipid rafts, and caused abnormal perinuclear accumulation of Src. Along with these alterations of Src localization and targeting, there was elevated Src activation in myotubes expressing the TFT mutation and an increased incidence of apoptosis in those cells compared with control myotubes. The results of this study demonstrate that caveolin-3 mutations associated with LGMD-1C disrupt normal cellular signal transduction pathways associated with caveolae and cause apoptosis in muscle cells, all of which may reflect pathogenetic pathways that lead to muscle degeneration in these disorders.
Caveosomes and endocytosis of lipid rafts
Authors: Nichols Ben
Published: November 2003

Endocytosis of various endogenous plasma membrane molecules, including signalling receptors, glycosphingolipids and glycosylphosphatidylinositol (GPI)-linked proteins, occurs in the absence of functional clathrin-coated pits. Most of these molecules are found in biochemically defined lipid rafts, which suggests that at least some clathrin-independent endocytosis may be raft specific or raft mediated. However, recent studies of the uptake of raft markers have revealed a diversity of internalization methods. Although lipid rafts may somehow be recognized by endocytic machinery, at this stage the data do not readily fit with the idea of a single raft-specific or raft-dependent endocytic pathway. Many studies report uptake of raft molecules by caveolar endocytosis (defined by sensitivity to cholesterol depletion and to overexpression of a specific mutant of dynamin 2). It is now apparent that this is a highly regulated process, and caveolin 1, one of the characteristic protein components of caveolae, might in fact act to slow or inhibit endocytosis. The molecular details of caveolar endocytosis have yet to be elucidated. Several sources indicate that clathrin-independent uptake to a distinct class of caveolin-1-containing endosome, termed the caveosome, allows different types of endocytic mechanisms to have different functional consequences for the cell. It is likely that there are mechanisms that allow recruitment and targeting of specific molecules to caveosomes.
Self-assembled Monolayers of Spironaphthoxazine–Thioether for UV-controlled Complexation
Authors: Chen Huan , Li Yapeng , Huo Fengwei , Wang Zhiqiang , Zhang Xi
Published: November 2003

We have demonstrated that the self-assembled monolayer (SAM) of spironaphthoxazine-thioether (SNOTE) can complex metal ions based on the complexation property of the open ring form of spironaphthoxazine induced by UV irradiation, and the well-isolated sensing species in SAMs show a kinetic advantage over the closely packed ones.
Efficient Method for the Preparation of Primary, Inverted Secondary and Tertiary Alkyl Carboxylates from Alcohols and Carboxylic Acids by a New Type of Oxidation–Reduction Condensation Using Simple 1,4-Benzoquinone
Authors: Shintou Taichi , Mukaiyama Teruaki
Published: November 2003

A new type of oxidation–reduction condensation using in situ formed alkoxydiphenylphosphines (i.e., diphenylphosphinite esters), easily available 1,4-benzoquionone and carboxylic acids provides a new and efficient method for the preparation of alkyl carboxylates from the corresponding alcohols under mild and neutral conditions. Further, the yields of the corresponding inverted carboxylates were equally high in the case of chiral secondary or tertiary alcohols.
Secondary Prevention of Coronary Heart Disease in the Elderly
Authors: Dornbrook-Lavender Kimberly A , Roth Mary T , Pieper John A
Published: November 2003

OBJECTIVE:

To review relevant literature supporting the use of aspirin, β-blockers, lipid-lowering agents, and angiotensin-converting enzyme (ACE) inhibitors for the secondary prevention of coronary heart disease (CHD) in an elderly patient population aged ≥65 years.

DATA SOURCES:

A MEDLINE search (1990–May 2003) was conducted using the key terms coronary heart disease, secondary prevention and elderly.

STUDY SELECTION AND DATA EXTRACTION:

Primary and tertiary literature relating to the use of aspirin, β-blockers, lipid-lowering agents, and ACE inhibitors in the elderly were reviewed.

DATA SYNTHESIS:

CHD is the leading cause of morbidity and mortality in persons ≥65 years of age, and the use of pharmacologic agents has created a considerable opportunity for reducing recurrent events in those with established disease. This, combined with the aging of the US population, is creating an increase in the number of older adults eligible for secondary prevention. In 2002, the American Heart Association issued a scientific statement on the benefits of specific secondary prevention risk factor interventions in older adults. This article reviews pertinent findings from this statement, along with additional data supporting the use of pharmacologic agents for the secondary prevention of CHD in the elderly.

CONCLUSIONS:

Data suggest that use of aspirin, β-blockers, lipid-lowering agents, and ACE inhibitors are effective in secondary prevention of CHD in individuals aged ≥65 years. This benefit is similar to, and often greater than, that observed in younger patients. We believe that these agents should be prescribed for all elderly patients without contraindications. Ongoing studies and future clinical trials will more clearly elucidate the benefits of secondary prevention of CHD, particularly in persons ≥75 years of age, to determine the magnitude of benefits that can be achieved in this population.
Relationship of Atypical Antipsychotics with Development of Diabetes Mellitus
Authors: Citrome Leslie L , Jaffe Ari B
Published: November 2003

OBJECTIVE:

To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus.

DATA SOURCES:

A MEDLINE search (1990–March 2003) was conducted.

STUDY SELECTION AND DATA EXTRACTION:

The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted.

DATA SYNTHESIS:

Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain.

CONCLUSIONS:

Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity.
The structure of self‐reported emotional experiences: A mixed‐effects Poisson factor model
Authors: Böckenholt Ulf , Kamakura Wagner A. , Wedel Michel
Published: November 2003

Multivariate count data are commonly analysed by using Poisson distributions with varying intensity parameters, resulting in a random‐effects model. In the analysis of a data set on the frequency of different emotion experiences we find that a Poisson model with a single random effect does not yield an adequate fit. An alternative model that requires as many random effects as emotion categories requires high‐dimensional integration and the estimation of a large number of parameters. As a solution to these computational problems, we propose a factor‐analytic Poisson model and show that a two‐dimensional factor model fits the reported data very well. Moreover, it yields a substantively satisfactory solution: one factor describing the degree of pleasantness and unpleasantness of emotions and the other factor describing the activation levels of the emotions. We discuss the incorporation of covariates to facilitate rigorous tests of the random‐effects structure. Marginal maximum likelihood methods lead to straight‐forward estimation of the model, for which goodness‐of‐fit tests are also presented.
Type I errors and power of the parametric bootstrap goodness‐of‐fit test: Full and limited information
Authors: Tollenaar Nikolaj , Mooijaart Ab
Published: November 2003

In sparse tables for categorical data well‐known goodness‐of‐fit statistics are not chi‐square distributed. A consequence is that model selection becomes a problem. It has been suggested that a way out of this problem is the use of the parametric bootstrap. In this paper, the parametric bootstrap goodness‐of‐fit test is studied by means of an extensive simulation study; the Type I error rates and power of this test are studied under several conditions of sparseness. In the presence of sparseness, models were used that were likely to violate the regularity conditions. Besides bootstrapping the goodness‐of‐fit usually used (full information statistics), corrected versions of these statistics and a limited information statistic are bootstrapped. These bootstrap tests were also compared to an asymptotic test using limited information. Results indicate that bootstrapping the usual statistics fails because these tests are too liberal, and that bootstrapping or asymptotically testing the limited information statistic works better with respect to Type I error and outperforms the other statistics by far in terms of statistical power. The properties of all tests are illustrated using categorical Markov models.
Does the ADF fit function decrease when the kurtosis increases?
Authors: Olsson Ulf Henning , Foss Tron , Troye Sigurd V.
Published: November 2003

In this study we demonstrate how the asymptotically distribution‐free (ADF) fit function is affected by (excessive) kurtosis in the observed data. More specifically, we address how different levels of univariate kurtosis affect fit values (and therefore fit indices) for misspecified factor models. By using numerical calculation, we show (for 13 factor models) that the probability limit F0 of F for the ADF fit function decreases considerably as the kurtosis increases. We also give a formal proof that the value of F0 decreases monotonically with the kurtosis for a whole class of structural equation models.
Strategic Foretelling: Communication-Based Antecedents of a Firm's Propensity to Preannounce
Authors: Calantone Roger J. , Schatzel Kim E.
Published: November 2003

The authors examine preannouncements as strategic marketing communications aimed at influencing the perceptions and attitudes of industry stakeholders. The growth of the Internet points to the expanded importance of preannouncements. With an investigation of 265 chief executive officers (CEOs) and presidents from manufacturers of new products, the authors examine the effects of three firm-specific factors (first-mover predisposition, firm information interactivity, and competitive equity building) and one environmental construct (industry dynamism) on a firm's propensity to preannounce its future intended actions. The results indicate that competitive equity building, defined as a firm's tendency to pursue a high-profile leadership position within its industry, is the main driver of a firm's propensity to preannounce. Future directions for research include the development of a normative preannouncement framework and investigation of the role of preannouncements within the context of CEO marketing activities.
Understanding the Customer Base of Service Providers: An Examination of the Differences between Switchers and Stayers
Authors: Ganesh Jaishankar , Arnold Mark J. , Reynolds Kristy E.
Published: November 2003

Creating and maintaining customer loyalty has become a strategic mandate in today's service markets. Recent research suggests that customers differ in their value to a firm, and therefore customer retention and loyalty-building efforts should not necessarily be targeted to all customers of a firm. Given these sentiments, it is becoming increasingly necessary for firms to have a thorough understanding of their customer base. Yet current knowledge is limited in providing insights to firms regarding the differences within their customer base. This research comprises two studies in which the authors examine the differences among internal customer groups in a service industry. As theory suggests and as is empirically validated here, customers who have switched service providers because of dissatisfaction seem to differ significantly from other customer groups in their satisfaction and loyalty behaviors. The findings offer some interesting implications for both marketing theory and practice.
On the Profitability of Long-Life Customers in a Noncontractual Setting: An Empirical Investigation and Implications for Marketing
Authors: Reinartz Werner J. , Kumar V.
Published: November 2003

Relationship marketing emphasizes the need for maintaining long-term customer relationships. It is beneficial, in general, to serve customers over a longer time, especially in a contractual relationship. However, it is not clear whether some of the findings observed in a contractual setting hold good in noncontractual scenarios: relationships between a seller and a buyer that are not governed by a contract or membership. The authors offer four different propositions in this study and subsequently test each one in a noncontractual context. The four propositions relate to whether (1) there exists a strong positive customer lifetime–profitability relationship, (2) profits increase over time, (3) the costs of serving long-life customers are less, and (4) long-life customers pay higher prices. The authors develop arguments both for and against each of the propositions. The data for this study, obtained from a large catalog retailer, cover a three-year window and are recorded on a daily basis. The empirical findings observed in this study challenge all the expectations derived from the literature. Long-life customers are not necessarily profitable customers. The authors develop plausible explanations for findings that go against the available evidence in the literature and identify three indicators through discriminant analysis that can help managers focus their efforts on more profitable customers. The authors draw several marketing implications and acknowledge the limitations of the study.
Strategic Interdependence in Organizations: Deconglomeration and Marketing Strategy
Authors: Varadarajan P. Rajan , Jayachandran Satish , White J. Chris
Published: November 2003

Although strategy exists at multiple levels in a firm (corporate, business, and functional), there is a dearth of research in marketing literature that focuses on the dependency among strategy at different levels. The authors address this issue by examining the relationship between deconglomeration and marketing strategy. Deconglomeration refers to the divestiture behavior of a conglomerate firm and the transformation of its business portfolio from one that is largely composed of several unrelated businesses to one composed of fewer and related businesses. Drawing on multiple theoretical perspectives, the authors propose a conceptual model delineating the environmental and organizational drivers of deconglomeration and its outcomes for marketing. The authors suggest that after deconglomeration, (1) a firm can be expected to be more competitor and customer oriented, (2) multimarket contact with competing firms and seller concentration will increase, (3) businesses retained by the firm will be more innovative and place greater emphasis on advertising compared with sales promotion, and (4) the firm's culture may become more externally oriented. Furthermore, the locus of decision making for marketing strategy may shift more toward senior management levels. In summary, changes in a firm's corporate strategy could lead to significant changes in the marketing strategy of its business units.
Biosafety concerns for shared flow cytometry core facilities
Authors: Schmid Ingrid , Merlin Steven , Perfetto Stephen P.
Published: November 2003

Many researchers who need flow cytometry for their projects have neither sufficient funds nor the work volume to justify the purchase of an analytic cytometer or cell sorter. In shared flow cytometry facilities, costs for instrument purchases, cytometer maintenance, and personnel are pooled to provide economic services for a multitude of users when they are required. Owing to the diverse nature of the samples that are submitted to core facilities, the biohazard potential of the samples can vary dramatically. For the safety of facility personnel and users, it is critical that information about hazards contained in the samples be transmitted to instrument operators before flow cytometry experiments are started. During 1999 the former Biosafety Committee of the International Society for Analytical Cytology formulated a framework biosafety questionnaire for shared facilities designed to request information about the hazard potential of experimental samples from investigators who wish to use the facility. In this report we review safety issues that are pertinent to flow cytometry core facilities by discussing the individual components of this biosafety questionnaire. Cytometry Part A 56A:113–119, 2003. © 2003 Wiley‐Liss, Inc.
Lectinocytochemical detection of apoptotic murine leukemia L1210 cells
Authors: Bilyy R. O. , Stoika R. S.
Published: November 2003

Background

Various cytomorphologic and biochemical markers of apoptosis are found in different compartments (plasma membrane, cytoplasm, nucleus, and mitochondria) of target cells. Although the plasma membrane is an easily accessible cellular compartment, relatively little is known about its changes during apoptosis. We investigated whether specific changes in the expression of plasma membrane glycoproteins take place during apoptosis and whether these changes could be used for a quantitative estimation of apoptosis.

Methods

Lectin cytochemical study of normal and apoptotic murine leukemia cells of the L1210 line was done. Horseradish peroxidase–labeled Laburnum anagyroides bark agglutinin, Phaseolus vulgaris agglutinin, Pisum sativum lectin (PSL), Ricinus communis agglutinin (RCA‐120; 120 kDa), Solanum tuberosum agglutinin, Triticum vulgaris lectin (wheat germ agglutinin), Viscum album agglutinin, Canavalia ensiformis lectin (concanavalin A), and Helix pomatia lectin were used to compare specific glycoprotein expressions in normal and apoptotic murine leukemia cells of the L1210 line sensitive (L1210) and resistant (L1210R) to apoptosis induction by cisplatin.

Results

The data demonstrated significantly increased binding of α‐D‐mannose–specific PSL lectin (P < 0.01) and β‐D‐galactose–specific RCA‐120 lectin (P < 0.001) by the apoptotic cells of the L1210 and L1210R lines in comparison with the intact cells. That binding was shown to be specific because it was blocked by the corresponding inhibitory sugars.

Conclusions

Lectins specific to α‐D‐mannose (PSL) and β‐D‐galactose (RCA‐120) can be used to distinguish between native and apoptotic murine leukemia L1210 cells and to quantitatively estimate apoptosis in a population of these cells. Cytometry Part A 56A:89–95, 2003. © 2003 Wiley‐Liss, Inc.
Stability of the breakoff point in a high‐speed cell sorter
Authors: Petersen Timothy W. , van den Engh Ger
Published: November 2003

Background

High‐speed jet‐in‐air cytometric sorting requires knowledge of the time it takes a particle to travel from the laser to the point where the jet breaks into droplets. Variations in this breakoff time will result in poorer yields and poorer sort purities.

Methods

This work examined the physical mechanisms that lead to the break up of the jet into droplets and calculated the stability of the droplet breakoff time relative to physical parameters, which govern the behavior of the jet.

Results

We derived the variations in the breakoff time and found that small variations in the drive frequency, temperature, pressure, and drive amplitude can lead to correspondingly large changes in the breakoff time. We found explicitly that the time it takes the jet to break up is not necessarily correlated with the distance to the breakoff point.

Conclusions

Many high‐speed cell sorters use active means to control the breakoff time. A common method to monitor the breakoff time is to visually monitor the breakoff point. This technique in fact may decrease the sorting purity and efficiency by inadvertently correcting for breakoff time variations. We show explicitly the breakoff time's dependence on a number of physical parameters that can be monitored to increase the stability of the breakoff time. Cytometry Part A 56A:63–70, 2003. © 2003 Wiley‐Liss, Inc.
Development of a photoaffinity label for respiratory syncytial virus inhibitors
Authors: Dischino Douglas D. , Cianci Christopher W. , Civiello Rita , Krystal Mark , Meanwell Nicholas A. , Morimoto Hiromi , Williams Philip G. , Yu Kuo‐Long
Published: November 2003

The syntheses of tritiated and radio‐iodinated respiratory syncytial virus inhibitor photoaffinity labels are reported. 3H‐1‐Isopropyl‐3‐(1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)‐ethyl]‐1H‐benzoimidazol‐2‐yl)methyl)‐1,3‐dihydrobenzoimid‐azol‐2‐one (1), was prepared in two steps by the initial tritiation of N‐isopropenyl‐2‐benzimidazolone followed by coupling to 2‐chloromethyl‐1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)ethyl]‐1H‐benzoimidazole. The mono and diiodo‐radio‐iodinated derivatives of 1‐(4‐hydroxybenzyl)‐3‐(1‐[2‐(3‐methyl‐3H‐diazirin‐3‐yl)‐ethyl]‐2,3‐dihydro‐1H‐benzo‐imidazol‐2‐ylmethyl)‐1,3‐dihydro‐benzoimidazol‐2‐one (2, 3), were prepared by the radio‐iodination of the corresponding phenol with Na125I and iodogen. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and evaluation of tritium labelled 10‐methylgalanthamine iodide: a novel compound to examine the mechanism of interaction of galanthamine derivatives with the nicotinic acetylcholine receptors
Authors: Schildan Andreas , Schirrmacher Ralf , Schirrmacher Esther , Samochocki Marek , Christner Claudia , Maelicke Alfred , Rösch Frank
Published: November 2003

A new promising galanthamine derivative, 10‐[3H]methylgalanthamine iodide, was synthesized for binding studies to nicotinic acetylcholine receptors expressed in Torpedo electric ray electroplaques. Galanthamine was reacted with [3H]methyl iodide to yield 10‐[3H]methylgalanthamine iodide with a radiochemical yield of >70% and a specific activity of 32 Ci/mmol after purification via solid phase extraction. To test the ligand properties of the radioligand, calcium imaging and electrophysiology of the non‐radioactive analogue were performed to obtain an EC50 of 270 nM, a Hill coefficient of 1.9 and the induced cell current. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis of [18F]Fluoroclofilium as a potential cardiac imaging agent for PET studies
Authors: Yu K. H. , Kim Y. S. , Kim S. W. , Park J. H. , Yang S. D. , Herdering W. , Knoechel A.
Published: November 2003

N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐[18F]fluoroheptylammonium ([18F]‐fluoroclofilium) has been prepared as a potential cardiac imaging agent. For the synthesis of this radiolabelled ammonium salt, its tosyloxylated analogue was prepared as a precursor, and the non‐radioactive fluorine analogue was synthesized as a reference compound. Radiofluorination was achieved by the treatment of N‐4‐(4‐chlorophenyl)butyl‐N,N‐diethyl‐7‐(p‐toluenesulfonyloxy)heptylammonium p‐toluenesulfonate with 18F− in the presence of Kryptofix‐2.2.2 in acetonitrile. Copyright © 2003 John Wiley & Sons, Ltd.
Hierarchic finite element bases on unstructured tetrahedral meshes
Authors: Ainsworth Mark , Coyle Joe
Published: November 2003

The problem of constructing hierarchic bases for finite element discretization of the spaces H1, H(curl), H(div) and L2 on tetrahedral elements is addressed. A simple and efficient approach to ensuring conformity of the approximations across element interfaces is described. Hierarchic bases of arbitrary polynomial order are presented. It is shown how these may be used to construct finite element approximations of arbitrary, non‐uniform, local order approximation on unstructured meshes of curvilinear tetrahedral elements. Copyright © 2003 John Wiley & Sons, Ltd.
A 4‐node assumed strain quasi‐conforming shell element with 6 degrees of freedom
Authors: Kim K. D. , Lomboy G. R. , Voyiadjis G. Z.
Published: November 2003

Quasi‐conforming formulations of 4‐node stress‐resultant shell elements are presented. The element formulations use interrelated displacement–rotation interpolations. The formulation also includes drilling degrees of freedom, which improves membrane behavior and allows the modeling of stiffened plates and shells. The proposed treatment for bending provides very good results in the 4‐node shell element. The stiffness matrices for the present elements are explicitly expressed and the stresses are taken accurately at the nodal points. Compared to elements using Gauss integration, where the stresses are most accurate at the integration points, the extrapolation procedure needed for post‐processing is eliminated in the present shell element. A lot of numerical tests were carried out for the validation of the present 4‐node shell element and the results are in good agreement with references. Copyright © 2003 John Wiley & Sons, Ltd.
Error surface calculations on the parameters defining oxygen depth profile models fitted to ARXPS data obtained from polystyrene exposed to an oxygen/helium plasma
Authors: Paynter R. W.
Published: November 2003

Error surfaces are calculated for the fitting of concentration–depth profiles to angle‐resolved x‐ray photoelectron spectroscopy (ARXPS) data. The shapes of the error surfaces indicate that model parameters related to composition (especially at the very surface of the sample) are well constrained by the data, whereas parameters related to depth have a less significant impact on the fit. It is then shown that certain parameters in the different depth profile models employed are highly correlated and that the different models convey essentially the same information in different ways. Finally, a compromise profile definition is proposed for the fitting of constrained but flexible depth profiles to ARXPS data. Copyright © 2003 John Wiley & Sons, Ltd.
Detection of chemical threat agents in drinking water by an early warning real‐time biomonitor
Authors: Green U. , Kremer J. H. , Zillmer M. , Moldaenke C.
Published: November 2003

Having a safe water supply for civilian organizations and military personnel is an important objective to avoid toxic contamination of civilians and soldiers. Chemical warfare (CW) agents, especially organophosphorous nerve compounds, are the most toxic of known chemical agents. The Daphnia Toximeter system is a continuously working test system that uses Daphnia magna as a sensitive organism for monitoring drinking water. Both small doses (allowable for short‐term water ingestion) and graduated higher concentrations induced toxic reactions in the Daphnia Toximeter system, leading to alarms sounding. The system is sensitive to a wide range of CW agents and their hydrolysis products. Concentrations below acute human toxicity can be discovered in a very short time, with the actual time depending on the concentrations applied. In every case alarms were triggered within 2 h at concentrations in water low enough for that water to be allowed for use as drinking water in exceptional conditions. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 368–374, 2003.
Acute CO2 tolerance during the early developmental stages of four marine teleosts
Authors: Kikkawa T. , Ishimatsu A. , Kita J.
Published: November 2003

Ocean sequestration of CO2 is proposed as a possible measure to mitigate climate changes caused by increasing atmospheric concentrations of the gas, but its impact on the marine ecosystem is unknown. We investigated the acute lethal effect of CO2 during the early developmental stages of four marine teleosts: red sea bream (Pagrus major), Japanese whiting (Sillago japonica), Japanese flounder (Paralichthys olivaceus), and eastern little tuna (Euthynnus affinis). The percentages of larvae that hatched and survived were not affected by exposure to water with a PCO2 of 1.0 kPa (= 7.5 mmHg) within 24 h. Median lethal PCO2 values for a 360‐min exposure were 1.4 kPa (cleavage), 5.1 kPa (embryo), 7.3 kPa (preflexion), 4.2 kPa (flexion), 4.6 kPa (postflexion), and 2.5 kPa (juvenile) for red sea bream; 2.4 kPa (cleavage), 4.9 kPa (embryo), 5.9 kPa (preflexion), 6.1 kPa (flexion), 4.1 kPa (postflexion), and 2.7 kPa (juvenile) for Japanese whiting; 2.8 kPa (cleavage) and > 7.0 kPa (young) for Japanese flounder; and 11.8 kPa (cleavage) for eastern little tuna. Red sea bream and Japanese whiting of all ontogenetic stages had similar susceptibilities to CO2: the most susceptible stages were cleavage and juvenile, whereas the most tolerant stages were preflexion and flexion. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 375–382, 2003