Subtype-selective noncompetitive or competitive inhibition of human alpha(1)-adrenergic receptors by rho-TIA

The 19-amino acid conopeptide (rho-TIA) was shown previously to antagonize noncompetitively alpha(1B)-adrenergic receptors (ARs). Because this is the first peptide ligand for these receptors, we compared its interactions with the three recombinant human alpha(1)-AR subtypes (alpha(1A), alpha(1B), and alpha(1D)). Radioligand binding assays showed that rho-TIA was 10-fold selective for human alpha(1B)- over alpha(1A)- and alpha(1D)-ARs. As observed with hamster alpha(1B)-ARs, rho-TIA decreased the number of binding sites (B-max) for human alpha(1B)-ARs without changing affinity (K-D), and this inhibition was unaffected by the length of incubation but was reversed by washing. However, rho-TIA had opposite effects at human alpha(1A)-ARs and alpha(1D)-ARs, decreasing KD without changing Bmax, suggesting it acts competitively at these subtypes. rho-TIA reduced maximal NE-stimulated [H-3] inositol phosphate formation in HEK293 cells expressing human alpha(1B)-ARs but competitively inhibited responses in cells expressing alpha(1A)- or alpha(1D)-ARs. Truncation mutants showed that the amino-terminal domains of alpha(1B)- or alpha(1D)-ARs are not involved in interaction with rho-TIA. Alanine-scanning mutagenesis of rho-TIA showed F18A had an increased selectivity for alpha(1B)-ARs, and F18N also increased subtype selectivity. I8A had a slightly reduced potency at alpha(1B)-ARs and was found to be a competitive, rather than noncompetitive, inhibitor in both radioligand and functional assays. Thus rho-TIA noncompetitively inhibits alpha(1B)-ARs but competitively inhibits the other two subtypes, and this selectivity can be increased by mutation. These differential interactions do not involve the receptor amino termini and are not because of the charged nature of the peptide, and isoleucine 8 is critical for its noncompetitive inhibition at alpha(1B)-ARs.

Exploring the role of market learning capability in competitive strategy

It has been argued that a firm's capacity to learn from its market is a source of both innovation and competitive advantage. However, past research has failed to conceptualize market-focused learning activity as a capability having the potential to contribute to competitive advantage. Prior innovation research has been biased toward technological innovation. However, there is evidence to suggest that both technological and non-technological innovations contribute to competitive advantage reflecting the need for a broader conceptualization of the innovation construct. Past research has also overlooked the critical role of entrepreneurship in the capability building process. Competitive advantage has been predominantly measured in terms of financial indicators of performance. In general, the literature reflects the need for comprehensive measures of organizational innovation and competitive advantage. This paper examines the role of market-focused learning capability in organizational innovation-based competitive strategy. The paper contributes to the strategic marketing theory by developing and refining measures of entrepreneurship, market-focused learning capability, organizational innovation and sustained competitive advantage, testing relationships among these constructs.

Quantitation of alternatively spliced NMDA receptor NR1 isoform mRNA transcripts in human brain by competitive RT-PCR

The N-methyl-D-aspartate (NMDA)-selective subtype of ionotropic glutamate receptor is of importance in neuronal differentiation and synapse consolidation, activity-dependent forms of synaptic plasticity, and excitatory amino acid-mediated neuronal toxicity [Neurosci. Res. Program, Bull. 19 (1981) 1; Lab. Invest. 68 (1993) 372]. NMDA receptors exist in vivo as tetrameric or pentameric complexes comprising proteins from two families of homologous subunits, designated NR1 and NR2(A-D) [Biochem. Biophys. Res. Commun. 185 (1992) 826]. The gene coding for the human NR1 subunit (hNR1) is composed of 21 exons, three of which (4, 20 and 21) can be differentially spliced to generate a total of eight distinct subunit variants. We detail here a competitive RT-PCR (cRT-PCR) protocol to quantify endogenous levels of hNR1 splice variants in autopsied human brain. Quantitation of each hNR1 splice variant is performed using standard curve methodology in which a known amount of synthetic ribonucleic acid competitor (internal standard) is co-amplified against total RNA. This method can be used for the quantitation of hNR1 mRNA levels in response to acute or chronic disease states, in particular in the glutamatergic-associated neuronal loss observed in Alzheimer's disease [J. Neurochem. 78 (2001) 175]. Furthermore, alterations in hNR1 mRNA expression may be reflected at the translational level, resulting in functional changes in the NMDA receptor. (C) 2003 Elsevier Science B.V. All rights reserved.

Quantitation of human brain GABAA receptor isoforms by competitive RT-PCR

We have developed a competitive RT-PCR assay, adapted from Lewohl et al. [Brain Res. Brain Res. Protoc. 1 (1997) 347]. for the quantitation of GABA, receptor beta isoforms in human brain using an internal standard that shares high sequence homology to the targets. The internal standard is identical to the beta(1) sequence except for a 61 bp deletion and the incorporation of a Hind III restriction enzyme site. Unlike traditional competitive RT-PCR, which requires a range of internal standard concentrations to be titrated against a constant amount of unknown, this method relies on a standard curve for quantitation of each sample and thus permits increased sample throughput. This method is suitable for the quantitation of beta(1), beta(2) and beta(3) isoforms of the GABA(A) receptor in human alcoholic and control brain. (C) 2003 Elsevier Science B.V. All rights reserved.

Exploring the characteristics of the market-driven firms and antecedents to sustained competitive advantage

During the last few decades, identifying and examining the characteristics of market-driven firms have been a dominant theme in strategic marketing research. It has been argued that market-driven firms are superior in their market sensing and customer linking capabilities, enabling market-driven firms to outperform their competitors. This paper reports the findings of a study that examines the role market-focused learning capability and marketing capability in innovation-based competitive strategy on sustainable competitive advantage. The findings indicate that entrepreneurship is an important factor in sustained competitive advantage (SCA) and while market-focused learning capability leads to higher degrees of innovation, marketing capability enables SCA. (C) 2003 Elsevier Inc. All rights reserved.

Competitive advantage in public-sector organizations: explaining the public good/sustainable competitive advantage paradox

Resource-based views of the firm and in particular Kay's (Why Firms Succeed. Oxford: Oxford Univ. Press, 1995) model of sustainable competitive advantage have been used to advance an understanding of differences in the competitive advantage of private-sector firms. We extend the analysis to a public-sector firm where its major purpose includes engaging in public good by giving away its knowledge base and services. The case highlights the paradox that many public-sector organizations face in simultaneously pursuing public good and sustainable competitive advantage. While Kay's model is applicable for understanding intergovernmental agency competition, we find it necessary to incorporate resource dependency theory to address the paradox. Implications for theory and practice are provided. (C) 2002 Elsevier Inc. All rights reseved.

“Suffragettes in Satin Shorts”? Gender and Competitive Boxing

This study is an empirical and theoretical contribution to the burgeoning literature on gender and competitive boxing. By using Connell's concepts of labor, power, cathexis, and representation and a combination of content and semiotic analysis, interviews, and observations, we argue that competitive boxing can be studied productively as a paradoxical gender regime that simultaneously enables and constrains how women do gender. On one hand, the sport encourages individual women to display physical aggression when such behavior traditionally has been deemed the antithesis of femininity. Some feminists argue that this form of physical feminism enables women to transcend essentialist discourses that restrict their corporeal power. On the other hand, women boxers in general also encounter resistance to their aspirations. For example, they are still positioned by essentialist discourses about both their bodies and capacity to develop the requisite form of controlled aggression. Strongly gendered links between bodily labor and bodily capital also mean that women have less access to resources than do men and, consequently, fewer opportunities to develop their pugilistic capital. We also maintain that competitive women boxers are implicated in a body project that tends to replicate sporting practices that some feminists and pro-feminists argue are damaging to both men and women.

Genetic algorithm-based spinning reserve dispatching in a competitive electricity market

Power systems rely greatly on ancillary services in maintaining operation security. As one of the most important ancillary services, spinning reserve must be provided effectively in the deregulated market environment. This paper focuses on the design of an integrated market for both electricity and spinning reserve service with particular emphasis on coordinated dispatch of bulk power and spinning reserve services. A new market dispatching mechanism has been developed to minimize the ISO's total payment while ensuring system security. Genetic algorithms are used in the finding of the global optimal solutions for this dispatching problem. Case studies and corresponding analyses haw been carried out to demonstrate and discuss the efficiency and usefulness of the proposed market.