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Managers face many challenges as they bring breakthrough products to market. Increasing pressures for short-term returns often make these longer-term, breakthrough product development projects less attractive. At the same time, the array of external sourcing options available to managers has grown dramatically over the last decade, allowing firms to outsource more and more of their core processes. Taken together, managers often find it appealing to minimize their internal exposure to breakthrough projects, instead choosing to either focus on incremental projects (with quicker, more certain paybacks), or to outsource the high risk elements of these breakthrough projects. Although outsourcing decreases risk, it also allows other firms to develop critical expertise and competence. As such, there is an increasing need for strategies that help firms build new core competencies as they move these breakthrough projects forward. Significant gaps exist in understanding what kinds of competencies emerge and how to manage them in the context of breakthrough product development. As such, the primary objective of this study is to explore and document the development and management of these competencies within the context of materials processing firms undergoing breakthrough innovation. Utilizing a multi-case perspective allows for the delineation of common elements within these domains that provided their respective firms advantage. The findings of this study are put forth as propositions and support the notion that managers need to be cognizant of three domains of competencies (market, technology, and integrative) (Coates and McDermott, 2002; Danneels, 2002), that emerge from breakthrough innovations

Background & Aims: Stimulation of gamma-aminobutyric acid B metabotropic receptors (GBRs) by baclofen reduces the incidence of transient lower esophageal sphincter (LES) relaxations. The GBR effect may be a result of a central site of action in the dorsal vagal complex, where upper gastrointestinal vagal reflexes are integrated. Therefore, we first localized GBR immunostaining in the dorsal vagal complex. Next, we tested the hypothesis that baclofen modulates LES motor tone via GBR expressed by vagal efferent neurons. Methods: An antibody against the human GBR1b isoform was characterized and used for immunocytochemistry in rats and ferrets. Functional studies involved microinjection of L-glutamate into the caudal dorsal motor nucleus of the vagus to evoke an LES relaxation in decerebrate unanesthetized ferrets. Results: In both species, GBR1b was expressed in preganglionic motor neurons and, in ferrets, the receptor was highly expressed in identified LES-projecting preganglionic neurons. GBR1b immunostaining was also pronounced in the subnucleus centralis of the nucleus tractus solitarius. This distribution implicates GBR in control of the esophageal phase of swallowing at the level of the central program generator. In functional studies, centrally evoked LES relaxation (−73% ± 8% mm Hg) was significantly attenuated after 7 μmol/kg intravenous baclofen (−37% ± 10%; N=5). Conclusions: These data all suggest that GBR agonists inhibit LES relaxation via a site of action associated with vagal motor outflow to the LES. GASTROENTEROLOGY 2001;120:1749-1762

Technology is playing an increasingly important role in many service industries. However, a survey of the existing classification systems of services shows that they are not designed specifically for the management of technology in services, and, thus, fall short when applied to such an environment. This paper describes and provides illustrations of a new framework which is useful for technology management in the service sector. The framework focuses on managing according to where the value is added in the service: in the technology (knowledge-embedded) or in the worker him/herself (knowledge-based). Additionally, the extent to which the service has a product component is also argued to be critical to the successful management of technology.

Cyanobacterial toxins, especially the microcystins (MCYST), are found in eutrophied waters throughout the world. These toxins cause hepatocyte damage by inhibiting protein phosphatases 1 and 2A, resulting in hyperphosphorylation of cytoskeletal proteins. Acute intoxication of animals and humans has been reported following MCYST exposure. Okadaic acid, a marine biotoxin, has a similar mechanism of action to MCYST and has been shown to cause apoptosis, a form of programmed cell death, in a variety of cell types. In this study, primary rat hepatocytes (in suspension and monolayer culture), human fibroblasts, human endothelial cells, human epithelial cells, and rat promyelocytes were observed following treatment with MCYST for morphological and biochemical changes typical of apoptosis. Hepatocytes underwent cell membrane blebbing, cell shrinkage, organelle redistribution, and chromatin condensation as early as 30 min following MCYST application (0.8 microM). Other cell types treated with MCYST (100 microM) also showed these morphological changes, but required a longer period of treatment. DNA fragmentation and "ladder" formation occurred in most cell types exposed to MCYST. These observations demonstrate that MCYST causes apoptosis in a variety of mammalian cells.

The development of reliable, sensitive immunoassay techniques for detection of microcystins in water is becoming increasingly important. We have developed an enzyme-linked immunosorbent assay (ELISA) potentially able to detect microcystins at concentrations as low as 95 pg microcystin/ml water. The procedure uses antibodies extracted from the eggs of immunized chickens, eliminating the need to collect blood from laboratory rabbits. The antibody is able to recognize microcystin-LR, and -RR, and may recognize other forms of microcystin. The newly developed ELISA technique was utilized to measure the amount of microcystin in waters of northeastern Wisconsin. Of the water samples analyzed, 87% contained measurable amounts of microcystin (0.2-200 ng/ml). Organisms of the genus Microcystis were identified most frequently from microcystin-containing waters. The distribution of microcystin-producing cyanobacterial strains was apparently random throughout the sampling area.

Acyloxyacyl hydrolase, a lysosomal enzyme that deacylates and thus detoxifies lipopolysaccharide (endotoxin) has been identified in bovine peripheral blood and milk neutrophils. Enzymatic activity increases on a per neutrophil basis during cases of experimental Escherichia coli mastitis. The objective of this study was to quantify acyloxyacyl hydrolase activity from milk neutrophils collected from mammary glands naturally infected with a variety of bacteria. Acyloxyacyl hydrolase activity was detectable in milk neutrophils isolated from cases of both Gram-negative and Gram-positive bacterial infections, with highest activities found in milk neutrophils from glands infected with organisms known to cause the most severe forms of mastitis. In addition, acyloxyacyl hydrolase activity was inhibited to varying degrees in mastitic milk by a nonprotein inhibitory substance. Nonenzymatic deacylation of endotoxin also occurred in mastitic milk, but to a lesser degree than enzymatic deacylation. Nonenzymatic deacylation of endotoxin was not found to occur in clinically normal milk. Severity of coliform mastitis in individual cows may be dependent in part on the interaction of endotoxin with milk neutrophil acyloxyacyl hydrolase activity, inhibition of acyloxyacyl hydrolase activity by an inhibitory substance, and the inherent ability of milk to deacylate endotoxin nonenzymatically.

Summary form only as given. This paper proposes a new conceptual approach in investigating the implementation of advanced manufacturing technology (AMT). This approach considers underlying implementation processes to provide theoretical explanations for hypothesized relationships between organizational variables such as culture and success in AMT implementation.