bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fuzzy Front End of New Product Development for Discontinuous Innovations: A Theoretical Model
Authors: Reid Susan E. , De Brentani Ulrike 
Published: April 2004

The fuzzy front end of the new product development (NPD) process, the time and activity prior to an organization's first screen of a new product idea, is the root of success for firms involved with discontinuous new product innovation. Yet understanding the fuzzy front‐end process has been a challenge for academics and organizations alike. While approaches to handling the fuzzy front end have been suggested in the literature, these tend to be relevant largely for incremental new product situations where organizations are aware of and are involved in the NPD process from the project's beginning. For incremental new products, structured problems or opportunities typically are laid out at the organizational level and are directed to individuals for information gathering. In the case of discontinuous innovations, however, we propose that the process works in the opposite direction—that is, that the timing and likelihood of organizational‐level involvement is more likely to be at the discretion of individuals. Such individuals perform a boundary‐spanning function by identifying and by understanding emerging patterns in the environment, with little or no direction from the organization. Often, these same individuals also act as gatekeepers by deciding on the value to the organization of externally derived information, as well as whether such information will be shared. Consequently for discontinuous innovations, information search and related problems/opportunities are unstructured and are at the individual level during the fuzzy front end. As such, the direction of initial decisions about new environmental information tends to be inward, toward the corporate decision‐making level, rather than the other way around.In order to cope with the special and complex nature of decisions made at the fuzzy front end of NPD for discontinuous innovations, this process is detailed as a series of decisions occurring over three proposed interfaces: boundary, gatekeeping, and project. The difference between each interface lies in the nature of the decisions made: At the boundary and gatekeeping interfaces, the primary impetus is individual‐level decision‐making; at the project interface, decisions occur at the organizational level. By articulating these processes in the form of a model, we achieve two objectives: (1) We outline a more detailed and comprehensive approach to understanding the nature of the front‐end decision making process for discontinuous innovations; and (2) we detail specific propositions for future research on each stage of the process.
Adaptation of the brucellae to their intracellular niche
Authors: Roop R. Martin , Bellaire Bryan H. , Valderas Michelle Wright , Cardelli James A. 
Published: April 2004

SummaryMembers of the bacterial genus Brucella are facultative intracellular pathogens that reside predominantly within membrane‐bound compartments within two host cell types, macrophages and placental trophoblasts. Within macrophages, the brucellae route themselves to an intracellular compartment that is favourable for survival and replication, and they also appear to be well‐adapted from a physiological standpoint to withstand the environmental conditions encountered during prolonged residence in this intracellular niche. Much less is known about the interactions of the Brucella with placental trophoblasts, but experimental evidence suggests that these bacteria use an iron acquisition system to support extensive intracellular replication within these host cells that is not required for survival and replication in host macrophages. Thus, it appears that the brucellae rely upon the products of distinct subsets of genes to adapt successfully to the environmental conditions encountered within the two cell types within which they reside in their mammalian hosts.
Staphylococcal NreB: an O2‐sensing histidine protein kinase with an O2‐labile iron–sulphur cluster of the FNR type
Authors: Kamps Annegret , Achebach Stephanie , Fedtke Iris , Unden Gottfried , Götz Friedrich 
Published: April 2004

SummaryThe nreABC (nitrogen regulation) operon encodes a new staphylococcal two‐component regulatory system that controls dissimilatory nitrate/nitrite reduction in response to oxygen. Unlike other two‐component sensors NreB is a cytosolic protein with four N‐terminal cysteine residues. It was shown that both the NreB–cysteine cluster and Fe ions are required for function. Isolated NreB was converted to the active form by incubation with cysteine desulphurase, ferrous ions and cysteine. This activation is typical for FeS‐containing proteins and was reversed by oxygen. During reconstitution an absorption band at 420 nm and a yellow‐brownish colour (typical for an FNR‐type iron–sulphur cluster formation) developed. After alkylation of thiol groups in NreB and in the cysteine mutant NreB(C62S) almost no iron–sulphur cluster was incorporated; both findings corroborated the importance of the cysteine residues. Comparison of the kinase activity of (i) the reconstituted (ii) the unreconstituted, and (iii) the unreconstituted and deferrated NreB–His indicated that NreB kinase activity depended on iron availability and was greatly enhanced by reconstitution. NreB is the first direct oxygen‐sensing protein described in staphylococci so far. Reconstituted NreB contains 4–8 acid‐labile Fe and sulphide ions per NreB which is in agreement with the presence of 1–2 iron–sulphur [4Fe‐4S]2+ clusters of the FNR‐type. Unlike FNR, NreB does not act directly as transcriptional activator, but transfers the phosphoryl group to the response regulator NreC.
Use of arthropods for the evaluation of the olive‐orchard management regimes
Authors: Ruano Francisca , Lozano Carlos , Garcia Pedro , Peña Aranzazu , Tinaut Alberto , Pascual Felipe , Campos Mercedes 
Published: April 2004

Abstract  1 The presence and abundance of arthropods were compared in three olive orchards under organic, integrated and conventional management regimes. In each olive orchard, trees were sampled in the canopy by beating branches and soil arthropods by placing pitfall traps. Contrary to expectations, the highest abundance of arthropods occurred in the integrated management orchard. The most abundant groups were Formicidae and the species Euphyllura olivinae (Homoptera: Psyllidae).2 Canopies and the soil under the tree canopy (interior soil) were selected as the most informative sites for sampling. The months with the strongest differences were May, June and July, especially June. In the canopy, Araneae, Coleoptera, Diptera, Heteroptera, Hymenoptera, Homoptera, Lepidoptera, Neuroptera and Thysanoptera were the most abundant, and showed significant differences in abundance among orchards with different management regimes. Moreover, in the canopies, Coleoptera and Lepidoptera showed a seasonal pattern of abundance and consistent significant differences between the organic orchard vs. the integrated and conventional ones in both years of study. In the soil, 12 orders showed significant differences in abundance among management regimes at some point of the sampling season.3 In a search for biological indicators that could help to distinguish between management regimes, a discriminant analysis applied to the data indicated that only the samples from the canopy were classified according to their management regime in a consistent way over time. The groups selected by the analysis to establish differences among management regimes were Coleoptera, Diptera, Heteroptera, Lepidoptera and Thysanoptera. The analysis applied to compare organic vs. non‐organic olive orchards, again identified Coleoptera and Lepidoptera as suitable groups. The results suggest that these two orders are potential bioindicators to distinguish, in a simple way, organic olive orchards from non‐organic ones.
Dispersal patterns and chromatic response of Scaphoideus titanus Ball (Homoptera Cicadellidae), vector of the phytoplasma agent of grapevine flavescence dorée
Authors: Lessio Federico , Alma Alberto 
Published: April 2004

Abstract  1 Scaphoideus titanus Ball, a nearctic leafhopper introduced into Europe in the 1950s, is known to be the vector of the phytoplasma agent of flavescence dorée (FD), a persistent disease of grapevine. Knowledge of its dispersal patterns is thus very important to prevent disease outbreaks.2 Yellow sticky traps were used to study the seasonal flight activity of S. titanus, its vertical flight, its movement outside the vineyard and the influence of plant density. Sticky traps of different colours (yellow, red, blue, and white) were also compared. The behaviour of males and females was tested for all those conditions.3 Abundance was greater in normal than in low plant density conditions, and a positive relationship was found between number of plants per square metre and presence of S. titanus. Leafhoppers did not appear capable of spreading significantly outside a vineyard. Few individuals were trapped above the canopy. Red sticky traps caught more individuals than white, yellow or blue, with the latter showing a poor attractiveness. Sex ratio was almost always male biased.4 Scaphoideus titanus is monophagous and appears incapable of great dispersal away from its host plant, and females are less likely to fly than males. Further studies on the influence of different factors on the behaviour of this leafhopper are suggested.
Expression of an 11 kDa methionine‐rich delta‐zein in transgenic soybean results in the formation of two types of novel protein bodies in transitional cells situated between the vascular tissue and storage parenchyma cells
Authors: Kim Won‐Seok , Krishnan Hari B. 
Published: April 2004

SummarySoybean (Glycine max (L.) Merr.) is an important protein source in human diets and animal feeds. The sulphur content of soybean seed proteins, however, is not optimal for ration formulations. Thus, increasing the methionine and cysteine content of soybean seed proteins would enhance the nutritional quality of this widely utilized legume. We have earlier reported the isolation of an 11 kDa δ‐zein protein rich in methionine from the endosperm of the maize (Zea mays L.) inbred line W23a1 [Kim, W.‐S. and Krishnan, H.B. (2003) Allelic variation and differential expression of methionine‐rich‐δ‐zeins in maize inbred lines B73 and W23a1. Planta, 217, 66–74]. Using Agrobacterium‐mediated transformation, a construct consisting of the coding region of the cloned δ‐zein gene under regulation of the β‐conglycinin α′‐promoter was introduced into the soybean genome. The 11 kDa δ‐zein gene was expressed in the seeds of transgenic soybeans, although low‐level expression was also detected in the leaves. In situ hybridization indicated that the 11 kDa δ‐zein mRNA was expressed predominantly in transitional cells located between the vascular tissue and storage parenchyma cells. Immunohistochemistry of developing transgenic soybeans revealed that the accumulation of the 11 kDa δ‐zein occurred primarily in these transitional cells. Expression of the 11 kDa δ‐zein gene in transgenic soybean resulted in the formation of two endoplasmic reticulum‐derived protein bodies that were designated as either spherical or complex. Immunocytochemical localization demonstrated that both the spherical and complex protein bodies accumulated the 11 kDa δ‐zein. Although expression of the 11 kDa δ‐zein gene elevated the methionine content of the alcohol‐soluble protein fraction 1.5–1.7‐fold above that of the non‐transgenic line, the overall methionine content of seed flour was not increased. Our results suggest that the confined expression of the 11 kDa δ‐zein gene in transitional cells could be limiting the increase in methionine content in transgenic soybean seeds.
Reduction of starch granule size by expression of an engineered tandem starch‐binding domain in potato plants
Authors: Ji Qin , Oomen Ronald J. F. J. , Vincken Jean‐Paul , Bolam David N. , Gilbert Harry J. , Suurs Luc C. J. M. , Visser Richard G. F. 
Published: April 2004

SummaryGranule size is an important parameter when using starch in industrial applications. An artificial tandem repeat of a family 20 starch‐binding domain (SBD2) was engineered by two copies of the SBD derived from Bacillus circulans cyclodextrin glycosyltransferase via the Pro‐Thr‐rich linker peptide from Xyn10A from Cellulomonas fimi. SBD2 and a single SBD were introduced into the amylose‐free potato mutant, amf, using appropriate signal sequences. The accumulation of SBD2 into transgenic starch granules was much higher than that of SBD. In a number of transformants, particularly amfSS3, the starch granules were much smaller than in control plants. The amfSS3 mean granule size was 7.8 µm, compared with 15.2 µm in the control, whereas other starch properties were unaltered. This new starch combines the advantage of the high purity of potato starch with that of the small granule size of other crop species, such as cassava, taro and wheat. This starch may find application in the manufacture of biodegradable plastic films. Both genes were also expressed in Escherichia coli and the affinity for soluble starch of the purified recombinant proteins was determined. SBD2 had an approximately 10‐fold higher affinity for starch than SBD, indicating that the two appended SBDs act in synergy when binding to their target polysaccharide ligand.
Accumulation of rotavirus VP6 protein in chloroplasts of transplastomic tobacco is limited by protein stability
Authors: Birch‐Machin Ian , Newell Christine A. , Hibberd Julian M. , Gray John C. 
Published: April 2004

SummaryRotavirus VP6 is a highly immunogenic major capsid protein that may be useful as a subunit vaccine. The expression of a bovine group A rotavirus VP6 cDNA was examined in tobacco chloroplasts following particle bombardment. Constructs containing the VP6 cDNA under the control of plastid rrn or psbA promoters, or the Escherichia coli trc promoter, were inserted, together with the aadA selectable marker gene, between the rbcL and accD genes of the tobacco plastid genome. The 40‐kDa VP6 protein accumulated to about 3% of total soluble protein in seedlings and young leaves of homoplasmic transplastomic plants containing the VP6 cDNA under the control of the rrn promoter. Lower amounts of VP6 (∼0.6% total soluble protein) accumulated in plants containing the VP6 cDNA under the control of the psbA promoter, and VP6 was undetectable in plants containing the VP6 cDNA under the control of the trc promoter. The VP6 protein in chloroplasts was shown to form trimers, as found in the rotavirus virion. However, the amount of VP6 protein declined as the leaves matured, although VP6 transcripts were still present, suggesting that the protein was susceptible to proteolytic degradation in chloroplasts.
Efficacy of Novel Hemagglutinin-Neuraminidase Inhibitors BCX 2798 and BCX 2855 against Human Parainfluenza Viruses In Vitro and In Vivo
Authors: Alymova Irina V. , Taylor Garry , Takimoto Toru , Lin Tsu-Hsing , Chand Pooran , Babu Y. Sudhakara , Li Chenghong , Xiong Xiaoping , Portner Allen 
Published: April 2004

ABSTRACT

Human parainfluenza viruses are important respiratory tract pathogens, especially of children. However, no vaccines or specific therapies for infections caused by these viruses are currently available. In the present study we characterized the efficacy of the novel parainfluenza virus inhibitors BCX 2798 and BCX 2855, which were designed based on the three-dimensional structure of the hemagglutinin-neuraminidase (HN) protein. The compounds were highly effective in inhibiting hemagglutinin (HA) and neuraminidase (NA) activities and the growth of hPIV-1, hPIV-2, and hPIV-3 in LLC-MK
2
cells. The concentrations required to reduce the activity to 50% of that of a control ranged from 0.1 to 6.0 μM in HA inhibition assays and from 0.02 to 20 μM in NA inhibition assays. The concentrations required to inhibit virus replication to 50% of the level of the control ranged from 0.7 to 11.5 μM. BCX 2798 and BCX 2855 were inactive against influenza virus HA and NA and bacterial NA. In mice infected with a recombinant Sendai virus whose HN gene was replaced with that of hPIV-1 [rSV(hHN)], intranasal administration of BCX 2798 (10 mg/kg per day) and of BCX 2855 (50 mg/kg per day) 4 h before the start of infection resulted in a significant reduction in titers of virus in the lungs and protection from death. Treatment beginning 24 h after the start of infection did not prevent death. Together, our results indicate that BCX 2798 and BCX 2855 are effective inhibitors of parainfluenza virus HN and may limit parainfluenza virus infections in humans.
Molecular Mechanisms of Anti-Inflammatory Action of Erythromycin in Human Bronchial Epithelial Cells: Possible Role in the Signaling Pathway That Regulates Nuclear Factor-κB Activation
Authors: Desaki Masashi , Okazaki Hitoshi , Sunazuka Toshiaki , Omura Satoshi , Yamamoto Kazuhiko , Takizawa Hajime 
Published: April 2004

ABSTRACTLong-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-κB (NF-κB) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of IκBα, suggesting the molecular target for EM was not the dissociation of NF-κB from IκB. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-κB DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-κB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-κB signaling pathway in the downstream of the dissociation from IκB, resulting in the inhibition of NF-κB.
Genetic and Biochemical Characterization of a Chromosome-Encoded Carbapenem-Hydrolyzing Ambler Class D β-Lactamase fromShewanella algae
Authors: Héritier Claire , Poirel Laurent , Nordmann Patrice 
Published: April 2004

ABSTRACTA chromosome-encoded β-lactamase gene fromShewanella algaeclinical isolate KB-1 was cloned and expressed inEscherichia coli. It encoded the Ambler class D enzyme OXA-55, sharing less than 55% identity with any other oxacillinases. Although conferring a narrow-spectrum β-lactam resistance phenotype, OXA-55 had carbapenem-hydrolyzing activity that mirrored the reduced susceptibility to imipenem observed inS. algaeKB-1. Very similar oxacillinases were found in otherS. algaeisolates.
Role of the Multidrug Efflux System MexXY in the Emergence of Moderate Resistance to Aminoglycosides among
Pseudomonas aeruginosa
Isolates from Patients with Cystic Fibrosis
Authors: Vogne Christelle , Aires Julio Ramos , Bailly Christiane , Hocquet Didier , Plésiat Patrick 
Published: April 2004

ABSTRACT

This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of
Pseudomonas aeruginosa
. Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-CF strains moderately resistant to AGs. As demonstrated by immunoblot experiments, pump MexY was strongly overproduced in all of the resistant bacteria. This MexXY upregulation was associated with a 2- to 16-fold increase in the MICs of AGs in the S/R pairs and lower intracellular accumulation of dihydrostreptomycin. Alterations in
mexZ
, the repressor gene of operon
mexXY
, were found in all of the AG-resistant CF isolates and in one non-CF strain. Complementation of these bacteria with a plasmid-borne
mexZ
gene dramatically reduced the MICs of AGs, thus highlighting the role played by MexXY in the development of moderate resistance in CF patients. In contrast, complementation of the three non-CF strains showing wild-type
mexZ
genes left residual levels of resistance to AGs. These data indicate that a locus different from
mexZ
may be involved in overproduction of MexXY and that other nonenzymatic mechanisms contribute to AG resistance in
P. aeruginosa
.
Pseudomonas aeruginosa
LasA Protease in Treatment of Experimental Staphylococcal Keratitis
Authors: Barequet Irina S. , Ben Simon Guy J. , Safrin Mary , Ohman Dennis E. , Kessler Efrat 
Published: April 2004

ABSTRACT

LasA protease is a staphylolytic endopeptidase secreted by
Pseudomonas aeruginosa
. We have examined the effectiveness of LasA protease in the treatment of staphylococcal keratitis caused by methicillin-sensitive
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA) isolates in a rabbit model. Keratitis was induced by intrastromal injection of the bacteria. The eyes were treated topically, and the efficacy of LasA protease was compared to those of lysostaphin (a staphylolytic protease secreted by
Staphylococcus simulans
) and vancomycin. When treatment was initiated early (4 h) after infection, practically all of the MSSA- and MRSA-infected corneas were sterilized by LasA protease, and its efficacy in eradicating the bacteria was comparable to those of lysostaphin and vancomycin. By contrast, most of the control corneas were heavily infected, with median values of 4.5 × 10
6
(MSSA) and 5 × 10
5
(MRSA) CFU/cornea (
P
< 0.001). When treatment was initiated late (10 h) after infection, LasA protease reduced the numbers of CFU in both MSSA- and MRSA-infected corneas by 3 to 4 orders of magnitude compared to the numbers of CFU for the controls (median values, 1,380 and 30 CFU/cornea, respectively, for the treated animals compared to 1.2 × 10
6
and 5 × 10
5
CFU/cornea for the respective controls [
P
= 0.001]), and it was more effective than vancomycin in eradicating MRSA cells (
P
= 0.02). In both the early- and the late-treatment protocols, the clinical scores for eyes treated with LasA protease were significantly lower than those for the eyes of the corresponding controls and comparable to those for the lysostaphin- and vancomycin-treated eyes. We conclude that LasA protease is effective in the treatment of experimental
S. aureus
keratitis in rabbits and may have potential for the treatment of disease in humans.