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Results for “exploitation competition”

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PubMed1991

A mediator required for activation of RNA polymerase II transcription in vitro.

Activator proteins bind to enhancer DNA elements and stimulate the initiation of transcription. It has been proposed that activators contact general initiation factors at a promoter, and evidence for such direct interaction has been obtained. Studies of transcription in vitro, however, have suggested that activators might function through an intermediary molecule(s) distinct from the general factors. In the first of these studies, we exploited the finding that one activator could inhibit transcription stimulated by a second activator (activator interference or 'squelching'). This inhibition, which is attributed to competition between the activators for a common target factor, could not be relieved by addition of a large excess of general initiation factors, suggesting that the target for which activators compete is distinct from these factors. Similar conclusions came from the observation that TFIID's expressed from cloned genes fail to replace partially purified 'natural' TFIID fractions in supporting activation, evidently because they lacked some component present in the impure fractions. While these lines of evidence for a novel 'mediator' of activation were negative, we also showed that a partially purified fraction from yeast would reverse activator interference. This positive effect of a presumptive mediator provided an assay for its activity, but its role in activation was still only inferred. We now present direct evidence for a mediator which is required for stimulation of transcription in vitro by the activators GAL4-VP16 and GCN4, but which has no effect on transcription in the absence of activator protein.

DNA-Binding Proteins↗
PubMed1991

Beefing up operations in service firms.

Many articles exhort service firm managers to empower workers and first-line supervisors, exploit technology, focus on the customer, and, above all, provide outstanding service. This article proposes a framework to help you evaluate your company's competitive standing in each of these areas. It discusses four types of companies on a continuum, from the company that is simply "available for service" to the firm that delivers world class service. The authors focus on operations, the function that controls the service encounter, and apply the manufacturing strategy paradigm to services as a means of implementing change.

Consumer Behavior↗
PubMed1998

Developing winning products, Part I.

Successful product development relies on several factors. This two-part article explores the role of the designer in creating winning products that people really want to buy. Part I examines two important issues: identifying under-exploited market need and the designer as champion of the end-user.

Economic Competition↗
PubMed2002

An alternative focus in strategic research on disease vectors: the potential of genetically modified non-biting mosquitoes.

We examine the constraints and the feasibility of field experiments involving the release of genetically modified (GM) pathogen-resistant mosquitoes, and whether there are alternatives to the research line based on the production of refractory strains. The production of a GM mosquito strain characterized instead by obligate primiparous and parous autogeny and by disrupted host seeking and biting behaviour could make the release more acceptable by the general public. Genetic transformation should act in this case to reverse some of the essential steps of the evolutionary process that gave rise to hematophagy. The replacement strategy could be based on the mass release of both sexes in a well defined ecological niche made temporarily empty of the natural population, thus avoiding the problems related to the need of sexual competitiveness of the released material. This option is encouraged by the growing evidence that competitive exclusion mechanisms influence the pattern of distribution of different taxa within Anopheles gambiae s.s. and by the fact that the plesiomorphic characteristics of vitellogenesis without a blood meal (autogeny), which exploits fat body reserve accumulated during larval life and food other than blood in adult life, persist as genetic variants in various hematophagous insect groups, and it has been found secondarily fixed in others showing stable reversions to primiparous and parous autogeny. If this has been the result of natural selection, then the artificial production of non-biting mosquito strains, by selection and/or transgenesis, should be feasible.

Animals↗
PubMed2001

Olefin epoxidation by molybdenum and rhenium peroxo and hydroperoxo compounds: a density functional study of energetics and mechanisms.

A density functional study on olefin epoxidation by rhenium and molybdenum peroxo complexes has been carried out. Various intermediates and transition structures of the systems CH3ReO3/H2O2, H3NMoO3/H2O2, and H3NOMoO3/H2O2 were characterized, including ligated and unligated mono- and bisperoxo intermediates as well as hydroperoxo derivatives. For the rhenium system the bisperoxo complex CH3ReO(O2)2*H2O was found to be most stable and the one with the lowest transition state for epoxidation of ethylene (activation barrier of 16.2 kcal/mol), in line with experimental findings. However, participation of monoperoxo and hydroperoxo complexes in olefin epoxidation cannot be excluded. For both molybdenum systems, hydroperoxo species with an additional ammonia model ligand in axial position were calculated to be most stable. Inspection of calculated activation barriers of ethylene epoxidation reveals that, in both molybdenum systems, hydroperoxo mechanisms are competitive if not superior to peroxo mechanisms. The reaction barriers of the various oxygen transfer processes can be rationalized by structural, orbital, and charge characteristics, exploiting a model that interprets the electrophilic nature of the reactive oxygen center.

Journal Article↗
PubMed1996

Models of parasite virulence.

Several evolutionary processes influence virulence, the amount of damage a parasite causes to its host. For example, parasites are favored to exploit their hosts prudently to prolong infection and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. Thus parasites face a tradeoff between prudent exploitation and rapid reproduction-a life history tradeoff between longevity and fecundity. Other tradeoffs among components of parasite fitness also influence virulence. For example, competition among parasite genotypes favors rapid growth to achieve greater relative success within the host. Rapid growth may, however, lower the total productivity of the local group by overexploiting the host, which is a potentially renewable food supply. This is a problem of kin selection and group selection. I summarize models of parasite virulence with the theoretical tools of life history analysis, kin selection, and epidemiology. I then apply the theory to recent empirical studies and models of virulence. These applications, to nematodes, to the extreme virulence of hospital epidemics, and to bacterial meningitis, show the power of simple life history theory to highlight interesting questions and to provide a rich array of hypotheses. These examples also show the kinds of conceptual mistakes that commonly arise when only a few components of parasite fitness are analysed in isolation. The last part of the article connects standard models of parasite virulence to diverse topics, such as the virulence of bacterial plasmids, the evolution of genomes, and the processes that influenced conflict and cooperation among the earliest replicators near the origin of life.

Animals↗
PubMed2005

[Does improvement of symptoms four weeks after the begin of psychodynamic inpatient psychotherapy correspond to long term outcome?].

OBJECTIVES: This study was conducted to explore differentiated aspects of outcome throughout and one year after psychodynamic inpatient psychotherapy with special regard to symptomatic distress and interpersonal behaviour. METHODS: Sixty-four patients of the Department of Psychotherapeutic Medicine of the Jerichow Hospital (Saxonia-Anhaltina) were investigated with the SCL-90-R and the IIP-D four times: at the beginning of inpatient psychotherapy (t0), four weeks after (t1), at the end (t2), and one year after discharge (t3). RESULTS: The improvement of symptoms four weeks after the beginning of psychodynamic inpatient psychotherapy is equivalent with long term outcome. The Global Severity Index of SCL-90-R demonstrated a statistically significant change from markedly psychological distress to lack of distress after four weeks psychodynamic inpatient psychotherapy (effect-size d(GSI) = 0.82). At the end of psychotherapy, three weeks later, the effect-size was d = 1.11, and one year after discharge the effect-size decreased again to d = 0.85. Major improvements demonstrated the SCL-90-R subscales Depression, Anxiety, and Obsessive/Compulsive. Regarding interpersonal problems, the subscales Dominance, and Competitive demonstrated statistically significant changes from low Stanine-scores at t0 to higher scores one year after discharge. The subscales Socially avoidant, Nonassertive, and Exploitable demonstrated statistical significant changes from high levels at t0 to lower scores after one year. DISCUSSION: In conclusion the first four weeks of psychodynamic psychotherapy are not sufficient to demonstrate an optimum level of low psychological distress as well as an optimum change in interpersonal problems. Regarding stability of the effects of psychodynamic inpatient psychotherapy it was demonstrated that the first four weeks initiated changes which improved at the end of psychotherapy until one year after discharge.

Adaptation, Psychological↗
PubMed2005

Evaluation of composted sewage sludge as nutritional source for horticultural soils.

Water deficit and soil degradation have become some of the major problems for crop production in semi-arid regions, as it is the South East of Spain. As a matter of fact, considerable productivity loss and risk of erosion have to be taken into account in these areas, especially those with an horticultural use (Davis, 1989). Utilization of sewage sludge in agriculture. Agricultural Progress 64, 72-80]. Horticultural soils are highly vulnerable and prone to erosion, as vegetables are generally fast-growing species under intensive exploitation regimes. High-rate chemical inputs contribute to horticultural soil degradation and have a dramatic effect on soil microbial population and nutrient balance whilst, at the same time, have a counter-effect on price competitiveness of the vegetables to be commercialized. In this paper we monitored variations in physical, chemical and biological properties of a cauliflower plot where four increasing quantities of compost were applied. We carried out a three-stage sampling schedule in order to check the effect of compost applications doses. We conclude that a 2 kg compost/m2 application had a positive effect on physical and biological properties of the soil and provides a supply of nutrients to grow cauliflowers on its surface under intensive exploitation regimes without loss in biomass yield.

Agriculture↗
PubMed2004

Take command of your growth.

Ask senior managers to pare costs by 10%, and they know just what to do. Ask them to boost growth by 10%, and they're stymied, assuming that growth is not really something they can influence. But managers can control their company's growth if they have better information about where their revenues are coming from. Rather than sort sales by geographic market, business unit, or product line, they should break them out in a way that reveals which part of their strategy is responsible for what part of their revenue. This article presents a tool--the sources of revenue statement (SRS)--that does just that. Through straightforward calculations using data taken from a company's balance sheet, along with estimations of customer-churn and industry growth rates, the SRS enables managers to classify their revenue according to five sources of growth: continuing sales to established customers (base retention); sales won from the competition (share gain); sales that fell into their laps because the market was expanding (market position); sales from moves into adjacent markets; and sales from entirely new lines of business. Once sorted in this way, revenue can be viewed as the outgrowth of manageable circumstances. At one company, seemingly healthy 10% total revenue growth masked substantial customer defections counter-balanced only by sales in a fast-expanding market--a market that actually grew faster than the company did. Rather than doing well, the company was ceding customers and market share to competitors. Comparing the sources of revenue across divisions can uncover similarly profound insights, which can suggest smart ways to change strategy or set stretch goals. Hundreds of companies are perched atop enormous potential that they can't see and so don't exploit. The SRS can endow them with sight and, more important, with understanding.

Commerce↗
PubMedDate not supplied

[Occult child abuse (opinions, considerations, personal observations)].

At the beginning of the statement the authors point out some lesser aspects of child's ill-treatment (previously suggested by them in other occasions) as expressions of very strict educational systems which strongly limit childrens' freedom or impose them several extrascholastic activities (such as: athletics, music with participation in competitive examination, studies of foreign languages, Latin and so on) where the child must excel in (composex of the "leader-child"). Then these authors suggest using the term "abuse" to mean lexically every excessive, undue, arbitrary use and not only "sexual". They point out the seriousness of abuse as far as juvenile exploitation is concerned both in case of manual labour and prostitution. But the pay particularly attention to the problem of sport when it is gone in for too intensively (as athletics). These authors infact sum up the harms that sport can cause when it is gone in for during the age under the stabilized puberty. Physical harms may occur especially during the practice of risky sports such as: Alpine skiing, cycling on the road, swimming combined with diving, fencing, boxing) and during tiring condition, while psychic harms can entail a fall in scholastic performances, irritability, insomnia, anxiety. The authors depreciate the behaviour of those parents who stimulate their children' aggressiveness during competitions and scold them when their performances are insufficient, or give them forbidden stimulants of hormonal anabolic drugs instead of taking care of their children in order to keep away from the arms mentioned above. However, after all these observations and considerations about competitive sports in juvenile age, these authors can firmly state that all this could be meant as an important aspects of the juvenile exploitation that must be taken in great consideration.

Child↗
PubMed1991

A single amino acid substitution in the Ak molecule fortuitously provokes an alloresponse.

We discovered by chance that the R28 T cell hybridoma has dual specificity. It responds to a peptide derived from ribonuclease presented by cells displaying Ak molecules and it reacts, in the absence of added antigen, to cells expressing Ak complexes with a single amino acid substitution at position 69 of the alpha chain. Modelling and functional studies suggest that residue 69 is a peptide contact residue, prompting the hypothesis that R28's alloreactivity is a cross-reactive response to an unknown peptide bound in the 'groove' of the mutant Ak complex. In this report, we employ a competition assay to confirm that this alloresponse involves a groove-binding peptide, demonstrate that this peptide derives from or depends on fetal calf serum and exploit a panel of antigen-presenting cell lines--each displaying an Ak complex with a different position 69 substitution--to establish that the alloresponse is not just a heteroclitic response to ribonuclease, itself. We speculate that much of the alloreactivity against murine class II molecules that is revealed in vitro may prove to be directed at bovine serum-derived peptides, suggesting that in this context, alloreactivity is a misnomer.

Amino Acid Sequence↗
PubMed2006

GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels.

Many phosphorylation signal transduction pathways in the eukaryotic cell are modulated by posttranslational modification of specific serines/threonines with N-acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate biological processes as diverse as the cell cycle, insulin signaling, and protein degradation. The two enzymes involved in this dynamic and abundant modification are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently revealed that the O-GlcNAcase possesses an active site with significant structural similarity to that of the human lysosomal hexosaminidases HexA/HexB. PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human cell lines, also inhibits these hexosaminidases. Here, we have exploited recent structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition state as revealed by X-ray crystallography. This compound is able to raise O-GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus provides a novel, potent tool for the study of the role of O-GlcNAc in intracellular signal transduction pathways.

Acylation↗
PubMed2004

Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

BACKGROUND: Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. METHODS: The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. RESULTS: In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. CONCLUSION: These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

Animals↗
PubMed2004

Ligand-directed functional heterogeneity of histamine H1 receptors: novel dual-function ligands selectively activate and block H1-mediated phospholipase C and adenylyl cyclase signaling.

The autacoid and neurotransmitter histamine activates the H(1) G protein-coupled receptor (GPCR) to stimulate predominantly phospholipase C (PLC)/inositol phosphate (IP) signaling and, to a lesser extent, adenylyl cyclase (AC)/cAMP signaling in a variety of mammalian cells and tissues, as well as H(1)-transfected clonal cell lines. This study reports that two novel H(1) receptor ligands developed in our laboratory, (-)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (trans-PAT) and (+/-)-cis-5-phenyl-7-dimethylamino-5,6,7,8-tetrahydro-9H-benzocycloheptane (cis-PAB), activate H(1) receptors to selectively stimulate AC/cAMP formation and PLC/IP formation, respectively, in Chinese hamster ovary cells transfected with guinea pig H(1) receptor cDNA. trans-PAT and cis-PAB also are shown to be functionally selective antagonists of H(1)-linked PLC/IP and AC/cAMP signaling, respectively. Whereas cis-PAB H(1) receptor activity is shown to be typically competitive, trans-PAT displays a complex interaction with the H(1) receptor that is not competitive regarding antagonism of saturation binding by the standard H(1) antagonist radioligand [(3)H]mepyramine or H(1)/PLC/IP functional activation by histamine. trans-PAT, however, does competitively block H(1)/PLC/IP functional activation by cis-PAB. Molecular determinants for trans-PAT versus cis-PAB differential binding to H(1) receptors, which presumably leads to differential activation of AC/cAMP versus PLC/IP signaling, likely involves stereochemical factors as well as more subtle steric influences. Results suggest the trans-PAT and cis-PAB probes will be useful to study molecular mechanisms of ligand-directed GPCR multifunctional signaling. Moreover, because most untoward cardiovascular-, respiratory-, and gastrointestinal H(1) receptor-mediated effects proceed via the PLC/IP pathway, PAT-type agonists that selectively enhance H(1)-mediated AC/cAMP signaling provide a mechanistic basis for exploiting H(1) receptor activation for drug design purposes.

Adenylyl Cyclases↗
PubMed2004

Competition between ammonia-oxidizing bacteria and benthic microalgae.

The abundance, activity, and diversity of ammonia-oxidizing bacteria (AOB) were studied in prepared microcosms with and without microphytobenthic activity. In the microcosm without alga activity, both AOB abundance, estimated by real-time PCR, and potential nitrification increased during the course of the experiment. AOB present in the oxic zone of these sediments were able to fully exploit their nitrification potential because NH(4)(+) did not limit growth. In contrast, AOB in the alga-colonized sediments reached less than 20% of their potential activity, suggesting starvation of cells. Starvation resulted in a decrease with time in the abundance of AOB as well as in nitrification potential. This decrease was correlated with an increase in alga biomass, suggesting competitive exclusion of AOB by microalgae. Induction of N limitation in the oxic zone of the alga-colonized sediments and O(2) limitation of the majority of AOB in darkness were major mechanisms by which microalgae suppressed the growth and survival of AOB. The competition pressure from the algae seemed to act on the entire population of AOB, as no differences were observed by denaturing gradient gel electrophoresis of amoA fragments during the course of the experiment. Enumeration of bacteria based on 16S rRNA gene copies and d-amino acids suggested that the algae also affected other bacterial groups negatively. Our data indicate that direct competitive interaction takes place between algae and AOB and that benthic algae are superior competitors because they have higher N uptake rates and grow faster than AOB.

Ammonia↗
PubMed2004

Using the written description requirement to limit broad patent scope, allow competition, and encourage innovation in biotechnology.

The biotechnology research and development process is extremely expensive and companies must attract investors to this high-risk industry to pay for these costs. Biotechnology companies rely on their ability to exclude others from exploiting the benefits of their research through patent protection to attract these investors. Consequently, they seek strong patent protection for their inventions by claiming a broad scope of patent protection for their inventions. Biotechnology is an industry where the scope of protection should be limited. Science-based technologies exploit the perceived technological opportunities from recent scientific developments, concentrating the attention of many inventors on the same areas. This poses several unique problems. First, only the first of several inventors will receive a patent to the invention. Second, due to publicly available, basic techniques, the actual contribution made by the inventor may be relatively small. Finally, there is a significant risk that permitting an overbroad patent scope may permit original patentees to control a variety of improvements and a number of applications. Additionally, a broad scope of protection for an invention tends to cause underutilization of many potential inventions or improvements. By limiting the scope of protection, one allows competitors to utilize these potential inventions or improvements and encourages the advancement of the technology. Traditionally, courts have used the scope of the disclosure to limit a patent with an overly broad scope of protection. The Federal Circuit is correctly applying the written description requirement as part of the disclosure to limit broad claim scope in biotechnology patents. The written description requirement is separate from the enablement requirement and applies to all claims. By requiring a written description to allow a PHOSITA to determine the structural characteristics of the claimed invention, the Federal Circuit is able limit biotechnology patents with overly broad patent scope. Recognizing that particular technologies will become more established as biotechnology matures giving rise to different issues in setting the appropriate level of patent scope, the court allowed the written description requirement to mature in tandem with advances in biotechnology to meet these new developments.

Biotechnology↗
PubMed2001

Protein-based alignment in 3D QSAR of 26 indole inhibitors of human pancreatic phospholipase A2.

An automated docking procedure was applied on a series of 26 reversible and competitive indole inhibitors of human pancreatic phospholipase A2 (hp-PLA2). X-ray data of this enzyme are not available and the structure was then reconstructed exploiting its protein sequence and the crystallographic data of a bovine pancreatic source. The docking data were used to build a three-dimensional quantitative structure-activity relationship (3D QSAR) model, established using the comparative molecular field analysis (CoMFA) method. This model, joined to the previous one developed for the indole inhibitors of human non-pancreatic secretory phospholipase A2 (hnps-PLA2), an enzyme involved in inflammation processes, will allow for the selection of new strong anti-inflammatory drugs with negligible side effects, at least at the level of hp-PLA2.

Animals↗
PubMed1995

Effect of noradrenergic lesions on subtypes of alpha 2-adrenoceptors in rat brain.

The binding of [3H]rauwolscine to alpha 2A- (also referred to as alpha 2D-) and alpha 2C-adrenoceptors in homogenates of rat cerebral cortex was measured by exploiting the selectivity of oxymetazoline for alpha 2A-adrenoceptors. Inhibition of [3H]rauwolscine binding by oxymetazoline was modeled best assuming binding to two sites (p < 0.001). Competition curves for oxymetazoline were shifted rightward by the addition of GTP (250 microM) but were still fit best by a two-site model (p < 0.001). A concentration of oxymetazoline was calculated that would optimally antagonize [3H]rauwolscine binding (with GTP present) to oxymetazoline-sensitive alpha 2A-adrenoceptors, minimally inhibiting binding to alpha 2C-adrenoceptors. Subsequently, [3H]rauwolscine binding to alpha 2A- and alpha 2C-adrenoceptors in cortex was examined 3 weeks after destruction of noradrenergic terminals. Binding to alpha 2C-adrenoceptors was increased significantly after treatment with 6-hydroxydopamine, (6-OHDA) compared with vehicle-treated controls, whereas binding to alpha 2A-adrenoceptors was unchanged. Pretreatment of rats with desipramine before 6-hydroxydopamine, to protect noradrenergic neurons, resulted in no changes in binding to either alpha 2A- or alpha 2C-adrenoceptors. Thus, alpha 2C-adrenoceptors are regulated by changes in synaptic availability of norepinephrine. alpha 2A-Adrenoceptors are either not regulated by synaptic norepinephrine or are located both post- and presynaptically so that up-regulation of postsynaptic alpha 2A-adrenoceptors is offset by a loss of presynaptic alpha 2A-adrenoceptors.

5,7-Dihydroxytryptamine↗