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71.
Discrimination of simple visual attributes can improve significantly with practice. We have trained human observers to perform peripherally presented tasks involving the localization of short line segments and examined the specificity of the learning for the visual location, orientation, and geometric arrangement of the trained stimulus. Several weeks of training resulted in dramatic threshold reductions. The learning was specific for the orientation and location of the trained stimulus, indicating the involvement of the earliest cortical stages in the visual pathway where the orientation and location of stimuli are mapped with highest resolution. Furthermore, improvement was also specific for both the configuration of the trained stimulus and the attribute of the stimulus that was under scrutiny during training. This degree of specificity suggests that the learning cannot be achieved by cortical recruitment alone, as proposed in current models, but is likely to involve a refinement of lateral interactions within the cortex and possibly a gating of lower level changes by attentional mechanisms. 相似文献
72.
Cancer invasion and metastasis are associated with matrix degradation. We describe a novel in vivo model of invasion by squamous epithelial neoplastic cells derived from transgenic mice grown on acellular human dermis. Human dermis was subjected to multiple freeze-thaw cycles to render it acellular, maintaining the basement membrane of the former dermal-epidermal junction. Cells representing discrete stages of a multistep transgenic mouse model of epidermal carcinogenesis (neonatal transgenic keratinocytes, moderately/poorly differentiated squamous cell carcinoma, and lymph node metastasis) were seeded onto the basement membrane surface, grown in culture for 4 days, grafted in a subpannicular pocket of athymic mice, and harvested after 3 weeks. Histological analysis demonstrated that neonatal transgenic keratinocytes did not degrade the basement membrane or invade the underlying dermis. In contrast, malignant cells derived from both a moderately differentiated squamous carcinoma and a lymph node metastasis were highly invasive. Immunohistochemical analysis revealed collagenase only in nests of invading malignant cells in contact with the dermal matrix, but not in the tumor mass remaining above the basement membrane, suggesting that this proteinase may be required for stromal invasion. This novel model recapitulates the events seen in malignant invasion: transgenic keratinocytes are unable to penetrate the dermis while cells from a moderately differentiated carcinoma and from lymph node metastasis consistently invade. 相似文献
73.
To address the hypothesis that tumor necrosis factor (TNF)-alpha has a role in obesity-associated insulin resistance or the regulation of in vivo lipid metabolism, mice with targeted disruption of the TNF-alpha gene were generated and studied. The absence of TNF-alpha protein in TNF-null (-/-) mice was confirmed. Lean or obese (gold-thioglucose [GTG]-injected) homozygous (-/-) mice were compared with lean or obese age- and sex-matched wild-type (+/+) mice derived from the same line at 13, 19, and 28 weeks of age. The following parameters were significantly affected in lean -/- versus +/+ mice: Body weight was not affected until week 28 (decreased by 14%); epididymal fat pad weight also decreased (25%) at this time, as did percentage body fat (16%), while percentage body protein was increased 13%. Fed plasma insulin levels decreased 47% (28 weeks), triglyceride levels decreased (all three ages; maximum 35% at 19 weeks), and fed plasma leptin decreased 33% (28 weeks). Fasting glucose was slightly (10%) reduced, but the glucose response to an oral glucose tolerance test (OGTT) was not affected. There was a trend (NS) toward increased total adipose tissue lipoprotein lipase in -/- versus +/+ mice. GTG-treatment resulted in obese -/- and +/+ mice with equal mean body weights (42 and 58% increased weight versus lean mice). The following parameters were significantly different in obese -/- mice: fasting plasma glucose decreased 13% (28 weeks), fed plasma insulin decreased 67% (28 weeks), and insulin response to OGTT was decreased by 50%. For both groups of obese mice, glucose levels during the OGTT were substantially increased compared with those in lean mice; however, mean stimulated glucose levels were 20% lower in obese -/- versus +/+ mice. We conclude 1) that TNF-alpha functions to regulate plasma triglycerides and body adiposity and 2) that although TNF-alpha contributes to reduced insulin sensitivity in older or obese mice, the absence of TNF-alpha is not sufficient to substantially protect against insulin resistance in the GTG hyperphagic model of rodent obesity. 相似文献
74.
Few studies have prospectively examined the characteristics associated with worksite adoption of tobacco-control initiatives. Data were collected as part of the Community Intervention Trial (COMMIT) for Smoking Cessation, which conducted interventions in 11 communities. This smoking cessation intervention was based on community organization principles and delivered through multiple community channels, including worksites, health care providers, the media, and cessation resources. This article reports results from telephone interviews of intervention community worksites having 50 or more employees, conducted at baseline and the end of the intervention period. Among worksites that responded to both baseline and final surveys, 83% had not adopted a smoke-free policy at baseline, and 61% did not offer any cessation aid or quitting resources at baseline. By the final survey, 34% of those with no smoking ban at baseline had become smoke-free, and 36% of those offering no cessation assistance at baseline were offering cessation resources at the follow-up. The prevalence of policy adoption was higher among worksites employing more female employees and offering other health-promotion activities; manufacturing businesses were significantly less likely than businesses other than service and wholesale/retail businesses to adopt policies. Adoption of cessation programs was significantly more likely among worksites employing 100 to 249 workers, compared with those employing 50 to 99 workers; those predominantly employing men; those offering other types of health-promotion activities; and those with a higher rate of turnover. These results provide important information about the characteristics of worksites likely to engage in tobacco-control efforts. Health educators and others may choose to target those worksites most ready for adoption of tobacco control policies and programs, as indicated by these findings. 相似文献
75.
W. Sjoerd Kijlstra Joop C.M.L. Daamen Jolinde M. van de Graaf Bart van der Linden Eduard K. Poels Alfred Bliek 《Applied catalysis. B, Environmental》1996,7(3-4):337-357
The effect of water on the selective catalytic reduction (SCR) of nitric oxide with ammonia over alumina supported with 2–15 wt.-% manganese oxide was investigated in the temperature range 385–600 K, with the emphasis on the low side of this temperature window. Studies on the effect of 1–5 vol.-% water vapour on the SCR reaction rate and selectivity were combined with TPD experiments to reveal the influence of water on the adsorption of the single SCR reactants. It turned out that the activity decrease due to water addition can be divided into a reversible inhibition and an irreversible deactivation. Inhibition is caused by molecular adsorption of water. TPD studies showed that water can adsorb competitively with both ammonia and nitric oxide. Additional kinetic experiments revealed that adsorbed ammonia is present in excess on the catalyst surface, even in the presence of water. Reduced nitric oxide adsorption is responsible for the observed reversible decrease in the reaction rate; the fractional reaction order changes from 0.79 in the absence of water to 1.07 in its presence. Deactivation is probably due to the dissociative adsorption of water, resulting in the formation of additional surface hydroxyls. As the amount of surface hydroxyls formed is limited to a saturation level, the deactivating effect on the catalyst is limited too. The additional hydroxyls condense and desorb in the temperature range 525–775 K, resulting in a lower degree of deactivation at higher temperature. A high temperature treatment at 775 K results in a complete regeneration. The amount of surface hydroxyls formed per unit surface area decreases at increasing MnOx-loading. The selectivity to the production of nitrogen is enhanced significantly by the presence of gas phase water. 相似文献
76.
M Hessing D Kanters H Takeya C van 't Veer TM Hackeng S Iwanaga BN Bouma 《Canadian Metallurgical Quarterly》1993,317(3):228-232
Human C4b-binding protein (C4BP) functions as a cofactor to factor I in the degradation of C4b and accelerates the decay rate of the C4b2a complex. In this study we describe a monoclonal antibody directed against the alpha-chain of C4BP that inhibits the binding of C4b to C4BP. In order to identify the structural domain of the alpha-chain of C4BP that interacts with C4b, tryptic fragments of C4BP were generated. Amino acid sequence analysis of the fragments revealed that the residues Ser333-Arg356 of the alpha-chain of C4BP contain the epitope of this antibody, and as a consequence, that this part of the alpha-chain of C4BP is likely to be involved in the interaction with C4b. 相似文献
77.
BACKGROUND: Monocytic tissue factor (TF), initiating the extrinsic blood coagulation pathway, is often upregulated under septic or inflammatory conditions. The complex activating mechanism remains largely unclear and no effective strategy has been firmly established. In this study, we used a model monocytic cell line (human leukemic THP-1 promonocytes) to address (1) the nature of TF activation in response to bacterial endotoxin and (2) the application of anti-inflammatory cytokines in relieving monocytic hypercoagulation. RESULTS: TF in THP-1 cells was substantially activated by exposure to bacterial endotoxin (LPS; 5 micrograms/ml) for 6 h. Human recombinant IL-4 (500 ng/ml) and IL-10 (500 ng/ml) inhibited TF activation induced by LPS. To determine if these cytokines depressed LPS recognition resulting in such inhibition, we employed an anti-CD14 mAb (UCHM-1; Sigma Chemical) to address the role of CD14 in LPS transmembrane signaling. LPS-induced TF activation was depressed by 35% upon inclusion of the anti-CD14 mAb (1:10 dilution). This antibody alone mimicked TF activation which accounted for 35% of the LPS-induced TF activation, suggesting the activating role of CD14 ligation. In addition, the anti-CD14 mAb elicited the production of nitric oxide (NO) which was found to be independent of TF activation. NO production could serve as an independent index for monitoring LPS recognition. IL-4 depressed the anti-CD14 mAb-induced TF activation as well as NO elicitation, indicating the blockade of CD14 ligation. In contrast, IL-10 showed differential inhibitory activities. TF activation induced by either LPS or anti-CD14 mAb was inhibited by IL-10 which did not show any inhibition on NO elicitation under these conditions. In a separate approach, neither IL-4 nor IL-10 inhibited phorbol ester-induced NO elicitation. More direct evidence came from an epifluorescent demonstration showing that IL-4 blocked binding of FITC-conjugated LPS and anti-CD14 mAb to THP-1 cells. CONCLUSIONS: Taken together, the results suggest that LPS action in relation to TF activation consists of CD14-independent and -dependent signaling including CD14 ligation. We also showed that anti-inflammatory cytokines (IL-4 and -10) significantly depressed TF activation. IL-4 antagonized CD14-dependent LPS recognition leading to the depression in TF activation. 相似文献
78.
79.
Measuring knowledge transfer between fields of science 总被引:4,自引:2,他引:2
Rinia Ed J. van Leeuwen Thed N. Bruins Eppo E. W. van Vuren Hendrik G. van Raan Anthony F. J. 《Scientometrics》2002,54(3):347-362
In this paper we report on the results of an exploratory study of knowledge exchange between disciplines and subfields of
science, based on bibliometric methods. The goal of this analysis is twofold. Firstly, we consider knowledge exchange between
disciplines at a global level, by analysing cross-disciplinary citations in journal articles, based on the world publication
output in 1999. Among others a central position of the Basic Life Sciences within the Life Sciences and of Physics within
the Exact Sciences is shown. Limitations of analyses of interdisciplinary impact at the journal level are discussed. A second
topic is a discussion of measures which may be used to quantify the rate of knowledge transfer between fields and the importance
of work in a given field or for other disciplines. Two measures are applied, which appear to be proper indicators of impact
of research on other fields. These indicators of interdisciplinary impact may be applied at other institutional levels as
well.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
80.
Aard J. Groen Petra C. De WeerdNederhof Inge C. Kerssensvan Drongelen Rob A.J. Badoux Gerard P.H. Olthuis 《Creativity & Innovation Management》2002,11(1):2-16
In this paper we describe a framework for analysing the creation and justification of Research & Development. The 4S framework is developed for analysing the scope, scale, skills and social network aspects of Research & Development value. The framework is based on social system theory, a process contingency model, and recent Research & Development metrics. We present a first empirical assessment based on a workshop using the 4S framework for leveraging Research & Development. Results that assist in the assessment of value creation utilising R & D within networks are very relevant in high tech industries. The multi–dimensional process approach of this framework seems promising for understanding and managing R&D value creation, but needs further operationalisation. Case studies are described and a Dutch network on leveraging R&D has been initiated. 相似文献