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  • Springer  (22)
  • Blackwell Publishing Ltd  (2)
  • 1990-1994  (10)
  • 1985-1989  (12)
  • 1975-1979
  • 1960-1964
  • 1870-1879  (2)
  • 1
    ISSN: 1467-9310
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Economics
    Notes: Drug regulation and pricing have put strong pressure on the cost-benefit ratio of the innovative pharmaceutical industry. Therefore a study has been conducted in fourteen large and medium sized companies to determine some important organisational and managerial factors influencing success in pharmaceutical innovation. The study consists of structured interviews with Research Directors and questionnaires, submitted to the heads of the different research departments. The following conclusions are tentatively drawn. Firstly, the data suggest that a threshold investment of approximately $150–200 million is needed to maintain the innovative potential. Above approximately $750 million, ‘economies of scale’ seem to appear in pharmaceutical innovation. Secondly, an incremental strategy aimed at reducing the duration of the development process seems to be more successful than a radical strategy which lays more emphasis on discovery. Thirdly, pure play pharmaceuticals seem to be more successful than the pharmaceutical divisions of conglomerates. Management control, especially the way in which reorganisations are performed, is assessed more positively in pure play pharmaceuticals. Fourthly, the greater emphasis on human resources management in Anglo-American companies, in comparison to continental European companies, seems to be an important explanatory factor for their greater success on the pharmaceutical market.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    R & D management 18 (1988), S. 0 
    ISSN: 1467-9310
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Economics
    Notes: The paper contains a report of a test of Cooper's NewProd model for predicting success and failure of product development projects. Based on Canadian data, the model has been shown to make predictions which are 84% correct. Having reservations on the reliability and validity of the model on theoretical grounds, we set out to test it using data collected in the Netherlands.Following Cooper's methodology, we selected 19 projects, which had already been marketed and of which 9 were clearcut successes and 10 clearcut failures. We also studied 9 additional projects, which had not yet been commercialised, as the basis for a future a priori test. The projects were given a product score according to Cooper's criteria, and predictions compared with the actual experience. Eightyfour percent were correctly classified, as in Cooper's work. From a practical point of view however the variance was too large to allow the predictions from NewProd to be used with confidence to predict outcomes unless they are clearcut.We believe that the drawback of the methodology is that the product score is a simple combination of the various factors involved. No allowance is made for the possibility that one factor alone might be responsible for failure. We have therefore introduced the concept of a threshold value for each factor. A project for which any factor falls below this value will be deemed a failure. Based on a very limited sample of 19 cases an improvement of reliability was made to 95% of 18 out of 19 products correctly classified. The NewProd concept so modified is being applied to the sample of 9 as yet uncompleted projects, and its predictions will eventually be compared with actual outcomes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Inelastic and elasticJ/ψ (3097) photoproduction on Li6 are measured at a mean γ energy of 90 GeV in an open spectrometer. TheJ/ψ are identified by their decays intoμ + μ − ore + e −. A signal of ψ′(3685) intoμ + μ − andJ/ψπ + π − is also seen. The inelastic cross-section withZ=E ψ/Eγ〈0.9 is compared in shape and magnitude with the colour singlet model of photon-gluon fusion.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    De economist 22 (1873), S. 459-487 
    ISSN: 1572-9982
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    De economist 22 (1873), S. 321-338 
    ISSN: 1572-9982
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 92 (1989), S. 397-406 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We have produced a small library of colonic mucosa and colorectal carcinoma reactive monoclonal antibodies (MoAbs) by immunizations with extracts of human colon cancer tissue and a human colon cancer cell line. Hybridoma supernatants were tested on (normal and neoplastic) human tissues by immunoperoxidase methods to evaluate organ or tissue specificity. Initial biochemical characterization of the target antigens was performed by gelpermeation chromatography, Western blotting and competition assays. Based upon the immunoreactivity patterns and the characteristics of the antigen four groups of MoAbs could be distinguished. The first group concerns the antibodies PAR-LAM 3, 9 and 10. These antibodies react with an 87 kDa protein moiety in high molecular weight (2–5×106 Da) glycoproteins. In intestinal and colon mucosa these antibodies showed diffuse binding with goblet cells. In colon carcinoma decreased reactivity with these MoAbs was found. The second group consists of antibodies PARLAM 8, 12 and 13. These antibodies react with large (〉5×106 Da) glycoproteins, most likely with carbohydrate epitopes. By immunohistochemistry in normal colon mucosa the antibodies all show granular supranuclear reactivity with goblet cells. These antibodies show increased reactivity with colon adenomas and adenocarcinomas. A third group is formed by PARLAM 2, which also reacts with a large (〉5×106 Da) glycoprotein, showing a granular distribution in goblet cells. In colon carcinomas more extensive expression is found than in normal colonic mucosa. Finally, the fourth group consists of PARLAM 11, which also reacts with a large (〉5×106 Da) glycoprotein, located in the brush border of colonic columnar cells. These antibodies might be useful tools for the analysis of the expression of mucin related glycoproteins in normal, preneoplastic and neoplastic colon mucosa.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of materials science 27 (1992), S. 4107-4114 
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The molecular ordering in the bulk of a low molar mass-type liquid crystalline (LC) material is visualized by examining with scanning electron microscopy LC diacrylate films, in which the low molar mass-type LC ordering is fixed by UV polymerization. Micrographs of the fracture surfaces of these films exhibit a fine texture, illustrating the presence of a layered structure in the samples. This layered structure correlates with the director orientation in LC materials aligned by surface interaction.
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  • 8
    ISSN: 1573-5028
    Keywords: Antibody ; coordinated expression ; genetic engineering ; protein assembly ; root ; secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To explore the feasibility of employing antibodies to obtain disease resistance against plant root pathogens, we have studied the expression of genes encoding antibodies in roots of transgenic plants. A model monoclonal antibody was used that binds to a fungal cutinase. Heavy and light chain cDNAs were amplified by PCR, fused to a signal sequence for secretion and cloned behind CaMV 35S and TR2′ promoters in a single T-DNA. The chimeric genes were cloned both in tandem and in a divergent orientation. The roots of tobacco plants transformed with these constructs produced antibodies that were able to bind antigen in an ELISA. Immunoblotting showed assembly to a full-size antibody. In addition, a F(ab′)2-like fragment was observed, which is probably formed by proteolytic processing. Both antibody species were properly targeted to the apoplast, but the full-size antibody was partially retained by the wall of suspension cells. The construct with divergent promoters showed a better performance than the construct with promoters in tandem. It directed the accumulation of functional antibodies to a maximum of 1.1% of total soluble protein, with half of the plants having levels higher than 0.35%. The high efficiency of this construct probably results from coordinated and balanced expression of light and heavy chain genes, as evidenced by RNA blot hybridization.
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  • 9
    ISSN: 1432-2048
    Keywords: Daucus (somatic embryogenesis) ; Embryogenesis (somatic) ; Peroxidase, cationic (isoenzymes) ; Protein glycosylation ; Glycoprotein secretion ; Somatic embryogenesis ; Tunicamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Somatic embryogenesis of carrot (Daucus carota L.) is inhibited by the glycosylation inhibitor tunicamycin. This inhibition is reversible by the addition of correctly glycosylated glycoproteins which have been secreted into the culture medium. To identify the proteins responsible for complementation, glycoproteins present in the medium of embryo cultures were purified and tested for their activity in the tunicamycin inhibition/ complementation assay. A 38-kDa glycoprotein was purified that could restore embryogenesis to more than 50% of that in untreated controls. This 38-kDa glycoprotein was identified as a heme-containing peroxidase on the basis of its A405/A280 ratio (Reinheit Zahl or RZ) and enzyme activity. The 38-kDa peroxidase consisted of four different cationic isoenzymes of which only one or possibly two appeared active in the complementation assay. The cationic peroxidase isoenzymes from the carrot medium could be effectively replaced by cationic horseradish peroxidases which depended on their catalytic properties for their ability to restore tunicamycin-inhibited somatic embryogenesis.
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  • 10
    ISSN: 1573-5052
    Keywords: Bana ; Leaves ; Phytomass ; Root/shoot ratio ; Spodosol ; Structure ; Tropical forest ; Wetland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Bana, or Low Amazon Caatinga is an evergreen sclerophyllous woodland. It occurs on bleached quartz sands in the lowlands of SW Venezuela, where it occupies relatively small ‘islands’ amidst Tall Amazon Caatinga which is exclusively developed on tropaquods. There is an outer vegetation belt about 20 m in width in which trees over 10 m in height occur (Tall Bana); its structure and floristic composition resemble Tall Amazon Caatinga. Low Bana (maximum tree height usually below 5 m) follows next. The central part is occupied by Open Bana in which even lower trees are very widely spaced. Destructive phytomass sampling was carried out for chemical analyses in seven plots along a 150 m line across the zonation. The total dry matter of living plants including roots of Tall Bana (30–32 kg/m2) compares rather well with 41 kg/m2 in Tall Amazon Caatinga. This is only 9–14 kg/m2 in Low Bana, and 4–6 kg/m2 in Open Bana. The average root % of total phytomass increases from 41% in Tall Bana to 63% in Low Bana, and is 88% in Open Bana. Average total dry dead above-ground phytomass (including standing trees and stumps) declines from 1 kg/m2 in Tall Bana to 0.2 kg/m2 in Open Bana. An accumulation of dead matter in Low and Open Bana, relative to the above-ground phytomass of living plants, is noted and this contrasts with the general absence of raw humus in the soil. Eighty-two species of woody plants (dbh≥1 cm) were recorded on the total plot area (640 m2); 90% of the species are also known to occur in Tall Amazon Caatinga. The species number declines from 59 in Tall Bana to 18 in Open Bana. Mesophylls sensu strictu dominate in Tall Bana, while notophylls are dominant in Low and Open Bana. Herbaceous species are less numerous: most of them belong to the Araceae, Bromeliaceae, Orchidaceae, Droseraceae, Eriocaulaceae and Xyridaceae.
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