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A monoclonal antibody, designated NAT-9 II:3F-6F (IgM), was generated by hybridization of mouse myeloma cells with spleen cell from mice immunized with normal human bone marrow cells. The antibody reacted with 40-60% of bone marrow cells as analysed on samples from 40 normal individuals and only with a subpopulation of human acute myeloid leukemia (AML) cells of the M2 class (20/20 tested) and M4 class (12/12 tested) (subclasses of the French-American-British (FAB) classification), but not with leukemic cells of the M1 (0/12 tested) and M5 (0/12 tested) FAB subclasses. This is in contrast to many other myeloid-specific monoclonal antibodies. Fluorescence-activated cell sorter (FACS) analyses and morphological examination of cells stained with peroxidase as based on the NAT-9 II:3F-6F monoclonal antibody showed that this antibody reacted with a distant differentiation antigen which is absent on myeloblasts, but expressed on promyelocytes, myelocytes, metamyelocytes, band neutrophils, and on a minority of mature granulocytes. NAT-9 II:3F-6F did not bind to circulating monocytes, T and B cells, erythrocytes and a variety of different human cell culture lines. Immunoblotting demonstrated that the antibody bind to a cellular component with a Mr approximately 97.400 dalton. The antibody may be useful in immunological subclassification of non-lymphoid leukemias and in studies on hematopoiesis.

Cell proliferation in the murine thymus was studied in vivo under normal conditions and from 0 to 24 hr after a single injection of a water-soluble extract from mouse thymus, mouse spleen, and mouse skin. The thymus extract reduced during the first 24 hr the mitotic activity 40%; the spleen extract had a weaker inhibitory effect. The skin extract had no such effect. The thymus extract and spleen extract inhibited the flux of cells into the S phase 0–8 hr after the injection of the extract. Initial labelling index was also reduced in this period. Eight hours after injection of the thymus or spleen extracts the inhibited cells initiated DNA synthesis. The rate of progression of blast cells through the cell cycle was normal 24 hr after the injection of the extracts. It was deduced from the analysis that the thymus extract inhibits processes triggering Go/Gi cells into DNA synthesis, the inhibition of G2 efflux being of minor importance. Finally a model for the regulation of proliferating thymic blast cells and the emigration of small lymphocytes from the thymus is proposed.

A monoclonal antibody (designated K:1–6F) generated by hybridization of mouse myeloma cells with spleen cells from mice immunized with the erythroleukemic cell line K562 was found by fluorescence-activated cell sorter analysis, dot-blot assay and electroimmunoblotting to bind to a majority of cells in the K562 and HEL erythroleukemic cell lines, to a subset of cells of the erythroid lineage from normal bone marrow, to a subset of cells in all analysed cases (total 10) of erythroleukemia, and weakly to cells from patients with myeloid leukemia. The antibody did not bind to normal erythrocytes, monocytes, T- and B lymphocytes or granulocytes, as well as a panel of human malignant cell lines of hemopoietic origin (HL60, U937, Daudi, Molt-3, RH-L4 and U266). Biochemical characterization of the antigen defined by the antibody suggests that the epitope is defined by a carbohydrate structure alone or in combination with proteins. Four molecules with M, 100 kD, 65 kD, 45 kD and 18 kD respectively were immunoprecipitated from Triton X-100 extract of K562 erythroleukemia cells. Neuraminidase did not affect the binding of the antibody, whereas tunicamycin reduced the K:1–6F expression. The K:1–6F Mab was in normal bone marrow found to be specific for erythroid precursor cells and may therefore be useful in examination of normal and leukemic erythropoiesis.

The distribution coefficients of a large number of chlorinated phenols and phenolic compounds containing two aromatic nuclei have been determined on cross-linked polyvinylpyrrolidone and on anion exchangers in the acetate form. Solutes with low affinity for polyvinylpyrrolidone have been separated in 1 mM hydrochloric acid, while 3–7 M acetic acid has been used for chlorinated compounds. Acetic acid is a suitable eluent in chromatography on anion exchangers. Hydrogen bonding of phenolic protons to the resins, together with non-polar interactions, are mainly responsible for the sorption on both of these types of resins. Under the applied conditions, the relative importance of hydrogen bonding is greater for polyvinylpyrrolidone than for the anion exchanger.

The retention volumes of a large number of aromatic compounds in acetic acid and dilute hydrochloric acid were determined on two pellicular polyamide resins. With carboxylic acids, ion exchange is an important sorption mechanism in dilute eluents. Hydrogen bonding of the hydroxyl proton to the carbonyl group in the polyamide is the dominant sorption mechanism for non-electrolytes that contain hydroxyl groups. Intramolecular hydrogen bonding decreases the sorption of ortho-substituted solutes containing hydroxyl groups. Several solutes were separated within a few minutes but greater separation factors were required than in experiments with small, uniform beads.

The ultimate goal of resource monitoring is to analyse the spatial distribution of the balance between supply and demand of a certain resource. Remote sensing techniques are commonly used for the assessment of the supply of resources. By integrating remote sensing with the related techniques of geographical information systems and spatial modelling, the demand as well as the accessibility of resources can be analysed. The article gives an overview over methods for integrated resource monitoring. Examples from arid environments are also presented.

Aromatic compounds containing hydroxyl and carboxyl groups are retained in aqueous medium by cross-linked polyvinylpyrrolidone due to hydrogen bonding, with the resin serving as a proton acceptor. Efficient separations were obtained in 0.001 M hydrochloric acid. With substances containing seveal proton-donating groups, improved results were obtained by using a more efficient eluent, e.g., 5 M acetic acid.

Cooking over open fire with solid fuels results in incomplete combustion and indoor air pollution (IAP) causing respiratory and other diseases leading to nearly two million premature deaths per year. In urban areas, IAP interacts with outdoor pollutants in toxic chemical mixtures affecting also other citizens and damaging regional air quality in terms of 'brown clouds'. Deaths result mainly in women, children and infants, who are directly exposed to smoke in unventilated kitchens, thus reflecting differentiated and unequal impacts across population groups. Despite the heavy health burden and discomfort, IAP has only recently been recognised as associated with neglected diseases. In search of synergies between adaptation and mitigation, we seek gender sensitive social innovations to halt smoke, soot and early death while reducing deforestation and carbon emissions. Using transition arenas as a participatory method for experiments and social learning we engaged with local entrepreneurs and peasant farmers in sub-Saharan Africa to initiate co-production of efficient flue-piped stoves that save energy, labour and lives. Findings indicate that successful design, production and adoption of improved cooking stoves is possible, but the structural challenges of poverty, inequality and distrust may inhibit further diffusion and more profound processes of social learning. Insights from local studies must therefore be contextualised into broader understandings, as attempted here, while local adoption must be combined with wider initiatives and government policies into complex micro-to-macro solutions that provide forceful effects against IAP and its drivers.

It is urgent in science and society to address climate change and other sustainability challenges such as biodiversity loss, deforestation, depletion of marine fish stocks, global ill-health, land degradation, land use change and water scarcity. Sustainability science (SS) is an attempt to bridge the natural and social sciences for seeking creative solutions to these complex challenges. In this article, we propose a research agenda that advances the methodological and theoretical understanding of what SS can be, how it can be pursued and what it can contribute. The key focus is on knowledge structuring. For that purpose, we designed a generic research platform organised as a three-dimensional matrix comprising three components: core themes (scientific understanding, sustainability goals, sustainability pathways); cross-cutting critical and problem-solving approaches; and any combination of the sustainability challenges above. As an example, we insert four sustainability challenges into the matrix (biodiversity loss, climate change, land use changes, water scarcity). Based on the matrix with the four challenges, we discuss three issues for advancing theory and methodology in SS: how new synergies across natural and social sciences can be created; how integrated theories for understanding and responding to complex sustainability issues can be developed; and how theories and concepts in economics, gender studies, geography, political science and sociology can be applied in SS. The generic research platform serves to structure and create new knowledge in SS and is a tool for exploring any set of sustainability challenges. The combined critical and problem-solving approach is essential.

Although several magnetic separation methods have been used to provide some initial subdivision and characterization of the particulate emission products of fossil-fuel combustion1–5, only recently has there been any attempt to use magnetic properties to distinguish between different emission types6,7 and atmospheric particulate sources8. In the present study, we use several concentration-independent magnetic parameters and ratios to characterize dusts from different source types. Non-destructive measurements of saturation isothermal remanence, anhysteretic remanence and frequency-dependent susceptibility differentiate atmospheric dusts into groups characterized by distinctive magnetic mineral and grain size assemblages. These assemblages can be related to the source of the dusts as they reflect differences in the conditions under which the magnetic oxides developed. The magnetic parameters are sensitive to differences between dusts arising from fossil-fuel combustion and from other industrial processes, and those derived from soil erosion. Within the set of soil-derived dusts, the magnetic parameters distinguish between the weathering regimes operating in different source areas.

We report the establishment of human-human hybridomas producing monoclonal antibody of predefined antigenic specificity. The U-266 human myeloma cell line was incubated in the presence of 8-azaguanine, and a rapidly growing, 8-azaguanine-resistant, hypoxanthine/amethopterin/thymidine (HAT) medium-sensitive mutant line, U-266AR1, was selected. These cells were fused with lymphoid cells from uninvolved spleens removed at staging laparotomy from patients with untreated Hodgkin's disease who had been previously sensitized to the chemical allergen 2,4-dinitrochlorobenzne. Hybrid cell cultures growing in HAT medium were screened for IgG production. Positive cultures were selected and their supernatants were tested in a solid-phase radioimmunoassay for reactivity with dinitrophenyl hapten coupled to bovine serum albumin. Cultures producing specific antibody were subcloned and expanded, and their antibody products were shown to be monoclonal by biosynthetic labeling and sodium dodecyl sulfate/polyacrylamide gel electrophoresis.

The biological attributes and cellular origin of the malignant cells in Hodgkin's disease have been subject to numerous investigations both on fresh biopsy material and from long-term in vitro cultures of cells derived from Hodgkin's disease lesions. Studies on fresh biopsy material have led to suggestions that Hodgkin's cells are derived from T-lymphocytes, B-lymphocytes, or monocytes/macrophages. However, all these studies are hampered by the low amounts of Reed-Sternberg cells in the neoplastic lesions as well as some technical difficulties. It has consequently been desirable to establish long-term cell cultures of the malignant Hodgkin's cells, and the technical problems as well as the experimental outcome of these studies are reviewed. Among the technical, the potential and limitations in the use of monoclonal antibodies are described in particular. A number of cell lines from Hodgkin's disease lesions have been described, but a critical appraisal of these studies reveal that most of the published cell lines can be dismissed as being non-representative for Hodgkin's and ReedSternberg cells; most of the cell lines are thus EBV-transformed lymphocytes and in some cases even nonhuman cell lines. Two cell lines (L428 and SU/RH-HD-1), however, seem to be derived from the malignant cell population in Hodgkin's disease. The phenotypic analyses of these lines-and in particular the SU/RH-HD-1 line—strongly indicate that cells have monocyte/macrophage attributes, and it is concluded that Hodgkin's disease is a neoplasm of cells in the monocyte/macrophage lineage.

The phenotypic characteristics of a cloned giant cell line, SU/RH-HD-1, established from the spleen of a patient with Hodgkin's disease were studied. The cells grew slowly, adhered to the culture vessel surface, and had an elongated, irregular shape. After trypsinization, they became spherical and measured 30-100 micron in diameter. Although most cells were mononuclear, binucleated and multinucleated cells could be identified in expanded cultures. The cells phagocytized latex and ink particles and were nonspecific esterase-positive, but they did not secrete lysozyme. They were Epstein-Barr nuclear antigen-negative, and their culture fluid supernatants were devoid of reverse transcriptase activity. Electron microscopy revealed cells with a pronounced smooth endoplasmic reticulum, free ribosomes, some filaments, and mitochondria. Many 0.5- to 1.0-micron invaginations (pits) were seen along the cell membrane. Nucleoli were enlarged and prominent in the very heterochromatic nuclei. The SU/RH-HD-1 cells had 10- to 100-micron-long pseudopodia that were sometimes forked or branching, as well as multiple stress fibers. Electron microscopic appearance was suggestive of that of macrophages. This interpretation of the results was substantiated by monoclonal antibody studies, which revealed that the cells express antigenic determinants distinctive for cells of the monocyte-macrophage lineage and by functional studies demonstrating that the cells are capable of specific antigen presentation to immune T-cells. The SU/RH-HD-1 cells were aneuploid and could be cloned, first in liquid culture by limiting dilution and later in semisolid medium. It was likely that the SU/RH-HD-1 cells were derived from the neoplastic giant cell population in Hodgkin's disease and that they originated from cells of the mononuclear phagocyte-reticulum cell lineage.

Udgivelsesdato: 1985-null

Malignant, neoplastic cell populations are characterized by their autonomous growth, invasiveness and metastatic activity. These features, like normal cellular activities, are all dependant on the interaction between the cells and their microenvironment. The cell membrane therefore constitutes a crucial biological structure in neoplastic cell behaviour.

Comparative microspectropholometry of the DNA content of Feulgen-stained megakaryocytes from the bone marrow and from those retained in the pulmonary circulation showed that the ploidy classes 8 N, 16 N and 32 N are found in both bone marrow and pulmonary circulation, whereas the 64 N class is found in the bone marrow only. Electron microscopic examination of megakaryocytes retained in the lungs revealed typical ‘naked nuclei’.

Publisher Summary This chapter discusses the technical aspects of human-human monoclonal antibody producing hybridomas. Human monoclonal antibodies have potential applications in a broad spectrum of biomedical areas. The various steps outlined in this chapter provide a workable foundation for investigators trying to establish human-human hybridomas. Human-human hybridoma methodology differs in several respects from the conventional mouse hybridoma procedures. The chapter describes the present techniques for making human hybridomas along with some of the experience. Those methodological aspects that are similar to mouse-mouse (or mouse-rat) hybridoma technology are discussed briefly in the chapter.

Cloning and immortalization of antibody-producing human B lymphocytes are required to establish monoclonal cell lines that secrete human immunoglobulin of predefined specificity. Such cultures may be obtained either (1) by transformation of normal B lymphocytes, e.g., by virus, or (2) by somatic cell hybridization of normal B lymphocytes with malignant cells, resulting in cell hybrids that have preserved the secretion of specific antibody of the B lymphocyte and the growth properties of the malignant cells. The former method has been used almost exclusively with Epstein—Barr virus (EBV) as the transforming agent, and some human monoclonal antibodies with interesting specificity have been obtained by this method (Steinitz et al., 1979; Zurawski et al., 1978; Irie et al.,1982; Watson et al., 1983; Rosen et al.,1983).

Microspectrophotometric investigations of Feulgen-stained rat bone marrow megakaryocytes, comparing the traditional smear method and a new 1 G sedimentation and 40 degrees C evaporation (S. E.) method, have shown that the latter reveals a significant group of megakaryocytes (ca. 30 percent) with a DNA content of 64 N. This group is totally absent when the smear method is used.

Cloned human cell lines of squamous-cell lung carcinoma and small-cell lung carcinoma were treated with 5-azacytidine (5-azaC), 12-0-tetradecanoyl-phorbol-13 acetate (TPA), retinoic acid (RA), or a combination of these drugs, and the effects on cellular morphology, in vitro growth properties, antigenicity, tumorigenicity and metastatic activity in nude mice were studied. Antigenicity was measured by the expression of major histocompatibility antigens (MHC) and of lung-tumor-associated antigens. 5-AzaC treatment resulted in subclones with shorter population doubling times (from 40-50 hr down to 14-20 hr) and increased cloning efficiencies (from less than 1% to 5-50%). TPA and RA induced loss of proliferative activity in vitro and tumorigenicity in vivo of both lines. This was morphologically associated with the appearance of an abundance of large vaculated cells which by DNA-analysis were all found to be in G0-G1 phase. However, 2 of the 5-azaC-treated subclones were insensitive to both TPA and RA, whereas the remaining subclones (20) all responded like untreated lines to TPA and RA. One of the sublines insensitive to TPA and RA formed metastases in nude mice in contrast to all the other lines used. The density of lung-tumor-associated antigens was significantly reduced by TPA-RA treatment, whereas the expression of MHC antigens was unaffected. In contrast, 5-azaC resulted in some cases in increased density of MHC antigens. The effects of 5-azaC on cellular phenotypes were not directly correlated to the total genomic content of 5-methylcytosine. The data suggest that this experimental system is suitable for studies of phenotypic features of malignant cells as related to cellular differentiation.

A new era in immunology was introduced by Kohler and Milstein (1975, 1976) when they devised a method for the production of mouse “hybridomas” capable of secreting monoclonal antibodies of predefined antigenic specificity. Immunologists were liberated from the constraints and difficulties previously associated with the preparation and use of heteroantisera, since the clonal selection and immortality of hybridoma cell lines assure the monoclonality, monospecificity, and permanent availability of their antibody products. However, although monoclonal antibodies of murine or other rodent origin have been extraordinarily powerful new reagents in laboratory investigations, their clinical use is likely to be severely limited by the fact that they are foreign proteins. Human immunoglobulin-producing cells have been fused to mouse myeloma cells to generate chimeric hybridomas (Schwaber, 1975; Levy and Dilley, 1978). Although there have been rare instances in which long-term, stable production of human antibody has thus been achieved (Schlom et al., 1980), most such hybrids have tended to be highly unstable due to the selective loss of human chromosomes. An alternative approach to the generation of antibody-producing human lymphocyte cell lines has involved the transformation of human B-lymphocytes with Epstein-Barr virus (EBV) (Steinitz et al., 1977; Zurawski et al., 1978; Koskimies, 1979) but this method appears to be of limited practical usefulness because the cultures tend to cease antibody production after a variable period (Zurawski et al., 1978).

The immunological phenotypes of leukemia cell samples from 60 patients, of whom 54 had acute myeloid leukemia (AML), were assessed with a panel of monoclonal antibodies (Mabs) with specificity for the following epitopes: Epitopes associated with myeloid leukemia cells, Epitopes expressed only on immature myeloid cells (or subsets) and on monocytes, Epitopes only expressed on granulocytes or on granulocytes and mature myeloid cells (promyelocytes, myelocytes and monocytes), Epitopes on HLA-class II (DR) and HLA-class I molecules and on insulin receptors. This panel of Mabs proved useful to identify leukemia cells in blood and to assess their myeloid origin. The panel of Mabs was found also to be useful for immunophenotyping of leukemia cells. Furthermore, the analysis revealed considerable variations in the immunological phenotype of AML cells, reflecting antigenic heterogeneity within the individual leukemia cell population as well as abnormal or no expression of histocompatibility antigens and insulin receptors in some samples. Some of the Mabs bound preferentially to subgroups in the French-American-British (FAB) classification.

Treatment of adult AKR mice with tissue-specific mitotic inhibitor mol. wt. 1,000--20,000 extracted from the AKR thymus significantly delayed the onset of spontaneous thymus leukaemia, whereas extracts of other organs were without effect. A slight prolongation of survival time was found with spleen extract when administered to BALB/c mice infected with Rauscher virus, which causes leukaemia starting in the spleen. Thymus extracts of MW 100,000--300,000 caused myocardial degeneration in some leukaemic and nonleukaemic mice.

The currently available methods for the production of human monoclonal antibodies (Mabs) are: mouse-human hybrids, human-human hybrids, EBV transformation, and fusion of EBV-transformed specific B-lymphocytes with a malignant cell line. Each method has its advantages and drawbacks, but they are all inferior to an optimal functioning mouse hybridoma system. A significant obstacle is the lack of a reproducible method to obtain high amounts of antigen-specific B-lymphocytes. However, it seems that newly developed in vitro antigen-priming methods may be a significant aid to the solution of this problem. Human Mabs have already been obtained against some types of human cancer, and the reactivity pattern has provided some biological information that seems not to be obtainable with non-human Mabs. It furthermore seems that the technology for production of human Mabs now has progressed to the stage where it permits a realistic hope that they soon can be applied in the diagnosis and treatment of human cancer.

The murine Lewis lung carcinoma is a long-term grafted tumor that, after subcutaneous inoculation, forms metastases to the lungs. Forty-two cell lines were established from a primary tumor site and 40 were established from lung metastatic foci. Cloned sublines were established from the original 82 lines, and 2 sublines among 405 were found to be tumorigenic but not metastatic (T+/M-), whereas the remaining 403 sublines were both tumorigenic and metastatic (T+/M+). The T+/M- phenotype was shown to be stable for greater than 2 yr. However, treatment of the T+/M- cell lines for 3 days with 3 microM 5-azacytidine resulted in reexpression of the metastatic phenotype in otherwise stable T+/M- lines. Also, 5-azacytidine treatment could result in loss of the metastatic phenotype in lines that had been stable T+/M+. The changes in tumorigenic and metastatic phenotypes were not associated with altered immunogenicity of the cells. Monoclonal antibodies were generated against T+/M+ cells, and one antibody ( M36D3 ) was found to bind only to T+/M+ cells. Reactivity of the antibody was found to co-vary with expression of the metastatic phenotype. The antigen recognized by M36D3 antibody thus seems to be associated with metastatic capability. The antigen was found by two-dimensional gel electrophoretic analysis to be a cellular protein of Mr approximately equal to 45,000 and pI approximately equal to 6.7.

Cells of cloned lines derived from human squamous lung carcinomas spontaneously become heterogeneous with respect to several tumor-associated cell surface carbohydrates such as the sialosyl-Lea oligosaccharide antigen or the recently described oligosaccharide recognized by monoclonal antibody 43-9F. Subclones derived from these cultures are initially homogeneous with respect to the presence or absence of a specific cell surface carbohydrate but gradually revert back to a heterogeneous population. Cells of homogeneous subclones having both the sialosyl-LEa and 43-9F cell surface antigens and other subclones lacking them were injected subcutaneously in nude mice. All clones expressing these tumor-associated cell surface carbohydrates were found to be highly tumorigenic, whereas those lacking them were nontumorigenic or, at most, weakly tumorigenic. Clones having the tumor-associated cell surface carbohydrates were more resistant to cytotoxic attack by purified mouse natural killer cells than those clones lacking these carbohydrates, suggesting that the tumorigenicity of the former clones may be influenced by immunoprotective effects of these novel carbohydrates.

Human monocytes were prepared from peripheral blood by buoyant density centrifugation and subsequent absorption-elution on a column of gelatin beads. The eluted fraction containing 60-80% monocytes was used as feeder layer in cloning of the human lymphoma line RH-L4, the human myeloma line SKO-007, and a human hybridoma cell derived from the latter line. Cloning efficiencies were high in both liquid and semisolid media with all 3 cell lines tested. Feeder monocytes could also be successfully used after having been stored in liquid nitrogen.

Normal thymic lymphoid cell suspensions were studied in the electron microscope. The suspensions contained cells (6–23 per cent) in various degrees of lytic degeneration with swelling and disintegration of both nucleus and cytoplasm. Only a minority of the degenerating cells showed pyknotic changes and these cells had always a well preserved cytoplasm. The percentage of degenerating cells was compared with the percentage of cells stained in the nigrosin-dye exclusion test. A close relationship between these two values was found, suggesting that supravital staining primarily affects cells in lytic cell degeneration. It appears that vital stains only affect already degenerating cells with a subsequent increase of a preexisting intracellular edema. This suggestion was corroborated by the finding that addition of nigrosin dye to thymic cell suspensions does not depress aerobic metabolism.

Do altered land management practices offer possibilities to sequester carbon in the soil and thereby miti- gate increasing atmospheric CO2 as well as improve local soil fertility? This study investigates the impact of fallow periods on soil organic carbon in semiarid subsistence agroecosystems on sandy and poor soils in Kordofan, Sudan. The area is char- acterized by low-input cultivation of millet and sorghum in combination with livestock grazing. Recently, cultivation inten- sity has increased and the fallow periods have been short- ened. Soil carbon contents were assessed for sites that have been under various cultivation intensities, ranging from 30 years of fallow to 30 years of continuous cultivation. Soil or- ganic carbon showed a significant negative relationship with cultivation intensity. Measurements indicate a mean increase of approximately 4 g soil organic carbon (SOC) per square meter per year during fallow periods. The possibilities of in- creasing soil organic carbon by land management were also estimated through simulations using the Century model. Mod- eling suggested that reverting an intensely cropped millet site to permanent grassland would sequester approximately 1-2 g SOC/m 2 /yr, with higher rates during the early part of the pe- riod. Continuous intense cultivation could decrease the cur- rently low soil carbon levels even further. These results indi- cate that altered land management could contribute to transforming degraded semiarid agroecosystems from a source to a weak sink for atmospheric CO2. Possible data improvements and uncertainties are discussed.

In a combined stathmokinetic, autoradiographic, and microspectrophotometric study on the cytodynamics in mouse epidermis, cirdardian rhythms were observed in the number of cells within the various phases (except G/sub 2/) of the mitotic cell cycle, and in mitotic rate. S-Phase influx and efflux were computed and were found to vary during a 24-hr period. No diurnal rhythm was observed in mitotic rate in the epithelium of small intestine. /sup 3/H-Thymidine (1 ..mu..Ci/g; sp act 5 Ci/mmol) induced mitotic delay in labeled cells 2 to 8 hr after administration. A supranormal mitotic activity in unlabeled cells was observed 12 to 24 hr after injection of /sup 3/H-TdR. ''Cold'' thymidine had no effects on epidermal cell proliferation. S-Phase duration and average cell cycle time were estimated by traditional cell kinetic methods. The results suggest a /sup 3/H-TdR-induced synchrony in cells entering the S phase 0 to 15 hr after injection of the precursor. A mitotic delay was seen in small intestinal epithelium 2 to 6 hr after injection of the precursor.

International audience; The word “biorefinery” was coined to describe an industrial process of cracking biomass resembling the industrial cracking of fossil carbon (Kamm and Kamm, 2005). But it can also be seen as an "Intermediary Object" (Vinck 2009) socially constructed by macroactors in European projects such as "Star-Colibri", with a view to developing a particular vision of the transition towards the use of renewable resources. Narrative approaches are mobilized by sociologists to describe the complexity of systemic change in a multilevel perspective (Grin, Rotmans and Schot, 2010). Narratives have also been used in Economics and Management of Technologies since the works of David (1985) to Dumez and Jeunemaitre (2005), to identify and describe various potential technological trajectories. We used a similar (analysis, cognitive process, method, procedure.) in the course of an interdisciplinary approach involving economists chemists and biochemists. Our "narrative approach" aims at highlighting the diversity of technological expectations. In the dominant vision of the biorefinery, large-scale units crack the biomass into a limited number (top 10 chemical intermediates) of standardized "small molecules", easily purified and introduced into the traditional petrochemical processes. Production of liquid fuels ("bio"-fuels) would enable economic operators to reach this large scale, while chemicals with high added value should ensure their economic balance (Bozell, Petersen 2010). However, other technical routes are worth considering: For example the intrinsic complexity and self-organization properties of biomass materials can be used as a way to introducing principles of green chemistry in processes operating more systematically on the macromolecular level ("one pot", whole plant, "reactive extrusion", modified starches, photochemistry and so on ..). They minimize fractionation steps and thus the use of energy or water. They can also entail smaller scale chemical units, which would not need to be stitched to the existing network of large-scale commodities production (of "bio"fuels,) and would be better rooted in local production areas. The discussion on the transition must therefore integrate the diversity of possible technical (ways) (routes) and examine how institutional policies support either of these solutions.