125,619 research outputs found
[Letter from Charles Raddatz to Henry A. Wise, September, 1878]
No full textLetter from Charles Raddatz to Henry A. Wise. He writes about a teaching position Upshur B. Quinby is looking to fill at his school. He recommends Mr. H. M. Chenoweth for the position
Microbial transformation of tetralin
No full textBiocatalytic oxidation of cyclic hydrocarbons has many potential applications in the production of fine chemicals. Especially regioselective hydroxylation of aromatics and the stereospecific formation of secondary alcohols is of interest for the pharmaceutical and flavoring industries. Hydroxylating enzymes are active under mild reaction conditions allowing the controlled transformation of less stable substrates and formation of easily oxidizable products (e.g., catechols). Furthermore, application of microorganisms for the removal of cyclic hydrocarbons from waste streams provides a highly versatile method for the removal of toxic cyclic hydrocarbons.Major drawbacks in the application of biocatalysts, for these processes are the need for cofactor regeneration and the low stability as a result of inhibitory effects of the hydrocarbon substrates. The investigations described in this thesis have dealt with microbiological aspects of the design of a biocatalytic hydroxylation process. As a model for microbial oxy-functionalization, the dioxygenation of tetralin to 1,2,5,6,7,8-hexahydro- cis - naphthalene diol and the subsequent chemical rearrangement to 5,6,7,8-tetrahydro-1-naphthol has been studied. Tetralin provides a perfect model compound for specific hydroxylation since different sites of initial oxidative attack can be envisaged (Chapter 4). Moreover, different oxygenated derivatives of tetralin are of interest to pharmaceutical industries as precursors for the production of hormone-analogs, sedatives, and tranquilizers. Also for the production of fragrance compounds, oxygenated tetralins may be useful (Chapter 1 and 4). Special attention has been given to the mechanism of the toxicity of cyclic hydrocarbon substrates. In Chapter 2 literature data concerning inhibitory effects of cyclic hydrocarbons and other lipophilic compounds on microorganisms has been reviewed.Selection of suitable biocatalysts . Chapter 3 describes the procedure that has been followed to obtain microorganisms that are able to use tetralin as sole source of carbon and energy. Enrichment cultures on tetralin were set up with soil samples from polluted areas, and also cyclic hydrocarbon-utilizing strains from culture collections were tested. Initial attempts were unsuccessful, which was attributed to substrate inhibition. By lowering the concentration of tetralin in the incubation media, growth occurred in several enrichment cultures, but no pure strains were isolated. Eventually, a pure culture was isolated by supplying tetralin in subsaturating concentrations (lower than 125 μmol/liter). Initial studies on the inhibitory action of tetralin on this strain, Arthrobacter sp. strain T2, indicated that an aqueous concentration of approximately 100 μmol/liter). already impaired growth, whereas quantities above the saturation concentration (approximately 125 μmol/liter) fully inhibited growth of the starved cells. These findings were taken into consideration in new attempts to isolate tetralin-utilizing strains. Addition of tetralin via the vapor phase, thus limiting the aqueous concentration, resulted in the selection of another bacterium from an enrichment culture set up with soil from a land farming facility. Furthermore, four strains that were previously isolated on o -xylene, styrene, or mesitylene respectively were also shown to degrade tetralin. Alternatively, enrichment cultures were set up with tetralin added in a non-miscible, non-biodegradable, and non-toxic organic solvent (Fluorocompound 40) which limits the aqueous concentration by serving as a reservoir for the toxic substrate. From these enrichment cultures, two different strains were obtained that were able to use tetralin as sole source of carbon and energy.In Chapter 4 a survey of initial oxidation steps that may be involved in the biotransformation of tetralin is presented together with experimental data on the accumulation of intermediates oxygenated intermediates from tetralin. The knowledge on the initial oxidative steps has been used to evaluate the potentialities of the selected strains. It appeared that five strains started with an initial oxidation of the benzylic carbon atom, resulting in the formation of a-tetralol and a-tetralone. Two strains exhibited aspecific oxidations yielding products characteristic of both oxidation of the aromatic and the alicyclic moiety. Only one strain, Corynebacterium sp. strain C125, degraded tetralin by initially oxidizing the benzene nucleus. The metabolic pathway of tetralin in Corynebacterium sp. strain C125 has been studied in detail. The results, which are presented in Chapter 5, show that the aromatic moiety is attacked by a dioxygenase at the carbon atoms proximal to the cycloalkane substituent. The cis-dihydro diol that is formed in this reaction is further metabolized via a dehydrogenase to 5,6,7,8-tetrahydro-1,2-dihydroxynaphthalene, which is a substrate for an extra-diol cleaving catechol dioxygenase. Acidrearrangement of 1,2,5,6,7,8-hexahydro- cis -1,2-naphthalene diol yielded the corresponding phenols, 5,6,7,8-tetrahydro-1-naphthol and 5,6,7,8-tetrahydro-2-naphthol, in a ratio of 1:6. The apparent preference for the 2-naphthol limits the feasability of this system for the formation of the desired fragrance compound, 5,6,7,8-tetrahydro-1-naphthol However, the specificities of the different tetralin- transforming strains enable the formation of some high-value precursors for the synthesis of pharamaceuticals (Chapter 1 and 4).Mechanism of the inhibitory action of tetralin and other cyclic hydrocarbons .From the results presented in Chapter 3 it is clear that tetralin has a deleterious effect not only on tetralin-utilizing strains but also on other organisms. From incubations with possible intermediates of tetralin metabolism it appeared that tetralin, and not an intermediairy reaction product, was responsible for the observed toxicity. Similar observations for other cyclic hydrocarbons suggested that the inhibitory action of these compounds resulted from interaction with the membrane(s) of microbial cells (Chapter 2).In Chapter 6 the mechanism of the toxic action of tetralin on microorganisms has been investigated in intact cells of tetralin-utilizing and non-utilizing bacteria, as well as in liposomes. The results of these investigations indicated that tetralin was accumulated in the membrane, which lead to a significant increase in membrane surface area. Similar studies with other cyclic hydrocarbons, as described in Chapter 7, showed that in addition to the increase in surface area also an increased membrane fluidity was observed. The effective concentrations of the cyclic hydrocarbons necessary for disturbing membrane integrity decreased with increasing hydrophobicity (measured as partition coefficient in an octanol/water system). The hydrophobicity of the hydrocarbon compounds provides a good measure for the partition coefficients of these compounds between the aqueous environment and the membrane (Chapter 7). From the estimated membrane/buffer partition coefficients the actual concentrations of the different in the membrane could be calculated and related to their effects on the membrane properties.As a result of the membrane expansion and increase in bilayer fluidity, the integrity of the membrane was impaired. Consequently, the passive permeability of the membrane to protons (ions) was increased and the activity of the membrane embedded proton-pump cytochrome c oxidase was reduced. As a result of an increased permeability for protons and impairment of proton-pumping activity, the proton motive force was dissipated and internal pH homeostasis was disturbed. The dissipation of the proton motive force may result in the depletion of metabolic energy, but lowering of the internal pH may lead to complete inactivation of enzymes.In Chapter 8 some implications of the postulated mechanism of the toxic action of cyclic hydrocarbons have been discussed in relation to the application of microorganisms for the biotransformation of such compounds. Also some aspects of the adapation of the cells have been treated in connection with a general response of cells to stress. Finally, some methods to prevent deleterious effects of cyclic hydrocarbons have been discussed in view of the proposed toxicity mechanism
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Quality assessment of prenatal cytogenetic diagnosis : some guidelines for handling amniotic fluid and chorionic villus material
No full textOngeveer 1 op de 200 baby's wordt geboren met een chromosoomafwijking. De gevolgen daarvan kunnen sterk uiteenlopen, van verwaarloosbaar (het kind zal er in zijn of haar ontwikkeling geen last van ondervinden) tot aan 'niet levensvatbaar'. Veel chromosomale afwijkingen blijken gepaard te gaan met hartafwijkingen, ontwikkelingsachterstand en uiterlijke bijzonderheden.
Zie: Samenvatting
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Ungewohnte Perspektiven auf das Subjekt. Bedeutung von Schmutz und alltäglichen Körpergesten
No full textThiessen B. Ungewohnte Perspektiven auf das Subjekt. Bedeutung von Schmutz und alltäglichen Körpergesten. In: Raddatz A, ed. Versuchungen, ein Fest : Dokumentation eines Abschieds. Oldenburger Beiträge zur Geschlechterforschung. Vol 12. 2006: 35-38
Influence of NFκB inhibitors on IL-1β-induced chemokine CXCL8 and -10 expression levels in intestinal epithelial cell lines: glucocorticoid ineffectiveness and paradoxical effect of PDTC
No full textActivation of intestinal epithelial cell (IEC) nuclear factor kappa B (NF kappa B) and the consequent chemokine upregulation are crucial events in inflammatory bowel disease (IBD) pathogenesis. Not much is known about the consequences of NF kappa B inhibition in terms of chemokine expression in intestinal cells. Therefore, we aimed to evaluate the efficacy of compounds known to disrupt the NF kappa B pathway on NF kappa B transcriptional activity and CXCL8 and CXCL10 gene expression in intestinal cell lines. The influence of NF kappa B inhibitors (dexamethasone, pyrrolidine dithiocarbamate (PDTC) and BAY 11-7082) on IL-1 beta-induced NF kappa B transcriptional activity was investigated by transient transfection of Caco-2 cells with an NF kappa B-secreted alkaline phosphatase reporter plasmid. Il-1 beta stimulated CXCL8 and CXCL10 mRNA and protein expression and was studied in Caco-2 and HT29 cells in the presence and absence of the NF kappa B inhibitors by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent serologic assay, respectively. To reveal alternative signalling cascades, experiments were also performed in the presence of the p38MAPK inhibitor SB 203580 and the ERK inhibitor PD 98059. Dexamethasone did not downregulate chemokine expression sufficiently, probably due to a lack of glucocorticoid receptors in these cells. While BAY11-7082 inhibited chemokine expression, PDTC led to a paradoxical upregulation of CXCL8 in Caco-2 cells, which could be prevented by inhibition of p38MAPK. These data explain the frequent unresponsiveness of IBD to glucocorticoid treatment and suggest that alternative NF kappa B inhibition in IECs might be of use in IBD therapy. Drug development based on measuring anti-NF kappa B activity might be misleading and should therefore also include studies on relevant gene products
NF-κB-dependent synergistic regulation of CXCL10 gene expression by IL-1β and IFN-γ in human intestinal epithelial cell lines
No full textBackground and aims Little is known about the intestinal epithelial expression and secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and monocytes. We aimed to study CXCL10 gene expression and regulation by the pro-inflammatory cytokines interleukin (IL)-1 beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in intestinal epithelial cell lines. Materials and methods CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29 and DLD1 human colon epithelial cells, treated with IL-1 beta, TNF-alpha, IFN-gamma alone or in combination with each other by real-time polymerase chain reaction (PCR), Northern blotting and enzyme-linked immunoabsorbent assay (ELISA). Transient transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10-kappa B2 mutant promoter and gelshifts and supershifts for nuclear factor (NF)-kappa B were also performed. Results Real-time PCRs and ELISA experiments revealed that IL-1 beta was the strongest and earliest inducer of CXCL10 messenger ribonucleic acid (mRNA) expression and protein secretion in Caco-2 cell line, whereas INF-gamma had a delayed kinetics. There was a strong synergistic effect of either TNF-alpha or IL-1 beta with IFN-gamma both on CXCL10 mRNA expression and protein secretion in all three cell lines. Real-time PCR and ELISA experiments using a specific NF-kappa B inhibitor and transfection experiments with a NF-kappa B-binding defective CXCL10 promoter construct revealed that the induction of CXCL10 by IL-1 beta and its synergism with IFN-gamma is NF-kappa B dependent. Conclusion These data demonstrate that in colonic epithelial cells, depending on the cellular context and utilizing the NF-kappa B pathway, IL-1 beta alone and/or in synergism with IFN-gamma may play a major role in the induction of CXCL10
The Introduction of Arrays in Prenatal Diagnosis: A Special Challenge
No full textGenome-wide arrays are rapidly replacing conventional karyotyping in postnatal cytogenetic diagnostics and there is a growing request for arrays in the prenatal setting. Several studies have documented 1-3% additional abnormal findings in prenatal diagnosis with arrays compared to conventional karyotyping. A recent meta-analysis demonstrated that 5.2% extra diagnoses can be expected in fetuses with ultrasound abnormalities. However, no consensus exists as to whether the use of genome-wide arrays should be restricted to pregnancies with ultrasound abnormalities, performed in all women undergoing invasive prenatal testing or offered to all pregnant women. Moreover, the interpretation of array results in the prenatal situation is challenging due to the large numbers of copy number variants with no major phenotypic effect. This also raises the question of what, or what not to report, for example, how to deal with unsolicited findings. These issues were discussed at a working group meeting that preceded the European Society of Human Genetics 2011 Conference in Amsterdam. This article is the result of this meeting and explores the introduction of genome-wide arrays into routine prenatal diagnosis. We aim to give some general recommendations on how to develop practical guidelines that can be implemented in the local setting and that are consistent with the emerging international consensus. Hum Mutat 33: 923-929, 2012. (C) 2012 Wiley Periodicals, Inc
Pragmatic Case Studies as a Source of Unity in Applied Psychology
No full textTo unify or not to unify applied psychology: that is the question. In this article we review pendulum swings in the historical efforts to answer this question—from a comprehensive, positivist, “top-down,” deductive yes between the 1930s and the early 60s, to a postmodern no since then. A rationale and proposal for a limited, “bottom-up,” inductive yes in applied psychology is then presented, employing a case-based paradigm that integrates both positivist and postmodern themes and components. This paradigm is labeled “pragmatic psychology” and, its specific use of case studies, the “Pragmatic Case Study Method” (“PCS Method”). We call for the creation of peer-reviewed journal-databases of pragmatic case studies as a foundational source of unifying applied knowledge in our discipline. As one example, the potential of the PCS Method for unifying different angles of theoretical regard is illustrated in an area of applied psychology, psychotherapy, via the case of Mrs. B. The article then turns to the broader historical and epistemological arguments for the unifying nature of the PCS Method in both applied and basic psychology.Peer reviewe
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