Automated information retrieval using CLIPS

Expert systems have considerable potential to assist computer users in managing the large volume of information available to them. One possible use of an expert system is to model the information retrieval interests of a human user and then make recommendations to the user as to articles of interest. At Cal Poly, a prototype expert system written in the C Language Integrated Production System (CLIPS) serves as an Automated Information Retrieval System (AIRS). AIRS monitors a user's reading preferences, develops a profile of the user, and then evaluates items returned from the information base. When prompted by the user, AIRS returns a list of items of interest to the user. In order to minimize the impact on system resources, AIRS is designed to run in the background during periods of light system use

Transferrin-polycation conjugates as carriers for DNA uptake into cells.

We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbumin, has been covalently linked to the small DNA-binding protein protamine or to polylysines of various sizes through a disulfide linkage. These modified transferrin molecules maintain their ability to bind their cognate receptor and to mediate efficient iron transport into the cell. The transferrin-polycation molecules form electrophoretically stable complexes with double-stranded DNA, single-stranded DNA, and modified RNA molecules independent of nucleic acid size (from short oligonucleotides to DNA of 21 kilobase pairs). When complexes of transferrin-polycation and a bacterial plasmid DNA containing the gene for Photinus pyralis luciferase are supplied to eukaryotic cells, high-level expression of the luciferase gene occurs, demonstrating transferrin receptor-mediated endocytosis and expression of the imported DNA. We refer to this delivery system as "transferrinfection.

Ectopic expression of the erythrocyte band 3 anion exchange protein, using a new avian retrovirus vector

12 pages, 5 figures, 3 tables.A retrovirus vector was constructed from the genome of avian erythroblastosis virus ES4. The v-erbA sequences of avian erythroblastosis virus were replaced by those coding for neomycin phosphotransferase, creating a gag-neo fusion protein which provides G418 resistance as a selectable marker. The v-erbB sequences following the splice acceptor were replaced by a cloning linker allowing insertion of foreign genes. The vector has been tested in conjunction with several helper viruses for the transmission of G418 resistance, titer, stability, transcription, and the transduction and expression of foreign genes in both chicken embryo fibroblasts and the QT6 quail cell line. The results show that the vector is capable of producing high titers of Neor virus from stably integrated proviruses. These proviruses express a balanced ratio of genome length to spliced transcripts which are efficiently translated into protein. Using the Escherichia coli beta-galactosidase gene cloned into the vector as a test construct, expression of enzyme activity could be detected in 90 to 95% of transfected target cells and in 80 to 85% of subsequently infected cells. In addition, a cDNA encoding the avian erythrocyte band 3 anion exchange protein has been expressed from the vector in both chicken embryo fibroblasts and QT6 cells and appears to function as an active, plasma membrane-based anion transporter. The ectopic expression of band 3 protein provides a visual marker for vector function in these cells.The support of the European Molecular Biology Laboratory during the initial phases of this work is acknowledged. S.F. was supported by the Swedish Medical Research Foundation, and A.M. was supported by the Juan March Foundation. Grants were obtained from the Swedish Cancer Society, the Wallenberg Foundation, the Children's Cancer Fund, and Kjell and Marta Beijer's Foundation.Peer reviewe

Classics in Miniature

The Faust-Idea. – A little seamstress is seduced and made wretched. A great scholar of all four disciplines is the culprit. Surely this could not have happened under ordinary circumstances? No, certainly not! Without the assistance of the devil incarnate the great scholar would never have pulled this off. – Could this really be the greatest German "tragic idea", as one can hear among Germans? Friedrich Nietzsche, Human all too Human.Die Faust-Idee. – Eine kleine Nähterin wird verführt und unglücklich gemacht; ein großer Gelehrter aller vier Fakultäten ist der Übeltäter. Das kann doch nicht mit rechten Dingen zugegangen sein? Nein, gewiß nicht! Ohne die Beihilfe des leibhaftigen Teufels hätte es der große Gelehrte nicht zustande gebracht. - Sollte dies wirklich der größte deutsche “tragische Gedanke” sein, wie man unter Deutschen sagen hört? Friedrich Nietzsche: Menschliches, allzu Menschliche

Zum Gedenken an Franz Firbas (1902-1964) anlässlich seines 100. Geburtstages

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Charakterisierung von EEPROM Tunneloxiden mittels transienter Strom- und Kapazitätsmessungen

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Narrative medicine and narrative practice: partners in the creation of meaning

Background Narrative medicine has emerged as an approach to whole person care and to support the clinician-patient therapeutic relationship. Although training in narrative medicine is usually based on the study of literary or artistic works, the same attitude of close reading can also be applied in conversations with patients or learners.MethodWe held a two-day narrative medicine workshop, incorporating two approaches: 'Conversations Inviting Change' (CIC) and humanities-based narrative medicine as taught by Columbia University. The workshop was primarily experiential, with theoretical components of both approaches. Participants brought active concerns for confidential breakout sessions and engaged in text-based and reflective writing exercises. Participants generated metaphors to describe these approaches to narrative medicine.Results Participants included a mix of community and hospital-based practitioners, pre-dominantly doctors. Participants considered the two approaches to be compatible and enhance each other. One metaphor generated was that Columbia style narrative medicine is ’like an individual lens which allows you to see things clearer’, it allows practitioners a different perspective on their patients and that CIC teaching ‘is a frame of glasses in which the lenses could be placed to enhance the ease of use’. Another metaphor was that the former ‘is like learning from a cadaver in the anatomy lab’, while the latter ‘is like running a clinical simulation’.Conclusion We believe this was the first workshop integrating these approaches to narrative medicine. They appear to be highly complementary. Both approaches lead to enhanced attention to narratives which has clear applicability to clinical practice

E-cadherin regulates cell growth by modulating proliferation-dependent β-catenin transcriptional activity

β-Catenin is essential for E-cadherin–mediated cell adhesion in epithelial cells, but it also forms nuclear complexes with high mobility group transcription factors. Using a mouse mammary epithelial cell system, we have shown previously that conversion of epithelial cells to a fibroblastoid phenotype (epithelial-mesenchymal transition) involves downregulation of E-cadherin and upregulation of β-catenin transcriptional activity. Here, we demonstrate that transient expression of exogenous E-cadherin in both epithelial and fibroblastoid cells arrested cell growth or caused apoptosis, depending on the cellular E-cadherin levels. By expressing E-cadherin subdomains, we show that the growth-suppressive effect of E-cadherin required the presence of its cytoplasmic β-catenin interaction domain and/or correlated strictly with the ability to negatively interfere with β-catenin transcriptional activity. Furthermore, coexpression of β-catenin or lymphoid enhancer binding factor-1 or T cell factor 3 with E-cadherin rescued β-catenin transcriptional activity and counteracted E-cadherin–mediated cell cycle arrest. Stable expression of E-cadherin in fibroblastoid cells decreased β-catenin activity and reduced cell growth. Since proliferating cells had a higher β-catenin activity than G1 phase–arrested or contact-inhibited cells, we conclude that β-catenin transcriptional activity is essential for cell proliferation and can be controlled by E-cadherin in a cell adhesion-independent manner

Igbp1 is part of a positive feedback loop in stem cell factor–dependent, selective mRNAtranslation initiation inhibiting erythroid differentiation

The authors thank Dr Victor de Jager for assistance with the Rosetta Resolver software; Dr Ivo Touw for many fruitful discussions and critical reading of the manuscript; Liu Wing for technical assistance; Drs Peter Seither, Andreas Weith (Boehringer Ingelheim, Biberach, Germany), Helmuth Dolznig, Thomas Waerner, and Sandra Pilat (IMP, Vienna, Austria) for mRNA profiling of erythroblasts, of which the complete data will be published elsewhere; Dr Bart Aarts (Erasmus MC, Rotterdam, The Netherlands) for assistance in confocal scanning microscopy; Dr David Brautigan (University of Virginia, Charlottesville) for anti-Igbp1 antibodies; Dr Manfred Boehm (National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, MD) for anti-Uhmk1 antibodies; and Ortho-Biotech (Tilburg, The Netherlands) for their kind gift of Eprex (erythropoietin).Stem cell factor (SCF)–induced activation of phosphoinositide-3-kinase (PI3K) is required for transient amplification of the erythroblast compartment. PI3K stimulates the activation of mTOR (target of rapamycin) and subsequent release of the cap-binding translation initiation factor 4E (eIF4E) from the 4E-binding protein 4EBP, which controls the recruitment of structured mRNAs to polysomes. Enhanced expression of eIF4E renders proliferation of erythroblasts independent of PI3K. To investigate which mRNAs are selectively recruited to polysomes, we compared SCF-dependent gene expression between total and polysome-bound mRNA. This identified 111 genes primarily subject to translational regulation. For 8 of 9 genes studied in more detail, the SCF-induced polysome recruitment of transcripts exceeded 5-fold regulation and was PI3K-dependent and eIF4E-sensitive, whereas total mRNA was not affected by signal transduction. One of the targets, Immunoglobulin binding protein 1 (Igbp1), is a regulatory subunit of protein phosphatase 2A (Pp2a) sustaining mTOR signaling. Constitutive expression of Igbp1 impaired erythroid differentiation, maintained 4EBP and p70S6k phosphorylation, and enhanced polysome recruitment of multiple eIF4E-sensitive mRNAs. Thus, PI3K-dependent polysome recruitment of Igbp1 acts as a positive feedback mechanism on translation initiation underscoring the important regulatory role of selectivemRNArecruitment to polysomes in the balance between proliferation and maturation of erythroblasts. (Blood. 2008; 112:2750-2760)peer-reviewe