1,582 research outputs found
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. â 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. â Could this really be the greatest German "tragic idea", as one can hear among Germans? Friedrich Nietzsche, Human all too Human.Die Faust-Idee. â Eine kleine Nähterin wird verfĂźhrt und unglĂźcklich gemacht; ein groĂer Gelehrter aller vier Fakultäten ist der Ăbeltäter. Das kann doch nicht mit rechten Dingen zugegangen sein? Nein, gewiĂ nicht! Ohne die Beihilfe des leibhaftigen Teufels hätte es der groĂe Gelehrte nicht zustande gebracht. - Sollte dies wirklich der grĂśĂte deutsche âtragische Gedankeâ sein, wie man unter Deutschen sagen hĂśrt? Friedrich Nietzsche: Menschliches, allzu Menschliche
Charakterisierung von EEPROM Tunneloxiden mittels transienter Strom- und Kapazitätsmessungen
[no abstract
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 âlike an individual lens which allows you to see things clearerâ, it allows practitioners a different perspective on their patients and that CIC teaching âis a frame of glasses in which the lenses could be placed to enhance the ease of useâ. Another metaphor was that the former âis like learning from a cadaver in the anatomy labâ, while the latter âis like running a clinical simulationâ.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-cadherinâmediated 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-cadherinâmediated 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 phaseâarrested 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 factorâdependent, 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)âinduced 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
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