gebhart/patrepeval huggingface dataset:
Gene therapy in plants (1999)

Genetics allows the elucidation of gene function through the analysis of gene malfunction. Modern genetics and genomics require ways for in situ modification of genes, by means of point mutations, deletions, and additions. The availability of sequence information of many organisms dictates rapid development of reverse genetics procedures. Until recently, targeting of genes with the help of introduced homologous sequences, here referred to as homologous recombination-dependent gene targeting (hrdGT), was the method of choice, at least for mammalian systems. However, in higher eukaryotic organisms such as mammals and plants, exogenously introduced DNA preferably integrates in random positions in the genome, by the process of illegitimate recombination, and only infrequently can targeted integration events be detected. Recently an alternative strategy became available for precise reverse genetics. Specific chimeric oligonucleotides, COs, consisting of DNA and RNA stretches, were found to induce point mutations in several mammalian genes tested (see below). This technique, here referred to as chimeric oligonucleotide-dependent mismatch repair, cdMMR, has now been used for plants: this issue of the Proceedings includes two reports describing stable changes in the genomes of tobacco and maize after treatment with chimeric oligonucleotides (1, 2).
Ultrasound of the small joints of the hands and feet: current status (2007)

The aim of this article was to review the current status of ultrasound imaging of patients with rheumatological disorders of the hands and feet. Ultrasound machines with high-resolution surface probes are readily available in most radiology departments and can be used to address important clinical questions posed by the rheumatologist and sports and rehabilitation physician. There is increasing evidence that ultrasound detects synovitis that is silent to clinical examination. Detection and classification of synovitis and the early detection of bone erosions are important in clinical decision making. Ultrasound has many advantages over other imaging techniques with which it is compared, particularly magnetic resonance. The ability to carry out a rapid assessment of many widely spaced joints, coupled with clinical correlation, the ability to move and stress musculoskeletal structures and the use of ultrasound to guide therapy accurately are principal amongst these. The use of colour flow Doppler studies provides a measure of neovascularisation within the synovial lining of joints and tendons, and within tendons themselves, that is not available with other imaging techniques. Disadvantages compared to MRI include small field of view, poor image presentation, and difficulty in demonstrating cartilage and deep joints in their entirety. Contrast-enhanced magnetic resonance provides a better measure of capillary permeability and extracellular fluid than does ultrasound. The ability to image simultaneously multiple small joints in the hands and feet and their enhancement characteristics cannot be matched with ultrasound, though future developments in 3-D ultrasound may narrow this gap. Magnetic resonance provides a more uniform and reproducible image for long-term follow-up studies.
Application of the Bivalent Ligand Approach to the Design of Novel Dimeric Serotonin Reuptake Inhibitors (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTApplication of the Bivalent Ligand Approach to the Design of Novel Dimeric Serotonin Reuptake InhibitorsAmir P. Tamiz, Jianrong Zhang, Mei Zhang, Cheng Z. Wang, Kenneth M. Johnson, and Alan P. KozikowskiView Author Information Drug Discovery Program Georgetown University Medical Center 3970 Reservoir Road, NW, Washington, D.C. 20007-219 Department of Pharmacology and Toxicology University of Texas Medical Branch Galveston, Texas 77555-1031 Cite this: J. Am. Chem. Soc. 2000, 122, 22, 5393–5394Publication Date (Web):May 18, 2000Publication History Received18 January 2000Published online18 May 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/ja000199fhttps://doi.org/10.1021/ja000199frapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views590Altmetric-Citations27LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amines,Ligands,Oligomers,Piperidines,Selectivity Get e-Alerts
Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease (2002)

We compared the antiplatelet effects of clopidogrel and the intravenous platelet P2Y(12) receptor antagonist AR-C69931MX, which acts on the same receptor as clopidogrel by a different and reversible mechanism and, unlike clopidogrel, is active in vitro. Thirteen patients with acute coronary syndromes entered into a phase II study of intravenous AR-C69931MX (Group 1) and eight patients undergoing intracoronary stent implantation and treated with clopidogrel (Group 2) were studied using a whole blood single-platelet counting aggregation assay. Group 2 patients were also studied using turbidimetry with ADP and TRAP as agonists and whole blood [(14)C]5HT release to study dense granule secretion in response to ADP, collagen and TRAP. In Group 2 studies, a therapeutic concentration of AR-C69931MX was added in vitro before and after clopidogrel administration. AR-C69931MX in Group 1 achieved greater inhibition of ADP-induced platelet aggregation than clopidogrel in Group 2 and AR-C69931MX in vitro added to the effects of clopidogrel on ADP-induced aggregation. AR-C69931MX but not clopidogrel inhibited TRAP-induced aggregation and granule secretion and AR-C69931MX had a more consistent inhibitory effect on collagen-induced responses. In conclusion, therapeutic administration of clopidogrel moderately inhibits platelet P2Y(12) receptor activation and substantially greater P2Y(12) receptor blockade can be achieved with AR-C69931MX.
Legal issues with robots (2013)

Who is responsible when property is damaged or someone is injured by an automated system? Existing product liability laws have not yet been tested in the context of robots.
Signal transduction through a biomolecular receptor tyrosine protein kinase composed of a platelet-derived growth factor receptor-CD4 chimera and the nonreceptor tyrosine protein kinase Lck. (1993)

We have generated a novel "receptor tyrosine kinase" by fusing the extracellular and transmembrane domain of the mouse platelet-derived growth factor receptor (PDGFR) to the cytoplasmic domain of CD4 and coexpressing the construct with the murine cytoplasmic tyrosine protein kinase p56lck. NMuMG cells, which are mouse mammary gland epithelial cells that lack endogenous platelet-derived growth factor (PDGF) receptor expression, were stably transfected with both PDGFR-CD4 and p56lck. The PDGFR-CD4 chimeric protein was expressed at the cell surface and formed a complex with p56lck. Addition of PDGF to these cells led to increased tyrosine phosphorylation of a 56-kDa protein likely to be p56lck and several unidentified cellular proteins. The enzymatic activity of p56lck was increased after treatment with PDGF, indicating that dimerization (or oligomerization) mediated by ligand binding at the cell surface is capable of inducing the activation not only of receptor tyrosine kinases but nonreceptor tyrosine kinases as well. However, the PDGFR-CD4.p56lck complex was, in contrast to the wild type PDGF receptor, not able to induce a PDGF-dependent mitogenic response or DNA synthesis in NMuMG cells. Analysis of several known substrates of the PDGFR-signaling pathway indicates an early block in the transduction of the signal generated by p56lck.
Electrical responses of coronary artery smooth muscle associated with the cardiac muscle action potential in the monkey. (1991)

1. In cardiac strips of the monkey ventricle which included a section of coronary artery (cardiac preparation), a depolarizing response, which appeared to be an excitatory junction potential (EJP), and a hyperpolarizing response were observed from the coronary artery smooth muscles when an action potential was generated in cardiac muscle by the application of electrical stimulation to the cardiac muscle alone. 2. In an isolated preparation of the coronary artery dissected from the ventricle (arterial preparation), similar responses, an EJP and a hyperpolarizing response, could be evoked by electrical stimulation. 3. In the cardiac preparation, the threshold of electrical stimulation for generation of the cardiac action potential and for production of an electrical response in the vascular smooth muscle were the same. 4. The EJP and the hyperpolarizing responses of the smooth muscle of the coronary artery ceased or were weakened by elimination of the adventitial connective tissues and endothelium, respectively, in both the cardiac preparation and the coronary artery preparation. 5. These results indicate that the action potential of cardiac muscle generated by electrical stimulation activates the nerves and the vascular endothelium, which, in turn, produce an EJP and a hyperpolarizing response of the coronary artery smooth muscle, respectively.
Die Reaktion von Carbonsäuren mit Acetalen des N, N‐Dimethylformamids: eine Veresterungsmethode (1965)

Abstract The reaction of carboxylic acids with acetals of N,N‐dimethylformamide represents a preparatively useful esterification method. Experiments bearing on the use, properties and scope of this reaction are described.
Inhibition of Stat3 activity by YC-1 enhances chemo-sensitivity in hepatocellular carcinoma (2007)

The present study investigated the effect of YC-1, a novel anti-cancer agent, on the chemo-sensitivity of hepatocellular carcinoma (HCC). YC-1 was administered with chemo-cytotoxic drug, cisplatin, both in vitro and in vivo. YC-1 alone downregulated the expression of phosphorylated form of signal transducers and activators of transcription 3 (P-Stat3[705]), a key mediator in chemo-resistance. When combined with cisplatin, YC-1 further promoted tumor cell apoptosis, decreased the expression of P-Stat3(705), Bcl-xL, CyclinD1 and survivin, and induced the cleavage of caspase 9 and PARP. Overexpression of Stat3 reversed YC-1 induced cell death. YC-1 inhibited Stat3 activity by enhancing the polyubiquitination of P-Stat3(705) induced by cisplatin. In the in vivo setting, YC-1 combined with cisplatin remarkably suppressed tumor growth in a HCC xenograft model, and this effect was also accompanied by YC-1 mediated downregulation of P-Stat3(705), Bcl-xL, Cyclin D1 and survivin, and induction of cleaved caspase 9 and PARP in the tumor tissues. In conclusion, the present study demonstrated a novel anti-cancer effect of YC-1 in enhancing chemo-sensitivity of HCC cells to cisplatin through a Stat3 dependent manner. This finding provides insight into design of a new therapeutic strategy to improve efficacy of chemotherapy in HCC patients.
Kinetic characterization of the interaction of biotinylated human interleukin 5 with an Fc chimera of its receptor α subunit and development of an ELISA screening assay using real‐time interaction biosensor analysis (1995)

The interaction of biotinylated human interleukin 5 ([BT]hIL5) with immobilized receptor was measured with a real-time biosensor, and these results were used as a basis for configuring an ELISA for screening antagonists of hIL5-receptor binding. The recombinant proteins used, hIL5 and shIL5R alpha-Fc (chimeric fusion receptor constructed by linking the soluble component of the hIL5 receptor alpha subunit to the constant domain (Fc) of immunoglobulin G), were produced by the expression of cloned vectors in Drosophila schneider (S2) cells. Initial attempts to develop a screening assay by direct immobilization of soluble IL5 receptor to microtiter plates proved unsatisfactory and led to use of the Fc chimera attached by oriented immobilization via protein A. Hence, shIL5R alpha-Fc was bound to protein A covalently immobilized on a carboxymethyl dextran (CM-5) biosensor chip. Specific binding was demonstrated of [BT]hIL5 to protein A/shIL5R alpha-Fc receptor complex. The binding was high affinity (Kdapp = 6 nM), reversible and saturable. The affinity of [BT]hIL5 was similar to that determined with the biosensor assay for unmodified hIL5. The observed kinetics of the interactions of Fc chimera with protein A (slow dissociation) and of [BT]hIL5 with immobilized Fc chimera (faster dissociation) were favorable for subsequently establishing a microtiter plate based ELISA assay. In the latter, Fc chimera was immobilized to the plate via protein A as in the biosensor experiment. Binding of [BT]hIL5 to immobilized Fc chimera in the ELISA was concentration dependent and was competed by both hIL5 and shIL5R alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
A symmetric patch-based correspondence model for occlusion handling (2005)

Occlusion is one of the challenging problems in stereo. In this paper, we solve the problem in a segment-based style. Both images are segmented, and we propose a novel patch-based stereo algorithm that cuts the segments of one image using the segments of the other, and handles occlusion areas in a proper way. A symmetric graph-cuts optimization framework is used to find correspondence and occlusions simultaneously. The experimental results show superior performance of the proposed algorithm, especially on occlusions, untextured areas and discontinuities
Volume‐Phase Holographic Gratings and the Efficiency of Three Simple Volume‐Phase Holographic Gratings (2000)

Volume‐phase holographic (VPH) gratings show great potential as an alternative dispersing element to the classical surface‐relief (SR) gratings presently used in most astronomical spectrographs. We present an introduction to this technology and give the results of an evaluation of three different VPH gratings: a 300 line mm−1 grating optimized at 1064 nm, a 1200 line mm−1 grating optimized at 532 nm, and a 2400 line mm−1 grating optimized for operation at 532 nm.
Drug-selected coexpression of human glucocerebrosidase and P-glycoprotein using a bicistronic vector. (1994)

Bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. Using the long 5' untranslated region of encephalomyocarditis virus as translational enhancer of the second gene, a bicistronic unit composed of cDNA for human P-glycoprotein [the product of the multidrug resistance gene, MDR1 (also called PGY1)] as selectable marker and cDNA for human glucocerebrosidase (GC; EC 3.2.1.45) (a membrane-associated lysosomal hydrolase) was constructed. NIH 3T3 cells transfected with a Harvey murine sarcoma virus retroviral vector carrying this bicistronic cassette (pHaMCG) express active P-glycoprotein and GC and expression of both proteins augments coordinately with selection for increased colchicine resistance. Percoll gradient analysis of homogenates showed that GC was targeted to the lysosomal fraction. The ability to select for expression of GC with natural product drugs after introduction of the pHaMCG retroviral vector may be useful in gene therapy strategies for Gaucher disease.
Contribución al estudio y diagnóstico de la micobiota patógena de la caña de azúcar (Saccharum sp. Híbrida) en Cuba (2000)

En la cana de azucar, nuestro principal cultivo, se presentan numerosos hongos causantes de enfermedades que pueden destruir las plantaciones o provocar grandes danos. La cana de azucar en el mundo se afecta por 137 patologias de origen fungico, de las cuales oficialmente en Cuba aparecen registradas 33 enfermedades, a pesar de tenerse fuertes evidencias de la existencia de otras que pasan inadvertidas.
Silicone Breast Implant Rupture: Pitfalls of Magnetic Resonance Imaging and Relative Efficacies of Magnetic Resonance, Mammography, and Ultrasound (1999)

The objective of this study was to evaluate the relative efficacies of magnetic resonance (MR) imaging, ultrasonography, and mammography in implant rupture detection and to illustrate pitfalls in MR image interpretation. Thirty patients referred by plastic surgeons with suspected breast implant rupture were prospectively evaluated using MR, ultrasonography, and mammography. Imaging examinations were interpreted independently and blindly for implant rupture and correlated to operative findings. Surgical correlation in 16 patients (53 percent) with 31 implants showed 13 (42 percent) were intact, 5 (16 percent) had severe gel bleed, and 13 (42 percent) were ruptured. MR sensitivity was 100 percent and specificity was 63 percent. Accuracy for rupture was 81 percent with MR, higher than with ultrasonography and mammography (77 and 59 percent, respectively). We describe a specific pitfall in MR interpretation, the "rat-tail" sign, composed of a medial linear extension of silicone along the chest wall. Seen in eight cases (four intact, three ruptures, one gel bleed), the rat-tail sign may lead to misdiagnosis of implant rupture if seen in isolation. Magnetic resonance imaging is more accurate and sensitive than ultrasonography and mammography in detecting breast implant rupture. We describe a new sign (rat-tail sign) composed of medial compression of the implant simulating silicone extrusion as a potential false-positive MR finding for rupture. This article presents clinical experience with magnetic resonance, mammography, and ultrasound in the diagnosis of implant rupture and defines and illustrates potential pitfalls of MR interpretation, including the new rat-tail sign.
P19-43. Regulatory T cell epitopes in a dendritic cell-targeted HIV vaccine delivery platform (2009)

Results Six highly promiscuous HLA class II T-cell epitopes in both the heavy and light chain constant domains of IgG were identified computationally. Epitopes were synthesized and shown to bind multiple HLA class II molecules with high affinity. These sequences specifically upregulate FoxP3 expression of CD4+CD25high T cells from healthy human donors. Co-incubation of these epitopes with various self and foreign antigens leads to antigen-specific suppression of effector T cell proliferation and cytokine secretion and an increase in IL-10 and CTLA-4 expression suggesting conversion of Teff to adaptive Tregs. The antiDEC-205 sequence was computationally screened for putative HLA DR4-restricted, regulatory T-cell epitopes using EpiMatrix. Epitopes were analyzed using OptiMatrix to select mutations that will reduce epitope binding affinity for HLA. Five regulatory T-cell epitopes were computationally identified. Per epitope, three modified sequences were selected and synthesized.
HIV-1-specific IFN-γ/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells (2005)

Functional and phenotypic characterization of virus-specific CD8 T cells against cytomegalovirus, Epstein-Barr virus, influenza (flu), and HIV-1 were performed on the basis of the ability of CD8 T cells to secrete IFN-gamma and IL-2, to proliferate, and to express CD45RA and CCR7. Two functional distinct populations of CD8 T cells were identified: (i) dual IFN-gamma/IL-2-secreting cells and (ii) single IFN-gamma-secreting cells. Virus-specific IFN-gamma/IL-2-secreting CD8 T cells were CD45RA-CCR7-, whereas single IFN-gamma CD8 T cells were either CD45RA-CCR7- or CD45RA+CCR7-. The proportion of virus-specific IFN-gamma/IL-2-secreting CD8 T cells correlated with that of proliferating CD8 T cells, and the loss of HIV-1-specific IL-2-secreting CD8 T cells was associated with that of HIV-1-specific CD8 T cell proliferation. Substantial proliferation of virus-specific CD8 T cells (including HIV-1-specific CD8 T cells) was also observed in CD4 T cell-depleted populations or after stimulation with MHC class I tetramer-peptide complexes. IL-2 was the factor responsible for the CD4-independent CD8 T cell proliferation. These results indicate that IFN-gamma/IL-2-secreting CD8 T cells may promote antigen-specific proliferation of CD8 T cells even in the absence of helper CD4 T cells.
Antiproliferative Activity of G-rich Oligonucleotides Correlates with Protein Binding (1999)

Oligonucleotides have been extensively studied as antisense or antigene agents that can potentially modulate the expression of specific genes. These strategies rely on sequence-specific hybridization of the oligonucleotide to mRNA or genomic DNA. Recently, it has become clear that oligonucleotides often have biological activities that cannot be attributed to their sequence-specific interactions with nucleic acids. Here we describe a series of guanosine-rich phosphodiester oligodeoxynucleotides that strongly inhibit proliferation in a number of human tumor cell lines. The presence of G-quartets in the active oligonucleotides is demonstrated using an UV melting technique. We show that G-rich oligonucleotides bind to a specific cellular protein and that the biological activity of the oligonucleotides correlates with binding to this protein. The G-rich oligonucleotide-binding protein was detected in both nuclear and cytoplasmic extracts and in proteins derived from the plasma membrane of cells. We present strong evidence that this protein is nucleolin, a multifunctional phosphoprotein whose levels are related to the rate of cell proliferation. Our results indicate that binding of G-rich oligonucleotides to nucleolin may be responsible for their non-sequence-specific effects. Furthermore, these oligonucleotides represent a new class of potentially therapeutic agents with a novel mechanism of action.