gebhart/patrepeval huggingface dataset:
Value and Cancer Care: Toward an Equitable Future (2010)

Health care expenses in the United States are increasing inexorably. At the current rate of growth, it is anticipated that 20% of the gross national product will consist of health-related expenditures within the next decade. Cancer is the second leading cause of death in the United States, and it is increasing in prevalence because of the aging of the population and the limited number of successful prevention strategies. As the biological characteristics of cancer come into sharper focus, targeted therapies are being developed that offer the promise of increased clinical benefit with fewer toxicities than are associated with conventional treatment. Although spectacular successes are infrequent with this approach, to date, the majority of targeted therapies are modestly effective at best, and extremely costly. This observation suggests that a broadly acceptable definition of value in a cancer therapeutic agent is not at hand, but is sorely needed from the vantage points of the patient and society. A corollary issue of enormous import is how to equitably distribute the health care dollar in the service of achieving the greatest good for the greatest number. Although cancer is responsible for only 5% of the health care budget, its cost is increasing and it can be viewed as paradigmatic when contemplating the problem of equity in health care. Here, a number of concepts are discussed that focus on this goal and its implications for the cancer patient and society at large.
Phase I Evaluation of STA-1474, a Prodrug of the Novel HSP90 Inhibitor Ganetespib, in Dogs with Spontaneous Cancer (2011)

This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients.
Spatially Selective Guided Growth of High-Coverage Arrays and Random Networks of Single-Walled Carbon Nanotubes and Their Integration into Electronic Devices (2006)

The chemical vapor deposition growth of unusual arrangements of single-walled carbon nanotubes (SWNTs) by the combined of use patterned catalysts and quartz substrates is reported. Nearly perfectly aligned, high-coverage arrays of SWNTs can be generated in this manner. High-coverage random networks of SWNTs can also be created in the same growth step, with good spatial alignment and electrical interfaces to the aligned arrays. Tubes with these geometries are ideally suited to applications in thin-film electronic devices. We demonstrate this possibility through the construction of thin-film-type transistors in which the random networks form the source and drain electrodes and the aligned arrays form the channel.
State of the Translational Science (2004)

A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.
Characterizing follicular dendritic cells: A progress report (2010)

In 1965, Mitchell and Abbot (Mitchell, J. and Abbot A, Nature 1965. 30: 500-502) discovered peculiar cells with filiform processes, which were capable of capturing and retaining antigens within secondary lymphoid organs. Yet half a century since the first description of follicular dendritic cells (FDC), their function and their histogenesis remain largely mysterious. FDC are thought to help with organization of the lymphoid follicles, to facilitate the germinal center reaction by presenting antigen to B cells, and to legislate the engulfment of apoptotic bodies, but it has proved difficult to stringently verify any of these functions. One reason for such slow progress is a dearth of markers specific to FDC and their precursors, which limits our ability to isolate, target, and follow FDC. Here we review the current state of FDC science with specific reference to a study in this issue of the European Journal of Immunology and its efforts in discovering new FDC markers.
Tracing pathways of transport protein evolution (2003)

We have conducted bioinformatic analyses of integral membrane transport proteins belonging to dozens of families. These families rarely include proteins that function in a capacity other than transport. Many transporters have arisen by intragenic duplication, triplication and quadruplication events, in which the numbers of transmembrane alpha-helical hydrophobic segments (TMSs) have increased. The elements multiplied may encode two, three, four, five, six, 10 or 12 TMSs and gave rise to proteins with four, six, seven, eight, nine, 10, 12, 20, 24 and 30 TMSs. Gene fusion, splicing, deletion and insertion events have also contributed to protein topological diversity. Amino acid substitutions have allowed membrane-embedded domains to become hydrophilic domains and vice versa. Some evidence suggests that amino acid substitutions occurring over evolutionary time may in some cases have drastically altered protein topology. The results summarized in this microreview establish the independent origins of many transporter families and allow postulation of the specific pathways taken for their appearance.
Inhibition of Rho Kinase (ROCK) Leads to Increased Cerebral Blood Flow and Stroke Protection (2005)

These findings indicate that the neuroprotective effect of ROCK inhibition is mediated by endothelium-derived NO and suggest that ROCK may be an important therapeutic target for ischemic stroke.
Sphingosine-dependent Protein Kinase-1, Directed to 14-3-3, Is Identified as the Kinase Domain of Protein Kinase Cδ (2003)

Some protein kinases are known to be activated by d-erythro-sphingosine (Sph) or N,N-dimethyl-d-erythro-sphingosine (DMS), but not by ceramide, Sph-1-P, other sphingolipids, or phospholipids. Among these, a specific protein kinase that phosphorylates Ser60, Ser59, or Ser58 of 14-3-3beta, 14-3-3eta, or 14-3-3zeta, respectively, was termed "sphingosine-dependent protein kinase-1" (SDK1) (Megidish, T., Cooper, J., Zhang, L., Fu, H., and Hakomori, S. (1998) J. Biol. Chem. 273, 21834-21845). We have now identified SDK1 as a protein having the C-terminal half kinase domain of protein kinase Cdelta (PKCdelta) based on the following observations. (i). Large-scale preparation and purification of proteins showing SDK1 activity from rat liver (by six steps of chromatography) gave a final fraction with an enhanced level of an approximately 40-kDa protein band. This fraction had SDK1 activity approximately 50000-fold higher than that in the initial extract. (ii). This protein had approximately 53% sequence identity to the Ser/Thr kinase domain of PKCdelta based on peptide mapping using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry data. (iii). A search for amino acid homology based on the BLAST algorithm indicated that the only protein with high homology to the approximately 40-kDa band is the kinase domain of PKCdelta. The kinase activity of PKCdelta did not depend on Sph or DMS; rather, it was inhibited by these sphingoid bases, i.e. PKCdelta did not display any SDK1 activity. However, strong SDK1 activity became detectable when PKCdelta was incubated with caspase-3, which releases the approximately 40-kDa kinase domain. PKCdelta and SDK1 showed different lipid requirements and substrate specificity, although both kinase activities were inhibited by common PKC inhibitors. The high susceptibility of SDK1 to Sph and DMS accounts for their important modulatory role in signal transduction.
Mapping of the ligand-selective domain of the Xenopus laevis corticotropin-releasing factor receptor 1: Implications for the ligand-binding site (1998)

The nonselective human corticotropin-releasing factor receptor 1 (hCRF-R1) and the ligand-selective Xenopus CRF-R1 (xCRF-R1) were compared. To understand the interactions of sauvagine and ovine CRF, both high-affinity ligands for hCRF-R1 but surprisingly weak ligands for xCRF-R1, chimeric receptors of hCRF-R1 and xCRF-R1 followed by double or multiple point mutations were constructed. Binding studies and cAMP assays demonstrated that the N-terminal domain exhibited the complete ligand selectivity of xCRF-R1. The important region was mapped between amino acids 70 and 89; replacement of amino acids Arg76, Asn81, Gly83, Leu88, and Ala89 in hCRF-R1 with the corresponding amino acids of xCRF-R1 (Gln76, Gly81, Val83, His88, and Leu89) resulted in a receptor that had approximately 30-fold higher affinity for human/rat CRF than for sauvagine. Mutagenesis of these amino acids in xCRF-R1 to the human sequence completely abolished the ligand selectivity of xCRF-R1. Mutagenesis of amino acids 88 and 89 in hCRF-R1 or xCRF-R1 had only a minor (approximately 2.5-fold) effect on the ligand selectivity of the mutant receptor. Substitution of Arg76, Asn81, and Gly83 in hCRF-R1 with the corresponding sequence of xCRF-R1 (Gln76, Gly81, and Val83) resulted in a receptor with approximately 11-fold higher affinity for human/rat CRF compared with ovine CRF or sauvagine. When only two of these three amino acids were mutated, no effect on the ligand selectivity was observed. On the basis of these data, it is suggested that amino acids 70-89 of CRF-R1 are important for the ligand binding site.
Fast skin color detector for face extraction (2005)

Human face detection is the first step for a fully automated face recognition system. It is also crucial to video surveillance systems, human computer interface, image/video retrieval systems. We consider color a very useful cue for face detection in color images. So that we propose a fast skin color detector for detecting in skin color patches in images with complex illumination and background. The accuracy and performance of this detector will have great affect on the upcoming feature extraction and verification processing. In our architecture, after applying a novel adaptive lighting compensation to alleviate the correct the illumination, a skin color filter based on normalized RGB color space is used to detect skin tone patches. Then, in order to remove noises and increase accuracy, morphological operations are used to refine the mask generated by the filter. Finally, the refined mask is used to gain the final result. For each step, including lighting compensation, color space modeling and final results, when compared to existing skin-tone color filtering algorithms, our algorithm is proven to be more robust and efficient by algorithm analysis and experiments results. After the processing, data amount is dramatically reduced and later algorithms can start with the skin patches remained.
Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts (2003)

We conclude that transplantation of EPCs may play a crucial role in reestablishing endothelial integrity in injured vessels, thereby inhibiting neointimal hyperplasia. These findings may have implications for novel and practical cell-based therapies for vascular disease.
The effects of morphology on 1H NMR spectra and relaxation in semicrystalline polyolefins (1984)

Abstract A brief résumé is given of the role of structural heterogeneity, magnetic dipolar couplings, molecular structure, and molecular motion in determining the 1 H NMR spectra and relaxation properties of heterogeneous solids such as semicrystalline polymers. Measurements of 1 H spin‐lattice relaxation in laboratory ( T 1 ) and rotating frames ( T ) are reported for a number of solid polyolefin samples. These include solution‐crystallized and melt‐crystallized polyethylene, annealed and quenched isotactic polypropene, and isotactic polybut‐1‐ene. In addition, broad‐line 1 H spectra, both normal and partially ( T ) relaxed, are reported for these materials as well as a number of pulsed NMR experiments having the philosophy of the so‐called Goldman–Shen experiment. Spin‐lattice relaxation ( T 1 ) for all samples is a single exponential process, whereas rotating‐frame relaxation comprises three exponential processes both on‐resonance (θ = 90°) and off‐resonance at the magic angle (θ = 54.7°), with the latter generally being much slower. The spectra show clearly the existence of components having differing degrees of mobility and, with the exception of the solution‐crystallized polyethylene, the partially ( T ) relaxed spectra indicate a correlation between breadth of resonance line and magnitude of T 1ρ . The Goldman–Shen‐type experiments indicate a spin‐diffusional transport of magnetization between the different spectral and ( T ) components. A computer program has been used to simulate the NMR behavior of a three‐region system comprising repeating units of infinite lamellae of different widths, each region having different intrinsic relaxation times and spin diffusion coefficients. The results demonstrate that the observed 1 H NMR behavior of these samples can be interpreted in terms of this model and that, inter alia , the long‐time T behavior reflects, qualitatively, the time taken for magnetization to diffuse a distance of the order of the dimensions of the region to which it corresponds.
Development of Improved Adenosine Deaminase Retroviral Vectors (1998)

A series of adenosine deaminase (ADA) retroviral vectors were designed and constructed with the goal of improved performance over the PA317/LASN vector currently used in clinical trials. First, the bacterial selectable-marker neomycin phosphotransferase (neo) gene was removed to create a "simplified" vector. Second, the Moloney murine leukemia virus long terminal repeat (LTR) promoter used for ADA expression was replaced with either the myeloproliferative sarcoma virus (MPSV) or SL3-3 LTR. Supernatant from each ADA vector was used to transduce ADA-deficient (ADA-) B- and T-cell lines as well as primary peripheral blood mononuclear cells (PBMC) from an ADA- severe combined immunodeficiency patient. Total ADA enzyme activity and ADA activity per integrant in the transduced cells demonstrated that the MPSV LTR splicing vector design provided the highest level of ADA expression per cell. This ADA(MPSV) vector was then tested in packaging cell lines containing either the gibbon ape leukemia virus envelope (PG13 cells), the murine amphotropic envelope (FLYA13 cells), or the feline endogenous virus RD114 envelope (FLYRD18 cells). The results indicate that FLYRD18/ADA(MPSV), a simplified ADA retroviral vector with the MPSV LTR, provides a 17-fold-higher level of ADA expression in human lymphohematopoietic cells than the PA317/LASN vector currently in use.
Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms (2004)

These studies describe the effects of nanosecond (10-300 ns) pulsed electric fields (nsPEF) on mammalian cell structure and function. As the pulse durations decrease, effects on the plasma membrane (PM) decrease and effects on intracellular signal transduction mechanisms increase. When nsPEF-induced PM electroporation effects occur, they are distinct from classical PM electroporation effects, suggesting unique, nsPEF-induced PM modulations. In HL-60 cells, nsPEF that are well below the threshold for PM electroporation and apoptosis induction induce effects that are similar to purinergic agonistmediated calcium release from intracellular stores, which secondarily initiate capacitive calcium influx through store-operated calcium channels in the PM. NsPEF with durations and electric field intensities that do or do not cause PM electroporation, induce apoptosis in mammalian cells with a well-characterized phenotype typified by externalization of phosphatidylserine on the outer PM and activation of caspase proteases. Treatment of mouse fibrosarcoma tumors with nsPEF also results in apoptosis induction. When Jurkat cells were transfected by electroporation and then treated with nsPEF, green fluorescent protein expression was enhanced compared to electroporation alone. The results indicate that nsPEF activate intracellular mechanisms that can determine cell function and fate, providing an important new tool for probing signal transduction mechanisms that modulate cell structure and function and for potential therapeutic applications for cancer and gene therapy.
37-kDa Laminin Receptor Precursor Modulates Cytotoxic Necrotizing Factor 1–mediated RhoA Activation and Bacterial Uptake (2003)

Cytotoxic necrotizing factor 1 (CNF1) is a bacterial toxin known to activate Rho GTPases and induce host cell cytoskeleton rearrangements. The constitutive activation of Rho GTPases by CNF1 is shown to enhance bacterial uptake in epithelial cells and human brain microvascular endothelial cells. However, it is unknown how exogenous CNF1 exhibits such phenotypes in eukaryotic cells. Here, we identified 37-kDa laminin receptor precursor (LRP) as the receptor for CNF1 from screening the cDNA library of human brain microvascular endothelial cells by the yeast two-hybrid system using the N-terminal domain of CNF1 as bait. CNF1-mediated RhoA activation and bacterial uptake were inhibited by exogenous LRP or LRP antisense oligodeoxynucleotides, whereas they were increased in LRP-overexpressing cells. These findings indicate that the CNF1 interaction with LRP is the initial step required for CNF1-mediated RhoA activation and bacterial uptake in eukaryotic cells.
Effect of Hyperthermia on Vascular Functions of Normal Tissues and Experimental Tumors: Brief Communication2 (1978)

The effect of hyperthermia on vascular volume and vascular permeability of the Walker carcinoma 256, skin, and muscle of inbred SD male rats was investigated. Whereas heating at 43 degrees C for 1 hour induced a significant increase in the functional vascular volume and vascular permeability in the skin and muscle, it did not change these vascular functions in the tumors. The increased vascular volume in the normal tissues suggested an increased circulation, which may enhance the dissipation of heat and result in a differential effect of hyperthermia on normal tissues and tumors.
Chemical Carcinogenesis: The Liver as a Model (1986)

Research Articles| October 01 2008 Chemical Carcinogenesis: The Liver as a Model Subject Area: Immunology and Allergy , Pathology and Cell Biology Emmanuel Farber; Emmanuel Farber Departments of Pathology and of Biochemistry, Medical Sciences Building, University of Toronto, Ont., Canada Search for other works by this author on: This Site PubMed Google Scholar D.S.R. Sarma D.S.R. Sarma Departments of Pathology and of Biochemistry, Medical Sciences Building, University of Toronto, Ont., Canada Search for other works by this author on: This Site PubMed Google Scholar Pathology and Immunopathology Research (1986) 5 (1): 1–28. https://doi.org/10.1159/000157000 Article history Published Online: October 01 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Emmanuel Farber, D.S.R. Sarma; Chemical Carcinogenesis: The Liver as a Model. Pathology and Immunopathology Research 1 January 1986; 5 (1): 1–28. https://doi.org/10.1159/000157000 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsSurvey and Synthesis of Pathology Research Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1986Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Reusable Polymer-Supported Catalyst for the [3+2] Huisgen Cycloaddition in Automation Protocols (2006)

[reaction: see text] A polymer-supported catalyst for Huisgen's [3+2] cycloaddition reaction between azides and alkynes was prepared from copper(I) iodide and Amberlyst A-21. This catalyst was then used in an automated synthesis of 1,4-disubstituted 1,2,3-triazoles giving access to these products in good yields. The catalyst has shown good activity, stability, and recycling capabilities.
Lysates of Turkey-Grown Pasteurella multocida: Protection Against Homologous and Heterologous Serotype Challenge Exposures (1981)

Pastereulla multocida organisms were separated from the blood of experimentally infected turkeys by differential centrifugation. An average of 92% of the residual host-cell contamination was removed from the pasteurellas by density gradient centrifugation in sucrose. Sucrose suspensions of the turkey-grown pasteurellas partially lysed after freezing and thawing. Treatment of freeze-thawed suspensions with DNAse, hyaluronidase, lysozyme, EDTA, and Triton X-100 did not influence their ability to induce protection against homologous and heterologous serotype challenge exposures. Lysozyme, EDTA, and Triton X-100 completely lysed the pasteurellas and rendered the cross-protection factor(s) filterable. Addition of adjuvant to completely lysed P multocida did not appear to enhance protection in turkeys against heterologous serotype challenge exposure. Adjuvant added to the pellet or supernatant fraction of centrifuged complete lysate enhanced protection in turkeys. Vaccines prepared from different serotypes of turkey-grown P multocida protected chickens and mice against homologous and heterologous serotype challenge exposures.