gebhart/patrepeval huggingface dataset:
High-Affinity Internalizing Human scFv-Fc Antibody for Targeting FGFR1-Overexpressing Lung Cancer (2017)

Abstract Targeted delivery of anticancer drugs using antibodies specific for tumor-associated antigens represents one of the most important approaches in current immuno-oncology research. Fibroblast growth factor receptor 1 (FGFR1) has been demonstrated to be a high-frequency targetable oncogene specific for smoking-associated lung cancers, present in over 20% of lung squamous cell carcinoma cases. This report describes the generation of a potent, fully human antibody fragment in scFv-Fc format efficiently targeting FGFR1. Antibody phage display was used to select high-affinity scFv antibody fragments against the extracellular domain of FGFR1(IIIc). Enzyme immunoassay (ELISA) and surface plasmon resonance (SPR) analysis were used for antibody screening and characterization. The best binder (named D2) was cloned to diabody and Fc fusion formats. All D2 antibodies demonstrated high affinity for FGFR1 with dissociation constants of 18 nmol/L (scFvD2), 0.82 nmol/L (scFvD2 diabody), and 0.59 nmol/L (scFvD2-Fc). scFvD2 was found to be exquisitely selective for FGFR1 versus other FGFR family members and bound FGFR1 even in the presence of its natural ligand FGF2, as shown by competitive analysis. Confocal microscopy revealed that scFvD2-Fc was specifically and rapidly internalized by a panel of cell lines overexpressing FGFR1. Finally, it was demonstrated that scFvD2-Fc mediated specific delivery of a cytotoxic payload into lung cancer cells harboring oncogenic FGFR1 gene amplifications. Implications: This study reports a highly specific internalizing antibody fragment that can serve as a therapeutic targeting agent for efficient delivery of cytotoxic drugs into FGFR1-positive lung cancer cells. Mol Cancer Res; 15(8); 1040–50. ©2017 AACR.
Omeprazole prevents indomethacin‐induced gastric ulcers in rabbits (1996)

We conclude from these observations that gastric acid plays a critical role in the formation of indomethacin-induced gastric ulcers in rabbits.
Gap junctions and the connexin protein family (2003)

Gap junctions (Gj) form conduits between adjacent cells that are composed of connexin (Cx) protein subunits and allow direct intercellular communication. To date, the connexin gene family comprises 20 members in the mouse and 21 members in the human genome, 19 of which can be grouped as sequence-orthologous pairs. The structure of connexin genes is relatively simple. An untranslated exon 1 is separated by an intron of different length from exon 2, containing the uninterrupted coding region and the 3'-untranslated region (3'-UTR). However, in some connexin genes, the untranslated regions and the reading frame are spliced. Among the known "cardiovascular" connexins, Cx37 and Cx40 were demonstrated to be functionally expressed in mouse and human endothelial cells and Cx40, Cx43 as well as Cx45 in cardiomyocytes of both species. Functional properties, like permeabilities, charge selectivity and unitary conductivity were investigated after directed expression of these connexins in cultured cell lines or paired Xenopus oocytes. Targeted deletion of their coding sequence in the mouse genome allowed study of the biological relevance of Cx37, Cx40, Cx43 and Cx45 with regard to cardiovascular morphology and function. After ablation of Cx37 or Cx40, mice were viable and could be used to study defects in the adult cardiovascular system but loss of Cx43 or Cx45 led to neonatal or embryonic lethality, respectively. Conditional and cell-type specific deletion of both connexins in the heart or blood vessels can help to overcome this obstacle. As yet only little is known about mutations in the human genes for Cx37, Cx40, Cx43 and Cx45. Thus, a profound comparison between human and mouse phenotypes is not yet possible.
Does Union Activity Damage Career Prospects? Implications For The Unionisation of Managers (1990)

Human Resource Management JournalVolume 1, Issue 2 p. 1-16 Does Union Activity Damage Career Prospects? Implications For The Unionisation of Managers Tom Redman, Tom Redman Teesside PolytechnicSearch for more papers by this authorEd Snape, Ed Snape University of StrathclydeSearch for more papers by this authorGreg J. Bamber, Greg J. Bamber University of QueenslandSearch for more papers by this author Tom Redman, Tom Redman Teesside PolytechnicSearch for more papers by this authorEd Snape, Ed Snape University of StrathclydeSearch for more papers by this authorGreg J. Bamber, Greg J. Bamber University of QueenslandSearch for more papers by this author First published: December 1990 https://doi.org/10.1111/j.1748-8583.1990.tb00221.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume1, Issue2December 1990Pages 1-16 RelatedInformation
Characterization of Virus-like Particles Released from the Hamster Cell Line CHO-K1 After Treatment with 5-Bromodeoxyuridine (1978)

Simple biochemical measurements have been shown to seriously overestimate the production of C-type particles by Chinese hamster ovary (CHO) cells treated with 5-bromodeoxyuridine. First, most particle-bound DNA polymerase activity released by induced cells was associated with particles which had a different density from C-type particles. Second, when labelled with radioactive uridine, induced CHO cells released small amounts of particle-bound radioactivity. Most of the radioactivity, however, was in DNA and did not sediment with the particle-bound polymerase. Thus, few particles which had RNA, an associated DNA polymerase, and the density typical of RNA tumour viruses were released by BrdUrd-induced CHO cells. In spite of this, some immature C-type forms were observed by electron microscopy in partially purified preparations of DNA polymerase-containing particles from induced CHO cells.
Lysophospholipid Receptors as Potential Drug Targets in Tissue Transplantation and Autoimmune Diseases (2005)

New therapies directed at ameliorating or altering autoimmune diseases represent an area of significant medical need. Included amongst autoimmune diseases are problems related to transplantation rejection, as well as a number of neurological diseases such as Multiple Sclerosis (MS). A new group of molecular targets that may lead to novel therapies are lysophospholipid (LP) receptors. A large range of biological activities has been attributed to the actions of these simple phospholipids that include well-studied members lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Documented cellular effects of these lipid molecules encompass growth-factor-like influences on cells, including but not limited to survival, migration, adhesion differentiation, as well as pathophysiological actions associated with cancer. In turn, these cellular effects have roles in developing and adult organ systems such as the nervous system, cardiovascular system, reproductive system and, of relevance here, the immune system. The mechanisms for these actions can be attributed to a growing family of cognate, 7-transmembrane G protein-coupled receptors (GPCRs), with documented validation through studies utilizing pharmacology, molecular genetics and an enlarging repertoire of chemical tools having agonist or antagonist properties. The growing literature on immunological effects of LP receptors, particularly those mediating the effects of S1P, has suggested possible therapeutic roles for this class of receptors. In particular, entry into humans of a non-selective S1P receptor agonist, FTY720, for kidney transplantation and possibly other indications (e.g., Multiple Sclerosis), has raised prospects for efficacious treatment of human diseases based on LP receptor targets. Here we provide a brief introduction to receptor-mediated lysophospholipid signaling and discuss its basic and potential therapeutic roles in autoimmune-related diseases.
Some 6-Substituted Uracils1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome 6-Substituted Uracils1JEROME P. HORWITZ and ARTHUR J. TOMSONCite this: J. Org. Chem. 1961, 26, 9, 3392–3395Publication Date (Print):September 1, 1961Publication History Published online1 May 2002Published inissue 1 September 1961https://pubs.acs.org/doi/10.1021/jo01067a091https://doi.org/10.1021/jo01067a091research-articleACS PublicationsRequest reuse permissionsArticle Views395Altmetric-Citations28LEARN 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-Alertsclose Get e-Alerts
Antigen Targeting to CD11b Allows Efficient Presentation of CD4+ and CD8+ T Cell Epitopes and In Vivo Th1-Polarized T Cell Priming (2004)

Bordetella pertussis adenylate cyclase (CyaA) is an invasive bacterial toxin that delivers its N-terminal catalytic domain into the cytosol of eukaryotic cells bearing the alpha(M)beta(2) integrin (CD11b/CD18), such as myeloid dendritic cells. This allows use of engineered CyaA for targeted delivery of CD8(+) T cell epitopes into the MHC class I pathway of APC and induction of robust and protective cytotoxic responses. In this study, we demonstrate that CyaA can efficiently codeliver both a CD8(+) T cell epitope (OVA(257-264)) and a CD4(+) T cell epitope (MalE(100-114)) into, respectively, the conventional cytosolic or endocytic routes of processing of murine bone marrow-derived dendritic cells. Upon CyaA delivery, a strong potentiation of the MalE(100-114) CD4(+) T cell epitope presentation is observed as compared with the MalE protein, which depends on CyaA interaction with its CD11b receptor and its subsequent clathrin-mediated endocytosis. In vivo, CyaA induces strong and specific Th1 CD4(+) and CD8(+) T cell responses against, respectively, the MalE(100-114) and OVA(257-264) epitopes. These results underscore the potency of CyaA for design of new vaccines.
Inflammatory mediators in naturally occurring rhinitis (1998)

These results indicate that in both naturally occurring seasonal allergic rhinitis and perennial allergic rhinitis mast cell and eosinophil activation occurs and this is accompanied by an increase in vascular permeability. These measurements in lavage fluid provide a method of monitoring the mucosal cellular events in response to therapy.
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment (2013)

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite initial responsiveness, 80% of EOC patients recur and present with chemoresistant and a more aggressive disease. This suggests an underlying biology that results in a modified recurrent disease, which is distinct from the primary tumor. Unfortunately, the management of recurrent EOC is similar to primary disease and does not parallel the molecular changes that may have occurred during the process of rebuilding the tumor. We describe the characterization of unique in vitro and in vivo ovarian cancer models to study the process of recurrence. The in vitro model consists of GFP+/CD44+/MyD88+ EOC stem cells and mCherry+/CD44-/MyD88- EOC cells. The in vivo model consists of mCherry+/CD44+/MyD88+ EOC cells injected intraperitoneally. Animals received four doses of Paclitaxel and response to treatment was monitored by in vivo imaging. Phenotype of primary and recurrent disease was characterized by quantitative polymerase chain reaction (qPCR) and Western blot analysis. Using the in vivo and in vitro models, we confirmed that chemotherapy enriched for CD44+/MyD88+ EOC stem cells. However, we observed that the surviving CD44+/MyD88+ EOC stem cells acquire a more aggressive phenotype characterized by chemoresistance and migratory potential. Our results highlight the mechanisms that may explain the phenotypic heterogeneity of recurrent EOC and emphasize the significant plasticity of ovarian cancer stem cells. The significance of our findings is the possibility of developing new venues to target the surviving CD44+/MyD88+ EOC stem cells as part of maintenance therapy and therefore preventing recurrence and metastasis, which are the main causes of mortality in patients with ovarian cancer.
Exact stochastic simulation of coupled chemical reactions (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExact stochastic simulation of coupled chemical reactionsDaniel T. GillespieCite this: J. Phys. Chem. 1977, 81, 25, 2340–2361Publication Date (Print):December 1, 1977Publication History Published online1 May 2002Published inissue 1 December 1977https://pubs.acs.org/doi/10.1021/j100540a008https://doi.org/10.1021/j100540a008research-articleACS PublicationsRequest reuse permissionsArticle Views28765Altmetric-Citations7236LEARN 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 options Get e-Alerts
Linkage of a Cardiac Arrhythmia, the Long QT Syndrome, and the Harvey ras -1 Gene (1991)

Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.
Random access DNA memory in a scalable, archival file storage system (2020)

ABSTRACT DNA is an ultra-high-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. To overcome the second barrier, here we encapsulate data-encoding DNA file sequences within impervious silica capsules that are surface-labeled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling efficient and direct selection of sets of files with Boolean logic. We demonstrate random access of image files from an image database using fluorescence sorting with selection sensitivity of 1 in 10 6 files, which thereby enables 1 in 10 6 N per N optical channels. Our strategy thereby offers retrieval of random file subsets from exabyte and larger-scale long-term DNA file storage databases, offering a scalable solution for random-access of archival files in massive molecular datasets.
Dominant Negative Mutants of Opaque2 Suppress Transactivation of a 22-kD Zein Promoter by Opaque2 in Maize Endosperm Cells (1993)

Erica Unger, Ronald L. Parsons, Robert J. Schmidt, Ben Bowen, Bradley A. Roth, Dominant Negative Mutants of Opaque2 Suppress Transactivation of a 22-kD Zein Promoter by Opaque2 in Maize Endosperm Cells, The Plant Cell, Vol. 5, No. 8 (Aug., 1993), pp. 831-841
CUUCGG hairpins: extraordinarily stable RNA secondary structures associated with various biochemical processes. (1988)

The mRNA of bacteriophage T4 contains a strikingly abundant intercistronic hairpin. Within the 55 kilobases of known T4 sequence, the hexanucleotide sequence CTTCGG is found 13 times in the DNA strand equivalent to mRNA sequences. In 12 of those occurrences, the sequence is flanked by inverted repeats predictive of RNA hairpins with UUCG in the loop. Avian myeloblastosis virus reverse transcriptase, which can traverse hairpins of larger calculated stability, terminates efficiently at these CUUCGG hairpins. Thermal denaturation studies of model hairpins show that the loop sequence UUCG dramatically stabilizes RNA hairpins when compared to a control sequence. These data, when combined with previously described parameters of helix stability, suggest that T4 has utilized this loop sequence to optimize the stability of intercistronic hairpins. The stability of CUUCGG hairpins is also utilized in the RNAs of many organisms besides T4.
Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro (2004)

BAC can induce corneal epithelial dysfunction, which can damage the corneal epithelial barrier. This effect occurs when BAC is used frequently or for periods over 30 min, even when the BAC concentration is low (0.001%).
CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPα 1 (2000)

The rat OX41 antigen is a cell surface protein containing three immunoglobulin superfamily domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM). It is a homologue of the human signal-regulatory protein (SIRP) also known as SHPS-1, BIT or MFR. Cell activation-induced phosphorylation of the intracellular ITIM motifs induces association with the tyrosine phosphatases SHP-1 and SHP-2. To identify the physiological OX41 ligand, recombinant OX41-CD4d3+4 fusion protein was coupled to fluorescent beads to produce a multivalent cell binding reagent. The OX41-CD4d3+4 beads bound to thymocytes and concanavalin A-stimulated splenocytes. This interaction was blocked by the monoclonal antibody (mAb) OX101. Affinity chromatography with OX101 mAb and peptide sequencing revealed the rat SIRP ligand to be CD47 (integrin-associated protein). A direct interaction between human SIRP and human CD47 was demonstrated using purified recombinant proteins and surface plasmon resonance ruling out the involvement of other proteins known to be associated with CD47. The affinity of the SIRP/CD47 interaction was K(d) approximately 8 microM at 37 degrees C with a k(off )>/=2.1 s(-1). The membrane-distal SIRP V-like domain was sufficient for binding to CD47.
Jumping Translocations of Chromosome 1q in Multiple Myeloma: Evidence for a Mechanism Involving Decondensation of Pericentromeric Heterochromatin (1998)

Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long arm of chromosome 1 presumably occur as secondary aberrations and are associated with tumor progression and advanced disease. Unfortunately, cytogenetic evidence is scarce as to how these unstable whole-arm rearrangements may take place. We report nonrandom, unbalanced whole-arm translocations of 1q in the cytogenetic evolution of patients with aggressive MM. Whole-arm or "jumping translocations" of 1q were found in 36 of 158 successive patients with abnormal karyotypes. Recurring whole-arm translocations of 1q involved chromosomes 5,8,12,14,15,16,17,19,21, and 22. A newly delineated breakpoint present in three patients involved a whole-arm translocation of 1q to band 5q15. Three recurrent translocations of 1q10 to the short arms of different acrocentric chromosomes have also been identified, including three patients with der(15)t(1;15)(q10;p10) and two patients each with der(21)t(1;21)(q10;p13) and der(22)t(1;22) (q10;p10). Whole-arm translocations of 1q10 to telomeric regions of nonacrocentric chromosomes included der(12)t(1;12) (q10;q24.3) and der(19)t(1;19)(q10;q13.4) in three and two patients, respectively. Recurrent whole-arm translocations of 1q to centromeric regions included der(16)t(1;16)(q10;q10) and der(19)t(1;19)(q10;p10). The mechanisms involved in the 1q instability in MM may be associated with highly decondensed pericentromeric heterochromatin, which may permit recombination and formation of unstable translocations of chromosome 1q. The clonal evolution of cells with extra copies of 1q suggests that this aberration directly or indirectly provides a proliferative advantage.
Drug-specific T cells derived from patients with drug-induced allergic hepatitis (1992)

Drug-induced allergic hepatitis is a tissue-specific inflammatory disease caused by hypersensitivity to a particular drug. Although the frequency of drug-induced allergic hepatitis appears to increase in proportion to the medicine, the mechanism by which tissue specificity is determined is still to be elucidated. In this study, we established CD4+ T cell clones specific for particular drugs from patients with drug-induced allergic hepatitis accompanied with mild blood eosinophilia and analyzed the possible role of liver protein as a directing factor of liver-specific inflammatory reactions. All CD4+ T cell clones obtained from two patients with this disease proliferated in response to a combination of the particular drug plus liver specific protein (LSP), which consists of over 30 proteins. Some T cell clones were responsive to an antigenic conformation consisting of the 200-kDa glycoprotein (partly purified LSP), a component of LSP, plus the causal drug. In contrast, all CD4+ T cell clones from a patient with simple drug-induced eosinophilia responded to the causal drug in the absence of LSP and partly purified LSP. These data suggested that LSP or partly purified LSP of the appropriate Ag is the target that leads to liver-specific inflammation in drug-induced allergic hepatitis. Furthermore, T cell lines derived from patients with drug-induced allergic hepatitis and simple drug-induced eosinophilia produced large amounts of IL-5 after the appropriate antigenic stimulation, whereas CD4+ T cell clones from donors with a normal amount of peripheral blood eosinophils secreted a much less IL-5. Taken together, these results indicate that overproduction of IL-5 by the allergen-sensitized T cells may result in blood eosinophilia.