gebhart/patrepeval huggingface dataset:
Identification of functional synergism between monoclonal antibodies. Application to the enhancement of plasminogen activator inhibitor‐1 neutralizing effects (1997)

The serpin plasminogen activator inhibitor-1 (PAI-1), an important risk factor for thrombotic disease can be neutralized by distinct mechanisms. We hypothesized that the combination of two compounds, with PAI-1 neutralizing properties based on different mechanisms, may result in a synergistic effect. Therefore, seven monoclonal antibodies with PAI-1 neutralizing properties were pairwise evaluated for the possible presence of synergistic or antagonistic effects. Out of 21 combinations, three particular combinations, i.e. MA-33H1/MA-33B8, MA-33B8/MA-7D4B7, and MA-7D4B7/MA-33H1 exhibited strong synergistic effects in comparison with their properties when evaluated individually. The observed synergism resulted in a maximum enhancement between 2- and 5-fold (P < 0.05, vs. theoretically expected effect calculated based on additive effects). Strikingly, synergism was only observed between monoclonal antibodies directed against different epitopes and with different molecular mechanisms of PAI-1 neutralization. This phenomenon of synergism opens new perspectives in the design of therapeutic or preventive strategies aimed at enhancing endogenous fibrinolysis through modulation of PAI-1 activity.
Fluorescence Microscopy: Reduced Photobleaching of Rhodamine and Fluorescein Protein Conjugates by n -Propyl Gallate (1982)

n-Prop]yl gallate (0.1 to 0.25 molar, in glycerol) reduces by a factor of 10 the rate of fading of fluorescence of cell structures labeled with tetramethylrhodamine or fluorescein-conjugated antibodies. Hence, prolonged photographic exposure of immunofluorescently labeled cells in the fluorescence microscope yields images with increased sensitivity, making feasible multiple data collection, as with serial optical sectioning.
Two-Color Labeling of Oligonucleotide Arrays via Size-Selective Scattering of Nanoparticle Probes (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTwo-Color Labeling of Oligonucleotide Arrays via Size-Selective Scattering of Nanoparticle ProbesT. Andrew Taton, Gang Lu, and Chad A. MirkinView Author Information Department of Chemistry and Center for Nanofabrication and Molecular Self-Assembly, Northwestern University 2145 Sheridan Road, Evanston, Illinois 60208 Cite this: J. Am. Chem. Soc. 2001, 123, 21, 5164–5165Publication Date (Web):May 5, 2001Publication History Received30 January 2001Published online5 May 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/ja0102639https://doi.org/10.1021/ja0102639rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views3066Altmetric-Citations356LEARN 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:Biopolymers,Genetics,Metal nanoparticles,Nanoparticles,Probes Get e-Alerts
Myelodysplastic syndromes standardized response criteria: further definition (2001)

We read with interest Dr Raza's letter[1][1] in response to the International Working Group's (IWG's) proposal to provide standardized response criteria in myelodysplastic syndromes (MDSs).[2][2] Developing consistent guidelines for MDSs presents a challenge since the clinical course of the disease
Tailored cancer immunotherapy using combinations of chemotherapy and a mixture of antibodies against EGF-receptor ligands (2010)

Growth factors are implicated in several processes essential for cancer progression. Specifically, growth factors that bind to ErbB family receptors have been implicated in cell proliferation and in resistance of solid tumors to chemotherapy. We quantified ligand secretion by several human cancer cell lines, and generated mAbs against two ligands, namely TGF-alpha and heparin-binding EGF-like growth factor. These growth factors are frequently secreted by pancreatic tumor cell lines, including BxPC3 cells. The monoclonal antibodies were tested for their antigen specificity and ability to inhibit growth of BxPC3 cells in vitro. Combining the two antibodies resulted in enhanced inhibition of BxPC3 cell growth, both in vitro and in tumor-bearing animals. Hence, we combined the two antibodies with gemcitabine, an effective chemotherapeutic drug commonly used to treat pancreatic cancer patients. Because treatment with a combination of two monoclonal antibodies enhanced the ability of chemotherapy to inhibit BxPC3 tumors in mice, we propose a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands.
Binding Stoichiometry of the Gene 32 Protein of Phage T4 in the Complex with Single Stranded DNA Deduced from Boundary Sedimentation (1986)

Short 145 base DNA fragments in complex with the helix destabilizing protein of bacteriophage T4, GP32, have been studied with boundary sedimentation. The sedimentation coefficient was determined as a function of concentration, protein-nucleic acid ratio, temperature and salt concentration. It can be concluded that the measured values reflect the properties of the saturated DNA-GP32 complex. A combination of the earlier obtained translational diffusion coefficient of the complex with the sedimentation coefficient yields its anhydrous molecular weight (Mw = 5.4.10(5) D), which corresponds to a size of the binding site of 10 nucleotides per protein. This procedure is not sensitive to the presence of non-binding protein molecules and to the assumed protein concentration, and therefore, it seems more reliable than a determination from titration experiments. Similar sedimentation measurements were performed with tRNA-complexes containing 76 nucleotides. The translational diffusion coefficient can be calculated from the measured rotational diffusion coefficient and assuming the same hydrodynamic diameter for this complex as obtained for the 145 b DNA complex. The molecular weight derived from the data then also leads to a binding site size of about 10 nucleotides. This suggests that also the short tRNA-complex forms an open, strongly solvated structure, as was proposed for the 145 b DNA-GP32 complex.
Kinetics of oligomerization of methyl ester of dehydrated castor oil fatty acid over molybdenum oxide on silica–alumina catalyst in comparison with the thermal oligomerization process (1984)

Abstract A process is described for the oligomerization of methyl ester of dehydrated castor oil fatty acid over molybdenum oxide on silica–alumina catalyst. The process is compared with thermal oligomerization. The nature of the reaction in both the processes are shown to be the same from the structural elucidation of the product despite the variation in product composition. The percentage of dimer in the product in both the processes is observed to attain an equilibrium value at around 270°C. The catalytic process is shown to follow a second‐order kinetics with respect to the monomer, whereas the thermal reaction follows a first‐order kinetics. The kinetic scheme derived for the catalytic process is shown to be consistent with the steps of the general mechanism proposed for oligomerization reactions over transition metal catalysts [V. G. Kumar, S. Venkatachalam, and K.V.C. Rao, J. Poly. Sci. Polym. Chem. Ed ., 22 , 3850 (1984)].
Antibody-directed liposomes: comparison of various ligands for association, endocytosis, and drug delivery. (1986)

We have developed and compared the cytotoxicity of methotrexate-gamma-aspartate encapsulated in several liposome formulations which bind mouse monoclonal antibody in order to define conditions for screening cell lines and antibodies for liposomal efficacy. Liposomes conjugated to Staphylococcus aureus Protein A were more potent than liposomes conjugated to either rabbit or affinity-purified goat anti-mouse immunoglobulin (Ig) when incubated with AKR/J SL2 cells sensitized with specific antibody. The antibody-directed Protein A liposomes were also 10-fold more potent than liposomes conjugated directly to specific antibody against the AKR/J SL2. We examined the effect of antibody specificity, concentration, and isotype on liposome-mediated drug delivery to AKR/J SL2 cells. The growth-inhibitory effect of the drug in the antibody-directed Protein A liposomes varied with the target antigen on the cell. The potency of the liposomes with a given antibody was proportional to their relative binding and endocytosis by the cells, and to the reactivity of the particular antibody with the cell as demonstrated by indirect immunofluorescence. The Protein A liposomes maintained maximal potency down to antibody concentrations as low as 1 microgram/ml with the anti-Thy 1.1-sensitized AKR/J SL2 cells, thus demonstrating the possible use of these liposomes for hybridoma screening. Use of isotype-switched variants of the anti-Thy 1.1 antibody with the AKR/J SL2 cells showed the superior efficacy of the IgG2a, IgG2b, and IgG3 isotypes to the IgG1 with the Protein A liposomes. The large differential potency of the free drug and the drug encapsulated in antibody-directed Protein A liposomes was maintained even at short incubation times, thus providing a system which may be useful for eradication of tumor cells from bone marrow in vitro.
Generic validation of structural content with parametric modules (2001)

We demonstrate a natural mapping from XML element types to ML module expressions. The mapping is inductive and definitions of common XML operations can be derived as the module expressions are composed. We show how to derive, in a generic way, the validation function, which checks an XML document for conformance to its DTD (Document Type Definition). One can view validation as assigning ML types to XML elements and the validation procedure a pre-requisite for typeful XML programming in ML. Our mapping uses the parametric module facility of ML in some contrived way. For example, in validating WML (WAP Markup Language) documents, we need to use 36ary type constructors, as well as higher-order modules that take in as many as 17 modules as input. That one can systematically model XML DTDs at the module level suggests ML-like languages are suitable for type-safe prototyping of DTD-aware XML applications.
Self-deleting retrovirus vectors for gene therapy (1996)

A new generation of retrovirus vectors for gene therapy has been developed. The vectors have the ability to excise themselves after inserting a gene into the genome, thereby avoiding problems encountered with conventional retrovirus vectors, such as recombination with helper viruses or transcriptional repression of transduced genes. The strategy exploited (i) the natural life cycle of retroviruses, involving duplication of terminal control regions U5 and U3 to generate long terminal repeats (LTRs) and (ii) the ability of the P1 phage site-specific recombinase (Cre) to excise any sequences positioned between two loxP target sequences from the mammalian genome. Thus, an independently expressed selectable marker gene flanked by a loxP target sequence was cloned into the U3 region of a Moloney murine leukemia virus vector. A separate cassette expressing the Cre recombinase was inserted between the LTRs into the body of the virus. LTR-mediated duplication placed vector sequences, including Cre, between loxP sites in the integrated provirus. This enabled Cre to excise from the provirus most of the viral and nonviral sequences unrelated to transcription of the U3 gene.
Mutations Uncouple Human Fibroblast Growth Factor (FGF)-7 Biological Activity and Receptor Binding and Support Broad Specificity in the Secondary Receptor Binding Site of FGFs (1999)

The fibroblast growth factor (FGF) family plays a key role in a multitude of physiological and pathological processes. The activities of FGFs are mediated by a family of tyrosine kinase receptors, designated FGFRs. The mechanism by which FGFs induce receptor activation is controversial. Despite their structural similarity, FGFs display distinct receptor binding characteristics and cell type specificity. Previous studies with FGF-2 identified a low affinity receptor binding site that is located within a loop connecting its 9th and 10th beta-strands. The corresponding residues in the other family members are highly variable, and it was proposed that the variability might confer on FGFs unique receptor binding characteristics. We studied the role of this loop in FGF-7 by both site-directed mutagenesis and loop replacement. Unlike the other members of the FGF family, FGF-7 recognizes only one FGFR isoform and is, therefore, ideal for studies of how the specificity in the FGF-FGFR interaction is conferred at the structural level. Point mutations in the loop of FGF-7 did not change receptor binding affinity but resulted in reduced mitogenic potency and reduced ability to induce receptor-mediated phosphorylation events. These results suggest that the loop of FGF-7 fulfills the role of low affinity binding site required for receptor activation. The observation that it is possible to uncouple FGF-7 receptor binding and biological activity favors a bivalent model for FGFR dimerization, and it may be clinically relevant to the design of FGF-7 antagonists. Reciprocal loop replacement between FGF-7 and FGF-2 had no effect on their known receptor binding affinities nor did it alter their known specificity in eliciting a mitogenic response. In conclusion, these results suggest that, despite the diversity in the loop structure of FGF-2 and FGF-7, the loop has a similar function in both growth factors.
DailyDialog: A Manually Labelled Multi-Turn Dialogue Dataset (2025)

We develop a high-quality multi-turn dialog dataset, DailyDialog, which is intriguing in several aspects. The language is human-written and less noisy. The dialogues in the dataset reflect our daily communication way and cover various topics about our daily life. We also manually label the developed dataset with communication intention and emotion information. Then, we evaluate existing approaches on DailyDialog dataset and hope it benefit the research field of dialog systems. The dataset is available on http://yanran.li/dailydialog
Capturing transient antibody conformations with DNA origami epitopes (2020)

Revealing antibody-antigen interactions at the single-molecule level will deepen our understanding of immunology. However, structural determination under crystal or cryogenic conditions does not provide temporal resolution for resolving transient, physiologically or pathologically relevant functional antibody-antigen complexes. Here, we develop a triangular DNA origami framework with site-specifically anchored and spatially organized artificial epitopes to capture transient conformations of immunoglobulin Gs (IgGs) at room temperature. The DNA origami epitopes (DOEs) allows programmed spatial distribution of epitope spikes, which enables direct imaging of functional complexes with atomic force microscopy (AFM). We establish the critical dependence of the IgG avidity on the lateral distance of epitopes within 3-20 nm at the single-molecule level. High-speed AFM imaging of transient conformations further provides structural and dynamic evidence for the IgG avidity from monovalent to bivalent in a single event, which sheds light on various applications including virus neutralization, diagnostic detection and cancer immunotherapy.
The fluorescence of a chelating two-photon-absorbing dye is enhanced with the addition of transition metal ions but quenched in the presence of acid (2016)

A pseudo-symmetric two-photon absorbing dye (1) containing a central piperazine unit substituted with (benzothiazol-2- yl)-9,9-diethylfluoren-2-yl pendant groups has been synthesized and characterized. The molecule has a two-photonabsorption cross-section of &sigma;<sub>2</sub> = 140 GM in tetrahydrofuran at ~ 740 nm and shows significant solvatochromism in the excited-state fluorescence spectra. The emission spectra broaden and the maxima bathochromically shift from 411 nm to 524 nm in n-hexane and acetonitrile, respectively. Moreover, the central piperazine moiety serves as a potential chelation site for ions. Addition of copper(I) hexafluorophosphate and zinc(II) triflate in acetonitrile indicate ground-state complexation with a shift in the emission maximum from 524 nm to 489 nm and 487 nm, respectively. Interestingly, the newly formed Cu and Zn complexes are more strongly emissive than the free dye. Finally, addition of <i>p</i>-toluenesulfonic acid in tetrahydrofuran also blue-shifts the emission maximum, but the intensity is quenched. Due to the photophysical changes induced by addition of metal ions and protons, the dye shows promise as a potential sensor.
Biological activity of tetramer of bispecific single-chain antibody against human prostate-specific antigen and CD3 molecule (2006)

AIM: To study the biological activity of tetramer of bispecific single-chain antibody against human prostate-specific antigen (PSA) and CD3 molecule. METHODS: Flow cytometry (FCM) was used to detect the binding activity of bispecific single -chain antibody to CD3-positive cell line Jurkat and prostate carcinoma cell line LNCaP. The efficacy of the antibodiy in mediating tumor cell lysis in vitro was determined by using the ~ 51 Cr -release test. For in vivo evaluation of the antibody's activity, a nude mouse model was used. The mice were inoculated with LNCaP prostate cancer cells. RESULTS: It was demonstrated that the tetramer of bispecific single-chain antibody could bind to the Jurkat and LNCaP cells with high specificity. The percents of the cells bond by the antibody were 70.4% and 81%, respectively. In vitro, with activated CTLs as effector cells, a specific lysis of LNCaP cells mediated by the antibody was confirmed by ~ 51 Cr-release assay. The specific lysis rate of LNCaP cells was positively correlated to tBsAb concentration or effector / target cell ratio. The highest specific lysis rates were (80.3±5.2)% and (78.6±5.5)% in fixed antibody concentration group and fixed effector/target cell ratio group, respectively. In vivo, the antibody could suppress the tumor growth in nude mice significantly as compared to the group treated only with CTLs and the untreated control group (P0.0001). CONCLUSION: The tetramer of bispecific single-chain antibody against human prostate-specific antigen and CD3 molecule has a good biological activity in binding antigens, mediating lysis of LNCaP cells and inhibiting tumor growth.
Assessment of Hydroxypropyl Methylcellulose, Propylene Glycol, Polysorbate 80, and Hydroxypropyl‐β‐Cyclodextrin for use in developmental and reproductive toxicology studies (2010)

Although HPβCD was not well tolerated in rabbits at doses of 500 and 1,000 mg/kg, PS80 and PG were comparable to MC and should be considered for use in developmental and reproductive toxicology studies.
Chemiluminescent detection of DNA: application for DNA sequencing and hybridization (1989)

A non-radioactive DNA detection chemistry is described and its application is shown for DNA hybridization and standard dideoxy DNA sequencing. The method employes a biotin-streptavidin system which binds an enzyme specifically to a target DNA and upon exposure to substrate, the enzyme catalyzes a chemiluminescent reaction. The image is captured within seconds by a Polaroid or X-ray film. The method is capable of detecting DNA in the hundred attomol range.
The virR/virS locus regulates the transcription of genes encoding extracellular toxin production in Clostridium perfringens (1996)

Extracellular toxin production in Clostridium perfringens is positively regulated by the two-component regulatory genes virR and virS. Northern (RNA) blots carried out with RNA preparations from the wild-type strain 13 and the isogenic virR and virS mutants TS133 and JIR4000 showed that the virR and virS genes composed an operon and were transcribed as a single 2.1-kb mRNA molecule. Primer extension analysis led to the identification of two promoters upstream of virR. Hybridization analysis of the mutants and their complemented derivatives showed that the virR/virS system positively regulated the production of alpha-toxin (or phospholipase C, theta-toxin (perfringolysin O), and kappa-toxin (collagenase) at the transcriptional level. However, the modes of regulation of these genes were shown to differ. The theta-toxin structural gene, pfoA, had both a major and a very minor promoter, with the major promoter being virR/virS dependent. The colA gene, which encodes the kappa-toxin, had two major promoters, only one of which was virR/virS-dependent. In contrast, the alpha-toxin structural gene, p1c, had only one promoter, which was shown to be partially regulated by the virR and virS genes. Comparative analysis of the virR/virS-dependent promoters did not reveal any common sequence motifs that could represent VirR-binding sites. It was concluded that either the virR/virS system modulates its effects via secondary regulatory genes that are specific for each toxin structural gene or the VirR protein does not have a single consensus binding sequence.
Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis (2013)

Cyclin F, capable of forming Skp1-Cul1-F-box protein ubiquitin ligase complex, is implicated in controlling centrosome duplication and preventing genome instability. Cyclin F oscillates during cell cycle with a similar pattern to cyclin A. However, its expression and significance in cancer remain obscure. In this study, we showed that cyclin F was noticeably decreased in 16 pairs of tissue samples of hepatocellular carcinoma (HCC) compared to paracarcinoma tissues, at both mRNA and protein levels. Immunohistochemical staining data revealed that in 71.8% (176/245) of HCC cases, cyclin F expression in tumor tissue was much lower than that in nontumorous tissue. Low cyclin F expression, defined by receiver operating characteristic curve analysis, was present in 69.0% of HCC patients. Low expression of cyclin F was significantly correlated with tumor size, clinical stage, serum alpha-fetoprotein level and tumor multiplicity. Further study showed that cyclin F expression was reversely associated with tumor differentiation in HCC. Kaplan-Meier analysis indicated that low cyclin F expression was related to poor overall survival and recurrence-free survival. The prognostic impact of cyclin F was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low cyclin F expression was an independent poor prognostic marker for overall survival. We conclude that cyclin F is downregulated in HCC and is a promising prognostic marker for patients suffering from this deadly disease.