gebhart/patrepeval huggingface dataset:
Identification of a hexapeptide that mimics a conformation-dependent binding site of acetylcholine receptor by use of a phage-epitope library. (1993)

Monoclonal antibody (mAb) 5.5 is directed against the ligand-binding site of the nicotinic acetylcholine receptor. The epitope for this antibody is conformation-dependent, and the antibody does not react with synthetic peptides derived from the receptor sequence. We have identified a ligand peptide that mimics this conformation-dependent epitope from a phage-epitope library composed of filamentous phage displaying random hexapeptides. Among 38 positive phage clones, individually selected from the library, 34 positive clones carried the sequence Asp-Leu-Val-Trp-Leu-Leu (DLVWLL), 1 positive clone had the sequence Asp-Ile-Val-Trp-Leu-Leu (DIVWLL), and 3 positive clones expressed the sequence Leu-Ile-Glu-Trp-Leu-Leu (LIEWLL), none of which are significantly homologous with the nicotinic acetylcholine receptor alpha subunit sequence. All of these phages bind specifically to mAb 5.5. The synthetic peptide DLVWLL inhibits binding of mAb 5.5 to the related peptide-presenting phage and to the nicotinic acetylcholine receptor in a concentration-dependent manner; the IC50 value is of the order of 10(-4) M. Bioactivity of the peptide "mimotope" DLVWLL was demonstrated in vivo in hatched chickens by inhibition of the mAb 5.5 effect by the peptide. The neuromuscular block and myasthenia gravis-like symptoms that are induced in chicken by passive transfer of mAb 5.5 were specifically abolished by DLVWLL. This study shows the potential of a random peptide phage-epitope library for selecting a mimotope for an antibody that recognizes a folded form of the protein, where peptides from the linear amino acid sequence of the protein are not applicable.
MicroRNA-221/222 Negatively Regulates Estrogen Receptorα and Is Associated with Tamoxifen Resistance in Breast Cancer (2008)

A search for regulators of estrogen receptor alpha (ERalpha) expression has yielded a set of microRNAs (miRNAs) for which expression is specifically elevated in ERalpha-negative breast cancer. Here we show distinct expression of a panel of miRNAs between ERalpha-positive and ERalpha-negative breast cancer cell lines and primary tumors. Of the elevated miRNAs in ERalpha-negative cells, miR-221 and miR-222 directly interact with the 3'-untranslated region of ERalpha. Ectopic expression of miR-221 and miR-222 in MCF-7 and T47D cells resulted in a decrease in expression of ERalpha protein but not mRNA, whereas knockdown of miR-221 and miR-222 partially restored ERalpha in ERalpha protein-negative/mRNA-positive cells. Notably, miR-221- and/or miR-222-transfected MCF-7 and T47D cells became resistant to tamoxifen compared with vector-treated cells. Furthermore, knockdown of miR-221 and/or miR-222 sensitized MDA-MB-468 cells to tamoxifen-induced cell growth arrest and apoptosis. These findings indicate that miR-221 and miR-222 play a significant role in the regulation of ERalpha expression at the protein level and could be potential targets for restoring ERalpha expression and responding to antiestrogen therapy in a subset of breast cancers.
Secondary metabolites: their function and evolution. (1992)

Partial table of contents: Origins of Secondary Metabolism (T. Cavalier-Smith) Genes for Polyketide Secondary Metabolic Pathways in Microorganisms and Plants (D. Hopwood & C. Khosla) Regulation of Gibberellin Formation by the Fungus Gibberella Fujikuroi (B. Br ckner) Genetic Regulation of Secondary Metabolic Pathways in Streptomyces (K. Chater) Role of Secondary Metabolites from Microbes (L. Vining) Self-Protection Mechanisms in Antibiotic Producers (E. Cundliffe) Secondary Metabolites from Marine Organisms (K. Rinehart) Roles for Secondary Metabolites in Plants (P. Waterman) Index of Contributors Subject Index.
Regression of Drug-Resistant Lung Cancer by the Combination of Rosiglitazone and Carboplatin (2008)

These data show that the PPARgamma ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy.
Multiple description transform coding of images (2002)

Generalized multiple description coding (GMDC) is source coding for multiple channels such that a decoder which receives an arbitrary subset of the channels may produce a useful reconstruction. This paper reports on applications of two recently proposed methods for GMDC to image coding. The first produces statistically correlated streams such that lost streams can be estimated from the received data. The second uses quantized frame expansions and hence is conceptually similar to block channel coding, except it is done prior to quantization.
Likelihood DNA Sequencing By Hybridization (1993)

Sequencing by hybridization (SBH) extracts local sequence information from a DNA fragment using hybridization with oligonucleotides and then reconstructs the sequence using the derived information. We describe an improvement to the SBH methodology which will allow it to work efficiently in the presence of hybridization errors. In particular, given a set of hybridizing probes, and the empirically derived rates of false positive and false negative hybridization, we can estimate the most likely DNA fragment to have produced the set of probes, and then estimate the probability that it generated the hybridization data. This methodology extends earlier results by identifying the most probable fragment to have generated the actual hybridization data. The methodology described will also generate longer unambiguous sequence fragments without the use of overlapping fragments.
Cerebral Amyloid Angiopathy (1996)

Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in cerebral blood vessels. It occurs most frequently in association with clinical Alzheimer's disease but also occurs in some nondemented elderly people. CAA is a cause of spontaneous cerebral hemorrhage and may therefore present as a sudden unexpected death in an elderly person. The amyloid is deposited in cortical blood vessels, and on hematoxylin-eosin sections takes the form of pink hyaline thickening of arteries and arterioles, often with narrowing of the lumina. For diagnosis apple-green birefringence after Congo red staining is the most widely practiced and reliable tool. CAA-related hemorrhage may also occur in any lobe of the cerebrum close to the external surface and may occur at multiple sites and at the same or different times. CAA-related hemorrhage may occur in the setting of trauma necessitating distinction between the two and raising the question of whether it precipitated trauma or vice versa. Usually CAA-related hemorrhage is infrequent in sites where traumatic hemorrhages occur, and traumatic hemorrhages are often associated with other hemorrhages in sites typical for trauma. Five cases demonstrating many of the clinical and pathological features of CAA-related hemorrhage are presented. In two of the five cases, the hemorrhage followed trauma, suggesting that trauma as a precipitating factor for CAA-related hemorrhage may be more common than is generally recognized. CAA-associated hemorrhage should be considered in the differential diagnosis of cerebral hemorrhage in the elderly whether or not dementia is present.
Transmembrane 7 superfamily member 4 regulates cell cycle progression in breast cancer cells. (2015)

To our knowledge, our data demonstrate for the first time that TM7SF4 plays an essential role in regulating cell cycle progression in breast cancer.
Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli (2005)

Activation of extracellular signal-regulated kinase (Erk) 1/2, which plays a critical role in diverse cellular processes, including cell proliferation, is known to be mediated by the canonical Raf-mitogen-activated protein kinase kinase (MEK) kinase cascade. Alternative MEK-independent signaling pathways for Erk1/2 activation in mammalian cells are not known. During our studies of human primary Schwann cell response to long-term infection of Mycobacterium leprae, the causative organism of leprosy, we identified that intracellular M. leprae activated Erk1/2 directly by lymphoid cell kinase (p56Lck), a Src family member, by means of a PKCepsilon-dependent and MEK-independent signaling pathway. Activation of this signaling induced nuclear accumulation of cyclin D1, G1/S-phase progression, and continuous proliferation, but without transformation. Thus, our data reveal a previously unknown signaling mechanism of glial cell proliferation, which might play a role in dedifferentiation as well as nerve regeneration and degeneration. Our findings may also provide a potential mechanism by which an obligate intracellular bacterial pathogen like M. leprae subverts nervous system signaling to propagate its cellular niche for colonization and long-term bacterial survival.
Pharmacokinetics and microdistribution of polyethylene glycol-modified humanized A33 antibody targeting colon cancer xenografts (2000)

Therapeutic proteins have been conjugated with polyethylene glycol (PEGylation) to reduce immunogenicity and enhance circulating dose. Here we have investigated the effect of PEGylation on immunogenicity, pharmacokinetics, and histologic microdistribution of tumor-targeting antibodies with humanized A33 antibody (huA33) as a model system. Conjugation of huA33 with methoxy-PEG of M(r) 5,000 (32%-34% of primary amines modified) or M(r) 20,000 (16%-18% modification) preserved >50% of native huA33 binding to SW1222 colon cancer cells. In mice, both PEGylated forms cleared from serum moderately slower than native huA33. After repeated immunization with PEG-huA33, antiantibody titers in immunocompetent mice were <5% of those in huA33-treated controls. Both PEG-huA33 forms reached approx. 75% of the maximum tumor dose of huA33 in SW1222-xenografted mice, but their tumor:blood ratios were considerably reduced. To demonstrate immunologic specificity of PEG-huA33 targeting in SW1222 tumor-bearing mice, antigenic sites were presaturated by injecting excess native huA33. This reduced subsequent uptake of PEG-huA33 by up to 80%, whereas presaturation with hu3S193 control antibody had no significant effect. To assess the microdistribution of antibody uptake in the same xenograft model, tumor tissue resected at different time points after antibody administration was examined for human IgG by immunohistochemistry. Both PEG preparations achieved the same peak staining intensity and homogeneity as native huA33 with a delay of several hours. Given the measured reduction in immunoreactivity in vitro, these results demonstrate that the tumor targeting potential of huA33 in vivo is preserved at PEGylation levels sufficient to suppress immunogenicity.
Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node (2014)

Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.
Estimation of Diffusion Coefficients for Gases and Vapors (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEstimation of Diffusion Coefficients for Gases and VaporsC. R. Wilke and C. Y. LeeCite this: Ind. Eng. Chem. 1955, 47, 6, 1253–1257Publication Date (Print):June 1, 1955Publication History Published online1 May 2002Published inissue 1 June 1955https://pubs.acs.org/doi/10.1021/ie50546a056https://doi.org/10.1021/ie50546a056research-articleACS PublicationsRequest reuse permissionsArticle Views5306Altmetric-Citations341LEARN 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
A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. (1999)

Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CEA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients' plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4. Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 10(6) DCs. There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies.
Treatment of mice with human recombinant interleukin-2 augments resistance to the facultative intracellular pathogen Listeria monocytogenes (1989)

The effects of exogenously administered human recombinant IL-2 (hrIL-2) on resistance to Listeria monocytogenes infection were examined. Intravenous injection of hrIL-2 significantly enhanced antibacterial resistance in both BDF1 and C3H/HeJ mice. The beneficial effect of hrIL-2 was observed with as little as 0.6 micrograms per mouse, whereas optimum protection occurred at 6 micrograms per mouse, hrIL-2 was equally protective when administered concomitant with the listeriae or up to 24 h prior to infection; it had little effect if given after the bacterial challenge. Kinetic experiments indicated that both the peak bacterial burden and the time lag before L. monocytogenes began to be cleared from the spleen and liver were reduced in hrIL-2-treated mice as compared with control mice. Histopathological examination of spleens and livers confirmed that hrIL-2-treated Listeria-infected mice experienced considerably less damage to these organs than did control mice. Spleen cells from Listeria-infected mice exhibited depressed levels of mitogen-induced proliferation coincident with the peak bacterial burden in the spleen and liver and during the subsequent recovery from the infection. Administration of hrIL-2 to uninfected mice had no effect on spleen cell proliferation in response to mitogens in vitro, nor did hrIL-2 treatment restore normal levels of splenocyte proliferative responses to Listeria-infected mice. In addition, hrIL-2 treatment resulted in attenuated levels of serum colony-stimulating activity in infected mice as compared with control infected mice. Coadministration of both hrIL-2 and human recombinant interleukin-1 alpha at various dose and time combinations had no detectable additive or synergistic effect. Although these data do not suggest an obvious mechanism of action, they clearly demonstrate that hrIL-2 can augment host defense against the facultative intracellular pathogen L. monocytogenes.
Degradation of protease inhibitors, immunoglobulins, and other serum proteins by Serratia protease and its toxicity to fibroblast in culture (1986)

We investigated the effect of the extracellular protease of Serratia marcescens on human serum constituents such as immunoglobulins, fibronectin, alpha 1-protease inhibitor, alpha 2-macroglobulin, lysozyme, and transferrin. At a very low concentration of Serratia 56-kilodalton protease (56K protease), purified human plasma fibronectin was degraded rapidly into three structural domains or small fragments. Immunoglobulin G3 (IgG3) and IgA1 were also degraded within 30 min with 1 microgram of this protease per ml, more rapidly than their other subclass of IgG or IgA. alpha 1-Protease inhibitor, which did not inhibit the 56K protease, was degraded similarly by the protease. These events were demonstrated by fluorescence polarization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protease was considerably inhibited by human alpha 2-macroglobulin and chicken ovomacroglobulin. However, when there was a 2 M excess of ovomacroglobulin or a 4 M excess of alpha 2-macroglobulin over the 56K protease, about 25 or 40% proteolytic activity remained, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protease degraded the alpha 2-macroglobulin extensively during prolonged incubation, which paralleled with regeneration of the protease activity. The protease also cleaved human lysozyme, although moderately. Human serum transferrin was degraded slightly, and human serum albumin was almost resistant to the 56K protease. The enzyme seemed to have no effect on reconstituted collagen, but it degraded rat tropocollagen and yielded fragments of beta and gamma chains by cleaving the intramolecular cross-links. Most of the above proteolysis by the 56K protease appears to result in a limited type of substrate specificity. Thus, the present study demonstrates that the protease is capable of degrading defense-oriented humoral proteins and tissue constituents. Furthermore, it is toxic to fibroblasts. These findings also clarified the possible role of Serratia protease as a virulence factor in the pathogenesis of serratial infections. We recently demonstrated this notion in vivo with rabbit cornea (R. Kamata et al., Ophthalmology 92:1452-1459, 1985).
Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson's disease (2003)

To study the putative association of dopamine agonists with sleep attacks in patients with Parkinson's disease (PD) and their relation to daytime sleepiness, we performed a survey of 2,952 PD patients in two German counties. In 177 patients, sudden, unexpected, and irresistible sleep episodes while engaged in some activity were identified in a structured telephone interview. Ninety-one of these patients denied the occurrence of appropriate warning signs. A total of 133 patients (75%) had an Epworth Sleepiness Scale (ESS) score >10; 65 (37%) >15. Thirty-one patients (18%) had an ESS score < or =10 and yet experienced sleep attacks without warning signs. Thus, although a significant proportion of patients at risk for sleep attacks might be identified using the ESS, roughly 1% of the PD patient population seems to be at risk for sleep attacks without appropriate warning signs and without accompanying daytime sleepiness. Sleep attacks occurred with all dopamine agonists marketed in Germany (alpha-dihydroergocryptine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole), and no significant difference between ergot and nonergot drugs was evident. Levodopa (L-dopa) monotherapy carried the lowest risk for sleep attacks (2.9%; 95% confidence interval [CI], 1.7-4.0%) followed by dopamine agonist monotherapy (5.3%; 95% CI, 1.5-9.2%) and combination of L-dopa and a dopamine agonist (7.3%; 95% CI, 6.1-8.5%). Neither selegeline nor amantadine or entacapone appeared to influence the occurrence of sleep attacks. A high ESS score, intake of dopamine agonists, and duration of PD were the main influencing factors for the occurrence of sleep attacks. The odds ratio for dopamine agonist therapy was 2.9 compared to 1.9 with L-dopa therapy and 1.05 for a 1-year-longer disease duration.
Multiple instability-regulating sites in the 3' untranslated region of the urokinase-type plasminogen activator mRNA. (1994)

In LLC-PK1 cells urokinase-type plasminogen activator (uPA) mRNA has a short half-life. It is stabilized by inhibition of protein synthesis and by downregulation of protein kinase C (PKC). In the present study on uPA mRNA metabolism, we focused our attention on the 3' untranslated region (3'UTR) of the uPA mRNA, as this region is long and highly conserved among several mammalian species, including mice and humans. To investigate the possible role of the 3'UTR of uPA mRNA in mRNA metabolism, we inserted this region into the 3'UTR of the rabbit beta-globin gene that is linked to the cytomegalovirus promoter and stably transfected it into LLC-PK1 cells. While the parental globin mRNA was stable, the chimeric mRNA was degraded as rapidly as endogenous uPA mRNA, suggesting that the 3'UTR of uPA mRNA contains most of the information required for its rapid turnover. Further analysis showed that there are at least three independent determinants of instability in the 3'UTR; one is an AU-rich sequence located immediately 3' of the poly(A) addition signal, and one is a sequence containing a stem structure. One determinant seems to require ongoing RNA synthesis for its activity. All chimeric unstable globin mRNAs became stable in the presence of cycloheximide, a protein synthesis inhibitor, suggesting that the stabilization of mRNA by protein synthesis inhibition is not through a specific sequence in the mRNA. In PKC-downregulated cells, globin mRNAs with the complete 3'UTR or the AU-rich sequence were stabilized, suggesting that PKC downregulation stabilizes uPA mRNA through the AU-rich sequence. Here we discuss the significance of multiple, independently acting instability determinants in the regulation of uPA mRNA metabolism.
Immunotoxins for Treatment of Leukemia and Lymphoma (1995)

Less than fifteen years have passed since the practical applications of antibody-directed cell targeting were conceived in the laboratory. In vitro and in vivo applications for immunotoxins are being developed in a variety of protocols to treat human cancer. Immunotoxins may be particularly well-suited for the treatment of hematological cancers where malignant cells are more accessible than in solid tumors. Experimental results and clinical responses have provided encouragement, especially in light of the complexities of cancer biology, while the problems do not appear insurmountable. Continued basic research in cell biology combined with advances in manufacturing techniques will undoubtedly propose improvements in immunotoxins as well as new applications.