gebhart/patrepeval huggingface dataset:
[Expression of chimeric anti-CD3 IgG antibody in mammalian cells and analysis of its biological activity]. (2003)

The anti-CD3 antibody can improve success rate of organs transplant. HIT3a, a mouse anti-CD3 antibody, was chimerized by using gene engineering methods to decrease its immunogenity. The anti-CD3 genes, heavy chain and light chain, were cloned using PCR from the vector pCANTAB 5E containing anti-CD3 scFv gene fragment, and two PCR fragments were recombined into the expression vector pKN100 with human antibody light constant domain and pG1D105 with human antibody heavy constant domain, respectively. The two vectors were co-transfected into CHO cells using liposome. The anti-CD3 antibody was detected by ELISA and Western blot assay in supernatant of transfected CHO cells culture. The primary results of competitive assays by FACS showed that anti-CD3 antibody could partially block the sites through which parent antibody (HIT3a) bind to CD3+ Jurkat cells. The result of 3H-TdR incorporation showed that the chimeric anti-CD3 antibody could stimulated proliferation of peripheral blood mononuclear cells (PBMC) as the parent antibody. In this thesis, the results of some experiments indicated that the chimeric anti-CD3 antibody expressed in CHO cells was an antibody with native biological activity, and it is possible to apply to in clinic in the future.
Chemistry of Lipid of the Posthemolytic Residue or Stroma of Erythrocytes (1968)

Glycolipids were obtained from rabbit erythrocytes and reticulocytes. A new glycolipid, galactosyl-( 1→3)-galactosyl-( 1→3)-N-acetyl-glucosaminyl-(l→3)-galactosyl-(l→4)-glucosyl ceramide, was found as the main component of erythrocyte glycolipids. Galactosyl-(1→4)-galactosyl-(1→4)-glucosyl ceramide and a small amount of dihexosyl ceramide were also found. Unlike mature erythrocyte glycolipids, those of reticulocytes contain much mono- and di-hexosyl ceramide and an unknown glycolipid in addition to trihexosyl ceramide and ceramide pentasaccharide, suggesting that these glycolipids are metabolized actively in immature cells. The structure of the carbohydrate moiety in the ceramide pentasaccharide is very similar to that of the blood group B active mucoid from body fluids and the glycolipid inhibited hemagglutination of human B-erythrocytes by the corresponding iso-antibody.
Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells (2009)

Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease.
Site-Specific Conjugation of an Enzyme and an Antibody Fragment (1994)

A site-specific immunoconjugate was prepared between an F(ab')2-like fragment of the monoclonal anti-CEA murine IgG1 A5B7 and a mutant of the dimeric enzyme carboxypeptidase G2 possessing an N-terminal Thr in place of Ala. First an aldehyde was introduced at the N-terminus of the enzyme by mild periodate oxidation and a residue of carbohydrazide was specifically introduced at the C-terminus of the truncated heavy chain of the F(ab')2-like fragment by reverse proteolysis. Then the two modified proteins were conjugated by the formation of a hydrazone bond between the hydrazide and the aldehyde groups. The conjugate obtained retained both enzymic activity and antigen-binding capacity. The antigen-binding capacity was better than that of a similar conjugate made conventionally by random reaction with side chains.
A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer (2012)

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.
Synthesis, Chaperoning, and Metabolism of Proteins Are Regulated by NT-3/TrkC Signaling in the Medulloblastoma Cell Line DAOY (2008)

The human medulloblastoma cell line DAOY was transfected with Tropomyosin receptor kinase (TrkC), a marker for good prognostic outcome. Following TrkC-activation by its ligand neurotrophin-3, protein extracts from DAOY cells were run on 2DE with subsequent MALDI-TOF-TOF analysis and quantification in order to detect downstream effectors. Protein levels of translational, splicing, processing, chaperone, protein handling, and metabolism machineries were shown to depend on neurotrophin-3-induced TrkC activation probably representing pharmacological targets.
An essential role for connexin43 gap junctions in mouse coronary artery development (2002)

Connexin43 knockout mice die neonatally from conotruncal heart malformation and outflow obstruction. Previous studies have indicated the involvement of neural crest perturbations in these cardiac anomalies. We provide evidence for the involvement of another extracardiac cell population, the proepicardial cells. These cells give rise to the vascular smooth muscle cells of the coronary arteries and cardiac fibroblasts in the heart. We have observed the abnormal presence of fibroblast and vascular smooth muscle cells in the infundibular pouches of the connexin43 knockout mouse heart. In addition, the connexin43 knockout mice exhibit a variety of coronary artery patterning defects previously described for neural crest-ablated chick embryos, such as anomalous origin of the coronary arteries, absent left or right coronary artery, and accessory coronary arteries. However, we show that proepicardial cells also express connexin43 gap junctions abundantly. The proepicardial cells are functionally well coupled, and this coupling is significantly reduced with the loss of connexin43 function. Further analysis revealed an elevation in the speed of cell locomotion and cell proliferation rate in the connexin43-deficient proepicardial cells. A parallel analysis of proepicardial cells in transgenic mice with dominant negative inhibition of connexin43 targeted only to neural crest cells showed none of these coupling, proliferation or migration changes. These mice exhibit outflow obstruction, but no infundibular pouches. Together these findings indicate an important role for connexin43 in coronary artery patterning, a role that probably involves the proepicardial and cardiac neural crest cells. We discuss the potential involvement of connexin43 in human cardiovascular anomalies involving the coronary arteries.
Wnt Signaling Is Regulated by Endoplasmic Reticulum Retention (2009)

Precise regulation of Wnt signaling is important in many contexts, as in development of the vertebrate forebrain, where excessive or ectopic Wnt signaling leads to severe brain defects. Mutation of the widely expressed oto gene causes loss of the anterior forebrain during mouse embryogenesis. Here we report that oto is the mouse ortholog of the gpi deacylase gene pgap1, and that the endoplasmic reticulum (ER)-resident Oto protein has a novel and deacylase-independent function during Wnt maturation. Oto increases the hydrophobicities of Wnt3a and Wnt1 by promoting the addition of glycophosphatidylinositol (gpi)-like anchors to these Wnts, which results in their retention in the ER. We also report that oto-deficient embryos exhibit prematurely robust Wnt activity in the Wnt1 domain of the early neural plate. We examine the effect of low oto expression on Wnt1 in vitro by knocking down endogenous oto expression in 293 and M14 melanoma cells using shRNA. Knockdown of oto results in increased Wnt1 secretion which is correlated with greatly enhanced canonical Wnt activity. These data indicate that oto deficiency increases Wnt signaling in vivo and in vitro. Finally, we address the mechanism of Oto-mediated Wnt retention under oto-abundant conditions, by cotransfecting Wnt1 with gpi-specific phospholipase D (GPI-PLD). The presence of GPI-PLD in the secretory pathway results in increased secretion of soluble Wnt1, suggesting that the gpi-like anchor lipids on Wnt1 mediate its retention in the ER. These data now provide a mechanistic framework for understanding the forebrain defects in oto mice, and support a role for Oto-mediated Wnt regulation during early brain development. Our work highlights a critical role for ER retention in regulating Wnt signaling in the mouse embryo, and gives insight into the notoriously inefficient secretion of Wnts.
The reaction of iodine and thiol-blocking reagents with human complement components C2 and factor B. Purification and N-terminal amino acid sequence of a peptide from C2a containing a free thiol group (1983)

Human complement components C2 and Factor B each contain one free thiol group/molecule. Reaction with p-chloromercuribenzoate destroyed the haemolytic activity of C2 but had no effect on Factor B. Reaction of C2 with I2 gave a 16-fold enhancement of its haemolytic activity. The pH optimum for the reaction was 7.0. The I2 reacted at the thiol group in C2 with a stoicheiometry of 1 mol of I2/mol of C2. The product of the reaction was unaffected by millimolar concentrations of dithiothreitol; however, azide and cyanide were inhibitory. Reaction with azide did not result in re-expression of the thiol group. Mild oxidation of the thiol group with m-chloroperbenzoic acid did not enhance the haemolytic activity. The results suggest that reaction with I2 causes intramolecular covalent, but not disulphide, bond formation. I2 reacted with Factor B at the free thiol group without affecting the haemolytic activity. A CNBr-cleavage peptide from C2a (obtained by cleavage of C2 by subcomponent C1s) containing the free thiol group was isolated. Automated Edman degradation of the peptide showed that it was the N-terminal peptide of C2a. The free thiol group was identified at position 18.
Synthesis, metal chelate stability studies, and enzyme digestion of a peptide-linked DOTA derivative and its corresponding radiolabeled immunoconjugates (1993)

By directly coupling a tetrapeptide to DOTA through an amide bond, we synthesized a novel DOTA derivative, DOTA-glycylglycylglycyl-L-p-nitrophenylalanine amide. We converted this new precursor bifunctional chelating agent to DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine++ + and conjugated it to monoclonal antibody Lym-1. Serum stability studies show that the radiolabeled conjugates are kinetically inert under physiological conditions. The rates of loss of radiometals in human serum are 0.1 +/- 0.1% per day for InIII, 0.02 +/- 0.15% per day for YIII, and 0.3 +/- 0.2% per day for CuII labeled immunoconjugates. In the presence of the liver enzyme cathepsin B, an in vitro digestion of 114mIn-labeled conjugate yields a small fragment containing 114mIn. Characterization of the cleavage products shows that this liver enzyme hydrolyzes the peptide linkage before the phenylalanine residue, freeing the In-DOTA-triglycine complex from the conjugate. However, the liver enzyme cathepsin D does not cleave the linkage over the span of 7 days.
Show and tell: A neural image caption generator (2015)

Automatically describing the content of an image is a fundamental problem in artificial intelligence that connects computer vision and natural language processing. In this paper, we present a generative model based on a deep recurrent architecture that combines recent advances in computer vision and machine translation and that can be used to generate natural sentences describing an image. The model is trained to maximize the likelihood of the target description sentence given the training image. Experiments on several datasets show the accuracy of the model and the fluency of the language it learns solely from image descriptions. Our model is often quite accurate, which we verify both qualitatively and quantitatively. For instance, while the current state-of-the-art BLEU-1 score (the higher the better) on the Pascal dataset is 25, our approach yields 59, to be compared to human performance around 69. We also show BLEU-1 score improvements on Flickr30k, from 56 to 66, and on SBU, from 19 to 28. Lastly, on the newly released COCO dataset, we achieve a BLEU-4 of 27.7, which is the current state-of-the-art.
Recognition of Glioma Stem Cells by Genetically Modified T Cells Targeting EGFRvIII and Development of Adoptive Cell Therapy for Glioma (2012)

No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII-specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-γ, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139-based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a γ-retroviral vector expressing this EGFRvIII CAR was produced for clinical application.
Selective inhibition of T cell activation by an inhibitor of S-adenosyl-L-homocysteine hydrolase (1993)

Defects in the enzymes involved in the pathway of S-adenosylmethionine (AdoMet) metabolism, or inhibition of those enzymes, results in profound immunodeficiency. We have examined MDL 28,842, a novel irreversible inhibitor of S-adenosyl-L-homocysteine hydrolase (AdoHcyase), an enzyme involved in AdoMet metabolism, to determine its effect on the immune system and to investigate its potential as an immunosuppressive agent. The stimulation of human mononuclear cell proliferation in vitro with Con A, a T cell mitogen, and PWM, a T-dependent B cell mitogen, were inhibited by MDL 28,842. The 50% inhibitory concentration for both were 0.33 microM. In murine spleen cells, MDL 28,842 was a potent, nontoxic, inhibitor of Con A-stimulated T cell proliferation (IC50 = 0.19 microM) but did not affect LPS-induced B cell proliferation. This selective suppression was also observed when enriched murine T and B cells were stimulated with mitogens, although S-adenosyl-L-homocysteine (AdoHcy), the substrate of AdoHcyase, was similarly elevated in both populations. In addition to proliferation in response to a number of stimuli, IL-2 production and the expression of IL-2R by mitogen-stimulated T cells were inhibited by MDL 28,842. These results suggest a direct effect of MDL 28,842 on T cells. In vivo, the antibody response to a T cell-dependent Ag, OVA, was inhibited by MDL 28,842. The response of splenic T cells from these animals to OVA in vitro were similarly depressed compared with controls. The results demonstrate that MDL 28,842 is a potent nontoxic immunosuppressive agent, which has selectivity for T cells and therefore may be useful in the treatment of T cell-mediated disorders, such as autoimmune disease and tissue transplantation.
Concepts and experiments in computational reflection (1987)

This paper brings some perspective to various concepts in computational reflection. A definition of computational reflection is presented, the importance of computational reflection is discussed and the architecture of languages that support reflection is studied. Further, this paper presents a survey of some experiments in reflection which have been performed. Examples of existing procedural, logic-based and rule-based languages with an architecture for reflection are briefly presented. The main part of the paper describes an original experiment to introduce a reflective architecture in an object-oriented language. It stresses the contributions of this language to the field of object-oriented programming and illustrates the new programming style made possible. The examples show that a lot of programming problems that were previously handled on an ad hoc basis, can in a reflective architecture be solved more elegantly.
Distinct Mechanisms of Entry by Envelope Glycoproteins of Marburg and Ebola (Zaire) Viruses (2000)

Since the Marburg (MBG) and Ebola (EBO) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. Pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the MBG virus or the Zaire subtype EBO virus glycoproteins (GP) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. In contrast, they exhibited differential sensitivities to treatment of target cells with tunicamycin, endoglycosidase H, or protease (pronase). Therefore, while they exhibit certain functional similarities, the MBG and EBO virus GP interact with target cells by distinct processes.
Epitaxial Brownmillerite Oxide Thin Films for Reliable Switching Memory (2016)

Resistive switching memory, which is mostly based on polycrystalline thin films, suffers from wide distributions in switching parameters-including set voltage, reset voltage, and resistance-in their low- and high-resistance states. One of the most commonly used methods to overcome this limitation is to introduce inhomogeneity. By contrast, in this paper, we obtained uniform resistive switching parameters and sufficiently low forming voltage by maximizing the uniformity of an epitaxial thin film. To achieve this result, we deposited an SrFeOx/SrRuO3 heteroepitaxial structure onto an SrTiO3 (001) substrate by pulsed laser deposition, and then we deposited an Au top electrode by electron-beam evaporation. This device exhibited excellent bipolar resistance switching characteristics, including a high on/off ratio, narrow distribution of key switching parameters, and long data retention time. We interpret these phenomena in terms of a local, reversible phase transformation in the SrFeOx film between brownmillerite and perovskite structures. Using the brownmillerite structure and atomically uniform thickness of the heteroepitaxial SrFeOx thin film, we overcame two major hurdles in the development of resistive random-access memory devices: high forming voltage and broad distributions of switching parameters.
Functional Analysis of the Twin-Arginine Translocation Pathway in Corynebacterium glutamicum ATCC 13869 (2006)

Compared to those of other gram-positive bacteria, the genetic structure of the Corynebacterium glutamicum Tat system is unique in that it contains the tatE gene in addition to tatA, tatB, and tatC. The tatE homologue has been detected only in the genomes of gram-negative enterobacteria. To assess the function of the C. glutamicum Tat pathway, we cloned the tatA, tatB, tatC, and tatE genes from C. glutamicum ATCC 13869 and constructed mutants carrying deletions of each tat gene or of both the tatA and tatE genes. Using green fluorescent protein (GFP) fused with the twin-arginine signal peptide of the Escherichia coli TorA protein, we demonstrated that the minimal functional Tat system required TatA and TatC. TatA and TatE provide overlapping function. Unlike the TatB proteins from gram-negative bacteria, C. glutamicum TatB was dispensable for Tat function, although it was required for maximal efficiency of secretion. The signal peptide sequence of the isomaltodextranase (IMD) of Arthrobacter globiformis contains a twin-arginine motif. We showed that both IMD and GFP fused with the signal peptide of IMD were secreted via the C. glutamicum Tat pathway. These observations indicate that IMD is a bona fide Tat substrate and imply great potential of the C. glutamicum Tat system for industrial production of heterologous folded proteins.
High-dose megestrol acetate. A possible treatment for cachexia (1987)

Weight loss and anorexia are significant complications of a variety of disorders and add morbidity to the underlying process. We observed marked weight gain (median, 5.1 kg; range, 0.9 to 20.1 kg) and appetite enhancement in 27 of the 28 patients with breast cancer receiving treatment consisting of high doses of oral megestrol acetate (480 to 1600 mg/d). Weight gain occurred regardless of pretreatment weight, extent of metastases, or response to therapy. Our results suggest a possible role for megestrol acetate in reversing anorexia and weight loss, thereby improving the quality of life of patients with cachexia. Further research is needed to establish the mechanism of weight gain and potential clinical applications. (<i>JAMA</i>1987;257:1195-1198)
Cutting Edge: Granzymes A and B Are Not Essential for Perforin-Mediated Tumor Rejection (2003)

Controversy still exists regarding the biological function of granzyme serine proteases released with perforin from the cytotoxic granules of NK cells and CTLs. In particular, it is not clear whether the major granzymes, A and B, play an essential role in tumor rejection mediated by the perforin pathway. We have now examined the relative importance of perforin and granzyme A and B clusters in five different tumor models that stringently distinguish their importance. We conclude that granzyme A and B clusters are not essential for CTL- and NK cell-mediated rejection of spontaneous and experimental tumors, raising the likelihood that either perforin alone or in combination with an additional granzyme or granule component(s) mediates cytotoxicity of tumor cells in vivo.
In Vitro Killing of Nosocomial Pathogens by Acid and Acidified Nitrite (2006)

Exposure to pH 1 or 2 buffers or acidic gastric contents resulted in the killing of vancomycin-resistant Enterococcus sp., Klebsiella pneumoniae, Staphylococcus aureus, and Candida glabrata but not Clostridium difficile spores. Nitrite enhanced killing under acidic conditions, but significant killing of C. difficile spores required nitrite concentrations above usual physiological levels.