gebhart/patrepeval huggingface dataset:
Production of therapeutic antibodies with controlled fucosylation (2009)

The clinical success of therapeutic antibodies is demonstrated by the number of antibody therapeutics that have been brought to market and the increasing number of therapeutic antibodies in development. Recombinant antibodies are molecular-targeted therapeutic agents and represent a major new class of drugs. However, it is still very important to optimize and maximize the clinical efficacy of therapeutic antibodies, in part to help lower the cost of therapeutic antibodies by potentially reducing the dose or the duration of treatment. Clinical trials using therapeutic antibodies fully lacking core fucose residue in the Fc oligosaccharides are currently underway, and their remarkable physiological activities in humans in vivo have attracted attention as next-generation therapeutic antibody approaches with improved efficacy. Thus, an industrially applicable antibody production process that provides consistent yields of fully non-fucosylated antibody therapeutics with fixed quality has become a key goal in the successful development of next-generation therapeutic agents. In this article, we review the current technologies for production of therapeutic antibodies with control of fucosylation of the Fc N-glycans.
Development of a human monoclonal antibody to ganglioside G(M2) with potential for cancer treatment. (1996)

A human B-lymphoblastoid cell clone, L55-81, that produces human monoclonal antibody (MAb) to ganglioside G(M2) was established from peripheral blood B lymphocytes of a melanoma patient. L55-81 secretes IgMkappa light chain antibody in a serum-free medium. G(M2) specificity of the antibody was tested by immune adherence assay, TLC immunostaining, and ELISA. Anti-G(M2) antibody was shown to have the ability to kill the G(M2)-rich human melanoma cell line M14 in the presence of human or rabbit complement. A purified L55-81 MAb (>99.5% purity in protein concentration) was biotinylated and tested for its reactivity to various histological-type biopsied tumor and normal tissues in an avidin-biotin detection system. L55-81 MAb (20 microg/ml) reacted with several types of tumor tissues such as melanoma (7 of 10), colon carcinoma (4 of 5), ovary carcinoma (4 of 5), breast carcinoma (1 of 5), kidney carcinoma (1 of 5), and prostate carcinoma (1 of 5). None of the normal tissues derived from 24 different organs and adjacent normal tissues surrounding the cancerous tissues were stained. Production of the antibody in a serum-free medium, the cytotoxic potential with human complement, the inability to react to normal tissues, and the ability to target antigen-specific target cells make L55-81 a potential therapeutic agent for the treatment of cancers expressing ganglioside G(M2).
Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease (2013)

Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalactonojirimycin (DGJ) as a tool to analyse the influence of individual mutations on subcellular organelle-trafficking and stability. We analysed a significant number of mutations and correlated the obtained properties to the clinical manifestation related to the mutation in order to improve our knowledge of the identity of functional relevant amino acids. Additionally, we illustrate the consequences of different mutations on plasma lyso-globotriaosylsphingosine (lyso-Gb3) accumulation in the patients' plasma, a biomarker proven to reflect the impaired substrate clearance caused by specific mutations. The established system enables us to provide information for the clinical relevance of PC therapy for a given mutant. Finally, in order to generate reliable predictions of mutant GLA defects we compared the different data sets to reveal the most coherent system to reflect the clinical situation.
Actinic keratosis treated with an immune response modifier: a case report of six patients (2003)

Actinic keratoses (AKs) are intraepidermal tumours, which result from the proliferation of transformed neoplastic keratinocytes. They are typically induced by chronic exposure to ultraviolet radiation, and can often develop into squamous cell carcinoma (SCC). Six patients, who presented with AKs located on the head, face and chest, were treated with the immune response modifier, imiquimod, as a 5% cream five times per week for up to 8 weeks. The majority of patients experienced mild to moderate side-effects, consisting of erythema, itching and burning. Topical application of imiquimod for 4-8 weeks resulted in complete clearance in all patients. No new or recurrent lesions were observed during a 6-8 month follow-up period.
Stereoselective Metabolism of Nicotine and Tobacco-Specific N-Nitrosamines to 4-Hydroxy-4-(3-pyridyl)butanoic Acid in Rats (1999)

The carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are believed to play a role in cancers associated with the use of tobacco products. Urinary metabolites of NNK and NNN could be used as biomarkers for an individual's ability to metabolically activate or detoxify these nitrosamines. While several metabolites of NNK can be quantified in human urine, no assay is available to determine human urinary levels of NNK and NNN metabolites resulting from the critical alpha-hydroxylation metabolic activation pathways. The major urinary metabolites resulting from alpha-hydroxylation of NNK and NNN in rodents are 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid). The major obstacle to the use of these metabolites as biomarkers of metabolic activation is the fact that they are also metabolites of nicotine, which is present at levels 1400-13000 times greater than those of the nitrosamines in cigarette smoke. However, the chirality of hydroxy acid could be useful in overcoming this problem. If different enantiomers of hydroxy acid were formed from nicotine versus the nitrosamines, and if the overall yield of hydroxy acid from nicotine were substantially smaller than that from the nitrosamines, then hydroxy acid might be useful as a urinary biomarker of NNK and NNN alpha-hydroxylation. To these ends, F-344 rats were administered either [5-3H]NNK, [5-3H]NNN, [5-3H]keto acid, or [2'-14C]nicotine. The levels of urinary hydroxy acid were determined by HPLC analysis. Its stereochemistry was determined by conversion to its methyl ester, reaction with (S)-(-)-alpha-methylbenzyl isocyanate, and separation and quantitation of the resulting diastereomers by HPLC. Urinary hydroxy acid accounted for 12% of the NNK dose and 31% of the NNN dose, but only 1 and 0.1% of the dose of keto acid and nicotine, respectively. Furthermore, metabolism of NNK produced mainly (S)-hydroxy acid in the urine, while metabolism of keto acid and nicotine gave predominantly (R)-hydroxy acid. Both enantiomers were present in the urine of NNN-treated rats. Therefore, in the rat, it is possible to distinguish the hydroxy acid derived from nicotine from that derived from the nitrosamines. If similar pathways occur in humans, (S)-hydroxy acid could potentially be developed as a urinary biomarker of NNK and NNN alpha-hydroxylation in smokers.
Desorption of ions from rat membranes: Selectivity of different ionization techniques (1989)

Complex lipid biomarkers, including phosphatidylcholines, cerebrosides and sulfatides, are shown to be desorbed intact from rat brain myelin and rat liver microsomes by liquid secondary ion mass spectrometry, by plasma desorption and by laser desorption. Different polar lipids are favored by the different desorption techniques and as negative or positive ions. These selectivities support current theories about ionization for the different techniques.
Quinoline‐Based Derivatives of Pirinixic Acid as Dual PPAR α/γ Agonists (2007)

Pirinixic acid is known for its peroxisome proliferator-activated receptor (PPAR) agonistic action. In a recent publication, we have shown that aliphatic alpha-substitution of pirinixic acid enhances both PPARalpha and PPARgamma agonism. The goal of this study was to evaluate, whether the PPAR agonism of pirinixic acid may be also maintained in quinoline-based derivatives. The present study revealed that the mere substitution of the dimethyl aniline moiety of pirinixic acid by quinoline leads to a total loss of PPARalpha/gamma agonism, whereas concomitant alpha-substitution with n-butyl or n-hexyl groups restores and even enforces PPAR activation, leading to potent dual PPARalpha/gamma agonists. In the following we report the synthesis of quinoline-based derivatives of pirinixic acid, which in a Gal4-based luciferase-reporter gene assay proved to be potent dual PPARalpha/gamma agonists. Molecular docking of compound 4 with FlexX suggests a binding mode resembling to that of tesaglitazar.
Biodiversity of cytochrome P450 redox systems (2005)

P450s (cytochrome P450 mono-oxygenases) are a superfamily of haem-containing mono-oxygenase enzymes that participate in a wide range of biochemical pathways in different organisms from all of the domains of life. To facilitate their activity, P450s require sequential delivery of two electrons passed from one or more redox partner enzymes. Although the P450 enzymes themselves show remarkable similarity in overall structure, it is increasingly apparent that there is enormous diversity in the redox partner systems that drive the P450 enzymes. This paper examines some of the recent advances in our understanding of the biodiversity of the P450 redox apparatus, with a particular emphasis on the redox systems in the pathogen Mycobacterium tuberculosis.
Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate. (1991)

Nerve growth factor-like substance(s) were identified in both conditioned media of a human prostatic tumor epithelial cell line (TSU-pr1) and a human prostatic stromal cell line (HPS) by Western blot analysis and bioassay of neurite outgrowth of PC12 cells. Nerve growth factor-beta (NGF) immunofluorescence was also localized to secretory vesicles in the cytoplasm of both the TSU-pr1 and HPS cells. Western blot of the TSU-pr1 and HPS cell-secreted protein identified an Mr 65,000 major protein which immunoreacted with murine NGF antibody. NGF Western blot of HPS cell-secreted protein also identified an Mr 42,000 minor band under reduced and nonreduced conditions and an Mr 61,000 minor band under reduced conditions. The secreted protein from the TSU-pr1 cells (50 micrograms/ml) and HPS (50 micrograms/ml), as well as murine NGF (50 ng/ml) or human recombinant NGF (50 ng/ml), stimulated neurite outgrowth from PC12 cells. This neurite outgrowth activity was partially inhibited by treatment with NGF antibody. Neither the serum containing growth medium nor bovine serum albumin (50 micrograms/ml) stimulated neurite outgrowth. The NGF-like secretory protein appeared to play a role in the paracrine regulation of prostatic growth between TSU-pr1 cells and HPS cells. The relative growth of TSU-pr1 cells, as indicated by [3H]thymidine incorporation, in response to HPS secretory protein was stimulated 2.8-fold in a dose-dependent manner. In the converse interaction, the relative growth of HPS cells in response to TSU-pr1 secretory protein was stimulated 1.8-fold in a dose-dependent manner. Immunoneutralization of TSU-pr1 and HPS secretory protein was performed with antibody against NGF, acidic fibroblast growth factor, and basic fibroblast growth factor. Removal of the NGF-like protein from the maximal stimulatory dose of TSU-pr1 secretory protein (100 micrograms/ml) with NGF antibody reduced HPS proliferation to 52% of maximal levels, and immunoneutralization of the NGF-like protein in the maximal stimulatory dose of HPS secretory protein (20 micrograms/ml) also reduced TSU-pr1 proliferation to 16% of maximal levels. Addition of normal rabbit serum or prior immunoprecipitation of either TSU-pr1 or HPS secretory protein with antibody against acidic fibroblast growth factor and basic fibroblast growth factor did not inhibit the proliferation of either cell type. These results suggest that TSU-pr1 tumor cells and HPS cells secrete NGF-like protein(s) which modulate their paracrine interactive growth in vitro.
Transplantation of adrenal medullary tissue to striatum in parkinsonism (1985)

Autologous adrenal medullary tissue was transplanted to the striatum in two patients with severe parkinsonism. The aim was to provide the striatum with a new cellular source of catecholamines. Some rewarding effects were registered. This is the first time that such tissue has been transplanted in the human brain. The results merit further clinical trials.
A Hierarchical Neural Autoencoder for Paragraphs and Documents (2015)

Jiwei Li, Thang Luong, Dan Jurafsky. Proceedings of the 53rd Annual Meeting of the Association for Computational Linguistics and the 7th International Joint Conference on Natural Language Processing (Volume 1: Long Papers). 2015.
18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significance (1989)

Cytogenetic, molecular genetic and clinical information was collected for 102 cases of diffuse large cell lymphoma (DLCL) ascertained in a diagnostic laboratory over a 3-year period. Nineteen cases showed evidence of either a t(14;18) or a rearrangement of one of three genomic probes for breakpoints at 18q21. Clinical and histologic evidence of transformation from follicular lymphoma or chronic lymphocytic leukaemia was available in six cases. Except for age, prognostic clinical variables (LDH, stage, extranodal involvement) were similar between the 18q21 rearranged patients and DLCL patients without 18q21 rearrangement. At a median follow-up in excess of 2 years for both groups, there was no difference in overall survival between the 18q21 rearranged group compared to DLCL patients lacking this genetic abnormality. The median disease-free survival for the 18q21 rearranged group, however, was significantly shorter and survival in partial remission longer. The propensity for extended survival of the 18q21 rearranged DLCL patients with residual or recurrent disease resembled the clinical behaviour of nodular lymphoma patients with t(14;18). These results suggest that cytogenic or molecular genetic identification of a chromosome 18q21 translocation may be of prognostic significance in the analysis of treatment protocols for patients with DLCL.
Expression of Apoptosis-Regulatory Genes in Renal Proximal Tubular Epithelial Cells Exposed to High Ambient Glucose and in Diabetic Kidneys (1997)

These studies suggest that the metabolic changes of the diabetic state modulate the expression of apoptosis-regulatory genes so as to favor apoptosis and that this modulation may be a factor in the pathogenesis of diabetic nephropathy.
Intracellular targeting of truncated secretory peptides in the mammalian heart and brain (2006)

Secretory polypeptides are vital for nervous system function, sleep, reproduction, growth, and metabolism. Ribosomes scanning the 5'-end of mRNA usually detect the first AUG site for initiating translation. The nascent propeptide chain is then directed via a signal-peptide into the endoplasmic reticulum, processed through the Golgi stacks, and packaged into secretory vesicles. By expressing prepropeptide-EGFP fusion proteins, we observed unusual destinations, mitochondria, nucleus, and cytoplasm, of neuropeptide Y (NPY), atrial natriuretic peptide, and growth hormone in living murine cardiac cells and hypothalamic slices. Subcellular expression was modulated by Zn++ or mutations of N-terminal prohormone sequences but was not due to overexpression in the trans-Golgi network. Mitochondrial targeting of NPY also occurred without the EGFP tag, was enhanced by site-directed mutagenesis of the first AUG initiation site, and abolished by mutation of the second AUG. Immunological methods indicated the presence of N-terminal truncated NPY in mitochondria. Imaging studies showed depolarization of NPY-containing mitochondria. P-SORT software correctly predicted the secondary intracellular destinations and suggested such destinations for many neuropeptides and peptide hormones known. Thus, mammalian cells may retarget secretory peptides from extracellular to intracellular sites by skipping the first translation-initiation codon and thereby alter mitochondrial function, gene expression, and secretion.
Energy harvesting and wireless power transmission by a hybridized electromagnetic–triboelectric nanogenerator (2019)

A rotating-disk-based hybridized electromagnetic–triboelectric nanogenerator exhibits a much better charging performance and provides a better platform for WPT.
Anti-inflammatory and Cellular Protective Effects on Hydrogen Peroxide-induced Cytotoxicity of Grasshopper Extracts (2006)

In order to investigate the anti-inflammatory and cellular protective effects of Atractomorpha lata Motschulsky, Oxya japonica japonica Thunberg and Stethophyma magister Rehn, we first examined hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells as well as antioxidant assays including DPPH and FRAP assays. We found that water, ethanol and methanol extracts of Oxya japonica japonica Thunberg and Stethophyma magister Rehn had potentials to anti-oxidant activity and especially water extract of Oxya japonica japonica Thunberg exhibited the most potent protective effects against -induced cytotoxicity in SH-SY5Y cells by MTT assay. Taken Together, these findings indicate that water extract of Oxya japonica japonica Thunberg could be useful insect resources for agrobiotechnological or oriental medicinal purposes.
Preventing spontaneous genetic rearrangements in the transgene cassettes of adenovirus vectors (2011)

First-generation, E1/E3-deleted adenoviral vectors with diverse transgenes are produced routinely in laboratories worldwide for development of novel prophylactics and therapies for a variety of applications, including candidate vaccines against important infectious diseases, such as HIV/AIDS, tuberculosis, and malaria. Here, we show, for two different transgenes (both encoding malarial antigens) inserted at the E1 locus, that rare viruses containing a transgene-inactivating mutation exhibit a selective growth advantage during propagation in E1-complementing HEK293 cells, such that they rapidly become the major or sole species in the viral population. For one of these transgenes, we demonstrate that viral yield and cytopathic effect are enhanced by repression of transgene expression in the producer cell line, using the tetracycline repressor system. In addition to these transgene-inactivating mutations, one of which occurred during propagation of the pre-viral genomic clone in bacteria, and the other after viral reconstitution in HEK293 cells, we describe two other types of mutation, a small deletion and a gross rearranging duplication, in one of the transgenes studied. These were of uncertain origin, and the effects on transgene expression and viral growth were not fully characterized. We demonstrate that, together with minor protocol modifications, repression of transgene expression in HEK293 cells during viral propagation enables production of a genetically stable chimpanzee adenovirus vector expressing a malarial antigen which had previously been impossible to derive. These results have important implications for basic and pre-clinical studies using adenoviral vectors and for derivation of adenoviral vector products destined for large-scale amplification during biomanufacture.
Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection (2006)

Immature dendritic cells (DCs) capture HIV type 1 (HIV-1) and can transmit captured virus particles to T cells. In this report, we show that HIV-1 particles captured by DCs can be transmitted to T cells by exocytosis without de novo infection. Captured HIV-1 particles were rapidly endocytosed to tetraspan protein (CD9, CD63)-positive endocytic compartments that were reminiscent of multivesicular endosomal bodies. Furthermore, some of the endocytosed virus particles were constitutively released into the extracellular milieu in association with HLA-DR1(+), CD1b(+), CD9(+), and CD63(+) vesicles (exosomes) and could initiate productive infections of CD4(+) target cells. Surprisingly, the exocytosed vesicle-associated HIV-1 particles from DCs were 10-fold more infectious on a perparticle basis than cell-free virus particles. These studies describe a previously undescribed mechanism of DC-mediated HIV-1 transmission and suggest that virus particle trafficking to multivesicular endosomal bodies and subsequent exocytosis can provide HIV-1 particles captured by DCs an avenue for immune escape.
Nucleation and Growth of CdSe on ZnS Quantum Crystallite Seeds, and Vice Versa, in Inverse Micelle Media (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleation and Growth of CdSe on ZnS Quantum Crystallite Seeds, and Vice Versa, in Inverse Micelle MediaA. R. Kortan, R. Hull, R. L. Opila, M. G. Bawendi, M. L. Steigerwald, P. J. Carroll, and Louis E. BrusCite this: J. Am. Chem. Soc. 1990, 112, 4, 1327–1332Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February 1990https://pubs.acs.org/doi/10.1021/ja00160a005https://doi.org/10.1021/ja00160a005research-articleACS PublicationsRequest reuse permissionsArticle Views4258Altmetric-Citations773LEARN 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