gebhart/patrepeval huggingface dataset:
Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant (2011)

No countermeasures currently exist for the prevention or treatment of the severe sequelae of Filovirus (such as Ebola virus; EBOV) infection. To overcome this limitation in our biodefense preparedness, we have designed monoclonal antibodies (mAbs) which could be used in humans as immunoprotectants for EBOV, starting with a murine mAb (13F6) that recognizes the heavily glycosylated mucin-like domain of the virion-attached glycoprotein (GP). Point mutations were introduced into the variable region of the murine mAb to remove predicted human T-cell epitopes, and the variable regions joined to human constant regions to generate a mAb (h-13F6) appropriate for development for human use. We have evaluated the efficacy of three variants of h-13F6 carrying different glycosylation patterns in a lethal mouse EBOV challenge model. The pattern of glycosylation of the various mAbs was found to correlate to level of protection, with aglycosylated h-13F6 providing the least potent efficacy (ED(50) = 33 μg). A version with typical heterogenous mammalian glycoforms (ED(50) = 11 μg) had similar potency to the original murine mAb. However, h-13F6 carrying complex N-glycosylation lacking core fucose exhibited superior potency (ED(50) = 3 μg). Binding studies using Fcγ receptors revealed enhanced binding of nonfucosylated h-13F6 to mouse and human FcγRIII. Together the results indicate the presence of Fc N-glycans enhances the protective efficacy of h-13F6, and that mAbs manufactured with uniform glycosylation and a higher potency glycoform offer promise as biodefense therapeutics.
Utilizing Ion-Pairing Hydrophilic Interaction Chromatography Solid Phase Extraction for Efficient Glycopeptide Enrichment in Glycoproteomics (2010)

Glycopeptide enrichment is a prerequisite to enable structural characterization of protein glycosylation in glycoproteomics. Here we present an improved method for glycopeptide enrichment based on zwitter-ionic hydrophilic interaction chromatography solid phase extraction (ZIC-HILIC SPE) in a microcolumn format. The method involves TFA ion pairing (IP) to increase the hydrophilicity difference between glycopeptides and nonglycosylated peptides. Three mobile phases were investigated, i.e., 2% formic acid (defined as IP(2% FA) ZIC-HILIC SPE), 0.1% TFA and 1% TFA (defined as IP(0.1% TFA) and IP(1% TFA) ZIC-HILIC SPE) all containing 80% acetonitrile. Samples of increasing complexities, i.e., digests of single glycoproteins, a five-glycoprotein mixture, and depleted plasma, were used in the study. The presence of TFA in the mobile phase significantly improved the glycopeptide enrichment for all complexities, as evaluated by enhanced glycopeptide detection using MALDI-TOF MS and RP-LC-ESI-MS/MS, e.g., the glycopeptide ion signals were increased by up to 3.7-fold compared to IP(2% FA) conditions. The enhanced glycopeptide detection was promoted by a substantial depletion of nonglycosylated peptides, offering an almost complete isolation of IgG glycopeptides using a single SPE enrichment step and a reduction from 711 nonglycosylated peptides observed in the IP(2% FA) ZIC-HILIC SPE retained plasma fraction, to only 157 and 97 when 0.1% and 1% TFA was used in the mobile phase. In conclusion, this systematic study has shown that TFA-containing mobile phases increase glycopeptide enrichment efficiency considerably for a broad range of sample complexities when using ZIC-HILIC SPE.
Identification and isolation of embryonic stem cells in reproductive endocrinology: theoretical protocols for conservation of human embryos derived from in vitro fertilization (2005)

The role of reproductive endocrinology in ESC research remains paramount. In this report, we hypothesize new and expand on existing strategies having the potential to enhance human ESC isolation, identification and in vitro maintenance.
Influenza virus genome consists of eight distinct RNA species. (1976)

The genomic RNA of the avian influenza A virus, fowl plague, was fractionated into eight species by electrophoresis in polyacrylamide-agarose gels containing 6 M urea. The separated 32P-labeled RNA species were characterized by digestion with RNase T1 and fractionation of the resulting oligonucleotides by two-dimensional gel electrophoresis; this demonstrated that each species has a distinct nucleotide sequence. A tentative correlation of each genome RNA species with the virus protein that it encodes was made.
Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution and immunogenicity relative to murine analog NR-LU-10. (1993)

A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma antigen recognition site as a previously studied murine monoclonal antibody (NR-LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60 mCi/m2 (seven patients) was administered. Mean serum disappearance half-time values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was excreted in the urine by 6 days. Tumor localization was demonstrated by gamma camera imaging in seven of nine patients. The percent injected dose per gram in a single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression in five of six evaluable patients who received 60 mCi/m2: median WBC nadir = 2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever, nausea, slight elevations of liver function tests and mild allergic reactions were seen in some patients. The chimeric antibody elicited low levels of anti-NR-LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10 which elicited higher levels of human anti-mouse antibody in all patients. This pilot study demonstrates the ability of the chimeric antibody to target tumors with reduced (but not absent) immunogenicity and delayed clearance relative to the murine antibody.
Immunogenetics of human IgE (1996)

Immunoglobulin E plays a central role in mediating the pathology of allergic disease. Conversely, it is involved in the normal protective immune responses against parasite infection. Both these biological processes depend on interaction between the variable regions (VH and VL) of IgE antibodies and target antigen. It is now feasible to investigate the molecular nature of VH regions used to encode IgE at the genetic level. Using this technology to analyze IgE in patients with asthma has revealed features which may have relevance for allergic disease. First, preferential choice of VH genes, with dominance of the small VH5 family, particularly the VH32 gene, has been found. This may implicate a B cell superantigen (superallergen) selectively driving the use of these genes. Second, VH5 genes in IgE are somatically mutated with clear hot spots of mutational activity. Mutational hotspots, which are a feature of the VH5 gene, are supplemented in IgE by ongoing mutations which may be involved in affinity maturation. Third, a single B cell can switch to either IgE or IgG4, with both variants coexisting in blood. These findings may provide clues to the mechanism by which IgE is generated, and suggest options for therapeutic intervention.
The MtsA Subunit of the Methylthiol:Coenzyme M Methyltransferase of Methanosarcina barkeri Catalyses Both Half-reactions of Corrinoid-dependent Dimethylsulfide: Coenzyme M Methyl Transfer (2001)

Methanogenesis from dimethylsulfide requires the intermediate methylation of coenzyme M. This reaction is catalyzed by a methylthiol:coenzyme M methyltransferase composed of two polypeptides, MtsA (a methylcobalamin:coenzyme M methyltransferase) and MtsB (homologous to a class of corrinoid proteins involved in methanogenesis). Recombinant MtsA was purified and found to be a homodimer that bound one zinc atom per polypeptide, but no corrinoid cofactor. MtsA is an active methylcobalamin:coenzyme M methyltransferase, but also methylates cob(I)alamin with dimethylsulfide, yielding equimolar methylcobalamin and methanethiol in an endergonic reaction with a K(eq) of 5 x 10(-)(4). MtsA and cob(I)alamin mediate dimethylsulfide:coenzyme M methyl transfer in the complete absence of MtsB. Dimethylsulfide inhibited methylcobalamin:coenzyme methyl transfer by MtsA. Inhibition by dimethylsulfide was mixed with respect to methylcobalamin, but competitive with coenzyme M. MtbA, a MtsA homolog participating in coenzyme M methylation with methylamines, was not inhibited by dimethylsulfide and did not catalyze detectable dimethylsulfide:cob(I)alamin methyl transfer. These results are most consistent with a model for the native methylthiol:coenzyme M methyltransferase in which MtsA mediates the methylation of corrinoid bound to MtsB with dimethylsulfide and subsequently demethylates MtsB-bound corrinoid with coenzyme M, possibly employing elements of the same methyltransferase active site for both reactions.
Genome Sequence of the Radioresistant Bacterium Deinococcus radiodurans R1 (1999)

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284,156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.
Exploration of peptides bound to MHC class I molecules in melanoma (2015)

Advancements in high-resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13,829 peptides were identified; 83-87% of these were 8-11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; mRNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA-type binding prediction for 10,078 9/10 mer peptides assigned 88-95% to a patient-specific HLA subtype, revealing a disparity in strength of predicted binding. HLA-B*27-specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells.
Detection of cancer cells in peripheral blood of breast cancer patients using reverse transcription-polymerase chain reaction for epidermal growth factor receptor. (1998)

The epidermal growth factor receptor (EGFR) has been reported to be expressed in high levels in primary breast cancer by immunohistochemistry. In the present study, a reverse transcription (RT)-PCR assay using EGFR primers was developed and evaluated for the detection of circulating micrometastases in the blood of breast cancer patients. Total RNA was extracted from breast cancer cell lines and from the blood of 23 control individuals and 37 breast cancer patients. After reverse transcription, outer and nested primers for EGFR were used for cDNA amplification. RNA integrity was confirmed with parallel RT-PCR amplification using beta2-microglobulin primers. PCR products were electrophoresed on agarose gels containing ethidium bromide and visualized by UV photography. Southern blotting was used to confirm EGFR specificity. The nested EGFR RT-PCR assay was capable of detecting a lower limit of 100 fg of total RNA from the A431 cell line. EGFR RNA was identified from the blood of 4 of 18 (22%) metastatic breast cancer patients, 0 of 6 locally recurrent breast cancer patients, 0 of 13 adjuvant breast cancer patients, and 0 of 23 controls (P = 0.03, metastatic versus control). The 18 metastatic breast cancer patients all had progressive disease at the time of blood sampling. The identity of the four EGFR-positive bands was confirmed by Southern blotting. The presence of RT-PCR positivity for EGFR was not a treatment-related phenomenon, because three of the four EGFR-positive patients were not receiving treatment at the time of blood collection. RT-PCR for EGFR is a sensitive and specific method for the detection of circulating micrometastases in a proportion of patients with metastatic breast cancer.
Effect of Gamma-Vinyl GABA in Friedreich’s Ataxia (1982)

Gamma-Vinyl GABA, an irreversible inhibitor of GABA-transaminase, was administered orally in two daily doses of 250 mg to 10 patients with cerebellar ataxia (9 with Friedreich's ataxia, one with olivo-ponto-cerebellar atrophy) for at least one month in an open study. No significant difference occurred in the disability scores of cerebellar symptomatology for the group as a whole, but seven patients showed some improvement in scores with treatment and two patients claimed marked subjective amelioration. Tolerance to Gamma-Vinyl-GABA treatment was excellent. These preliminary results suggest that further studies with well-tolerated agents which enhance CNS GABA-ergic function are warranted in patients with cerebellar ataxia.
Chromium-carbon bonds in aqueous solutions. Pulse radiolytic study (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChromium-carbon bonds in aqueous solutions. Pulse radiolytic studyH. Cohen and D. MeyersteinCite this: Inorg. Chem. 1974, 13, 10, 2434–2443Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/ic50140a027https://doi.org/10.1021/ic50140a027research-articleACS PublicationsRequest reuse permissionsArticle Views97Altmetric-Citations51LEARN 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
Probing the Roles of Key Residues in the Unique Regulatory NADH Binding Site of Type II Citrate Synthase of Escherichia coli (2003)

The citrate synthase of Escherichia coli is an example of a Type II citrate synthase, a hexamer that is subject to allosteric inhibition by NADH. In previous crystallographic work, we defined the NADH binding sites, identifying nine amino acids whose side chains were proposed to make hydrogen bonds with the NADH molecule. Here, we describe the functional properties of nine sequence variants, in which these have been replaced by nonbonding residues. All of the variants show some changes in NADH binding and inhibition and small but significant changes in kinetic parameters for catalysis. In three cases, Y145A, R163L, and K167A, NADH inhibition has become extremely weak. We have used nanospray/time-of-flight mass spectrometry, under non-denaturing conditions, to show that two of these, R163L and K167A, do not form hexamers in response to NADH binding, unlike the wild type enzyme. One variant, R109L, shows tighter NADH binding. We have crystallized this variant and determined its structure, with and without bound NADH. Unexpectedly, the greatest structural changes in the R109L variant are in two regions outside the NADH binding site, both of which, in wild type citrate synthase, have unusually high mobilities as measured by crystallographic thermal factors. In the R109L variant, both regions (residues 260 -311 and 316-342) are much less mobile and have rearranged significantly. We argue that these two regions are elements in the path of communication between the NADH binding sites and the active sites and are centrally involved in the regulatory conformational change in E. coli citrate synthase.
Packaging for high-pressure treatments in the food industry (2000)

This study highlights some important aspects of the package, such as packaging materials suitable for high-pressure treatments, package properties (barriers and flexibility) and package integrity. Six different types of package were tested. They consist of multilayer plastic packages (PA/PE), where thickness, permeability and stress varied at yield point and at breakage. They achieve a good heat seal and good protection from the pressure medium (water) surrounding them. Experiments were carried out at 200, 350 and 500 MPa for 30 min at ambient temperature, comparing the performance of pressurized multilayer plastic packages with untreated packages. Different simulants (water, 3% acetic acid, 15% ethyl alcohol and olive oil), in contact with the packages, were used to demonstrate the good integrity between package and foodstuff during treatment and shelf-life. Copyright © 2000 John Wiley & Sons, Ltd.
Regulation of Adenovirus Membrane Penetration by the Cytoplasmic Tail of Integrin β5 (2000)

Adenovirus (Ad) cell entry involves sequential interactions with host cell receptors that mediate attachment (CAR), internalization (alphavbeta3 and alphavbeta5), and penetration (alphavbeta5) of the endosomal membrane. These events allow the virus to deliver its genome to the nucleus. While integrins alphavbeta3 and alphavbeta5 both promote Ad internalization into cells, integrin alphavbeta5 selectively facilitates Ad-mediated membrane permeabilization and endosome rupture. In the experiments reported herein, we demonstrate that the intracellular domain of the integrin beta5 subunit specifically regulates Ad-mediated membrane permeabilization and gene delivery. CS-1 melanoma cells expressing a truncated integrin beta5 or a chimeric (beta5-beta3) cytoplasmic tail (CT) supported normal levels of Ad endocytosis but had reduced Ad-mediated gene delivery and membrane permeabilization relative to cells expressing a wild-type integrin beta5. Thin-section electron microscopy revealed that virion particles were capable of being endocytosed into cells expressing a truncated beta5CT, but they failed to escape cytoplasmic vesicles and translocate to the nucleus. Site-specific mutagenesis studies suggest that a C-terminal TVD motif in the beta5CT plays a major role in Ad membrane penetration.
Homogeneous chemiluminescent immunoassay based on complement-mediated hemolysis of red blood cells (1990)

A novel method was developed for the homogeneous chemiluminescent immunoassay using complement-mediated hemolysis of sheep red blood cells. The chemiluminescent reaction of luminol and H2O2 was catalyzed by hemoglobins leaked from hemolyzed sheep red blood cells. The chemiluminescence was measured by counting photons. When using nonhemolyzed cells, chemiluminescence was virtually not observed. Only hemoglobin released from the cells was chemiluminescent, so that the extent of hemolysis could be measured without separating hemolyzed and nonhemolyzed cells. The immunoassay was done for the immunoagents: complement, hemolysin (anti-sheep red blood cell antibody), and anti-human albumin antibody. In the assay of complement or anti-human albumin antibody, sheep red blood cells used were bound with hemolysin or human albumin, respectively. The cell was hemolyzed by the action of antigen-antibody binding and subsequent activation of complement. The extent of hemolysis depended on the concentration of the antibody or complement. The calibration curves were obtained by chemiluminometric measurements on the added diluted antibody or complement. The sensitivity was 0.047 CH50 unit/mL for complement and below 1.0 micrograms/mL of anti-human albumin antibody.
Imiquimod applied topically: A novel immune response modifier. (2001)

Imiquimod (S-26308, R-837) (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4 amine), and immune response modifier, was approved as a 5% cream (Aldara, 3M Pharmaceuticals) by the US FDA in February 1997, for the treatment of genital and perianal warts. Drug activity results primarily from induction of interferon alpha (IFN-alpha) and other cytokines in the skin, which stimulate several other aspects of the innate immune response. Imiquimod also stimulates acquired immunity, in particular the cellular arm, which is important for control of viral infections and tumors. It is expected to be effective where exogenous IFN-alpha has shown utility, and where enhancement of cell-mediated immunity is needed. Recently presented Phase II clinical studies demonstrated efficacy in treating UV induced skin lesions, basal cell carcinoma, and actinic keratosis. Case studies have reported benefit when treating molluscum and in prevention of keloids after surgery.
Artificial Disc Replacement (1993)

Artificial disc replacement was performed in six patients with an average age of 55 years and average follow-up of 3.4 years. Four of the six patients had juxtafusion degeneration, one had multilevel disc degeneration, and one patient had isolated disc resorption. The Acroflex disc (Acromed Corporation, Cleveland, OH), which was used in the replacement, is composed of a rubber core vulcanized to two titanium end plates. The latter have superior posts to provide for initial mechanical fixation and porous in-growth surfaces for long-term fixation. Satisfactory results occurred in four of six patients. Poor results occurred in the presence of deformity that resulted in prosthetic failure and isolated disc resorption. There was an average 8 degrees angular and 2.3-mm translational movement and satisfactory in-growth at all interfaces. Design objectives of endurance, biocompatibility, geometry, kinematics, constraint, dynamics, stability, and fail-safe were met; however, this study is preliminary in nature.