gebhart/patrepeval huggingface dataset:
MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer (1999)

The products of the MUC1 gene are known to be highly expressed in human breast cancer cells. The best characterized MUC1 protein is a polymorphic, type 1 transmembrane molecule containing a large extracellular domain composed primarily of a variable number of 20 amino acid tandem repeats. We have recently identified a novel protein product of the MUC1 gene, the MUC1/Y protein, that is also a transmembrane protein but is devoid of the tandem repeat array and its immediate flanking sequences. To analyze its expression in tumor cells we generated monoclonal antibodies directed against the MUC1/Y extracellular domain (anti-MUC1/Yex MAbs). Epitope mapping identified the MAb, 6E6, which recognized the MUC1/Y isoform with exquisite specificity- the repeat-array-containing MUC1 isoform could not compete out this immunoreactivity. A 30mer peptide which is unique for MUC1/Y and corresponds to the "join" region generated by the MUC1/Y specific splice, abrogated all 6E6 MAb immunoreactivity towards MUC1/Y. Immunoprecipitation of the MUC1/Y protein with 6E6 MAbs revealed that, in contrast with the proteolytic cleavage of the tandem-repeat-array-containing MUC1 isoform, MUC1/Y is not cleaved. Flow cytometry analyses using the 6E6 MAbs demonstrated that the MUC1/Y isoform is expressed on the cell surface of both MCF-7 breast cancer cells and malignant epithelial cells present in effusions obtained from breast and ovarian cancer patients. Our results unequivocally establish that the MUC1/Y protein is expressed on the surface of breast cancer cells and cells of other epithelial malignancies. The anti-MUC1/Y MAbs described here can target MUC1/Y expressing tumor cells in vivo and are likely to be important reagents both for epithelial tumor diagnosis and immunotherapy.
Identification of Novel Therapeutic Targets in COPD. (2011)

COPD is an important lung and airway disease with an increasing incidence particularly in developing countries. Worldwide, asthma and COPD affect the lives of ~300 and 200 million people, respectively (1). COPD is a chronic inflammatory disease for which smoking is the major risk factor in the developed world and is currently the fourth leading cause of death worldwide. It is predicted to become the third ranked disease by the year 2030 (2, 3). Unfortunately, there are no effective treatments for severe asthma and COPD due to a lack of clarity in disease mechanisms. However, new observations in the areas of signal transduction and epigenetics may provide new understanding of the pathogenesis of lung diseases. Understanding the pathways and mechanisms leading to mediator release may lead to better therapeutic approaches for these diseases. The inflammatory mediators involved in COPD have not been clearly delineated but are thought to include many lipid mediators, inflammatory peptides, reactive oxygen species (ROS) and nitrogen species, chemokines, cytokines and growth factors. These are
Gal-GalNAc: a biomarker of colon carcinogenesis. (1996)

The disaccharide tumor marker Gal-GalNAc visualized by galactose oxidase-Schiff sequence is commonly present in cancer cells and in rectal mucous of patients with colon cancer. The expression of this marker on tissue sections taken during experimental colon carcinogenesis shows excellent correlation with human precancerous lesions and even higher percentage of colon cancers express this marker, whereas, no expression is seen in the normal human large intestine. Multifocal expression of the marker is seen throughout the entire colon of patients with precancer and cancer; these include dysplasia, dilated and distorted crypts, regenerative dysplasia and hyperplastic crypts, as well as the morphologically normal crypts remote from cancer. Nearly identical pattern of Gal-GalNAc expression throughout the entire colon also appear during rat colon carcinogenesis induced by azoxymethane including non-expression by the normal and regenerative epithelia during wound healing following mechanical injury. Thus, Gal-GalNAc detected by the simple technique of galactose oxidase-Schiff sequence, is a biomarker that appears during the very early stages of progression of carcinogenesis. The expression pattern supports the field effect theory of carcinogenesis and also explains the basis for mass screening for cancer and precancerous conditions. Chemoprevention strategy using Gal-GalNAc as an intermediate marker detected by accurate and cost-effective rectal mucus test may have great potential.
Using ARP to implement transparent subnet gateways (1987)

This RFC describes the use of the Ethernet Address Resolution Protocol (ARP) by subnet gateways to permit hosts on the connected subnets to communicate without being aware of the existence of subnets, using the technique of "Proxy ARP" It is based on RFC-950 [1], RFC-922 [2], and RFC-826 [3] and is a restricted subset of the mechanism of . Distribution of this memo is unlimited.
Transient Transfection in Mammalian Cells (2006)

The aim of the presented work was to develop a cost-effective and easily scaleable transient transfection system with mammalian cells grown in serum-free suspension culture. For this purpose the cationic polyethylenimine (PEI) and the novel hybrid molecule dioleoyl-melittin (DOM) were used. Both substances are highly efficient transfection reagents for mammalian cells and have been described recently. The transfection complexes were made directly within the cell culture by consecutively adding plasmid and PEI (direct method). Alternatively, the DNA-PEI transfection complexes were performed in fresh medium (1/10 culture volume) and then added to the cells (indirect method). Here we have optimized the PEI-mediated transfection conditions for HEK293 and 293EBNA cells grown in serum-free suspension culture for large scale experiments. In a second part of the investigation the efficiency of gene expression was studied in labscale as well as in fermentor scale by combining DOM with PEI to form transfection complexes. Our data show the PEI-mediated transfection into EBNA cells can be used as a cost-effective transfection system in spinner culture scale up to 2-5L, to produce milligram amounts of recombinant protein. Fermentor scale experiments, however, are less efficient because the PEI- mediated transient gene expression is inhibited by the conditioned medium. Transfection experiments performed in the present of both DOM and PEI exhibited synergistic enhancement of gene expression in EBNA cells. The synergistic enhancement between DOM and PEI at low dose DNA (0, l-0,2μg/ml) was seen in spinner scale as well as in 10L and 23L fermentor
Stable isotopes in clinical research: safety reaffirmed (1991)

Approaching half a century of stable-isotope usage in human metabolic studies has been without documented significant adverse effect. Side-effects with acute D dosing are transitory with no demonstrated evidence of permanent deleterious action. The threshold of D toxicity has been defined in animals and is far in excess of concentrations conceivably used in human studies. The possibility that D may have additional beneficial pharmacological applications cannot be excluded. For isotopes other than D, evidence of observed toxicity remains to be produced even at dosages far in excess of the range used in metabolic studies. Absence of adverse effect may be attributable to small mass differences and the similar properties of tracer and predominantly abundant isotope. Absolute determination of stable isotope toxicity in humans is rendered impossible by ethical considerations. Also, the precision of extrapolating toxicity thresholds from animal studies remains unknown. However, should perturbation of the delicate homoeostatic characteristic of living organisms occur with use of stable isotopes, it is almost undoubtedly at some level of administration greatly in excess of those administered currently in biomedical research.
SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival (2012)

Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼ 75% incidence) and SRSF2 in chronic myelomonocytic leukemia (∼ 28% incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations were associated with shortened overall (P < .01) and leukemia-free (P < .01) survival; the adverse effect on survival was independent of DIPSS-plus (P = .01; HR = 1.9; 95% CI, 1.1-3.0) and IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.
Construction of di-scFv through a trivalent alkyne–azide 1,3-dipolar cycloaddition (2006)

Heterofunctional azide and alkyne PEG-linkers have been synthesized and site specifically conjugated to scFv via a reactive thiol functionality; two scFv were coupled by copper catalyzed 1,3-dipolar cycloaddition to make divalent scFv (di-scFv) with an inter-scFv distance defined to provide divalent binding; antigen binding was maintained for the di-scFv construct and increased several times compared to that of the parent scFv; the cycloaddition reaction reported herein represents an important ligation strategy to covalently link macromolecular proteins and retain sensitive structural conformations.
Nicotinic Stimulation of [3H]Acetylcholine Release from Mouse Cerebral Cortical Synaptosomes (1984)

The effects of nicotine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) on the release of newly synthesized [3H]acetylcholine in mouse cerebral cortical synaptosomes were examined. Nicotine and DMPP produced increases in [3H]acetylcholine release, over the level of spontaneous release, of 24% and 30%, respectively, of a maximum depolarization-induced release produced by 50 mM potassium. The maximum effect was achieved at a concentration of 1 X 10(-4) M for both agents. The time course of release indicated a slow onset of action, reaching a maximum effect at 15 min of incubation. Both nicotine and DMPP also produced a slightly greater release of total tritium, measured in the absence of cholinesterase inhibition, than of [3H]acetylcholine. The release induced by nicotine was completely antagonized by hexamethonium and was largely (58%) calcium-dependent. Nicotine also produced an increase in [3H]choline accumulation into synaptosomes. These results indicate that the nicotinic agonists nicotine and DMPP can produce a moderate enhancement of acetylcholine release by a receptor-mediated action on cholinergic nerve terminals in the central nervous system.
Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells. (1989)

A metabolic pathway by which L-arginine (L-arg) is converted to the biologically active compound NO. has recently been described in macrophages (M phi) and endothelial cells. This report demonstrates that transferable products from activated Kupffer cells (KC) induce the conversion of large quantities of L-arg to nitrogen oxides within hepatocytes (HC). In M phi and endothelial cells, citrulline and NO2-/NO3- are the stable endproducts of this metabolic pathway. In contrast, HC L-arg metabolism resulted in significantly greater production of NO2-/NO3- than citrulline. The generation of NO. within HC was associated with a concurrent decrease in total protein synthesis.
The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes (2005)

Immunodominance refers to the restricted antigen specificity of T cells detected in the immune response after immunization with complex antigens. Despite the presence of many potential peptide epitopes within these immunogens, the elicited T-cell response apparently focuses on a very limited number of peptides. Over the last two decades, a number of distinct explanations have been put forth to explain this very restricted specificity of T cells, many of which suggest that endosomal antigen processing restricts the array of peptides available to recruit CD4 T cells. In this review, we present evidence from our laboratory that suggest that immunodominance in CD4 T-cell responses is primarily due to an intrinsic property of the peptide:class II complexes. The intrinsic kinetic stability of peptide:class II complexes controls DM editing within the antigen-presenting cells and thus the initial epitope density on priming dendritic cells. Additionally, we hypothesize that peptides that possess high kinetic stability interactions with class II molecules display persistence at the cell surface over time and will more efficiently promote T-cell signaling and differentiation than competing, lower-stability peptides contained within the antigen. We discuss this model in the context of the existing data in the field of immunodominance.
Molecular cloning, expression and characterization of the human serine/threonine kinase Akt‐3 (1999)

Akt (also known as PKB or RAC-PK) is an intracellular serine/threonine kinase involved in regulating cell survival. Although this makes it a promising target for the discovery of drugs to treat human cancer, a complicating factor may be the role played by Akt in insulin signalling. Two human isoforms, Akt-1 and Akt-2, have been described previously and a third isoform has been identified in rats (here termed Akt-3, but also called RAC-PK-gamma or PKB-gamma). We describe the identification of the corresponding human isoform of Akt-3. The gene encoding human Akt-3 was localized to chromosome 1q43-44. The predicted protein sequence is 83% identical to human Akt-1 and 78% identical to human Akt-2, and contains a pleckstrin homology domain and a kinase domain. In contrast to the published rat Akt-3 isoform, human and mouse Akt-3 also possess a C-terminal 'tail' that contains a phosphorylation site (Ser472) thought to be involved in the activation of Akt kinases. In addition to phosphorylation of Ser472, phosphorylation of Thr305 also appears to contribute to the activation of Akt-3 because mutation of both these residues to aspartate increased the catalytic activity of Akt-3, whereas mutation to alanine inhibited activation. Akt-3 activity could be inhibited by the broad spectrum kinase inhibitor staurosporine and by the PKC inhibitor Ro 31-8220, but not by other PKC or PKA inhibitors tested. Although Akt-3 is expressed widely, it is not highly expressed in liver or skeletal muscle, suggesting that its principle function may not be in regulating insulin signalling. These observations suggest that Akt-3 is a promising target for the discovery of novel chemotherapeutic agents which do not interfere with insulin signalling.
CARD9 Is a Novel Caspase Recruitment Domain-containing Protein That Interacts With BCL10/CLAP and Activates NF-κB (2000)

BCL10/CLAP is an activator of apoptosis and NF-kappaB signaling pathways and has been implicated in B cell lymphomas of mucosa-associated lymphoid tissue. Although its role in apoptosis remains to be determined, BCL10 likely activates NF-kappaB through the IKK complex in response to upstream stimuli. The N-terminal caspase recruitment domain (CARD) of BCL10 has been proposed to function as an activation domain that mediates homophilic interactions with an upstream CARD-containing NF-kappaB activator. To identify upstream signaling partners of BCL10, we performed a mammalian two-hybrid analysis and identified CARD9 as a novel CARD-containing protein that interacts selectively with the CARD activation domain of BCL10. When expressed in cells, CARD9 binds to BCL10 and activates NF-kappaB. Furthermore, endogenous CARD9 is found associated with BCL10 suggesting that both proteins form a pre-existing signaling complex within cells. CARD9 also self-associates and contains extensive coiled-coil motifs that may function as oligomerization domains. We propose here that CARD9 is an upstream activator of BCL10 and NF-kappaB signaling.
Glycoengineering of Human IgG1-Fc through Combined Yeast Expression and in Vitro Chemoenzymatic Glycosylation (2008)

The presence and precise structures of the glycans attached at the Fc domain of monoclonal antibodies play an important role in determining antibodies' effector functions such as antibody-dependent cell cytotoxicity (ADCC), complement activation, and anti-inflammatory activity. This paper describes a novel approach for glycoengineering of human IgG1-Fc that combines high-yield expression of human IgG1-Fc in yeast and subsequent in vitro enzymatic glycosylation, using the endoglycosidase-catalyzed transglycosylation as the key reaction. Human IgG1-Fc was first overproduced in Pichia pastoris. Then the heterogeneous yeast glycans were removed by Endo-H treatment to give the GlcNAc-containing IgG1-Fc as a homodimer. Finally, selected homogeneous glycans were attached to the GlcNAc-primer in the IgG1-Fc through an endoglycosidase-catalyzed transglycosylation, using sugar oxazolines as the donor substrates. It was found that the enzymatic transglycosylation was efficient with native GlcNAc-containing IgG1-Fc homodimer without the need to denature the protein, and the reaction could proceed to completion to give homogeneous glycoforms of IgG1-Fc when an excess of oligosaccharide oxazolines was used as the donor substrates. The binding of the synthetic IgG1-Fc glycoforms to the FcgammaIIIa receptor was also investigated. This novel glycoengineering approach should be useful for providing various homogeneous, natural or synthetic glycoforms of IgG1-Fc for structure-function relationship studies, and for future clinical applications.
CIE guides to insects of importance to man. 2. Thysanoptera. By J. M. Palmer, L. A. Mound and G. J. duHeaume. Edited by C. R. Betts. (London: CAB International Institute of Entomology, British Museum) (Natural History, 1989). 73 pp. Soft cover £10.00. ISBN 0-85198-634-X. ISSN 0952-1461. (1990)

CIE guides to insects of importance to man. 2. Thysanoptera. By J. M. Palmer, L. A. Mound and G. J. duHeaume. Edited by C. R. Betts. (London: CAB International Institute of Entomology, British Museum) (Natural History, 1989). 73 pp. Soft cover £10.00. ISBN 0-85198-634-X. ISSN 0952-1461. - Volume 80 Issue 4
Nine color eleven parameter immunophenotyping using three laser flow cytometry (1999)

Nine color flow cytometry is capable of providing measurements with high information content. The choice of reagent-dye combinations and the ability to compensate in multi-parameter measurement space are crucial to obtaining satisfactory results.
Molecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy (2004)

The process of human infection by group B Streptococcus (GBS) is complex and multifactorial. While this bacterium has adapted well to asymptomatic colonization of adult humans, it remains a potentially devastating pathogen to susceptible infants. Advances in molecular techniques and refinement of in vitro and in vivo model systems have elucidated key elements of the pathogenic process, from initial attachment to the maternal vaginal epithelium to penetration of the newborn blood-brain barrier. Sequencing of two complete GBS genomes has provided additional context for interpretation of experimental data and comparison to other well-studied pathogens. Here we review recent discoveries regarding GBS virulence mechanisms, many of which are revealed or magnified by the unique circumstances of the birthing process and the deficiencies of neonatal immune defence. Appreciation of the formidable array of GBS virulence factors underscores why this bacterium remains at the forefront of neonatal pathogens.
Photoinduced destabilization of liposomes (1992)

The stability of two-component liposomes composed of the polymerizable 1,2-bis-[10-(2',4'-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphati dylcholine (SorbPC) and either a phosphatidylethanolamine (PE) or a phosphatidylcholine (PC) were examined via fluorescence leakage assays. Ultraviolet light exposure of SorbPC-containing liposomes forms poly-SorbPC, which phase separates from the remaining monomeric lipids. If the nonpolymerizable lipids are PE's, then the photoinduced polymerization destabilizes the liposome with loss of aqueous contents. The permeability of the control dioleoylPC/SorbPC membranes was not affected by photopolymerization of SorbPC. The photodestabilization of dioleoylPE/SorbPC (3:1) liposomes required the presence of oligolamellar liposomes. NMR spectroscopy of extended bilayers of dioleoylPE/SorbPC (3:1) showed that the photopolymerization lowers the temperature for the appearance of 31P NMR signals due to the formation of isotropically symmetric lipid structures. These observations suggest the following model for the photoinduced destabilization of liposomes composed of PE/SorbPC; photopolymerization induced phase separation with the formation of enriched domains of PE, which allows the close approach of apposed regions of enriched PE lamellae and permits the formation of an isotropically symmetric structure between the lamellae. The formation of such an interlamellar attachment (ILA) between the lamellae of an oligolamellar liposome provides a permeability pathway for the light-stimulated leakage of entrapped water-soluble reagents.
Defects in mucosal immunity leading to ulcerative colitis (2005)

Evidence accumulated over the last decade demonstrates that what we call 'ulcerative colitis' is actually a heterogeneous group of diseases resulting from different pathogenic mechanisms with a common symptomatic expression. Subgroups of patients with ulcerative colitis can be stratified by presence or absence of serum autoantibodies, which are thought not to be pathogenic but to mark for a distinct disease phenotype. In recent years, animal-based experimental systems have emerged that reflect human ulcerative colitis and have potential to accelerate our understanding of its pathogenesis. Genetic and immunological data from human studies in combination with results from animal model systems are the foundation of a hypothesis, which includes a role for microbial antigen exposure in the initiation, perpetuation, and amplification of the disease. In ulcerative colitis, it appears as though the T-cell response to the antigens is not T-helper (Th) 1 dominant as in the case of Crohn's disease but rather is either Th2 [interleukin (IL)-4, IL-13] or is mediated by specialized cells such as natural killer (NK) T cells (IL-13). Lamina propria T cells from ulcerative colitis patients produce significantly greater amounts of IL-13. Ulcerative colitis is associated with an atypical Th2 response mediated by a distinct subset of NK T cells that produce IL-13 and are cytotoxic for epithelial cells. The way in which this response affects the ultimate cascade of inflammatory events has yet to be determined.