gebhart/patrepeval huggingface dataset:
Targeted Identification of Metastasis-associated Cell-surface Sialoglycoproteins in Prostate Cancer (2011)

Covalent attachment of carbohydrates to proteins is one of the most common post-translational modifications. At the cell surface, sugar moieties of glycoproteins contribute to molecular recognition events involved in cancer metastasis. We have combined glycan metabolic labeling with mass spectrometry analysis to identify and characterize metastasis-associated cell surface sialoglycoproteins. Our model system used syngeneic prostate cancer cell lines derived from PC3 (N2, nonmetastatic, and ML2, highly metastatic). The metabolic incorporation of AC(4)ManNAz and subsequent specific labeling of cell surface sialylation was confirmed by flow cytometry and confocal microscopy. Affinity isolation of the modified sialic-acid containing cell surface proteins via click chemistry was followed by SDS-PAGE separation and liquid chromatography-tandem MS analysis. We identified 324 proteins from N2 and 372 proteins of ML2. Using conservative annotation, 64 proteins (26%) from N2 and 72 proteins (29%) from ML2 were classified as extracellular or membrane-associated glycoproteins. A selective enrichment of sialoglycoproteins was confirmed. When compared with global proteomic analysis of the same cells, the proportion of identified glycoprotein and cell-surface proteins were on average threefold higher using the selective capture approach. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the vast majority of glycoproteins overexpressed in the metastatic ML2 subline were involved in cell motility, migration, and invasion. Our approach effectively targeted surface sialoglycoproteins and efficiently identified proteins that underlie the metastatic potential of the ML2 cells.
Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2 (2012)

Epigenetic regulation is involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogation of the functions of individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given the emerging need for such small molecules, we envisioned an approach to identify target-specific methyltransferase inhibitors by screening privileged small-molecule scaffolds against diverse methyltransferases. In this work, we demonstrated the feasibility of such an approach by identifying the inhibitors of SETD2. N-propyl sinefungin (Pr-SNF) was shown to interact preferentially with SETD2 by matching the distinct transition-state features of SETD2's catalytically active conformer. With Pr-SNF as a structure probe, we further revealed the dual roles of SETD2's post-SET loop in regulating substrate access through a distinct topological reconfiguration. Privileged sinefungin scaffolds are expected to have broad use as structure and chemical probes of methyltransferases.
Assessment of Intestinal Permeability in Rats by Permeation of Inulin-Fluorescein (2000)

The measurement of intestinal permeability is widely used to assess different aspects of mucosal barrier disorders and related disease states, and has been proposed for evaluation of disease activity. To provide a simple method for assessment of intestinal permeability, we examined the permeation of inulin-fluorescein (InFl) in rat models of small intestinal injury and colitis. Small intestinal or colonic inflammation was induced by either i.p. administration of indomethacin or rectal administration of trinitrobenzene sulfonic acid (TNBS), respectively. For monitoring of intestinal permeability, InFl was administered orally or rectally to rats with small intestinal or colonic inflammation, respectively, and its level in blood was determined by the fluorescence intensity in the plasma. In small intestinal injury, InFl reached its peak in plasma 3 h after oral administration, while in colitis the InFl peak was reached 1 h after rectal administration. The highest permeability was observed at 72 h or 12 h after induction of small intestinal or colonic inflammation, respectively. In small intestinal injury the InFl permeation, as measured by its plasma level prior to sacrifice, was in agreement with intestinal damage evaluated after sacrifice. In colitis, the permeability at 12 h after induction of the disease correlated well with mortality. These findings demonstrate that InFl can be used as a novel, safe and easy-to-use probe for the evaluation of gut permeation and follow-up of gastrointestinal injury.
Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. (1993)

Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associated peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmette-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce aggregates of growing dendritic cells. Cells within these aggregates are clearly phagocytic. If the developing cultures are exposed to particles, washed, and "chased" for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% contain internalized mycobacteria or latex particles. The mycobacteria-laden, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dendritic cells that are exposed to a pulse of organisms. A similar situation exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycobacterial antigens in draining lymph node and spleen. The administration of antigens to GM-CSF-induced, developing dendritic cells (by increasing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.
Expanding the Utility of β-Galactosidase Complementation: Piece by Piece (2009)

The ability to image and quantify multiple biomarkers in disease necessitates the development of split reporter fragment platforms. We have divided the beta-galactosidase enzyme into unique, independent polypeptides that are able to reassemble and complement enzymatic activity in bacteria and in mammalian cells. We created two sets of complementing pairs that individually have no enzymatic activity. However, when brought into close geometric proximity, the complementing pairs associated resulting in detectable enzymatic activity. We then constructed a stable ligand complex composed of reporter fragment, linker, and targeting moiety. The targeting moiety, in this case a ligand, allowed cell surface receptor targeting in vitro. Further, we were able to simultaneously visualize two cell surface receptors implicated in cancer development, epidermal growth factor receptor and transferrin receptor, using complementing pairs of the ligand-reporter fragment complex.
Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis (2007)

Activation of hepatic stellate cells (HSC), a key event in liver fibrosis, is caused by diminished adipogenic transcription. This study investigated whether Wnt signaling contributes to "antiadipogenic" activation of HSC and liver fibrogenesis. Culture-activated HSC from normal rats and HSC from cholestatic rat livers were examined for expression of Wnt, Frizzled (Fz) receptors, and coreceptors by quantitative PCR. Wnt signaling was assessed by nuclear beta-catenin and T cell factor (TCF) promoter activity. Dickkopf-1 (Dkk-1), a Wnt coreceptor antagonist, was transduced by an adenoviral vector to assess the effects of Wnt antagonism on culture activation of HSC and cholestatic liver fibrosis in mice. Messenger RNA for canonical (Wnt3a and 10b) and noncanonical (Wnt4 and 5a) Wnt genes, Fz-1 and 2, and coreceptors [low-density lipoprotein-receptor-related protein (LRP)6 and Ryk] are increased approximately 3-12-fold in culture-activated HSC compared with quiescent HSC. The nuclear beta-catenin level and TCF DNA binding are markedly increased in activated HSC. TCF promoter activity is stimulated with Wnt1 but inhibited by Chibby, a protein that blocks beta-catenin interaction with TCF, and by Dkk-1. Dkk-1 enhances peroxisome proliferator-activated receptor-gamma (PPARgamma)-driven PPAR response element (PPRE) promoter activity, a key adipogenic transcriptional parameter, abrogates agonist-stimulated contraction, and restores HSC quiescence in culture. High expression of Dkk-1 increases apoptosis of cultured HSC. Expression of Wnt and Fz genes is also induced in HSC isolated from experimental cholestatic liver fibrosis, and Dkk-1 expression ameliorates this form of liver fibrosis in mice. These results demonstrate antiadipogenic Wnt signaling in HSC activation and therapeutic potential of Wnt antagonism for liver fibrosis.
Adapting virtual machine techniques for seamless aspect support (2006)

Current approaches to compiling aspect-oriented programs are inefficient. This inefficiency has negative effects on the productivity of the development process and is especially prohibitive for dynamic aspect deployment. In this work, we present how well-known virtual machine techniques can be used with only slight modifications to support fast aspect deployment while retaining runtime performance. Our implementation accelerates dynamic aspect deployment by several orders of magnitude relative to mainstream aspect-oriented environments. We also provide a detailed comparison of alternative implementations of execution environments with support for dynamic aspect deployment.
Gum Arabic Glycoprotein Is a Twisted Hairy Rope (1991)

Separation of the wound exudate from Acacia senegal (L.) Willd., "gum arabic," on a preparative Superose-6 column gave two major fractions: a high molecular weight gum arabic glycoprotein (GAGP) containing about 90% carbohydrate and a lower molecular weight heterogenous gum arabic polysaccharide fraction. Hydrogen fluoride-deglycosylation of GAGP gave a large ( approximately 400 residue) hydroxyproline-rich polypeptide backbone (dGAGP). Alkaline hydrolysis of GAGP showed that most of the carbohydrate was attached to the polypeptide backbone as small ( approximately 30 residue) hydroxyproline (Hyp)-polysaccharide substituents. After partial acid hydrolysis of the Hyp-polysaccharide fraction we identified O-galactosylhydroxyproline as the glycopeptide linkage, identical with that of hydroxyproline-rich arabinogalactan-proteins (AGPs). However, unlike the acidic alanine-rich AGPs, GAGP is basic and notably deficient in alanine. Thus, while the GAGP polypeptide backbone more closely resembles that of the Hyp-rich cell wall protein extensin, the GAGP polysaccharide sidechains resemble AGPs. Possibly all three proteins comprise a phylogenetically related extensin superfamily of extended rod-like macromolecules. The "wattle-blossom" model for AGP and gum arabic predicts a few large polysaccharide substituents along the polypeptide backbone of a spheroidal macromolecule. On the contrary, our data imply a rodlike molecule with numerous small polysaccharide substituents (attached to 24% of the Hyp residues), regularly arranged along a highly periodic polypeptide backbone based, hypothetically, on a 10 to 12 residue repetitive peptide motif. Thus, a simple statistical model of the gum arabic glycoprotein predicts a repeating polysaccharide-peptide subunit of about 7 kilodaltons. The small polysaccharide substituents will maximize intramolecular hydrogen bonding if aligned along the long axis of the molecule, forming in effect a twisted hairy rope. Electron micrographs of rotary shadowed GAGP molecules support that prediction and may also explain how such apparently large molecules can exit the cell by endwise reptation through the small pores of the primary cell wall.
Residual Vibration Criteria Applied to Multiple Degree of Freedom Cam Followers (1981)

The vibration characteristics of a cam motion are generally presented by plotting the single degree of freedom residual vibration as a function of normalized operating speed. In this paper it is shown that by applying the methods of modal analysis, these residual vibration characteristics can be extended to the characterization of the vibration response of a multiple degree of freedom cam follower system.
A Pseudomonas syringae type III effector suppresses cell wall-based extracellular defense in susceptible Arabidopsis plants (2003)

Bacterial effector proteins secreted through the type III secretion system (TTSS) play a crucial role in causing plant and human diseases. Although the ability of type III effectors to trigger defense responses in resistant plants is well understood, the disease-promoting functions of type III effectors in susceptible plants are largely enigmatic. Previous microscopic studies suggest that in susceptible plants the TTSS of plant-pathogenic bacteria transports suppressors of a cell wall-based plant defense activated by the TTSS-defective hrp mutant bacteria. However, the identity of such suppressors has remained elusive. We discovered that the Pseudomonas syringae TTSS down-regulated the expression of a set of Arabidopsis genes encoding putatively secreted cell wall and defense proteins in a salicylic acid-independent manner. Transgenic expression of AvrPto repressed a similar set of host genes, compromised defense-related callose deposition in the host cell wall, and permitted substantial multiplication of an hrp mutant. AvrPto is therefore one of the long postulated suppressors of an salicylic acid-independent, cell wall-based defense that is aimed at hrp mutant bacteria.
18 F-2-Deoxyglucose Deposition and Regional Flow in Pigs With Chronically Dysfunctional Myocardium (1997)

These results demonstrate that pigs instrumented with a proximal LAD stenosis develop hibernating myocardium characterized by relative reductions in resting function and perfusion in association with increased uptake of FDG in the fasting state. The transmural variations in relative resting flow and FDG uptake suggest that myocardial adaptations consistent with hibernation are most pronounced in the subendocardial layers and vary in relation to local coronary flow reserve.
Serum and mucosal antibody responses and protection in pigs vaccinated againstMycoplasma hyopneumoniaewith vaccines containing a denatured membrane antigen pool and adjuvant (1997)

Pigs vaccinated with M hyponeumoniae antigens in the molecular size range of 70 to 85 kDa showed a significant reduction in lung lesions compared with unvaccinated control animals after experimental challenge. IgG and IgA antibody concentrations in serum and respiratory tract washings after vaccination do not provide a useful prognostic indicator of protection from enzootic pneumonia.
Activation of the c-fos gene by UV and phorbol ester: different signal transduction pathways converge to the same enhancer element. (1988)

In NIH3T3 cells stably transfected with the human c-fos gene, serum, platelet derived growth factor (PDGF), phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate, TPA), ultraviolet irradiation (UV) and 3'-5'-cyclic adenosine monophosphate (cAMP) cause a transient and rapid activation of both the endogenous and the transfected c-fos genes. While serum, TPA, UV and PDGF dependent activation of the gene is severely impaired, when the serum responsive element from position -319 to -300 (SRE, Treisman, 1985) is destroyed, a full response to cAMP is retained. Insertion of a synthetic oligonucleotide corresponding to the SRE element upstream of position -96 restores the responses to TPA and serum, and large parts of the responses to UV and PDGF. The signal transduction chains elicited by UV and TPA are blocked by an inhibitor of protein kinase. Only TPA, however, causes the translocation of protein kinase C to the membrane. UV and TPA treated cells become refractory to a second stimulation by the same agent at 3 or 24 hours after the first treatment. Alternating the agents, however, leads to full responses. In addition, saturating doses of UV and TPA are at least additive. Ca-ionophores severely reduce only UV induced c-fos expression. These data indicate, that different signal transduction pathways elicited by growth promoting agents and by UV induced stress converge onto the same enhancer element.
Retroposition in a family of carcinoma-associated antigen genes. (1993)

The gene encoding the carcinoma-associated antigen defined by the monoclonal antibody GA733 is a member of a family of at least two type I membrane proteins. This study describes the mechanism of evolution of the GA733-1 and GA733-2 genes. A full-length cDNA clone for GA733-1 was obtained by screening a human placental library with a genomic DNA probe. Comparative analysis of the cDNA sequence with the previously determined genomic sequence confirmed that GA733-1 is an intronless gene. The GA733-2 gene encoding the monoclonal antibody-defined antigen was molecularly cloned with a cDNA probe and partially sequenced. Comparison of GA733-2 gene sequences with the previously established cDNA sequence revealed that this gene consists of nine exons. The putative promoter regions of the GA733-1 and GA733-2 genes are unrelated. These findings suggest that the GA733-1 gene was formed by the retroposition of the GA733-2 gene via an mRNA intermediate. Prior to retroposition, the GA733-2 gene had been affected by exon shuffling. Analysis of GA733-2 exons revealed that many delineate structural motifs. The GA733-1 retroposon was localized either to chromosome region 1p32-1p31 or to 1p13-1q12, and the GA733-2 founder gene was localized to chromosome 4q.
Synthesis and characterization of dexamethasone‐conjugated linear polyethylenimine as a gene carrier (2010)

Linear polyethylenimine (25 kDa, LPEI25k) has been shown to be an effective non-viral gene carrier with higher transfection and lower toxicity than branched polyethylenimine (BPEI) of comparable molecular weight. In this study, dexamethasone was conjugated to LPEI25k to improve the efficiency of gene delivery. Dexamethasone is a synthetic glucocorticoid receptor ligand. Dexamethasone-conjugated LPEI25k (LPEI-Dexa) was evaluated as a gene carrier in various cells. Gel retardation assays showed that LPEI-Dexa completely retarded plasmid DNA (pDNA) at a 0.75:1 weight ratio (LPEI/pDNA). LPEI-Dexa had the highest transfection efficiency at a 2:1 weight ratio (LPEI-Dexa/DNA). At this ratio, the size of the LPEI-Dexa/pDNA complex was approximately 125 nm and the zeta potential was 35 mV. LPEI-Dexa had higher transfection efficiency than LPEI and Lipofectamine 2000. In addition, the cytotoxicity of LPEI-Dexa was much lower than that of BPEI (25 kDa, BPEI25k). In conclusion, LPEI-Dexa has a high transfection efficiency and low toxicity and can therefore be used for non-viral gene delivery.
CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells (2006)

Unmethylated CpG DNA activation of naive CD27- B cells has been reported to require B-cell-receptor (BCR) cross-linking. We describe a culture system using CpG DNA with sequential steps for T-cell-independent activation of naive CD19+CD27- human peripheral blood B cells that induces efficient CD138+ plasma-cell differentiation. CD27+ and CD27- B cells were cultured in a 3-step system: (1) days 0 to 4: CpG, IL-2/10/15; (2) days 4 to 7: IL-2/6/10/15 and anti-CD40L; (3) days 7 to 10: IL-6/15, IFN-alpha, hepatocyte growth factor, and hyaluronic acid. Both CD27+ and CD27- B cells up-regulated intracytoplasmic TLR-9 following CpG DNA activation. CD27- B-cell activation required cell-cell contact. Both naive and memory B cells progressed to a plasma-cell phenotype: CD19lowCD20lowCD27+CD38+HLA-DRlow. Seventy percent of the CD27--derived CD138+ cells demonstrated productive V chain rearrangements without somatic mutations, confirming their origin from naive precursors. Plasma cells derived from CD27+ B cells were primarily IgG+, while those from CD27- B cells were IgM+. Our results indicate that under certain conditions, naive B cells increase TLR-9 expression and proliferate to CpG DNA stimulation without BCR signaling. In addition to its immunologic significance, this system should be a valuable method to interrogate the antigenic specificity of naive B cells.
Complete solution classification for the perspective-three-point problem (2003)

We use two approaches to solve the perspective-three-point (P3P) problem: the algebraic approach and the geometric approach. In the algebraic approach, we use Wu-Ritt's zero decomposition algorithm to give a complete triangular decomposition for the P3P equation system. This decomposition provides the first complete analytical solution to the P3P problem. We also give a complete solution classification for the P3P equation system, i.e., we give explicit criteria for the P3P problem to have one, two, three, and four solutions. Combining the analytical solutions with the criteria, we provide an algorithm, CASSC, which may be used to find complete and robust numerical solutions to the P3P problem. In the geometric approach, we give some pure geometric criteria for the number of real physical solutions.
Expression of the Human Integrin β 6 Subunit in Alveolar Type II Cells and Bronchiolar Epithelial Cells Reverses Lung Inflammation in β 6 Knockout Mice (1998)

Inactivation of the integrin beta6 subunit gene in mice resulted in an unexpected phenotype-functionally significant inflammation of the skin and lungs. These findings suggested a role for ligation of the alphav beta6 integrin on epithelial cells in downregulating epithelial inflammation. However, the results of gene inactivation could have been due to inactivation of adjacent genes and provided no information about the role of this integrin in specific populations of epithelial cells. In the current study, we used transgenic mice constitutively expressing the human beta6 subunit in alveolar type II cells and bronchiolar epithelial cells to examine directly the significance of alphav beta6 in these cells. Expression of this transgene largely inhibited the increases in airspace lymphocytes and macrophages and the lymphocyte and macrophage activation caused by inactivation of the beta6 subunit gene, and reduced the peribronchial and perivascular accumulations of lymphocytes. In the genetically mixed mice used for this study, we identified airway eosinophilia as an additional effect of beta6 inactivation. This effect was also partially inhibited by limited expression of the human transgene. These results definitively identify a role for distal lung epithelial alphav beta6 in downregulating pulmonary inflammation and suggest that interventions augmenting beta6 expression or function in these cells could influence the course of inflammatory lung diseases.