gebhart/patrepeval huggingface dataset:
High performance liquid chromatography in biotechnology (1990)

The Design of Bonded Phases for Polypeptide and Protein Chromatography Based on Wide-Pore Silicas (M. Henry) On the Adsorption of Protein to Alkylksilica: Relevance to Reversed-Phase and Hydrophobic Interaction Chromatography (R. Barford) Bioactivity of Insulin and Iodinated Insulin After Reversed-Phase HPLC (B. Welinder, et al.) Scale Up of Protein Chromatographic Separations (D. Low) HPLC of Antigenic Proteins and Vaccines (R. Johnson) Utilization of Analytical Reverse-Phase HPLC in Biosynthetic Insulin Production (R. DiMarchi, et al.) High-Performance Ion-Exchange Chromatography of Proteins: A Review of Methods and Mechanisms (M. Henry) The Purification of Polypeptide Samples by Ion-Exchange Chromatography on Silica-Based Supports (M. Dizdaroglu) High Performance Affinity Chromatography: Isolation and Analysis of Biological Macromolecules (I. Chaiken) Design of Chromatographic Matrices for the Purification and Analysis of Antibodies (D. Nau) Characterization of Synthetic Polypeptides by Mass Spectrometry (D. Marshak & B. Fraser) Index.
Xa receptor EPR‐1 (1995)

Cellular inflammatory responses and early mechanisms of vascular injury are invariably associated with activation of blood coagulation and deposition of insoluble fibrin. This process occurs on vascular cell surfaces through the ability of the coagulation protease factor Xa to generate thrombin. However, experimental evidence accumulated during the past decade underscores how prothrombin activation is only one of the biological consequences of factor Xa assembly on vascular cells. Instead, binding of factor Xa to leukocytes, endothelium, and smooth muscle cells triggers complex pathways of intracellular signal transduction that participate, directly or indirectly, in the regulation of cellular growth. One of the cellular binding sites for factor Xa, designated effector cell protease receptor-1 (EPR-1), has recently emerged as a novel potential regulator of factor Xa-mediated mitogenic signaling. For its activation-dependent phenotype on leukocyte subsets, its ability to costimulate lymphocyte proliferation through release of intracellular second messengers, and its regulated cellular expression by alternative mRNA splicing, EPR-1 may influence vascular cell growth and aberrantly contribute to the earliest pathogenetic processes of vascular diseases.
Autoantibodies in Type 2 Diabetes Induce Stress Fiber Formation and Apoptosis in Endothelial Cells (2009)

Abstract Context: Macular edema contributes to visual impairment, and albuminuria is associated with increased cardiovascular mortality in adults with type 2 diabetes mellitus. These microvascular complications result from increased capillary leakage of plasma proteins whose causation is not completely understood. Objective: The objective of the present study was to test whether plasma from type 2 diabetes with maculopathy/albuminuria or control subjects contains autoantibodies that can induce apoptosis or activate Rho kinase (ROCK) in endothelial cells. Design: A cohort of Veterans Affairs Diabetes Trial adults (&amp;gt;40 yr of age) was randomized to standard vs. intensive glycemic treatment lasting 5–7.5 yr. Setting: The study was conducted in outpatient clinics. Patients: Case and age-matched control subjects who differed for the baseline presence of significant diabetic maculopathy and/or progression to macro-albuminuria were included in the study. Intervention: Pharmacological and lifestyle interventions in the Veterans Affairs Diabetes Trial generally resulted in substantially improved glycemic, blood pressure, and lipid levels. Results: Autoantibodies from patients with macular edema or progression to albuminuria potently induced caspase-dependent apoptosis in endothelial cells (up to 60%), whereas IgG from age-matched normal plasma caused much less apoptosis (&amp;lt;10%; P &amp;lt; 0.0001). The active inhibitory autoantibodies triggered stress fiber formation in endothelial cells likely through the activation of Rho guanosine 5′-triphosphatase, which could be nearly completed inhibited by 10 μm Y27632, a specific ROCK inhibitor. Conclusions: These results suggest that autoantibodies from a subset of advanced type 2 diabetes may contribute to diabetic vascular complications by activating ROCK, inducing stress fiber formation and apoptosis in endothelial cells.
Airway Remodeling Is Absent in CCR1−/− Mice During Chronic Fungal Allergic Airway Disease (2000)

Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C chemokines, eosinophilic inflammation, and persistent airway hyperresponsiveness follow pulmonary exposure to the spores or conidia from Aspergillus fumigatus fungus in sensitized individuals. In addition to these features, subepithelial fibrosis and goblet cell hyperplasia characterizes fungal-induced allergic airway disease in mice. Because lung concentrations of macrophage inflammatory protein-1alpha and RANTES were significantly elevated after A. fumigatus-sensitized mice received an intrapulmonary challenge with A. fumigatus spores or conidia, the present study addressed the role of their receptor, C-C chemokine receptor 1 (CCR1), in this model. A. fumigatus-sensitized CCR1 wild-type (+/+) and CCR1 knockout (-/-) mice exhibited similar increases in serum IgE and polymorphonuclear leukocyte numbers in the bronchoalveolar lavage. Airway hyperresponsiveness was prominent in both groups of mice at 30 days after an intrapulmonary challenge with A. fumigatus spores or conidia. However, whole lung levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2-inducible chemokines such as C10, eotaxin, and macrophage-derived chemokine were significantly lower in whole lung samples from CCR1-/- mice compared with CCR1+/+ mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet cells and less subepithelial fibrosis were observed around large airways in CCR1-/- mice at the same time after the conidia challenge. Thus, these findings demonstrate that CCR1 is a major contributor to the airway remodeling responses that arise from A. fumigatus-induced allergic airway disease.
Design principles for multichannel fringing electric field sensors (2006)

This paper presents general rules and principles for designing multichannel fringing electric field (FEF) sensors. A detailed analysis on how the design parameters, especially sensor geometry, affect the performance of FEF sensors is provided. Tradeoffs among different design objectives are explained, and qualitative design rules for balancing these tradeoffs are presented. The rules are illustrated with the design examples of two concentric FEF sensors. The effects of shielding electrode width and substrate thickness on sensor performance were evaluated through finite element simulations. In addition, the performance of the two sensors was compared based on the numerical calculations of penetration depth and signal strength. The comparison proves that the addition of shielding electrodes can improve the penetration depth of FEF sensors.
Preferential transposition of the maize element Activator to linked chromosomal locations in tobacco. (1990)

The autonomous maize transposon Activator (Ac) has been used in maize for gene isolation by tagging and may prove similarly useful in other species. To test the feasibility of gene tagging with heterospecific transposons, we have examined three key genetic properties of a slightly modified Ac in tobacco. First, we show that frequencies of germinal excision of this Ac element from the antibiotic resistance gene streptomycin phosphotransferase can be comparable with or slightly lower than in maize. Second, we show that about half of the progeny carrying a germinal excision product also carry a transposed Ac. Last, we have mapped transposed Ac locations relative to the streptomycin transferase gene excision product and have shown that as in maize Ac in tobacco preferentially transposes to genetically linked sites.
Identification of "Staphylococcus staphylolyticus" NRRL B-2628 as a Biovar of Staphylococcus simulans (1982)

“Staphylococcus staphylolyticus” NRRL B-2628, the lysostaphin-producing organism, is identified as a biovar of S. simulans. The membership of this organism in the genus Staphylococcus is based on the guanine-plus-cytosine content of its deoxyribonucleic acid, its anaerobic growth in thioglycolate medium, the presence of teichoic acids in its cell wall, and the composition of its cell wall peptidoglycan. The identification of the organism as a member of S. simulans is based on its lack of production of coagulase and acetylmethylcarbinol, its carbohydrate reaction pattern, similarities in other biochemical characteristics, and the results of deoxyribonucleic acid-deoxyribonucleic acid hybridization studies.
Effect of phospholipase A2 inhibitors on mouse T lymphocytes. II. Phospholipase A2 inhibitors induce T cell hybridomas and a T cell clone for the formation of glycosylation-inhibiting factor (1990)

The mouse T cell hybridoma 12H5 cells constitutively form glycosylation-enhancing factor (GEF) and produce both IgE-potentiating factor and ovalbumin (OVA)-binding GEF upon antigenic stimulation with OVA-pulsed macrophages. Culture of the 12H5 cells either with nonspecific glycosylation inhibiting factor (GIF) or with a phospholipase A2 (PLA2) inhibitor, ONO-RS-082, stopped the formation of GEF and induced the same cells to form GIF. Induction of the GIF formation by a PLA2 inhibitor was observed even when the 12H5 cells had been treated with mitomycin C, indicating that the switching from the GEF formation to the GIF formation was not due to selective proliferation of a GIF-producing subclone. The OVA-binding GIF produced by the PLA2-inhibitor-treated, antigen-stimulated 12H5 cells binds to homologous antigen (ovalbumin), and shares both antigenic determinant recognized by the monoclonal antibody 14-30 and the lipomodulin-determinant with antigen-specific suppressor inducer factor (TsiF). The present experiments also showed that a typical helper T cell clone, D10, G4.1 cells, constitutively formed GEF and that preculture of the T cell clone with IL-2 and the PLA2 inhibitor switched the cells from the formation of GEF to the formation of GIF. Upon stimulation with antigen-pulsed macrophages, the inhibitor-treated D10.G4.1 cells formed GIF having affinity for conalbumin. The results indicated that the same T cells have the capacity to form either GIF or GEF under different conditions, and suggested that the GIF-producing suppressor T cells may be a phenotype of a subset of helper T cells. Switching of the same cells from the GEF formation to the GIF formation by the PLA2 inhibitor and the ability of the inhibitor to enhance GIF formation suggested that PLA2-inhibitory activity or GIF activity of TsiF is involved in the suppressor T cell cascade.
A method for constraint-based six degree-of-freedom haptic interaction with streaming point clouds (2013)

This paper presents a constraint-based method for haptic interaction between an arbitrary voxelized polygon tool and a streaming point cloud derived from a depth sensor. Using the presented method, a user can interact with both dynamic as well as static point cloud representations of real objects captured in real-time. Every depth image frame is filtered and surface normals are calculated in real-time. For movement of the virtual tool, a `quasi-static' simulation is used. The innovations of this work include the extension of haptic rendering from streaming point clouds to six degrees of freedom. This is appropriate for co-robotic tasks where haptic feedback to the user is combined with remote control of a robot.
Human junction adhesion molecule regulates tight junction resealing in epithelia (2000)

Epithelial cells form a highly selective barrier and line many organs. The epithelial barrier is maintained by closely apposed cell-cell contacts containing tight junctions, the regulation of which is incompletely understood. Here we report the cloning, tissue localization and evidence for a role in epithelial barrier regulation of an immunoglobulin superfamily member that likely represents the human homolog of murine junction adhesion molecule (JAM). Analysis of the primary structure of human JAM, cloned from T84 epithelial cells, predicts a transmembrane protein with an extracellular domain that contains two IgV loops. Monoclonal antibodies generated against the putative extracellular domain were reactive with a 35-39 kDa protein from both T84 epithelial cells and human neutrophils. By immunofluorescence, JAM mAbs labeled epithelial cells from intestine, lung, and kidney, prominently in the region of tight junctions (co-localization with occludin) and also along lateral cell membranes below the tight junctions. Flow cytometric studies confirmed predominant JAM expression in epithelial cells but also revealed expression on endothelial and hematopoietic cells of all lineages. Functional studies demonstrated that JAM specific mAbs markedly inhibited transepithelial resistance recovery of T84 monolayers after disruption of intercellular junctions (including tight junctions) by transient calcium depletion. Morphologic analysis revealed that, after disassembly of cell-cell junctions, anti-JAM inhibition of barrier function recovery correlated with a loss of both occludin and JAM, but not ZO-1, in reassembling tight junction structure. Reassembly of the major adherens junction component E-cadherin was not affected by JAM specific mAbs. Our findings suggest that JAM plays an important role in the regulation of tight junction assembly in epithelia. Furthermore, these JAM-mediated effects may occur by either direct, or indirect interactions with occludin.
Integrin Bidirectional Signaling: A Molecular View (2004)

Cells receive and send signals across the plasma membrane using the integrin family of receptors. What is it about their structure that can mediate their function?
Bone morphogenetic protein and Notch signalling crosstalk in poor‐prognosis, mesenchymal‐subtype colorectal cancer (2017)

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1. (1994)

The plasma protein fibronectin is an important opsonin in wound repair and host defense. To better understand the process of fibronectin-mediated phagocytosis, we have transfected K562 cells, which endogenously express alpha 5 beta 1, with alpha v beta 3. In these transfectants, antibodies to alpha v beta 3 block phagocytosis of fibronectin-opsonized beads completely, even though half the ingestion occurs through endogenous alpha 5 beta 1 receptors. alpha 5 beta 1-mediated adhesion to fibronectin-coated surfaces is unaffected by alpha v beta 3 ligation. Neither alpha v beta 5 nor alpha M beta 2 ligation affects alpha 5 beta 1 phagocytic function in transfectants expressing these receptors. Pharmacologic data suggest that alpha v beta 3 ligation suppresses the phagocytic competence of high affinity alpha 5 beta 1 receptors through a signal transduction pathway, perhaps involving protein kinase C. In addition to its significance for phagocytosis, alpha v beta 3 regulation of alpha 5 beta 1 function may be significant for its roles in cell migration, metastasis, and angiogenesis.
Morphological identification of alpha‐I‐antitrypsin in the human small intestine (1982)

Alpha-I-antitrypsin immunoreactivity was demonstrated by immunofluorescence in epithelial cells of the normal human small intestine. Its presence was also confirmed in biopsies of patients with Crohn's disease. Specific fluorescence was observed in only four out of 14 adult patients with coeliac disease. These results implicate the human small intestinal epithelium as a possible source of alpha-I-antitrypsin. The absence of positive cells may have implications in the aetiology of coeliac disease.
How Far Could We Go with Open Data – A Case Study for TRPV1 Antagonists (2013)

Publicly open databases of small compounds have become an indispensable tool for chemoinformaticians for collection and preparation of datasets suitable for drug discovery questions. Since these databases comprise compounds coming from structure-activity relationship (SAR) studies performed by different research groups, they are very diverse with respect to the biological assays used. In the present study we analyzed the applicability of a thoroughly curated dataset gathered from open sources for ligand-based studies, using the transient receptor potential vanilloid type 1 (TRPV1) as use case. Thorough curation of compounds according to the biological assay type and conditions led to a dataset of comparable bioactive chemicals. Subsequent exhaustive analysis of the obtained dataset using classification algorithms demonstrated that the models obtained in most of the cases possess reliable quality. Analysis of constantly misclassified compounds showed that they belong to local SAR series, where small changes in structure lead to different class labels. These small structural differences could not be captured by the classification algorithms. However application of the 3D alignment-independent QSAR technique GRIND for local, structurally related series overcomes this problem.
MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells. (2001)

Transcriptional repression of the transforming growth factor (TGF)-1P type II receptor (TPRII) gene appears to be a major mechanism to inactivate TGF-beta responsiveness in many human cancers. Because histone acetylation/deacetylation plays a role in transcriptional regulation, we have examined the effect of MS-275, a synthetic inhibitor of histone deacetylase, in human breast cancer cell lines. MS-275 showed antiproliferative activity against all human breast cancer cell lines examined and induced TbetaRII mRNA, but not TGF-beta type I receptor mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total cellular chromatin. An increase in the accumulation of acetylated histones H3 and H4 was detected in the TbetaRII promoter after treatment with MS-275. However, the level of histone acetylation did not change in chromatin associated with the TGF-beta type I receptor gene. MS-275 treatment enhanced TGF-beta1-induced plasminogen activator inhibitor 1 expression. Thus, antitumor activity of MS-275 may be mediated in part through the induction of TbetaRII expression and consequent potentiation of TGF-beta signaling.
p53 and its isoforms in cancer (2007)

p53, p63 and p73 are members of the p53 gene family involved in development, differentiation and response to cellular stress. p53 gene is a transcription factor essential for the prevention of cancer formation. The p53 pathway is ubiquitously lost in human cancer either by p53 gene mutation (60% of cancers) or by lost of cell signalling upstream and downstream of p53 in the remaining cancers expressing WTp53 gene. As p53 pathway inactivation is a common denominator to all cancers, the understanding of p53 tumour suppressor activity is likely to bring us closer to cancer therapy. However, despite all the experimental evidences showing the importance of p53 in preventing carcinogenesis, it is difficult in clinical studies to link p53 status to cancer treatment and clinical outcome. The recent discovery that p53 gene encodes for nine different p53 proteins (isoforms) may have a profound impact on our understanding of p53 tumour suppressor activity. Studies in several tumour types have shown that the nine different p53 isoforms are abnormally expressed in tumour tissues compared to normal cells. p53 protein isoforms modulate p53 transcriptional activity and cell fate outcome in response to stress. Regulation of p53 function in normal and tumour tissues in man is likely to be more complex than has been hitherto appreciated. Therefore, the tumour p53 status needs to be determined more accurately by integrating p53 isoform expression, functional p53 mutation analysis and a panel of antibodies specific of p53 and of its target genes.
Uterine artery Doppler at 11 + 0 to 13 + 6 weeks in the prediction of pre‐eclampsia (2007)

Maternal variables together with uterine artery PI at 11 + 0 to 13 + 6 weeks' gestation provide sensitive prediction of the development of PET, especially of severe early-onset PET.
Design and Synthesis of Ley-Bearing Glycopeptides that Mimic Cell Surface LeyMucin Glycoprotein Architecture (2000)

Five Lewisy-based glycopeptide anti-cancer vaccine candidates have been designed and synthesized to target tumor-associated cell-surface glycoprotein antigens and to improve the immunizing performance in comparison to related vaccines. The peptide backbone consisted of two regions, a glycodomain AcNH-SSS- and a nonglycosylated sequence, -AVAV-. The resultant glycopeptide was conjugated, via an additional spacer, to the lipid carrier PamCysSer. In this series of totally synthetic molecular vaccine candidates, one or three of the sequentially arranged serine residues were glycosylated. Furthermore, the Ley tetrasaccharide determinant region was kept constant while the internal glycan core was systematically varied. Glycal assembly was used to prepare the glycosyl donors, and two strategies were applied to provide the serine-O-linked polysaccharide domains. In the first approach, a protected serine derivative was attached directly to the fully elaborated glycan. Following this course, both α- and β-Ser derivatives were accessed. In the second route, a GalNAc-α-Ser was joined with a glycosyl donor to afford exclusively the desired α-serine-linked product. The glycopeptides were assembled using iterative solution phase peptide coupling. Following global deprotection, the lipid carrier was then coupled to the glycopeptide, resulting in the targeted constructs. The synthesis of these molecular vaccine candidates constitutes an important advance that should enable rationalization of carbohydrate-induced immune response as well as identification of optimal Ley-based anti-cancer vaccine leads.