gebhart/patrepeval huggingface dataset:
Characterization of a complement receptor 2 (CR2, CD21) ligand binding site for C3. An initial model of ligand interaction with two linked short consensus repeat modules. (1995)

Human CR2 (CD21, EBV receptor) is an approximately 145-kDa receptor and a member of the regulators of complement activation gene family. Regulators of complement activation proteins are characterized by the presence of repeating motifs of 60 to 70 amino acids that are designated short consensus repeats (SCR). CR2 serves as a receptor for four distinct ligands. Three of these ligands (complement C3, gp350/220 of EBV, and CD23) interact with the amino terminal 2 of 16 SCR (SCR 1 and 2). Previous studies have determined that at least four sites are important in allowing CR2 to efficiently bind EBV. Two of these sites are also important for binding mAb OKB7, a reagent that blocks both EBV and iC3b/C3dg binding to CR2. We have identified and characterized important sites of iC3b ligand binding by utilizing human-mouse CR2 chimeras, a rat anti-mouse CR2 mAb designated 4E3 that blocks receptor binding to C3, and human CR2-derived peptides. In addition to demonstrating an important role for the same sequence in SCR 1 that is part of the mAb OKB7 and EBV binding site, we have identified a new region within SCR 2 that interacts with C3. These results, when compared with a model of a dual SCR solution structure derived from human factor H SCR, predict that two distinct largely surface-exposed sites on CR2 interact with iC3b. A relative twist of 130 degrees about the long axis of the second SCR in this model would be necessary for these sites to form a single patch for iC3b binding on CR2.
Vaxfectin Adjuvant Improves Antibody Responses of Juvenile Rhesus Macaques to a DNA Vaccine Encoding the Measles Virus Hemagglutinin and Fusion Proteins (2013)

DNA vaccines formulated with the cationic lipid-based adjuvant Vaxfectin induce protective immunity in macaques after intradermal (i.d.) or intramuscular (i.m.) delivery of 0.5 to 1 mg of codon-optimized DNA encoding the hemagglutinin (H) and fusion (F) proteins of measles virus (MeV). To characterize the effect of Vaxfectin at lower doses of H+F DNA, rhesus macaques were vaccinated twice with 20 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.m. or 100 μg of DNA plus phosphate-buffered saline (PBS) i.m. using a needleless Biojector device. The levels of neutralizing (P = 0.036) and binding (P = 0.0001) antibodies were higher after 20 or 100 μg of DNA plus Vaxfectin than after 100 μg of DNA plus PBS. Gamma interferon (IFN-γ)-producing T cells were induced more rapidly than antibody, but were not improved with Vaxfectin. At 18 months after vaccination, monkeys were challenged with wild-type MeV. None developed rash or viremia, but all showed evidence of infection. Antibody levels increased, and IFN-γ- and interleukin-17-producing T cells, including cells specific for the nucleoprotein absent from the vaccine, were induced. At 3 months after challenge, MeV RNA was detected in the leukocytes of two monkeys. The levels of antibody peaked 2 to 4 weeks after challenge and then declined in vaccinated animals reflecting low numbers of bone marrow-resident plasma cells. Therefore, Vaxfectin was dose sparing and substantially improved the antibody response to the H+F DNA vaccine. This immune response led to protection from disease (rash/viremia) but not from infection. Antibody responses after challenge were more transient in vaccinated animals than in an unvaccinated animal.
The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions (2003)

The endoplasmic reticulum (ER)-resident heat shock protein Gp96 is involved in protein folding and is released into the extracellular space after necrotic cell death. In this context, Gp96 has immunostimulatory properties: it activates dendritic cells or macrophages and delivers associated peptides into the antigen presentation pathway, resulting in the induction of specific T-cell responses. The inflammatory response after necrotic tissue damage leads to the recruitment of polymorphonuclear neutrophils (PMNs) and monocytes, allowing them to make their first encounter with Gp96. We therefore investigated whether PMNs and monocytes interact with Gp96. We were able to show that PMNs and monocytes specifically bind fluorescein isothiocyanate (FITC)-conjugated Gp96. The binding of Gp96-FITC was competed by lipopolysaccharide (LPS) or fucoidan, a known inhibitor of scavenger receptors. Interestingly, the binding of LPS-FITC was also competed not only by fucoidan, but by Gp96, suggesting that LPS and Gp96 share a common receptor on PMNs. One important effector function of PMNs is the clearance of an inflammatory site by phagocytosis. We therefore assessed the influence of Gp96 on phagocytic activity using fluorochrome-labeled polystyrene beads. We found a marked enhancement of phagocytosis in the presence of Gp96 and concluded that PMNs not only bind Gp96, but are also activated by it. Additionally, Gp96-stimulated PMNs and especially monocytes release large amounts of interleukin-8, a potent neutrophil-attracting chemokine. In conclusion, we demonstrate that Gp96 specifically binds to and activates PMNs and monocytes, extending the function of Gp96 as a danger signal to additional members of the innate immune system.
Resveratrol causes COX‐2‐ and p53‐dependent apoptosis in head and neck squamous cell cancer cells (2008)

Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by inhibition of either ERK1/2 or p53 activation. Resveratrol also caused p53 binding to the p21 promoter and increased abundance of COX-2 protein in UMSCC-22B cell nuclei. Resveratrol-induced nuclear COX-2 accumulation was dependent upon ERK1/2 activation, but not p53 activation. Activation of p53 and p53-dependent apoptosis were blocked by the COX-2 inhibitor, NS398, and by transfection of cells with COX-2-siRNA. In UMSCC-22B cells, resveratrol-induced apoptosis and induction of nuclear COX-2 accumulation share dependence on the ERK1/2 signal transduction pathway. Resveratrol-inducible nuclear accumulation of COX-2 is essential for p53 activation and p53-dependent apoptosis in these cancer cells.
Stem Cells in the Central Nervous System (1997)

In the vertebrate central nervous system, multipotential cells have been identified in vitro and in vivo. Defined mitogens cause the proliferation of multipotential cells in vitro, the magnitude of which is sufficient to account for the number of cells in the brain. Factors that control the differentiation of fetal stem cells to neurons and glia have been defined in vitro, and multipotential cells with similar signaling logic can be cultured from the adult central nervous system. Transplanting cells to new sites emphasizes that neuroepithelial cells have the potential to integrate into many brain regions. These results focus attention on how information in external stimuli is translated into the number and types of differentiated cells in the brain. The development of therapies for the reconstruction of the diseased or injured brain will be guided by our understanding of the origin and stability of cell type in the central nervous system.
Neutrophils migrate across intestinal epithelium usingβ2 integrin (CD11b/CD18)-independent mechanisms (2004)

Recruitment of polymorphonuclear leucocytes (PMN) across the intestinal epithelium is dependent on specific adhesion molecules and chemoattractants diffusing from the intestinal lumen. The present understanding is that in response to fMLP, PMN migration across a T84 colon carcinoma monolayer is dependent on the beta(2) integrin, Mac-1 (CD11b/CD18). To further understand PMN transepithelial migration, we sought to determine whether migration to C5a, IL-8 and LTB(4) was similarly Mac-1-, or even CD18-dependent. T84 epithelial cell monolayers growing on Transwell filters were used in combination with radiolabelled peripheral blood PMN. The number of migrated PMN was established by the amount of radioactivity recovered from the well after the migration period. Monoclonal antibodies were used to block integrin function. Whereas essentially all migration to fMLP across T84 monolayers was prevented by anti-CD18 antibody, significant migration to C5a, IL-8 or LTB(4) persisted despite anti-CD18 antibody, indicating PMN are capable of beta(2) integrin-independent transepithelial migration. An antibody to CD11b but not CD11a blocked migration to an extent similar as with anti-CD18. CD18-independent PMN migration to C5a occurred only in the basolateral-to-apical direction across epithelial cells. Co-stimulation of PMN with C5a and fMLP or IL-8 plus LTB(4) and fMLP still resulted in CD18-independent migration. Thus CD18 use during PMN migration across this model epithelium is a function of the chemoattractant inducing migration. The finding of CD18-independent migration mechanisms needs to be considered when developing antiadhesion molecule strategies to reduce or reverse intestinal inflammation.
Activation of Discoidin Domain Receptor 1 Isoform b with Collagen Up-Regulates Chemokine Production in Human Macrophages: Role of p38 Mitogen-Activated Protein Kinase and NF-κB (2004)

Macrophages produce an array of proinflammatory mediators at sites of inflammation and contribute to the development of inflammatory responses. Important roles for cytokines, such as IL-1 or TNF-alpha, and bacterial products, such as LPS, in this process have been well documented; however, the role for the extracellular matrix proteins, such as collagen, remains unclear. We previously reported that discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor, is expressed during differentiation of human monocytes into macrophages, and the interaction of the DDR1b isoform with collagen facilitates their differentiation via the p38 mitogen-activated protein kinase (MAPK) pathway. In this study, we report that the interaction of DDR1b with collagen up-regulates the production of IL-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 in human macrophages in a p38 MAPK- and NF-kappaB-dependent manner. p38 MAPK was critical for DDR1b-mediated, increased NF-kappaB trans-activity, but not for IkappaB degradation or NF-kappaB nuclear translocation, suggesting a role for p38 MAPK in the modification of NF-kappaB. DDR1b-mediated IkappaB degradation was mediated through the recruitment of the adaptor protein Shc to the LXNPXY motif of the receptor and the downstream TNFR-associated factor 6/NF-kappaB activator 1 signaling cascade. Taken together, our study has identified NF-kappaB as a novel target of DDR1b signaling and provided a novel mechanism by which tissue-infiltrating macrophages produce large amounts of chemokines during the development of inflammatory diseases. Intervention of DDR1b signaling may be useful to control inflammatory diseases in which these proteins play an important role.
Electrocatalytic Pathways on Carbon-Supported Platinum Nanoparticles:  Comparison of Particle-Size-Dependent Rates of Methanol, Formic Acid, and Formaldehyde Electrooxidation (2002)

The voltammetric electrooxidation rates of formic acid, formaldehyde, and methanol in acidic electrolyte on carbon-supported platinum nanoparticle films with varying particle diameters (d) in the range of ca. 2−9 nm are examined with the objective of comparing the nanoparticle size sensitivity for these related yet distinct electrocatalytic processes. The reaction rates on the larger nanoparticles (d > 4 nm) are similar to those observed on polycrystalline Pt when normalized to the same microscopic Pt surface area. As noted previously, the rates of methanol electrooxidation decrease for Pt nanoparticle diameters below 4 nm. However, formic acid electrooxidation exhibits the opposite behavior, with rates increasing markedly for d < 4 nm, while formaldehyde electrooxidation displays little sensitivity to the Pt nanoparticle size. However, the extent of chemisorbed CO formation from all three reactants, as deduced from voltammetric and infrared spectral data, diminishes with decreasing d, the CO coverages for a given nanoparticle size being in the order methanol < formic acid < formaldehyde. These nanoparticle-size-dependent electrocatalytic and CO adsorptive findings are consistent with the occurrence of a Pt site “ensemble effect”, where reactant dehydrogenation to form CO, and also in the case of formaldehyde and especially methanol to yield the reactive intermediate en route to CO2 production, is impeded by the sharply decreasing availability of contiguous Pt terrace sites for d < 4 nm. This structural model is consistent with infrared measurements using CO as a nanoparticle structural probe, which show a rapidly decreasing proportion of terrace relative to edge Pt sites for d < 4 nm, in harmony with atomic packing considerations. The markedly enhanced electrocatalyic rates for formic acid oxidation on the smaller nanoparticles are attributed to the lack of a “Pt site ensemble” requirement for this process, coupled with decreased CO poisoning: unlike the other two reactions, oxygen addition (from coadsorbed −OH) is not necessarily required in order to produce CO2 from formic acid.
Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery (2008)

Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.
Immunoglobulin classes in the hen's egg: Their segregation in yolk and white (1974)

Abstract Hen's egg yolk contains at least two antigen‐binding subclasses of IgG, derived from the hen serum and transmitted to the chick. IgM and IgA, absent in yolk and in newly hatched chick serum, were detected in the white of unembryonated eggs, in the amniotic fluid of embryonating eggs and in the digestive tract of 19‐day embryos, which also contained IgG. The dual mode of transfer found for maternal Ig of different classes in the fowl is compared with the transfer of maternal immunity in mammals.
Molecular basis for a polymorphism of human Fc gamma receptor II (CD32). (1990)

The IgG Fc receptor II on human monocytes is polymorphic in its ability to bind mIgG1, and its isoelectric focusing pattern. To study the molecular basis of this polymorphism, a cDNA library from cell line K562, expressing two different allelic forms (high responder [HR] and low responder [LR]) of Fc gamma RII, was used for cDNA cloning. We report the isolation and identification of different Fc gamma RII cDNA clones, comprising the LR form of Fc gamma RII, as was evident from studies using a new HR-specific anti-Fc gamma RII mAb 41H16, and from rosetting experiments. Sequence analysis revealed that HR and LR forms differ by two amino acids, both located in the external domain. In the cloned LR form, a glutamine is substituted by a tryptophan residue at aa position 27, located in the first Ig-like domain, and an arginine residue by a histidine residue at aa position 131 in the second Ig-like domain. Furthermore, an Fc gamma RII cDNA clone was isolated with a deletion of 123 bp, overlapping the predicted transmembrane segment. Data showing the presence of an alternatively spliced mRNA detected by using polymerase chain reaction (PCR) might suggest the existence of a soluble form of the human Fc gamma RII, in addition to the membrane-bound forms.
Ellagitannin Consumption Improves Strength Recovery 2-3 d after Eccentric Exercise (2010)

Supplementation with ellagitannins from pomegranate extract significantly improves recovery of isometric strength 2-3 d after a damaging eccentric exercise.
Visual Literacy and the Time-Varying Icon (1983)

The decreasing cost and increasing capability of computer graphics offers the opportunity to consider a new dynamic, or time-varying, iconic form of written language. Conventional ideographic writing forms, being static, require a very large number of symbols and are hard to learn. The new technology addresses both of these problem areas. Western culture Oriented iconic writing languages already exist, and one, based on American Signing, would really shine if adapted to a dynamic or time-varying presentation form using computer graphics. Some exciting, important, but distant benefits could result from the adoption of such a language form.
The progins progesterone receptor gene polymorphism is not related to endometriosis-associated infertility or to idiopathic infertility (2010)

The data suggest that PROGINS is not related either to endometriosis-associated infertility or to idiopathic infertility in the population studied.
Mitotic Kinases and p53 Signaling (2012)

Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy.
Quantitative Detection of Promoter Hypermethylation in Multiple Genes in the Serum of Patients with Colorectal Cancer (2005)

The quantitative detection of aberrant DNA methylation in serum may be a promising high-throughput approach for the noninvasive screening and monitoring of colorectal cancer.
Peculiarities of the Electronic Structure of Cytochrome P450 Compound I:  CASPT2 and DFT Modeling (2007)

CASSCF/CASPT2 ab initio formalism has been applied to a thiolate model of cytochrome P450 compound I. A2u ground state of porphyrin radical character was found in agreement with experimental results. A strong mixing of CASSCF reference states in multistate CASPT2 was observed, which is an interesting phenomenon, rare for the ground state near the equilibrium geometry. Details of the CASSCF/CASPT2 procedure (including the construction of the active space) are discussed. Parallel DFT calculations revealed that relative energies and the scheme of spin coupling are qualitatively reproduced by hybrid DFT (B3LYP); however, results from nonhybrid functionals (BLYP, BP86) are significantly different in these aspects.
AN N-GRAM BASED APPROACH TO THE AUTOMATIC CLASSIFICATION OF WEB PAGES BY GENRE (2009)

The extraordinary growth in both the size and popularity of the World Wide Web has generated a growing interest in the identification of Web page genres, and in the use of these genres to classify Web pages. Web page genre classification is a potentially powerful tool for filtering the results of online searches. Although most information retrieval searches are topic-based, users are typically looking for a specific type of information with regard to a particular query, and genre can provide a complementary dimension along which to categorize Web pages. Web page genre classification could also aid in the automated summarization and indexing of Web pages, and in improving the automatic extraction of metadata.\n\nThe hypothesis of this thesis is that a byte n-gram representation of a Web page can be used effectively to classify the Web page by its genre(s). The goal of this thesis was to develop an approach to the problem of Web page genre classification that is effective not only on balanced, single-label corpora, but also on unbalanced and multi-label corpora, which better represent a real world environment. This thesis research develops n-gram representations for Web pages and Web page genres, and based on these representations, a new approach to the classification of Web pages by genre is developed.\n\nThe research includes an exhaustive examination of the questions associated with developing the new classification model, including the length, number, and type of the n-grams with which each Web page and Web page genre is represented, the method of computing the distance (dissimilarity) between two n-gram representations, and the feature selection method with which to choose these n-grams. The effect of preprocessing the data is also studied. Techniques for setting genre thresholds in order to allow a Web page to belong to more than one genre, or to no genre at all are also investigated, and a comparison of the classification performance of the new classification model with that of the popular support vector machine approach is made. Experiments are also conducted on highly unbalanced corpora, both with and without the inclusion of noise Web pages.
5,6,7-Trisubstituted 4-Aminopyrido[2,3-d]pyrimidines as Novel Inhibitors of Adenosine Kinase (2003)

The synthesis and structure-activity relationship of a series of 5,6,7-trisubstituted 4-aminopyrido[2,3-d]pyrimidines as novel nonnucleoside adenosine kinase inhibitors is described. A variety of alkyl, aryl, and heteroaryl substituents were found to be tolerated at the C5, C6, and C7 positions of the pyridopyrimidine core. These studies have led to the identification of analogues that are potent inhibitors of adenosine kinase with in vivo analgesic activity.
Immunological weapons against acute myeloid leukaemia (2002)

A better understanding of the biology of malignant cells and of the host immune system together with dramatic advances in technology have led to the design of innovative immune-mediated approaches to control neoplastic clones, including various haematological malignancies. One of the major problems with conventional cancer therapies is their inability to eradicate residual cancer cells that are resistant to therapy, hence immune intervention might improve the clinical outcome of patients. This mini-review will focus mainly on immunological approaches to the therapy of acute myeloid leukaemia (AML), a subset of a much larger family of leukaemias. Immune-mediated approaches ranging from allogeneic lymphocyte transplants to cytokine therapy, immune-gene therapy and vaccination by dendritic-cell-based vaccines will be discussed.