gebhart/patrepeval huggingface dataset:
Cell Cycle Checkpoints and DNA Repair in Nijmegen Breakage Syndrome (1997)

Nijmegen breakage syndrome is characterized by a variable T cell and B cell immunodeficiency, growth failure, and an increased risk of malignancy. It is inherited in an autosomal recessive manner and is biochemically related to ataxia-telangiectasia. Cells from a patient with Nijmegen breakage syndrome were unable to arrest cell cycle progression after exposure to ionizing radiation, and BrdU incorporation into newly synthesized DNA was uninhibited, demonstrating that these cells have an aberrant response to radiation exposure. Although gross chromosomal breakage was observed, dinucleotide repeat segments were stable over time, suggesting that other types of DNA stability were not affected. DNA-PK activity, which is mediated by a protein related to the ataxia-telangiectasia gene product and is intimately involved in DNA repair and VDJ recombination, was normal in cells from an NBS patient. Therefore, cells from patients with Nijmegen breakage syndrome have an abnormal response to radiation exposure similar to that seen in ataxia-telangiectasia.
Vitamin E Reduces the Uptake of Oxidized LDL by Inhibiting CD36 Scavenger Receptor Expression in Cultured Aortic Smooth Muscle Cells (2000)

This study indicates that CD36 is expressed in cultured human SMCs. In these cells, CD36 transports oxLDL into the cytosol. alpha-Tocopherol inhibits oxLDL uptake by a mechanism involving downregulation of CD36 mRNA and protein expression. Therefore, the beneficial effect of alpha-tocopherol against atherosclerosis can be explained, at least in part, by its effect of lowering the uptake of oxidized lipoproteins, with consequent reduction of foam cell formation.
Interaction of Human Macrophage C-type Lectin withO-Linked N-Acetylgalactosamine Residues on Mucin Glycopeptides (1999)

A fluorescein-labeled synthetic peptide, PTTTPITTTTK, was converted into O-glycosylated glycopeptides with various numbers of attached N-acetyl-D-galactosamines (GalNAcs) by in vitro glycosylation with UDP-GalNAc and a microsomal fraction of LS174T human colon carcinoma cells. Glycopeptides with 1, 3, 5, and 6 GalNAc residues (G1, G3, G5, and G6) were obtained, and their sizes were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Their sequences were determined by a peptide sequencer to be PTTTGalNAcPITTTTK for G1, PTGalNAcTTPITGalNAcTGalNAcTTK for G3, PTTGalNAcTGalNAcPITGalNAcTGalNAcTGalNAcTK for G5, and PTGalNAcTGalNAcTGalNAcPITGalNAcTGalNAcTGalNAcTK for G6. A calcium-type human macrophage lectin (HML) was prepared in a recombinant form, and its interaction with these glycopeptides was investigated by surface plasmon resonance (SPR) spectroscopy and fluorescence polarization. The affinity of recombinant HML (rHML) for immobilized glycopeptides increased, as revealed by SPR, in parallel with the number of GalNAc. The highest affinity was obtained when the G6-peptide was immobilized at high density. Fluorescence polarization equilibrium-binding assays also revealed that the affinity of rHML for soluble gly-copeptides increased, depending on the number of attached GalNAcs. Carbohydrate recognition domain (CRD) fragments of HML were prepared, and their affinity for these four glycopeptides was also determined, this affinity was apparently lower than that of rHML. Affinity constants of rHML for the G3- and G5-peptides were 11- and 38-fold higher, respectively, than for the G1-peptide, whereas those of CRD fragments were only 2- and 6-fold higher, respectively. A chemical cross-linking study revealed that rHML but not recombinant CRD forms trimers in an aqueous solution. Thus, preferential binding of densely glycosylated O-linked glycopeptides should be due to the trimer formation of rHML.
Antifreeze glycopeptides and peptides in Antarctic fish species from the Weddell Sea and the Lazarev Sea (1996)

Antifreeze glycopeptides and peptides have been isolated from 37 species of Antarctic fish representing the families Nototheniidae, Artedidraconidae, Bathydraconidae, Channichthyidae, Muraenolepididae. Liparididae, Zoarcidae and Myctophidae. Amino acid and carbohydrate analysis as well as antifreeze activity indicate that all investigated notothenioids contain antifreeze glycopeptides [AFGP). Pleuragramma antarcticurn, Lepidonotothen kempi, Bathydraco rnarri and Dolloidraco longedorsalis synthesize additional antifreeze molecules. The non-notothenioid species possess antifreeze peptides (AFP), except Muraenolepis marrnoratus and Macrourus holotrachys, which possess a glycosylated antifreeze pept~de similar to the AFGP found in the notothenio~d species. A novel glycopeptide comprised of the carbohydrate residue N-acetylglucosamine and the amino acids asparagine, glutamine, glycine, alanine, and traces of arginine, valine, leucine and threonine was isolated and characterized from P. antarcticum. The level of antifreeze concentration was dependent on the ambient water temperature, the depth of catch and life cycle of the species. Antifreeze activity of AFGP varies between 0.52 (Neopagetopsis ionah) and 1.20C ( P antarctjcum) at a concentration of 20 mg ml-' Antifreeze activity of AFP is lower than 0.50C. A linear increase in activity of the AFGP could be demonstrated concomitant with decreasing ice content. The structural diversity of antifreeze molecules and their occurrence in a wide range of Arctic and Antarctic fish species suggest that they evolved from precursor proteins before the continental drift and recently during Cenozoic glaciation into the various antifreeze molecules.
Induction of Tumor Regression by Administration of B7-Ig Fusion Proteins: Mediation by Type 2 CD8+ T Cells and Dependence on IL-4 Production (2004)

CD28 signals contribute to either type 1 or type 2 T cell differentiation. Here, we show that administration of B7.2-Ig fusion proteins to tumor-bearing mice induces tumor regression by promoting the differentiation of antitumor type 2 CD8(+) effector T cells along with IL-4 production. B7.2-Ig-mediated regression was not induced in IL-4(-/-) and STAT6(-/-) mice. However, it was elicited in IFN-gamma(-/-) and STAT4(-/-) mice. By contrast, IL-12-induced tumor regression occurred in IL-4(-/-) and STAT6(-/-) mice, but not in IFN-gamma(-/-) and STAT4(-/-) mice. Moreover, B7.2-Ig treatment was effective in a tumor model not responsive to IL-12. B7.2-Ig administration elicited elevated levels of IL-4 production. Tumor regression was predominantly mediated by CD8(+) T cells, although the induction of these effector cells required CD4(+) T cells. Tumor regression induced by CD8(+) T cells alone was inhibited by neutralizing the IL-4 produced during B7.2-Ig treatment. Thus, these results indicate that stimulation in vivo of CD28 with B7.2-Ig in tumor-bearing mice results in enhanced induction of antitumor type 2 CD8(+) T cells (Tc2) leading to Tc2-mediated tumor regression.
A Duplex Quantitative Polymerase Chain Reaction Assay Based on Quantification of α-Methylacyl-CoA Racemase Transcripts and Prostate Cancer Antigen 3 in Urine Sediments Improved Diagnostic Accuracy for Prostate Cancer (2009)

Urinary AMACR and PCA3 tests were superior to a serum prostate specific antigen test for detecting prostate cancer. Their combined use in a dual marker test further improved sensitivity and accuracy, and could serve as a surveillance test after repeat negative prostate biopsies.
The use of deoxyfluoro-d-glucopyranoses and related compounds in a study of yeast hexokinase specificity (1972)

1. 2-Deoxy-2-fluoro-d-glucose, 2-deoxy-2-fluoro-d-mannose and 2-deoxy-2,2-difluoro-d-arabino-hexose are good substrates for yeast hexokinase. 2. 3-Deoxy-3-fluoro-d-glucose and 4-deoxy-4-fluoro-d-glucose are poor substrates and have very similar K(m) values (8x10(-2)m). 3. Neither alpha- nor beta-d-glucopyranosyl fluoride is a substrate or inhibitor. 4. Studies with 2-chloro-2-deoxy- and 2-O-methyl derivatives of d-glucose and d-mannose have revealed that little chemical modification is possible at position 2 without substantial loss in substrate binding. 5. The variation in the value of K(m) for the d-hexose derivatives was associated with a corresponding change in the value of K(m) for MgATP(2-) showing that the binding of MgATP(2-) is modified by the binding of the sugar.
Dipeptidyl peptidase 4 inhibition with sitagliptin: a new therapy for Type 2 diabetes (2007)

Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the treatment of Type 2 diabetes, both as a monotherapy and for use in combination with metformin or a thiazolidinedione. In clinical trials of < or = 1-year duration, sitagliptin improves glycaemic control by reducing both fasting and postprandial glucose concentrations, leading to clinically meaningful reductions in glycosylated haemoglobin levels. It is safe and well tolerated, with a side-effect profile that is similar to that of the placebo, a low incidence of hypoglycaemia and body weight neutrality. Further clinical experience with sitagliptin will reveal its long-term durability, safety and efficacy.
The Molecular Basis of Blood Diseases. (1987)

The recent application of the techniques of molecular biol- ogy to the study of human diseases has made it possible to obtain information unavailable-and, in some instances, unimaginable-a decade ago.Because of the rapidity with which developments have occurred, many clinicians and scientists may be unaware of them and of the insights they provide into the origin of diseases.To address the needs of this audience, four noted authorities in the field, George Stamatoyannopoulos, Arthur Nienhuis, Philip Leder, and Philip Majerus, have recruited 27 of their colleagues to describe what is currently known about the molecular basis of blood diseases.The first chapter introduces the reader to the methods of molecular cloning and analysis of gene structure that have generated much of the information pre- sented subsequently.Several chapters then describe gene structure, expression, and regulation, using the globin genes as a model.After this general introduction, specific groups of diseases are addressed.Each area of classic hematology-the red cell, the white cell (both normal and malignant), and the soluble and cellular components of the hemostatic system (including hemostasis, thrombosis, and fibrinolysis)-is taken up in turn.In addition, three chap- ters present immunological topics-immunoglobulin and T-cell receptor genes (as well as lymphocyte differentia- tion), enzyme deficiencies associated with immunological disorders, and molecular mechanisms of complement ac-
Alveolar macrophage replication. One mechanism for the expansion of the mononuclear phagocyte population in the chronically inflamed lung. (1984)

Within any chronically inflamed tissue, there is an increased number of macrophages, pluripotential phagocytic cells that, while critical to host defenses, are also able to profoundly damage parenchymal structure and function. Because of their central role in the inflammatory response, considerable attention has been focused on the mechanisms resulting in an expansion of the macrophage population within an inflamed tissue. Although recruitment of precursor monocytes from the circulation into inflamed tissues clearly plays an important role in macrophage accumulation, it is also possible that replication of tissue macrophages contributes to the expansion of macrophage numbers in inflammation. Because of the accessibility of tissue macrophages with the technique of bronchoalveolar lavage, the lung provides an ideal opportunity to test this hypothesis in humans. To accomplish this, bronchoalveolar lavage was performed to obtain alveolar macrophages from normals (n = 5) and individuals with chronic lung inflammation (normal smokers [n = 5], idiopathic pulmonary fibrosis [n = 13], sarcoidosis [n = 18], and other chronic interstitial lung disorders [n = 11]). Alveolar macrophage replication was quantified by three independent methods: (a) DNA synthesis, assessed by autoradiographic analysis of macrophages cultured for 16 h in the presence of [3H]thymidine; (b) DNA content, assessed by flow cytometric analysis of macrophages fixed immediately after recovery from the lower respiratory tract; and (c) cell division, assessed by cluster formation in semisolid medium. While the proportion of replicating macrophages in normals was very low, there was a 2- to 15-fold increase in this proportion in patients with chronic lung inflammation. In addition, morphologic evaluation demonstrated that individuals with chronic lung inflammation had alveolar macrophages undergoing mitosis. These results suggest that local tissue macrophage replication may play a role in the expansion of the macrophage population in chronic inflammation.
Probiotics Ameliorate Recurrent Th1-Mediated Murine Colitis by Inducing IL-10 and IL-10-Dependent TGF-β-Bearing Regulatory Cells (2005)

Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4+ T cells bearing surface TGF-beta in the form of latency-associated protein (LAP) (LAP+ T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP+ T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-beta at the initiation of recurrent colitis induction or depletion of LAP+ T cells from LPMC abolished the latter's capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-beta-bearing regulatory cells.
Treatment of adults with attention-deficit/hyperactivity disorder (2008)

This review focuses on the treatment of attention deficit hyperactivity disorder (ADHD) in adults. It briefly addresses prevalence, diagnostic and differential diagnostic issues specific to adults. Stimulant medication, non-stimulant medication, and psychosocial treatments are thoroughly reviewed. For each class of medication possible mechanism of action, efficacy and side effects are summarized. Special attention is given to the pharmacological treatment for patients with adult ADHD and various comorbidities. In summary, stimulant medications are most effective and combined medication and psychosocial treatment is the most beneficial treatment option for most adult patients with ADHD.
Towards Controlled Graft Polymerization of Poly[styrene‐co‐(maleic anhydride)] on Functionalized Silica Mediated by Oxoaminium Bromide Salt. Facile Synthetic Pathway Using Nitroxide Chemistry (2007)

Abstract A TEMPO bromide salt is used to functionalize a silica surface with nitroxyl moieties. The functionalization reaction takes place in 48 h under mild conditions. In a second step, grafts of styrene‐maleic anhydride copolymer are grown from the functionalized silica surface by heating it in the presence of the monomers. FT‐IR and TGA analysis show that the silica was first functionalized with nitroxide moieties, and then that grafts of styrene‐maleic anhydride grew from the functionalized silica surface. A reaction mechanism is proposed in order to explain the findings. The results suggest that the oxoaminium salts are good candidates for the functionalization and grafting of surfaces that contain hydroxy groups and for the generation of hybrid materials with improved properties. magnified image
Bone Resorption in Tissue Culture. Factors Influencing the Response to Parathyroid Hormone * (1965)

vivo (7-14), by local application (15, 16), or in tissue culture (5, 17-21).
Novel Tryptophan Catabolic Enzyme IDO2 Is the Preferred Biochemical Target of the Antitumor Indoleamine 2,3-Dioxygenase Inhibitory Compound d -1-Methyl-Tryptophan (2007)

Small-molecule inhibitors of indoleamine 2,3-dioxygenase (IDO) are currently being translated to clinic for evaluation as cancer therapeutics. One issue related to trials of the clinical lead inhibitor, D-1-methyl-tryptophan (D-1MT), concerns the extent of its biochemical specificity for IDO. Here, we report the discovery of a novel IDO-related tryptophan catabolic enzyme termed IDO2 that is preferentially inhibited by D-1MT. IDO2 is not as widely expressed as IDO but like its relative is also expressed in antigen-presenting dendritic cells where tryptophan catabolism drives immune tolerance. We identified two common genetic polymorphisms in the human gene encoding IDO2 that ablate its enzymatic activity. Like IDO, IDO2 catabolizes tryptophan, triggers phosphorylation of the translation initiation factor eIF2alpha, and (reported here for the first time) mobilizes translation of LIP, an inhibitory isoform of the immune regulatory transcription factor NF-IL6. Tryptophan restoration switches off this signaling pathway when activated by IDO, but not IDO2, arguing that IDO2 has a distinct signaling role. Our findings have implications for understanding the evolution of tumoral immune tolerance and for interpreting preclinical and clinical responses to D-1MT or other IDO inhibitors being developed to treat cancer, chronic infection, and other diseases.
A unified approach to the linear camera calibration problem (1990)

The camera calibration process relates camera system measurements (pixels) to known reference points in a three-dimensional world coordinate system. The calibration process is viewed as consisting of two independent phases: the first is removing geometrical camera distortion so that rectangular calibration grids are straightened in the image plane, and the second is using a linear affine transformation as a map between the rectified camera coordinates and the geometrically projected coordinates on the image plane of known reference points. Phase one is camera-dependent, and in some systems may be unnecessary. Phase two is concerned with a generic model that includes 12 extrinsic variables and up to five intrinsic parameters. General methods handling additional constraints on the intrinsic variables in a manner consistent with explicit satisfaction of all six constraints on the orthogonal rotation matrix are presented. The use of coplanar and noncoplanar calibration points is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Substance P Activates the Release of Histamine from Human Skin Mast Cells through a Pertussis Toxin-Sensitive and Protein Kinase C-Dependent Mechanism (1996)

Using pharmacologic agents, we explored the mechanism by which a potent neuropeptide, substance P, induces the secretion of histamine from human skin mast cells and compared their effects on substance P-induced histamine release to the secretion activated by anti-IgE. Histamine release from human cutaneous mast cells induced by substance P was inhibited by the Ge-protein inhibitor pertussis toxin that, in turn, did not affect the IgE-mediated secretion. Similarly to anti-IgE, two activators of protein kinase C, tetradecanoylphorbol acetate (TPA) and bryostatin 1, significantly inhibited the substance P-induced response. In contrast, drugs that enhance intracellular levels of cAMP, an inhibitor of protein kinases, genistein, and a protease inhibitor, AEBSF, did not affect substance P-induced histamine secretion, whereas these compounds significantly reduced the response initiated by anti-IgE. Our data demonstrate that substance P activates human cutaneous mast cells by acting on G proteins and protein kinase C. Our results also suggest that the biochemical pathways underlying mast cell activation by substance P and anti-IgE are to a great extent unrelated.
PdhR (Pyruvate Dehydrogenase Complex Regulator) Controls the Respiratory Electron Transport System in Escherichia coli (2007)

The pyruvate dehydrogenase (PDH) multienzyme complex plays a key role in the metabolic interconnection between glycolysis and the citric acid cycle. Transcription of the Escherichia coli genes for all three components of the PDH complex in the pdhR-aceEF-lpdA operon is repressed by the pyruvate-sensing PdhR, a GntR family transcription regulator, and derepressed by pyruvate. After a systematic search for the regulation targets of PdhR using genomic systematic evolution of ligands by exponential enrichment (SELEX), we have identified two novel targets, ndh, encoding NADH dehydrogenase II, and cyoABCDE, encoding the cytochrome bo-type oxidase, both together forming the pathway of respiratory electron transport downstream from the PDH cycle. PDH generates NADH, while Ndh and CyoABCDE together transport electrons from NADH to oxygen. Using gel shift and DNase I footprinting assays, the PdhR-binding site (PdhR box) was defined, which includes a palindromic consensus sequence, ATTGGTNNNACCAAT. The binding in vitro of PdhR to the PdhR box decreased in the presence of pyruvate. Promoter assays in vivo using a two-fluorescent-protein vector also indicated that the newly identified operons are repressed by PdhR and derepressed by the addition of pyruvate. Taken together, we propose that PdhR is a master regulator for controlling the formation of not only the PDH complex but also the respiratory electron transport system.
Comparison of Optical Coherence Tomography Imaging of Cataracts With Histopathology (1999)

This paper presents a comparison of in vivo optical coherence tomography (OCT) captured cataract images to subsequent histopathological examination of the lenticular opacities. OCT imaging was performed on anesthetized Rhesus monkeys, known as the delayed effects colony (DEC), with documented cataracts. These monkeys were exposed to several types of radiation during the mid and late 1960s. The radiation and age related cataracts in these animals were closely monitored using a unique grading system developed specifically for the DEC. In addition to this system, a modified version of a common cataract grading scheme for use in humans was applied. Of the original 18 monkeys imaged, lenses were collected at necropsy from seven of these animals, processed, and compared to OCT images. Results showed a direct correlation between the vertical OCT images and the cataractous lesions seen on corresponding histopathologic sections of the lenses. Based on the images obtained and their corresponding documented comparison to histopathology, OCT showed tremendous potential to aid identification and characterization of cataracts. There can be artifactual problems with the images related to movement and shadows produced by opacities. However, with the advent of increased speed in imaging and multiplanar imaging, these disadvantages may easily be overcome. © 1999 Society of Photo-Optical Instrumentation Engineers.