gebhart/patrepeval huggingface dataset:
Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. (1986)

HLp is a human liver cytochrome P-450 that is immunochemically related to the glucocorticoid-inducible liver cytochrome P-450p in the rat and its homologue in the rabbit, P-450 LM3c. To investigate the structure and regulation of HLp, we used a monoclonal antibody that recognizes purified HLp to screen a human liver cDNA library in lambda gt11. We isolated and sequenced two overlapping cDNA clones that span the entire 2011 bases of an mRNA that codes for a protein of 504 amino acids. The predicted amino-terminal amino acid sequence of this protein is identical to the first 20 residues determined from purified HLp. HLp mRNA shares more than 70% sequence homology with related proteins from the rat and rabbit but less than 40% homology with other published cytochrome P-450 genes. Moreover, Southern blot analysis of human and rat genomic DNA revealed 50 and 60 kilobases of DNA, respectively, hybridizable to the HLp cDNAs. Blot analysis of human liver RNA from five patients revealed major (2.2 kilobase) and minor (3.0 kilobase) bands that hybridized to HLp cDNAs. The apparent concentration of these hybridizable mRNAs as well as the amounts of immunoreactive HLp protein in microsomes from the same liver were increased in a dose-dependent relationship in three patients who received dexamethasone, a potent glucocorticoid. Furthermore, in samples of RNA and of microsomes isolated from cultures of a human hepatoma cell line (Hep G2) incubated for 120 hr in medium containing dexamethasone, there was a 6-fold induction of the two mRNA species hybridizable to HLp cDNAs and a 3-fold induction of immunoreactive HLp protein as compared to the values for cultures incubated in steroid-free medium. We conclude that HLp is a human representative of a conserved glucocorticoid-inducible cytochrome P-450 gene family whose mechanism of induction involves accumulation of HLp mRNA.
Registration of three-dimensional cardiac catheter models to single-plane fluoroscopic images (1999)

Transvenous cardiac procedures require accurate positioning of catheters within the geometrically complex cavities of the heart. Recently, nonfluoroscopic catheter tracking technologies have been developed to quantitate the (degrees-of-freedom) three-dimensional positions of intracardiac catheters. This paper presents a projection-Procrustes method to register an animated three-dimensional (3-D) model of multiple intracardiac catheters with a single-plane fluoroscopic image. Applying the computed transformation to the catheter coordinates enables the animated 3-D model of the catheters to be viewed from the same perspective as the fluoroscopic image. Mathematical simulations show that the computed transformation parameters are sensitive to both the position errors in the 3-D catheter coordinates and to the spatial distribution of the catheter-mounted transducers. Simulations with a realistic geometric model of three catheters with four transducers per catheter showed an angular error of 1.91 degrees +/- 0.27 degree for 3-D catheter position errors of 2.0 mm. An in vitro experiment demonstrated the feasibility of the method using a water tank phantom of three catheters and fluoroscopic images taken over an 80 degrees range. The mean angular error was 0.61 degree +/- 0.48 degree. The results of this study indicate that the projection-Procrustes method is a useful tool for registering 3-D catheter tracking models to single-plane fluoroscopic images.
Analysis of rearranged T-cell receptor beta-chain genes by polymerase chain reaction (PCR) DNA sequencing and automated high resolution PCR fragment analysis (1995)

Polymerase chain reaction (PCR)-directed amplification and sequencing of rearranged immune genes for identification of clone-specific markers are increasingly being used in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) patients instead of the time consuming and labor intensive Southern analysis. In previous reports, no single common V beta and J beta sequence had been identified that allowed reliable amplification of the majority of rearranged T-cell antigen receptor (TCR)-beta V-D-J junctions at the DNA level because of the relatively large number of possible TCR-beta variable (V beta) and joining (J beta) gene segments involved in the rearrangement processes. In the present study we designed highly degenerate PCR primers directed against conserved sequences of the J beta genes. IN combination with a previously published consensus V beta primer, these J beta primers specifically amplify TCR- beta V-N(D)N-J junctions from genomic DNA. Using this approach we studied DNA extracted from biopsy material of nine patients with T-cell lymphoproliferative disorders, one c-ALL patient, and five patients with nonmalignant diseases. T-cell lines Molt 3, Jurkat, and HM 2 served as monoclonal controls. Individual PCR products were sequenced after cloning. The nucleotide sequences of 96 randomly chosen recombinant vectors were determined. In the polyclonal controls all analyzed clones differed in their TCR-beta V-N(D)N-J junctions. In the T-cell lines, in all of the T-cell malignancies, and in the c-ALL, monoclonal PCR products could be identified by demonstration of clonally restricted V-N(D)N-J junctions. The PCR results were confirmed by automated fluorescence quantification and size determination of PCR products after separation in a high-resolution polyacrylamide gel. The procedure allows rapid and specific characterization of clonal TCR-beta rearrangements from genomic DNA and will significantly simplify current experimental approaches to identify and to quantitate malignant T cells during initial staging and follow-up of T-lineage NHL and ALL patients.
Five-membered aromatic heterocycles as dienophiles in Diels-Alder reactions. Furan, pyrrole, and indole (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFive-membered aromatic heterocycles as dienophiles in Diels-Alder reactions. Furan, pyrrole, and indoleErnest. Wenkert, Peter D. R. Moeller, and Serge R. PiettreCite this: J. Am. Chem. Soc. 1988, 110, 21, 7188–7194Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://doi.org/10.1021/ja00229a039Request reuse permissionsArticle Views3003Altmetric-Citations113LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alertsclose Get e-Alerts
Autocrine TGF-β and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts (2010)

Much interest is currently focused on the emerging role of tumor-stroma interactions essential for supporting tumor progression. Carcinoma-associated fibroblasts (CAFs), frequently present in the stroma of human breast carcinomas, include a large number of myofibroblasts, a hallmark of activated fibroblasts. These fibroblasts have an ability to substantially promote tumorigenesis. However, the precise cellular origins of CAFs and the molecular mechanisms by which these cells evolve into tumor-promoting myofibroblasts remain unclear. Using a coimplantation breast tumor xenograft model, we show that resident human mammary fibroblasts progressively convert into CAF myofibroblasts during the course of tumor progression. These cells increasingly acquire two autocrine signaling loops, mediated by TGF-β and SDF-1 cytokines, which both act in autostimulatory and cross-communicating fashions. These autocrine-signaling loops initiate and maintain the differentiation of fibroblasts into myofibroblasts and the concurrent tumor-promoting phenotype. Collectively, these findings indicate that the establishment of the self-sustaining TGF-β and SDF-1 autocrine signaling gives rise to tumor-promoting CAF myofibroblasts during tumor progression. This autocrine-signaling mechanism may prove to be an attractive therapeutic target to block the evolution of tumor-promoting CAFs.
Lessons in Molecular Recognition:  The Effects of Ligand and Protein Flexibility on Molecular Docking Accuracy (2003)

The key to success for computational tools used in structure-based drug design is the ability to accurately place or "dock" a ligand in the binding pocket of the target of interest. In this report we examine the effect of several factors on docking accuracy, including ligand and protein flexibility. To examine ligand flexibility in an unbiased fashion, a test set of 41 ligand-protein cocomplex X-ray structures were assembled that represent a diversity of size, flexibility, and polarity with respect to the ligands. Four docking algorithms, DOCK, FlexX, GOLD, and CDOCKER, were applied to the test set, and the results were examined in terms of the ability to reproduce X-ray ligand positions within 2.0A heavy atom root-mean-square deviation. Overall, each method performed well (>50% accuracy) but for all methods it was found that docking accuracy decreased substantially for ligands with eight or more rotatable bonds. Only CDOCKER was able to accurately dock most of those ligands with eight or more rotatable bonds (71% accuracy rate). A second test set of structures was gathered to examine how protein flexibility influences docking accuracy. CDOCKER was applied to X-ray structures of trypsin, thrombin, and HIV-1-protease, using protein structures bound to several ligands and also the unbound (apo) form. Docking experiments of each ligand to one "average" structure and to the apo form were carried out, and the results were compared to docking each ligand back to its originating structure. The results show that docking accuracy falls off dramatically if one uses an average or apo structure. In fact, it is shown that the drop in docking accuracy mirrors the degree to which the protein moves upon ligand binding.
Growth factors increase amphotropic retrovirus binding to human CD34+ bone marrow progenitor cells (1993)

Gene transfer into human cells using murine amphotropic retroviral vectors is the basic technique used in most current gene therapy studies. The identity of the cell surface receptor for the amphotropic envelope remains unknown and thus its importance in gene transfer is poorly understood. We have measured specific retrovirus binding to cells to study amphotropic virus receptor regulation in human CD34+ bone marrow (BM) progenitors and primitive CD34+CD38- human hematopoietic cells. The rat monoclonal antibody 83A25 recognizes an epitope common to the envelope glycoprotein of all classes of Moloney murine leukemia virus. Indirect fluorescent labeling of 83A25 allows flow cytometric analysis of specific virus-cell interactions and is an indirect measure of specific receptors. Using this assay, amphotropic virus binding to fresh CD34+ cells was minimal. However, when CD34+ cells were cultured with or without growth factors for 4 days, specific binding of amphotropic retrovirus was readily shown. Inclusion of interleukin-3 (IL-3), IL-6, and Steel factor in cultures increased the fluorescence associated with amphotropic virus binding by twofold to four-fold (mean fold increase 2.7 +/- 0.84). Virus binding to CD34+CD38- cells was shown only in those cells culture in IL-3, IL-6, and Steel factor. These results suggest that certain cytokines may cause an increase in the number and/or affinity of amphotropic receptors on primitive human hematopoietic cells. Upregulation of viral receptor expression may be one of the mechanisms by which cytokines enhance gene transfer into primitive BM cells.
Characterization of the human biliverdin reductase gene structure and regulatory elements: promoter activity is enhanced by hypoxia and suppressed by TNF‐α‐activated NF‐κB (2010)

hBVR is a Ser/Thr/Tyr kinase/scaffold protein/transcription factor/intracellular transporter of regulators. hBVR is an upstream activator of the insulin/IGF-1/MAPK/PI3K signaling pathway, and of NF-kappaB. As a reductase, it converts biliverdin to the antioxidant, bilirubin. hBVR gene has 8 exons; exon 1 is not translated. We report the characterization of hBVR promoter and its negative and positive regulation, respectively, by TNF-alpha and hypoxia. The 5' end of exon 1 was defined by primer extension analyses; deletion of an inhibitor sequence 350-425 bp upstream of this exon enhanced the promoter activity. One of two NF-kappaB binding sites in the 836-bp promoter was functional; the P65 subunit of NF-kappaB and TNF-alpha acted as inhibitors. On the basis of EMSA and ChIP assays, TNF-alpha treatment increases binding of NF-kappaB to its regulatory element. Overexpression of IkappaB increased hBVR mRNA. Biliverdin, but not bilirubin, was as effective as TNF-alpha in inhibiting hBVR promoter activity. Only one of 4 hypoxia responsive elements (HREs) bound to HIF-1alpha and ARNT expressed in HEK293A cells. An abasic site was introduced at the 3' G of the HRE. This element bound HIF-1 in the gel shift and in in-cell luciferase assays. hBVR was detected in the nucleus at 1, 2, and 4 h after hypoxia (1% O(2)), at which times its kinase and reductase activities were increased. Because hypoxia positively influences hBVR promoter and phosphorylation and TNF-alpha activated NF-kappaB inhibits the promoter, while biliverdin inhibits both NF-kappaB activity and hBVR promoter, we propose a regulatory mechanism for NF-kappaB by hypoxia and TNF-alpha centered on hBVR/biliverdin.
High-efficiency white phosphorescent organic light-emitting devices with greenish-blue and red-emitting layers (2003)

We demonstrate high-efficiency white light emission from a phosphorescent organic light-emitting device with greenish-blue and red emissive layers. Bis{2-[3,5-bis(trifluoromethyl)phenyl]-pyridinato-N,C2′}iridium(III)picolinate [(CF3ppy)2Ir(pic)] and bis{2-[2′-benzo(4,5-a)thienyl]pyridinato-N,C3′}iridium(III)acetylacetonate were employed for the greenish-blue and red phosphorescent materials for the emissive layers. To enhance the emission efficiency of (CF3ppy)2Ir(pic), 4,4′-bis(9-carbazolyl)-2,2′-dimethyl-biphenyl was used as the charge-transporting host. White light emission was obtained by controlling the layer thickness and the concentration of each phosphorescent material in the emissive layers. A maximum external quantum efficiency of 12%, a luminance efficiency of 18 cd/A, and a maximum power efficiency of 10 lm/W were achieved at a current density of 0.01 mA/cm2. This high efficiency is primarily attributed to the improvement of greenish-blue emission efficiency due to the strong confinement of triplet excitons on the (CF3ppy)2Ir(pic) molecules.
Does erythropoietin modulate human hair follicle melanocyte activities in situ? (2009)

Erythropoietin (EPO) is now appreciated for not only drive erythopoiesis, but also to exert additional functions. Since we had previously shown that human hair follicles (HFs) are both an extra-renal source and an extra-medullary target of EPO, we have now studied whether one such function is the regulation of HF pigmentation. Human anagen VI HFs were treated with EPO (100 IU/ml) in serum-free organ culture. Unexpectedly, we noticed greatly divergent pigmentary effects of EPO, since both up- and down-regulation of HF melanin content and tyrosinase activity in situ was seen in HF derived from different individuals. These divergent effects could not be attributed to differences in skin regions, the total HF melanocyte number or specific traits of individual HF donors. Our pilot study provides first evidence suggesting that EPO may modulate normal human melanocyte functions under physiologically relevant conditions in situ.
THE EFFECTS OF PORPHYRIN STRUCTURE AND AGGREGATION STATE ON PHOTOSENSITIZED PROCESSES IN AQUEOUS AND MICELLAR MEDIA (1986)

Abstract The efficiency of several porphyrins at 10 μ M and 83 μ M as sensitizers of the photooxidation of 0.1 m M tryptophan and histidine via a singlet oxygen‐mechanism was studied in pH 7.4‐buffered aqueous solutions and in aqueous dispersions of Triton X‐100 micelles. The porphyrins were either solubilized in the bulk aqueous medium or associated with the micellar phase, whereas the amino acids were always located in the aqueous phase. With those porphyrins, such as uroporphyrin I, meso‐tetra (4‐sulfonatophenyl)porphine, meso‐tetra(4‐carboxyphenyl)porphine and meso‐tetra )N,N,N‐trimethylanilinium)porphine, which are &gt; 98% monomeric in both media, the efficiency of histidine photooxidation was independent of the site of O 2 ( 1 Δ g ) generation, as shown by the closely similar values for the photooxidation rate constant and oxygen‐consumption quantum yield in the presence and absence of Triton micelles; the same indications were provided by photokinetic experiments with tryptophan. Actually, laser flash photolysis studies showed that the micelle‐incorporation of the above mentioned porphyrins brought about only minor changes in their photophysical properties, including the relative yield of O 2 ( 1 Δ g ) generation. On the other hand, hematoporphyrin IX, its Zn 2+ ‐complex, and coproporphyrin III are largely aggregated in homogeneous aqueous solution; their incorporation into Triton micelles caused an increase of the triplet quantum yield and an enhancement of the oxygen‐consumption quantum yield and photooxidation rate constant for both histidine and tryptophan. The lower photosensitizing efficiency of aggregated porphyrin species in comparison with the corresponding monomeric porphyrin was confirmed by measuring the initial rate and quantum yield of oxygen consumption upon irradiation of 1 m M histidine and tryptophan in the presence of different hematoporphyrin concentrations within the 0.3‐100μ M range.
Regulatory mutations in the Klebsiella aerogenes structural gene for glutamine synthetase (1977)

Glutamine synthetase could be repressed several hundredfold rather than 6- to 10-fold as previously reported. Ammonia was not the primary repression signal for glutamine synthetase. Repression appeared to be mediated by a high level of glutamine and probably by a high ratio of glutamine to alpha-ketoglutarate. Mutations in glnA (the structural gene for glutamine synthetase) were seen to fall into three phenotypic groups: glutamine auxotrophs that produced no detectable glnA product; glutamine auxotrophs that produced a glnA product lacking enzymatic activity (and hence repressibility by ammonia) but were repressible under appropriate conditions; and glutamine synthetase regulatory mutants, whose glnA product was enzymatically active and not repressible under any conditions.
Treatment of Renal Osteodystrophy With 25-Hydroxycholecalciferol (1970)

Vitamin D<sub>3</sub>is converted by a liver enzyme system, calciferol-25-hydroxylase, to 25-hydroxycholecalciferol (25-HCC), the active hormonal form of the vitamin. This hydroxylase is feedback inhibited by 25-HCC, and probably represents an important physiologic control step for active vitamin D. The 25-HCC is further converted in intestine, kidney, and bone to two more polar metabolites which probably represent the metabolically active form of vitamin D<sub>3</sub>. Evidence has been presented that in uremia, excessive metabolism of vitamin D results in low plasma levels of 25-HCC. In chronically uremic rats, 25-HCC is at least one hundredfold more effective than vitamin D<sub>3</sub>in restoring calcium absorption. In uremics, treatment with 10,000 international units (IU) of 25-HCC/day, improves calcium absorption, increases urinary and plasma calcium and decreases plasma alkaline phosphatase. Thus, 25-HCC may be the drug of choice in bone disease of uremia.
Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells (2013)

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease.