gebhart/patrepeval huggingface dataset:
Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication. (1991)

Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection.
Dornase aerosol effect on sputum viscosity in cases of cystic fibrosis (1968)

<h3>To the Editor:—</h3> Deoxyribonucleic acid is not normally present in mucoid respiratory secretions but is a product of pulmonary inflammatory cellular debris.<sup>1,2</sup>The DNA in mucopurulent secretions seems to contribute to the chronicity of respiratory disease by increasing the viscosity of such secretions. A therapeutic attack upon the DNA content of purulent respiratory secretions would therefore appear to be worthwhile in an attempt to reduce morbidity from respiratory infection and to enhance the effectiveness of antibiotics.<sup>3</sup> Pancreatic dornase is a commercially available enzyme preparation which liquifies purulent sputum in vitro.<sup>4,5</sup>The reduction in viscosity occurs rapidly due to depolymerization of DNA<sup>5</sup>and the induction of intrinsic proteolysis.<sup>6-8</sup>Dornase aerosols have also been found to be useful in the evacuation of viscous mucopurulent secretions in bronchopulmonary disease.<sup>9-13</sup>I recently described a method for measuring the viscosity of sputum with a coneplate viscosimeter, thereby providing a
Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer (2010)

Tyrosine kinase (TK) fusions are attractive drug targets in cancers. However, rapid identification of these lesions has been hampered by experimental limitations. Our in silico analysis of known cancer-derived TK fusions revealed that most breakpoints occur within a defined region upstream of a conserved GXGXXG kinase motif. We therefore designed a novel DNA-based targeted sequencing approach to screen systematically for fusions within the 90 human TKs; it should detect 92% of known TK fusions. We deliberately paired 'in-solution' DNA capture with 454 sequencing to minimize starting material requirements, take advantage of long sequence reads, and facilitate mapping of fusions. To validate this platform, we analyzed genomic DNA from thyroid cancer cells (TPC-1) and leukemia cells (KG-1) with fusions known only at the mRNA level. We readily identified for the first time the genomic fusion sequences of CCDC6-RET in TPC-1 cells and FGFR1OP2-FGFR1 in KG-1 cells. These data demonstrate the feasibility of this approach to identify TK fusions across multiple human cancers in a high-throughput, unbiased manner. This method is distinct from other similar efforts, because it focuses specifically on targets with therapeutic potential, uses only 1.5 µg of DNA, and circumvents the need for complex computational sequence analysis.
&#945;-Fluorinated Ethers as &#x201C;Exotic&#x201D; Entity in Medicinal Chemistry (2007)

After nitrogen, fluorine occupies the position of second favorite heteroelement in life science-oriented research. In contrast, the trifluoromethoxy group is still perhaps the least well understood fluorine substituent, although its occurrence has significantly increased in the recent years. Today, significant application areas for trifluoromethoxy substituted pharmaceuticals are in the field of analgesics, anesthetics, cardiovascular drugs, respiratory drugs, psychopharmacologic drugs, neurological drugs, gastrointestinal drugs and anti-infective therapeutics. The present review will give an overlook of its use in medicinal chemistry.
PLA-Coated Gold Nanoparticles for the Labeling of PLA Biocarriers (2004)

Poly-dl-lactide end-capped by a protected thiol was synthesized by bulk ring-opening polymerization (ROP) of dl-lactide initiated by the reaction product of aluminum isopropoxide [Al (iOPr) 3] with α- (2,4-dinitrophenylsulfenyl) ethanol. After the thiol deprotection, PLA-SH was used to stabilize gold nanoparticles. Either these nanoparticles were prepared in the presence of PLA-SH, or PLA-SH was substituted for part of the undecanethiol (C11SH) that stabilized preformed gold nanoparticles. In contrast to C11SH-coated nanoparticles, those stabilized by PLA-SH were successfully entrapped into 100-nm PLA nanocarriers prepared by nanoprecipitation. This is an easy technique to label PLA biocarriers and therefore trace their fate in vivo.
Zur Chemie der „energiereichen Phosphate”, XVI1) Die Synthese der Argininphosphorsäure und die Reaktion von Isoureidophosphonaten mit Aminen (1962)

Abstract Argininphosphorsäure (I) läßt sich durch Phosphorylierung von α‐Cbo‐Argininestern mit Bis‐[4‐nitro‐benzyl]‐phosphorsäure‐chlorid und anschließende Hydrogenolyse der schützende Gruppen in 55‐proz. Ausbeute (bezogen auf N ‐Cbo‐Arginin) darstellen. Eine zweite Methode, nach der Ornithin in alkalisch‐wäß‐riger Lösung mit Isoureidophosphonat (VII) umgesetzt wird, liefert eine 75‐proz. Ausbeute an Argininphosphorsäure (I). Diese Reaktion ist allgemein zur Darstellung von Guanididophosphonaten geeignet; so entsteht Glykocyaminphosphorsäure in 65‐proz. Ausbeute. Ebenso lassen sich die entsprechenden O ‐Benzyl‐guanididophosphonate (XI) durch Reaktion von O ‐Benzyl‐cyanamidophosphonat (X), O ‐Benzyl‐[ O ‐methyl‐isoureido]‐phosphonat (IXa) bzw. O ‐Benzyl‐[S‐methyl‐isothioureido]phosphonat (IXb) mit Aminen darstellen.
Exploring Connectivity of the Brain's White Matter with Dynamic Queries (2005)

Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging method that can be used to measure local information about the structure of white matter within the human brain. Combining DTI data with the computational methods of MR tractography, neuroscientists can estimate the locations and sizes of nerve bundles (white matter pathways) that course through the human brain. Neuroscientists have used visualization techniques to better understand tractography data, but they often struggle with the abundance and complexity of the pathways. In this paper, we describe a novel set of interaction techniques that make it easier to explore and interpret such pathways. Specifically, our application allows neuroscientists to place and interactively manipulate box or ellipsoid-shaped regions to selectively display pathways that pass through specific anatomical areas. These regions can be used in coordination with a simple and flexible query language which allows for arbitrary combinations of these queries using Boolean logic operators. A representation of the cortical surface is provided for specifying queries of pathways that may be relevant to gray matter structures and for displaying activation information obtained from functional magnetic resonance imaging. By precomputing the pathways and their statistical properties, we obtain the speed necessary for interactive question-and-answer sessions with brain researchers. We survey some questions that researchers have been asking about tractography data and show how our system can be used to answer these questions efficiently.
Biocatalytic hydroxylation of linoleic acid in a double-fed batch system with lipoxygenase and cysteine (1998)

The enzymatic large-scale preparation of unsaturated fatty acid hydroperoxides is the first step in the preparation of the corresponding fatty acid hydroxides. Since hydroxides are more suitable than hydroperoxides as precursors of fine chemicals like certain flavour compounds, a convenient and effective reduction step of hydroperoxides is required. In this paper a double-fed batch procedure for the enzymatic preparation of fatty acid hydroperoxides including the application of cysteine as a mild reducing agent is described. A crude extract from defatted soybean flour was used as the source of lipoxygenase, while the primary substrate was linoleic acid from hydrolyzed safflower oil. Enzyme and substrate were fed synchronously into the bioreactor that already contained buffer solution and cysteine. Typically, reactions with 40 g/l substrate in a 7 l reactor were done on a 2 l scale. Without any intermediate work-up, a final product yield of 90% could be achieved consisting for nearly 96% of 13(S)-hydroxy-(9Z,11E)-octadeca-9,11-dienoic acid. Biokatalytische Hydroxylierung von Linolsäure in einem doppelt gespeisten Chargensystem mit Lipoxygenase und Cystein Die enzymatische Aufarbeitung von ungesättigten Fettsäure-Hydroperoxiden im größeren Maßstab ist der erste Schritt in der Präparation der entsprechenden Fettsäure-Hydroxide. Da Hydroxide als Vorstufen hochwertiger Chemikalien, wie z. B. bestimmte Aromastoffe, besser geeignet sind als Hydroperoxide, ist ein bequemer und effizienter Reduktionsschritt notwendig. In dieser Arbeit wird ein doppelt gespeistes Chargenverfahren zur enzymatischen Herstellung von Fettsäure-Peroxiden, welches den Einsatz von Cystein als milde reduzierende Komponente berücksichtigt, beschrieben. Ein Rohextrakt aus entfettetem Sojabohnenmehl wurde als Quelle für die Lipoxygenase verwendet, wobei das erste Substrat Linolsäure aus hydrolysiertem Safloröl stammt. Enzym und Substrat wurden gemeinsam in einen Bioreaktor gegeben, der bereits Pufferlösung und Cystein enthält. Gewöhnlicherweise wurden die Reaktionen in einer Größenordnung von 2 l und einer Substratkonzentration von 40 g/l in einem 7 l Reaktor durchgeführt. Ohne jede zwischenzeitliche Aufarbeitung konnte eine Endproduktausbeute von 90% erzielt werden, die nahezu aus 96% 13(S)-Hydroxy-(9Z, 11E)-octadeca-9,11-diensäure bestand.
Augmentation of Pedicle Screw Fixation Strength Using an Injectable Calcium Sulfate Cement (2008)

Results of this study demonstrate that the injectable calcium sulfate cement can significantly improve the immediate POS of pedicle screw fixation, and this effect can be maintained even if the calcium sulfate cement has been absorbed completely, which may result from that the calcium sulfate cement resorption paralleled bone ingrowth.
Combining IR spectroscopy with fluorescence imaging in a single microscope: Biomedical applications using a synchrotron infrared source (invited) (2002)

It has become increasingly clear that infrared microspectroscopy (IRMS) can be an extremely valuable analysis tool when determining the chemical composition of biological and biomedical samples. Frequently, fluorescence illumination is required for sample characterization, and is usually achieved on a separate and dedicated optical microscope. We report the development and use of a single microscope for concomitant fluorescence and synchrotron IRMS. This unique combination has been used to identify changes in the composition of newly remodeled bone after the onset of osteoporosis, misfolded protein structure in Alzheimer’s disease, and cellular changes in apoptosis.
SDF-1 is both necessary and sufficient to promote proliferative retinopathy (2005)

Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell-derived factor-1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen-4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell-derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy.
High gradient magnetic cell separation with MACS (1990)

A flexible, fast and simple magnetic cell sorting system for separation of large numbers of cells according to specific cell surface markers was developed and tested. Cells stained sequentially with biotinylated antibodies, fluorochrome-conjugated avidin, and superparamagnetic biotinylated-microparticles (about 100 nm diameter) are separated on high gradient magnetic (HGM) columns. Unlabelled cells pass through the column, while labelled cells are retained. The retained cells can be easily eluted. More than 10(9) cells can be processed in about 15 min. Enrichment rates of more than 100-fold and depletion rates of several 1,000-fold can be achieved. The simultaneous tagging of cells with fluorochromes and very small, invisible magnetic beads makes this system an ideal complement to flow cytometry. Light scatter and fluorescent parameters of the cells are not changed by the bound particles. Magnetically separated cells can be analysed by fluorescence microscopy or flow cytometry or sorted by fluorescence-activated cell sorting without further treatment. Magnetic tagging and separation does not affect cell viability and proliferation.
Chemokines Regulate IL-6 and IL-8 Production by Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis (2001)

Abstract Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce inflammatory cytokines and chemokines. The expressed chemokines are thought to be involved in the migration of inflammatory cells into the synovium. In this study we show that CCL2/monocyte chemotactic protein-1, CCL5/RANTES, and CXCL12/stromal cell-derived factor-1 enhanced IL-6 and IL-8 production by fibroblast-like synoviocytes (FLS) from patients with RA, and their corresponding receptors, CCR2, CCR5, and CXCR4, respectively, were expressed by RA FLS. The chemokines stimulated RA FLS more effectively than skin fibroblasts. Culture with CCL2 enhanced phosphorylation of extracellular signal-related kinase 1 (ERK1) and ERK2, but not phosphorylation of p38 or Src. Moreover, activation of ERK1/2 was inhibited by pertussis toxin, a Gi-coupled protein inhibitor, and RS-504393, CCR2 antagonist, suggesting that ERK1/2 was activated by CCL2 via CCR2 and Gi-coupled protein. On the other hand, CCL2, CCL5, and CXCL12 were expressed on RA FLS, and their production was regulated by TNF-α, IL-1β, and TGF-β1. Our results indicate that the chemokines not only play a role in inflammatory cell migration, but are also involved in the activation of FLS in RA synovium, possibly in an autocrine or paracrine manner.
A direct transfer of layer-area graphene (2010)

A facile method is reported for the direct (polymer-free) transfer of layer-area graphene from metal growth substrates to selected target substrates. The direct route, by avoiding several wet chemical steps and accompanying mechanical stresses and contamination common to all presently reported layer-area graphene transfer methods, enables fabrication of layer-area graphene devices with unprecedented quality. To demonstrate, we directly transfer layer-area graphene from Cu growth substrates to holey amorphous carbon transmission electron microscopy (TEM) grids, resulting in robust, clean, full-coverage graphene grids ideal for high resolution TEM.
A novel sialyl LewisX analog attenuates neutrophil accumulation and myocardial necrosis after ischemia and reperfusion. (1994)

Our results provide strong evidence that treatment with a unique carbohydrate analog of SLeX, CY-1503, significantly reduces the degree of myocardial injury associated with coronary artery ischemia and reperfusion. The profound cardioprotection appears to be related to a reduction in PMN accumulation within the ischemic-reperfused myocardium. Additional studies investigating more-prolonged periods of reperfusion are required to determine whether CY-1503 treatment merely delays the onset or actually reduces the full extent of myocardial necrosis after ischemia and reperfusion.
Further Characterization of a Rice AGL12 Group MADS-Box Gene,OsMADS26 (2008)

Plant MADS-box genes can be divided into 11 groups. Genetic analysis has revealed that most of them function in flowering-time control, reproductive organ development, and vegetative growth. Here, we elucidated the role of OsMADS26, a member of the AGL12 group. Transcript levels of OsMADS26 were increased in an age-dependent manner in the shoots and roots. Transgenic plants of both rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana) overexpressing this gene manifested phenotypes related to stress responses, such as chlorosis, cell death, pigment accumulation, and defective root/shoot growth. In addition, apical hook development was significantly suppressed in Arabidopsis. Plants transformed with the OsMADS26-GR (glucocorticoid receptor) fusion construct displayed those stress-related phenotypes when treated with dexamethasone. Microarray analyses using this inducible system showed that biosynthesis genes for jasmonate, ethylene, and reactive oxygen species, as well as putative downstream targets involved in the stress-related process, were up-regulated in OsMADS26-overexpressing plants. These results suggest that OsMADS26 induces multiple responses that are related to various stresses.
Organic disulfides and related substances. 38. Disulfide and trisulfide sulfinate salts as antiradiation drugs (1975)

The trisulfide disulfinate [Na32S(CH2)4S]2S (2) is an antiradiation drug which is atypical in having no nitrogen function. At low dose levels of 37.5 and 18.5 mg/kg intraperitoneally (ip), 2 protected respectively about 82 and 35% of lethally irradiated mice. By the oral route (po), 150 mg/kg of 2 protected about 73%, and 75 mg/kg protected about 20%. The LD50 either ip or po exceeded 900 mg/kg. Although a 2,3-diacetoxy analog 3 was inactive, cyclic disulfide and trisulfide sulfinate analogs showed promice. Among these, a sulfinate moiety is related to a di- or trisulfie moiety in the sense of 1,8 in a naphthyl system (4,5), 2,2' in a biphenyl system (6-9), and alpha,alpha' in an o-xylyl system (10,11). The 1,8-naphthyl disulfide sulfinate 4 was not tested biologically because a marked neighboring group effect of -SO2Na on -SS- caused rapid cyclization to the parent disulfide dioxide 14; the corresponding trisulfide 5 was more stable but only slightly protective. Other analogs lacking the coplanarity of 4 also were more stable. The biphenyl compounds 6 and 7 were quite active ip (e.g., 7 led to 90% survival at 4.6 mg/kg, with LD50 EQUALS 130 mg/kg, although protection with 6 and 7 at the doses given po was only fair). Dichloro counterparts 8 and 9 offered no advantages over 6 and 7. The xylylene compounds 10 and 11 were roughly comparable to each other by ip and op routes (e.g., given ip, 10 led to 93-100% survival at 75 mg/kg, with LD50 GREATER THAN 950 mg/kg; given po, 10 gave 100% survival at 60 mg/kg, with LD50 GREATER THAN 900 mg/kg). Compounds 7 and 11 join 2 as promising antiradiation drugs that lack the usual nitrogen function. The fact that sulfinate salts show activity, both ip and po, suggests that the -SO2Na moiety deserves more attention in medicinal chemistry. Hydration of sulfinate salts often made analytical characterization difficult. Confirmatory evidence for typical structures is given.
Exploiting Linked Data to Build Web Applications (2009)

Semantic Web technologies have been around for a while. However, such technologies have had little impact on the development of real-world Web applications to date. With linked data, this situation has changed dramatically in the past few months. This article shows how linked data sets can be exploited to build rich Web applications with little effort.
Vascular effects of cigarette smoke in isolated pig lungs. (1981)

To determine the local effects of cigarette smoke on the pulmonary vasculature, we measured pulmonary artery pressure--flow curves in isolated, blood-perfused pig lungs before and after 4 exposures to cigarette smoke. During each exposure, smoke was administered into the trachea for 3 to 4 min at a rate of 20 to 25 puffs/min and a puff volume of 35 to 50 ml with a smoking machine. During hypoxia (inspired PO2, 50 mmHg), when baseline vasomotor tone was high, cigarette smoke caused an acute transient vasodilation. During control (inspired PO2, 200 mmHg), when baseline tone was low, no significant effect was observed. In addition to this acute effect, cigarette smoke caused a depression of the pulmonary pressor response to hypoxia, which developed gradually during the course of the experiment. Indomethacin, at perfusate concentrations of 20 and 100 micrograms/ml, did not significantly alter the acute vasodilating effect of smoking, suggesting that prostaglandins synthesized by cyclooxygenase were not the mediators of this response. Indomethacin did, however, prevent the gradual depression of the pulmonary vasoconstrictor response to hypoxia.
Absolute configuration and conformation of the pure opioid antagonist (+)‐2,9α‐dimethyl‐5‐(m‐hydroxyphenyl)morphan (1992)

(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program.