gebhart/patrepeval huggingface dataset:
Comparison of flurpiridaz F 18 and FDG for assessment of left ventricular tissue mass following myocardial infarction in rats (2011)

1097 Objectives 18F fluorodeoxyglucose (FDG) cardiac imaging has been used to assess myocardial viability. Flurpiridaz F 18 is a newly developed PET myocardial perfusion imaging agent and its heart uptake shows a high agreement with flow at both cardiac stress and rest conditions. This study compared the non-defect tissue mass of the left ventricle measured by flurpiridaz F 18 imaging with the viable tissue mass detected by FDG imaging in normal and myocardial infarcted (MI) rats. Methods MI was induced in rats by 30 minutes of left coronary occlusion followed by reperfusion. Flurpiridaz F 18 (1 mCi) and FDG (1 mCi) cardiac imaging (2 days apart) was performed in rats before, two days (early MI) and four weeks (late MI) post surgery. A regimen of glucose and insulin was injected before FDG imaging to ensure optimal cardiac uptake. The non-defect or viable left ventricular mass was quantified as the myocardium having ≥50% of maximum activity from images acquired at 20-30 minutes post injection. Results In control rats before surgery, cardiac imaging with both flurpiridaz F 18 and FDG showed a well-defined left ventricular wall and the left ventricular tissue mass was measured as 1.17±0.04 and 1.11±0.07 cm3, respectively. In early and late stage MI rats, the myocardial defect area was clearly identified by imaging with both agents. The non-defect left ventricular tissue mass measured with flurpiridaz F 18 was slightly larger than the viable tissue mass measured with FDG at early (0.94±0.01 vs. 0.75±0.04 cm3) and late stage MI (1.18±0.04 vs. 0.99±0.09 cm3). In addition, flurpiridaz F 18 imaging showed similar non-defect left ventricular areas at 20 and 80 minutes post injection (suggesting no redistribution and refill-in) in both early and late stage MI. Conclusions Based on the left ventricular mass measured by the two imaging agents in MI, flurpiridaz F 18 may have the potential to be used to assess myocardial viability
Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors (2016)

A series of macrocyclic analogues were designed and synthesized based on the cocrystal structure of small molecule plasma kallikrein (pKal) inhibitor, <b>2</b>, with the pKal protease domain. This led to the discovery of a potent macrocyclic pKal inhibitor <b>29</b>, with an IC<sub>50</sub> of 2 nM for one olefinic isomer and 42.3 nM for the other olefinic isomer.
Histone Deacetylase Inhibitors: The Abbott Experience (2003)

Histone deacetylase inhibitors have generated significant interest as anti-cancer agents due to their ability to cause growth arrest, terminal differentiation and/ or apoptosis in carcinoma cells. Abbott entered this area after the serendipitous discovery of the biaryl hydroxamate A-161906 in a TGF beta mimetic screen and the subsequent identification of this compound as an inhibitor of selected HDACs. The complex biology of these enzymes became evident when cloning and expression of the HDACs demonstrated that they were present as multiprotein and, in some cases, multi-HDAC containing complexes in their active forms. This discovery suggested that any selectivity determinations would have to be considered in the context of these multi-protein/HDAC complexes. However, siRNA gene knockdown studies did demonstrate that reduction of the Class I HDACs resulted in a phenotype similar to that observed with small molecule HDAC inhibitors. Evaluation of the Abbott small molecule HDAC inhibitors utilized a Class I HDAC (HDAC 1/2) preparation and antiproliferation assays using HT1080 fibrosarcoma and MDA435 breast carcinoma cells. Characterization of several series of hydroxamic acids indicated that while many of these analogs possessed potent enzymatic and cellular activity, in general these compounds had unacceptable pharmacokinetic profiles and marginal antitumor effects. Replacement of the potentially labile hydroxamic acid moiety with a trifluoromethyl ketone or a ketooxazole gave measurable HDAC potency but only modest cellular and in vivo activity. However, hydroxamate replacement with an alpha-ketoamide moiety provided potent HDAC inhibitors (IC(50) values as low as 3 nM) with excellent cellular activity (IC50 values < 0.2 microM) and measurable anti-tumor activity in a flank tumor growth model.
Public Declarations of Professionalism Professionalism Symposium (2000)

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.
Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or poly(dimethyl siloxane). III. In vivo biocompatibility and biostability (2002)

To investigate the effects of polymer chemistry and topology (linear or graft copolymer) on in vivo biocompatibility and biostability based on cage implant system, various hydrogels, composed of short hydrophilic [polyethylene oxide (PEO)] and hydrophobic block, were prepared by polycondensation reaction. Poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS) was chosen as a hydrophobic block because of their wide utilization as a biomaterial. By using the specimens retrieved from rats killed after 1, 2, 3, 5, and 7 weeks' implantation, cellular and material responses were assessed. Most hydrogels showed a comparable value of macrophage density to Pellethane(R), control polymer, whereas they did significantly lower foreign body giant cell (FBGC) density and coverage because of the presence of PEO. However, PEO block length and polymer topology did not affect macrophage adhesion and FBGC formation in our polymer composition. The hydrogel based on PDMS alone showed significantly lower macrophage density and FBGC density than Pellethane(R), indicating that PDMS plays a role in inhibiting cellular adhesion. The results obtained from gel permeation chromatography curve and Fourier transform infrared spectra exhibited that all the polymers were susceptible to oxidative degradation in vivo. Although Pellethane(R) revealed surface degradation by 5 weeks in vivo, hydrogels showed rapid degradation in the bulk within 2 weeks because of the penetration of oxidative chemicals released from phagocytic cells into PEO domain of phase-separated hydrogels. The more significant degradation was observed in the hydrogels with longer PEO block and PTMO as a hydrophobic block instead of PDMS. It was evident that the minor degradation could be achieved by grafting PEO and adopting PDMS as a hydrophobic block in the hydrogel.
Tenascin and fibronectin distribution in human normal and pathological synovium. (1992)

Tenascin is a glycoprotein found mainly in the extracellular matrix of developing and malignant tissues. The distribution of this molecule in normal and pathological synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was investigated by indirect immunofluorescence utilizing specific monoclonal antibodies. The same technique was used to study total fibronectin (tFn) in synovial tissues as well as ED-A and ED-B containing fibronectin (Fn) isoforms (A-Fn, B-Fn), generated by alternative splicing of pre-mRNA. Tenascin was found in normal synovium just beneath the whole lining cell layer. However, a higher density and spreading pattern of distribution was observed in OA and RA sections. A-Fn and B-Fn isoforms were prominent and widespread throughout the normal synovial lining; in hypercellular synovial lining (in RA and OA samples), A-Fn and B-Fn were also observed spreading in the sublining, as well as tFn.
Cloning and expression of a cDNA for mouse prostaglandin F receptor. (1994)

A functional cDNA clone for mouse prostaglandin (PG) F receptor was isolated from a mouse cDNA library using polymerase chain reaction based on the sequence of cloned prostanoid receptors, and cross-hybridization screening. The mouse PGF receptor consists of 366 amino acid residues with putative seven transmembrane domains. The sequence revealed the highest homology to the EP1 subtype of PGE receptor and thromboxane (TX) A2 receptor. Ligand binding studies using membranes of COS cells transfected with the cDNA revealed specific [3H]PGF2 alpha binding. The binding was displaced with unlabeled PGs in the order of PGF2 alpha = 9 alpha, 11 beta PGF2 > PGF 1 alpha > PGD2 > STA2 (a stable TXA2 agonist) > PGE2 > iloprost (a stable PGI2 agonist). PGF2 alpha increased inositol trisphosphate formation in a concentration-dependent manner in COS cells expressing PGF receptor. RNA blot and in situ hybridization analyses demonstrated that the PGF receptor transcripts are abundantly expressed in luteal cells of corpus luteum and in a lesser amount in kidney, heart, stomach, and lung.
Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities (1996)

PIC 024-4 and PRO 2000 are naphthalene sulfonate polymers that bind to CD4 with nanomolar affinity and block binding of gp120. Both have activity against human immunodeficiency virus type 1 in H9 cells, peripheral blood mononuclear cells, and primary monocyte/macrophages, are synergistic with zidovudine, and do not inhibit tetanus toxoid-stimulated T-cell proliferation at anti-human immunodeficiency virus type 1 concentrations.
Electrochemical Reduction of Oxygen at Pyrolyzed Iron and Cobalt N4-Chelates on Carbon Black Supports (2000)

Besides platinum, various nonnoble metal compounds, when prepared appropriately, are suitable for the electrochemical reduction of oxygen in liquid electrolytes and PEM-fuel cells. Pyrolyzed N4-chelates, such as phthalocyanines, tetraazaannulenes and porphyrins with a central metal atom of iron or cobalt, are a very important group of compounds and have been investigated in the past. It was found that the catalytic activity, especially of phthalocyanines, was high when prepared on carbon black supports at high temperatures (400–900 °C). Investigations on tetraazaannulenes and porphyrins yielded similar results. Non-noble metal compounds of cyclame (1,4,8,11-tetraazacyclotetradecane), which are also N4-chelates, were not investigated as thoroughly. However, the catalytic activities of iron and cobalt cyclames were low, compared to those of phthalocyanines. With the (GC-MS) analysis of both decomposition products, it could be shown that the mechanism of the N4-chelate decomposition is of decisive importance for the catalytic activity.
Clinical evaluation of aortic coarctation with 4D flow MR imaging (2010)

4D Flow is a fast and reliable means of evaluating collateral blood flow in patients with aortic coarctation in order to establish hemodynamic significance. It also can detect distorted blood flow patterns in the descending aorta after coarctation repair.
Enantioselective Reductive Cyclization of 1,6-Enynes via Rhodium-Catalyzed Asymmetric Hydrogenation:  C−C Bond Formation Precedes Hydrogen Activation (2005)

Asymmetric hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alkylidene-substituted carbocycles and heterocycles in a completely atom economical fashion. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. Mechanistic studies involving hydrogen-deuterium crossover experiments, along with the observance of nonconjugated cycloisomerization products 14c and 15c, suggest rhodium(III) metallocyclopentene formation occurs in advance of hydrogen activation. This oxidative coupling-hydrogenolytic cleavage motif should play a key role in the design of related hydrogen-mediated couplings.
Has Programmed Trading Made Stock Prices More Volatile? (1987)

Numerous commentators have claimed that the recent application of computer techniques to monitor price differences and trigger trades between the spot, futures and options markets for stocks (called programmed trading) has increased the volatility of stock prices.
Characterization of phosphorus content of biological samples by ICP-DRC-MS: potential tool for cancer research (2004)

Phosphorus and sulfur are detected as phosphorus oxide and sulfur oxide ions (PO+ and SO+), produced by oxidation reactions with O2 performed in the reaction cell of the inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS), at sub-ng mL−1 detection limits. This allows pM mL−1 detection of phospho-proteins, with S used as an internal standard (see ref. 9). The method was applied to digests (in HCl) of in-vitro tyrosine kinase assays, both as an evaluation of kinase autophosphorylation and phosphorylation of substrate. Detecting the phosphorus/sulfur ratio (via measured PO+/SO+) in cell cultures is shown to provide a distinguishable difference between malignant cell lines and primary cultures. The PO+/SO+ ratio for human colorectal adenocarcinoma (CRC) tissue samples compared with matched normal (N) tissue samples from the same patients is shown to be higher, at (PO+/SO+)CRC/(PO+/SO+)N = 1.75 ± 0.18 (n = 4). Samples used in this analysis were of needle biopsy amounts (0.2–0.5 mg), with a greater than 70% tumor burden in CRC. The phospho-protein phosvitin is detected directly from dried one-dimensional polyacrylamide gels using laser ablation ICP-MS by detecting phosphorus at sub-nM amounts. The phosphorus detection limit for direct ablation, assessed from ablating gel doped with P and blank gel, is 0.6 µg g−1 in gel. Direct detection of sulfur from the gels is obscured by the high sulfur background for the blank gels, which is attributed to the sulfur-containing catalysts used in polymerization and to sodium dodecyl sulfate (SDS) used for protein denaturing.
Doubling the Size of the Glucocorticoid Receptor Ligand Binding Pocket by Deacylcortivazol (2007)

A common feature of nuclear receptor ligand binding domains (LBD) is a helical sandwich fold that nests a ligand binding pocket within the bottom half of the domain. Here we report that the ligand pocket of glucocorticoid receptor (GR) can be continuously extended into the top half of the LBD by binding to deacylcortivazol (DAC), an extremely potent glucocorticoid. It has been puzzling for decades why DAC, which contains a phenylpyrazole replacement at the conserved 3-ketone of steroid hormones that are normally required for activation of their cognate receptors, is a potent GR activator. The crystal structure of the GR LBD bound to DAC and the fourth LXXLL motif of steroid receptor coactivator 1 reveals that the GR ligand binding pocket is expanded to a size of 1,070 A(3), effectively doubling the size of the GR dexamethasone-binding pocket of 540 A(3) and yet leaving the structure of the coactivator binding site intact. DAC occupies only approximately 50% of the space of the pocket but makes intricate interactions with the receptor around the phenylpyrazole group that accounts for the high-affinity binding of DAC. The dramatic expansion of the DAC-binding pocket thus highlights the conformational adaptability of GR to ligand binding. The new structure also allows docking of various nonsteroidal ligands that cannot be fitted into the previous structures, thus providing a new rational template for drug discovery of steroidal and nonsteroidal glucocorticoids that can be specifically designed to reach the unoccupied space of the expanded pocket.
Purification of Soybean Mosaic Virus by Affinity Chromatography Using Monoclonal Antibodies (1986)

Summary Immunoaffinity columns were prepared by covalently binding monoclonal antibodies specific for soybean mosaic virus (SMV) to an agarose support matrix. SMV, purified by binding and elution, contained no contaminating proteins detectable by SDS-polyacrylamide gel electrophoresis. Affinity-purified SMV was essentially identical to virus purified by standard procedures in its infectivity, u.v. absorbance spectrum ratio of A 280/A 260, sedimentation coefficient, electrophoretic pattern of coat protein, morphology and antigenicity. This method of purification is rapid, reproducible, and yields highly purified virus preparations. It may therefore be applicable in the purification of a wide variety of plant viruses.
Complement Protein Isoforms in CSF as Possible Biomarkers for Neurodegenerative Disease (2005)

It has been suggested that the activation of the complement system is involved in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Here, the CSF expression levels of complement proteins C3b, C4b, factor B, and factor H were compared between normal subjects and patients diagnosed with AD, PD, MS, and neurosyphilis. The CSF proteins were initially separated using two-dimensional gel electrophoresis, which allowed the comparison of some of the individual complement isoforms. Patients with AD, PD, and MS all showed more than one complement isoform with a significant change (p < 0.05) in CSF expression level compared to normal subjects. PD patients were found to have the greatest number of significantly changed isoforms, all showing a decreased expression level in PD CSF. The complement isoforms examined were able to distinguish between some, but not all, of the diseases studied. The data suggest that when investigating a protein as a possible biomarker, it may be useful to compare individual protein isoform expression levels in addition to the more commonly measured total protein expression level.
Correction: Identifying and Characterizing Nodes Important to Community Structure Using the Spectrum of the Graph (2011)

Background: Many complex systems can be represented as networks, and how a network breaks up into subnetworks or communities is of wide interest. However, the development of a method to detect nodes important to communities that is both fast and accurate is a very challenging and open problem.
KIT Mutations Induce Intracellular Retention and Activation of an Immature Form of the KIT Protein in Gastrointestinal Stromal Tumors (2008)

These results show that GIST-type KIT mutations induce an activation-dependent alteration of normal maturation and trafficking, resulting in the intracellular retention of the activated kinase within the cell. These observations likely account for the absence of correlation between response to imatinib and KIT expression using immunohistochemistry and may deserve to be investigated in other tyrosine kinase-activated tumors.
Annular Josephson tunnel junctions in an external magnetic field: The dynamics (1997)

We have investigated the dynamical states in annular Josephson tunnel junctions in the presence of an externally applied uniform magnetic field parallel to the barrier plane. For electrically small and overdamped junctions we show that the Kulik perturbative theory for the Fiske singularities can easily and successfully be extended to the annular geometry even in the case of trapped fluxons. For electrically long annular junctions we present the results of the numerical simulations. Further, we report on the magnetic-field dependence of the amplitude of the so-called Fiske steps in specially designed high dissipation Nb/Al-${\mathrm{AlO}}_{\mathrm{x}}$-Al/Nb annular junctions having different normalized circumferences.
Multiple Immediate-Early Gene-Deficient Herpes Simplex Virus Vectors Allowing Efficient Gene Delivery to Neurons in Culture and Widespread Gene Delivery to the Central Nervous System In Vivo (2001)

Herpes simplex virus (HSV) has several potential advantages as a vector for delivering genes to the nervous system. The virus naturally infects and remains latent in neurons and has evolved the ability of highly efficient retrograde transport from the site of infection at the periphery to the site of latency in the spinal ganglia. HSV is a large virus, potentially allowing the insertion of multiple or very large transgenes. Furthermore, HSV does not integrate into the host chromosome, removing any potential for insertional activation or inactivation of cellular genes. However, the development of HSV vectors for the central nervous system that exploit these properties has been problematical. This has mainly been due to either vector toxicity or an inability to maintain transgene expression. Here we report the development of highly disabled versions of HSV-1 deleted for ICP27, ICP4, and ICP34.5/open reading frame P and with an inactivating mutation in VP16. These viruses express only minimal levels of any of the immediate-early genes in noncomplementing cells. Transgene expression is maintained for extended periods with promoter systems containing elements from the HSV latency-associated transcript promoter (J. A. Palmer et al., J. Virol. 74:5604-5618, 2000). Unlike less-disabled viruses, these vectors allow highly effective gene delivery both to neurons in culture and to the central nervous system in vivo. Gene delivery in vivo is further enhanced by the retrograde transport capabilities of HSV. Here the vector is efficiently transported from the site of inoculation to connected sites within the nervous system. This is demonstrated by gene delivery to both the striatum and substantia nigra following striatal inoculation; to the spinal cord, spinal ganglia, and brainstem following injection into the spinal cord; and to retinal ganglion neurons following injection into the superior colliculus and thalamus.
Multiplexed molecular interactions of nuclear receptors using fluorescent microspheres (2001)

This unique microsphere-based system is a sensitive and efficient method to simultaneously evaluate many receptor-coactivator interactions in a single assay volume. In addition, the system offers a powerful approach to study small molecule modulation of nuclear receptor binding.