gebhart/patrepeval huggingface dataset:
An amplified immunoperoxidase assay to detect bovine leukemia virus expression: development and comparison with other assays. (1985)

An amplified immunoperoxidase (AIP) assay using an avidin:biotin complex was developed to detect bovine leukemia virus (BLV) antigen expression in lymphocytes which had been cultured 24 h and fixed with acetone. Nonspecific reactions were eliminated by absorbing the test serum with 100% horse or cow serum. DNA synthesis inhibition did not decrease the number of AIP-positive cells, and there were no apparent preferential losses of major lymphocyte subpopulations during culture. Both viable and nonviable BLV-expressing cells were detected. Thus, the number of AIP-positive cells seems to be a good estimate of the minimum number of infected lymphocytes present in the uncultured blood cells. In direct comparisons, twice as many BLV-expressing cells were detected with the AIP assay as with an indirect immunofluorescence test. The AIP assay is as sensitive as the syncytia infectivity assay and only slightly less sensitive than an immunoperoxidase infectivity assay for detecting BLV-infected lymphocytes in the blood of infected cattle that were in early stages of infection and/or had low titers of antiviral antibodies. The AIP assay is the most sensitive, rapid, and reproducible procedure available for the identification of individual cells infected with BLV. This assay may be of great value in studies on the biology of BLV infection.
A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474 (1970)

1. Both MJ 1999 and AH 3474 protected guinea-pigs anaesthetized with urethane against ouabain-induced ventricular fibrillation.2. MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve.3. MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 x 10(-6)M (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain-induced fibrillation.4. MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q-Tc interval of the electrocardiogram in anaesthetized guinea-pigs. It is suggested that this effect contributes to anti-arrhythmic activity.5. At concentrations up to 80 x 10(-6)M AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 x 10(-6)M for chronotropic, and 162 x 10(-6)M for inotropic effects.
“Velcro” Engineering of High Affinity CD47 Ectodomain as Signal Regulatory Protein α (SIRPα) Antagonists That Enhance Antibody-dependent Cellular Phagocytosis (2015)

CD47 is a cell surface protein that transmits an anti-phagocytic signal, known as the "don't-eat-me" signal, to macrophages upon engaging its receptor signal regulatory protein α (SIRPα). Molecules that antagonize the CD47-SIRPα interaction by binding to CD47, such as anti-CD47 antibodies and the engineered SIRPα variant CV1, have been shown to facilitate macrophage-mediated anti-tumor responses. However, these strategies targeting CD47 are handicapped by large antigen sinks in vivo and indiscriminate cell binding due to ubiquitous expression of CD47. These factors reduce bioavailability and increase the risk of toxicity. Here, we present an alternative strategy to antagonize the CD47-SIRPα pathway by engineering high affinity CD47 variants that target SIRPα, which has restricted tissue expression. CD47 proved to be refractive to conventional affinity maturation techniques targeting its binding interface with SIRPα. Therefore, we developed a novel engineering approach, whereby we augmented the existing contact interface via N-terminal peptide extension, coined "Velcro" engineering. The high affinity variant (Velcro-CD47) bound to the two most prominent human SIRPα alleles with greatly increased affinity relative to wild-type CD47 and potently antagonized CD47 binding to SIRPα on human macrophages. Velcro-CD47 synergizes with tumor-specific monoclonal antibodies to enhance macrophage phagocytosis of tumor cells in vitro, with similar potency as CV1. Finally, Velcro-CD47 interacts specifically with a subset of myeloid-derived cells in human blood, whereas CV1 binds all myeloid, lymphoid, and erythroid populations interrogated. This is consistent with the restricted expression of SIRPα compared with CD47. Herein, we have demonstrated that "Velcro" engineering is a powerful protein-engineering tool with potential applications to other systems and that Velcro-CD47 could be an alternative adjuvant to CD47-targeting agents for cancer immunotherapy.
Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation (2004)

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line–derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase–positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.
p53 mutations in spontaneously immortalized 3T12 but not 3T3 mouse embryo cells. (1992)

We have asked whether p53 mutations are involved in the process of spontaneous immortalization of mouse embryo cells. Cells from Swiss mouse embryos were used to prepare 3T3 and 3T12 lines according to the protocol of Todaro & Green [(1963). J. Cell Biol., 17, 299-313]. After the cells emerged from crisis, p53 sequences were amplified by polymerase chain reaction (PCR) from both RNA and DNA. The sequence of the aggregated cDNA from each of six 3T3 lines showed no evidence of mutation. PCR-amplified p53 cDNA from two 3T3 lines was cloned, and individual clones in M13mp19 were partially sequenced. One cell ine showed a single, non-coding nucleotide change in 2/8 independent clones. Nine cDNA clones from the second 3T3 lines were sequenced, and no single nucleotide changes appeared more than once. The mutations which appeared only once were not detected in clones of genomic DNA. Since these apparent mutations are probably reverse transcriptase or Taq polymerase errors, we conclude that both the 3T3 lines contained only wild-type p53. In two out of three independent 3T12 lines however, missense mutations were readily observed in the aggregate cDNA sequence. Restriction fragment length polymorphism and Southern blot analyses of the genomic DNA indicated that these cells were homozygous for the mutations. The p53 protein molecules in four cell lines were analysed by immunoprecipitation: one 3T12 line showed the pattern of antibody reactivity characteristic of some p53 mutants, while the others displayed the wild-type pattern. We conclude that p53 mutations arise and are strongly selected for during immortalization according to the 3T12 but not the 3T3 protocol.
Serum B‐cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival (2012)

Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.
Evolution of a Unified, Stereodivergent Approach to the Synthesis of Communesin F and Perophoramidine (2014)

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Additionally, several novel and interesting intermediates en route to the target natural products, such as an intriguing propellane hexacyclic oxindole encountered in the communesin F sequence, are disclosed. Indeed, such unanticipated structures may prove to be convenient strategic intermediates in future syntheses.
Update on the Discovery and Development of Cholesteryl Ester Transfer Protein Inhibitors for Reducing Residual Cardiovascular Risk (2013)

Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester and triglycerides between plasma lipoprotein particles HDL and LDL/VLDL, resulting in equilibration between these lipoprotein fractions. Therapy that modulates HDL metabolism to increase HDL-c levels could be an effective strategy to reduce residual cardiovascular risk since it is estimated that for each mg/dL increase in plasma HDL cholesterol, there could be a 2-3% decrease in cardiovascular risk. Modification of the lipoprotein profile by CETP inhibitors is promising, but the beneficial effect of reducing coronary heart disease risk has not yet been proven. To date, four CETP inhibitors have advanced to phase 3 cardiovascular outcome clinical trials, and two have been terminated for off-target adverse effects and lack of efficacy. This perspective will summarize recent events, new research developments, and the discovery of new classes of CETP inhibitors.
A longitudinal study of gamma-interferon production by peripheral blood mononuclear cells from breast- and bottle-fed infants. (1986)

Production of gamma-interferon (gamma-IFN) in vitro by peripheral blood mononuclear cells (PBMC) from 15 breast-fed and 15 bottle-fed infants has been studied from birth to 9 months of age and compared with production by adult cells. Using a Terasaki plate microculture system with serum-free medium, PBMC were stimulated with staphylococcal enterotoxin A (SEA) and gamma-IFN production was assessed by an immunoradiometric assay. Cord blood mononuclear cells (CBMC) and PBMC from all infants secreted large quantities of gamma-IFN. The levels secreted did not change significantly with age over the 9 months of the study, nor did they differ from the levels secreted by adult cells. Cells from the bottle-fed infants secreted slightly more gamma-IFN than cells from breast-fed infants, but this difference was not significant. These results indicate that the potential for PBMC to secrete gamma-IFN in vitro is fully developed at birth in full-term infants and cannot therefore be further influenced by subsequent breast- or bottle-feeding. In addition, the greater susceptibility of infants than adults to certain bacterial and viral infections cannot be attributed to a deficiency in the potential of infant cells to secrete gamma-IFN in vitro.
Peptide Mimics of the M13 Coat Protein Transmembrane Segment (2000)

Sequence-specific noncovalent helix-helix interactions between transmembrane (TM) segments in proteins are investigated by incorporating selected TM sequences into synthetic peptides using the construct CKKK-TM-KKK. The peptides are of suitable hydrophobicity for spontaneous membrane insertion, whereas formation of an N-terminal S-S bond can bring pairs of TM helices into proximity and promote their parallel orientation. Using the propensity of the protein to undergo thermally induced alpha-helix --> beta-sheet transitions as a parameter for helix stability, we compared the wild type and mutant (V29A and V31A) bacteriophage M13 coat proteins with their corresponding TM peptide constructs (M13 residues 24-42). Our results demonstrated that the relevant helix-helix tertiary contacts found in the intact proteins persist in the peptide mimics. Molecular dynamics simulations support the tight "two in-two out" dimerization motif for V31A consistent with mutagenesis data. The overall results reinforce the notion of TM segments as autonomous folding domains and suggest that the generic peptide construct provides a viable reductionist system for membrane protein structural and computational analysis.
A carbohydrate domain common to both sialyl Le(a) and sialyl Le(X) is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1 (1991)

The specificity of endothelial cell leukocyte adhesion molecule-1, ELAM-1, for binding to a panel of carbohydrate structures was determined by a sensitive cell binding assay with immobilized synthetic glycoconjugates. ELAM-1 cDNA transfectants were found to bind Sialyl Lea (sialylated lacto-N-fucopentaose II) or sialylated Lewis a antigen (NeuAc alpha 2-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc), as well as or slightly better than Sialyl Lex (sialylated lacto-N-fucopentaose III) or sialylated Lewis X antigen (NeuAc alpha 2-3 Gal beta 1-4(Fuc alpha 1-3)GlcNAc). A monoclonal antibody, HECA-452, which has been identified recently as recognizing ELAM-1 ligands in addition to those containing Sialyl Lex, was also found to bind both Sialyl Lex and Sialyl Lea. Hard sphere exo-anomeric (HSEA) calculations were performed on these two hexasaccharides. The conformations indicate that Sialyl Lea and Sialyl Lex show a high degree of similarity in both the nonreducing and reducing termini. As Lea and Lex show much weaker reactivity, the determinants recognized by ELAM-1 and HECA-452 probably involve neuraminic acid and fucose residues which on one face of both Sialyl Lex and Sialyl Lea can be similarly positioned. The finding that Sialyl Lea is a potent ligand for ELAM-1 is important, as circulating Sialyl Lea and Sialyl Lex containing mucins which are elevated in the serum of many cancer patients may block leukocyte interactions with ELAM-1 and may contribute to the pathological immunodepression observed in these patients.
A hybrid-logic approach towards fault detection in complex cyber-physical systems (2010)

Existing data mining approaches to complex systems anomaly detection use uni-variate and/or multi-variate statistical hypothesis testing to assign anomaly scores to data streams associated with system components. The former approach assumes statistical independence of individual components, while the latter assumes substantial global systemic correlation. As a compromise between these two epistemological extremes, we present a data-mining approach hybridizing existing statistical techniques with theorem-proving methods to create a novel algorithm for anomaly detection, diagnosis and control in complex systems. Our algorithm takes sensor inputs from physical sensors providing system subcomponent performance data and outputs (i) a global systemic risk indicator and (ii) possible diagnosis hypotheses. We present results on three different systems, and in comparison with current state-of-the-art fault detection algorithms to demonstrate the viability of our approach. We ﬁnd that our algorithm proves robust towards increased data dimensionality in contrast with existing clustering-based fault detection methods and can also detect contextual faults that are undetectable using existing statistical techniques.
Synthesis and Biological Evaluation of Thiol-Based Inhibitors of Glutamate Carboxypeptidase II:  Discovery of an Orally Active GCP II Inhibitor (2003)

A series of 2-(thioalkyl)pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4.17.21). The inhibitory potency of these thiol-based compounds against GCP II was found to be dependent on the number of methylene units between the thiol group and pentanedioic acid. A comparison of the SAR of the thiol-based inhibitors to that of the phosphonate-based inhibitors provides insight into the role of each of the two zinc-binding groups in GCP II inhibition. The most potent thiol-based inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (IC(50) = 90 nM), was found to be orally bioavailable in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration.
Kinetics of Enzymatic Ring-Opening Polymerization of ε-Caprolactone in Supercritical Carbon Dioxide (2006)

The kinetics of enzymatic ring-opening polymerization (eROP) of ε-caprolactone in supercritical carbon dioxide (scCO2) was investigated using a new, high-pressure sampling autoclave. The polymerization was performed using Candida antarctica lipase B (CALB) as catalyst and was found to be approximately first order with respect to monomer up to 80% conversion. For the first time we have been able to present kinetic results on the eROP of caprolactone in scCO2. These results show that high molecular weight polymer could be obtained (up to 50 kDa) with polydispersities in the range of 2. The relatively poor molecular weight control was attributed to the large degree of enzyme-catalyzed transesterification that forms both cyclic species (intramolecular transesterification) and linear polymer (intermolecular transesterification). This effect has also been observed for eROP of ε-caprolactone in conventional solvents. The formation of cyclic oligomers of poly(caprolactone) (PCL) was investigated as a function of conversion, and comparisons were made to similar studies undertaken in conventional solvents.
Die Totalsynthese der Chinasäure (1954)

Abstract Chinasäure läßt sich auf einfache Weise synthetisieren, indem man ein in 4‐Stellung geeignet substituiertes Cyclohexanon‐Derivat über das Cyanhydrin in die entsprechende Oxazolidon‐Verbindung verwandelt, in 3‐, 4‐ und 5‐Stellung je eine Oxygruppe räumlich richtig einführt und das Reaktionsprodukt in die optischen Antipoden spaltet. Die Beobachtung, daß Chinasäure durch Erhitzen racemisierbar ist, wird theoretisch gedeutet.
65-W, 532-nm radiation by cw resonant external-cavity second-harmonic generation of an 18-W Nd:YAG laser in LiB_3O_5 (1991)

We report 6.5 W of TEM(00) cw 532-nm radiation generated by external resonant doubling in a LiB(3)O(5) crystal. An 18-W, cw, injection-locked single-frequency Nd:YAG laser was used to generate 532-nm second-harmonic output with a 3-dB heterodyne linewidth of 15 kHz.
Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy (2015)

Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.
A Versatile Synthesis of Block and Graft Copolymers by Bulk 'Living' Free Radical Procedures (1999)

The stability of alkoxyamine unimolecular initiators to a variety of reaction conditions, combined with the compatibility of nitroxide mediated 'living' free radical procedures with numerous functional groups, offers an unprecedented opportunity to prepare novel block and graft copolymer structures from a wide selection of different monomer units and chemistries. This unique feature is illustrated by three different approaches to block copolymers by solvent free 'living' radical polymerization; (i) controlled polymerization of macromonomers; (ii) formation of graft copolymers from multifunctional polymeric initiators; and (iii) synthesis of block copolymers by dual living polymerizations from a double headed initiator.
Danazol in treatment of angio-immunoblastic lymphadenopathy (1989)

The clinical manifestations of angio-immunoblastic lymphadenopathy (AILD) suggest that there is an abnormality in the immune system. Most patients with AILD die from opportunistic infections associated with lymphocyte depletion. As chemotherapy further increases the already high susceptibility of infections, the therapeutic management of AILD is difficult. The achievement of complete remission (CR) by the patient described here using a danazol-based regimen raises the hope that treatment of this disease with a noncytotoxic drug may be possible. The rationale behind and advantages of using danazol are discussed.
Multipurpose high sensitivity luminescence analyzer (LUANA): use in gel electrophoresis. (1996)

Many applications in molecular biology require the rapid and high-sensitivity detection of biological macromolecules. Here we describe a luminescence analyzer (LUANA), featuring xenon lamp-based illumination and a cooled CCD camera as detector. Luminescent samples (gels, membranes or microplates) are placed in a light-tight chamber, and computer software is used to control the camera and to display and analyze the images. LUANA can be used with a broad spectrum of excitation and emission wavelengths (200-1000 nm), allowing a choice of many fluorescent dyes and facilitating multicolor imaging. We show that LUANA is readily applicable to gel electrophoresis and highly sensitive; on gels we could detect < 100 fg of Cy5TM-labeled protein and 0.1 ng of plasmid DNA labeled with a fluorescent intercalator. We observed a linear response for sample concentrations differing by two orders of magnitude using a single acquisition time. This range could be further extended by using different acquisition times. We have also used LUANA in two-color imaging of DNA and for screening of antigen-antibody and peptide-protein complexes by gel bandshift.
A chiral poly(para-phenyleneethynylene) (PPE) derivative (1998)

We have investigated the chiroptical properties of novel PPEs containing chiral side chains. The synthesis of poly(2,5-bis[2-(S)-methylbutoxy]-1,4-phenyleneethynylene) (BMB-PPE) was achieved in a Heck-type aryl-aryl cross coupling (Mn = 10 000, Dp = 40). The very good solubility of BMB-PPE allows for a detailed study of its chiroptical properties. Our studies demonstrate that the bisignated CD spectra of BMB-PPE are associated with an intermolecular aggregation phenomena.