gebhart/patrepeval huggingface dataset:
Vaccinia virus recombinants expressing either the measles virus fusion or hemagglutinin glycoprotein protect dogs against canine distemper virus challenge (1991)

cDNA clones of the genes encoding either the hemagglutinin (HA) or fusion (F) proteins of the Edmonston strain of measles virus (MV) were expressed in vaccinia virus recombinants. Immunofluorescence analysis detected both proteins on the plasma membranes of unfixed cells as well as internally in fixed cells. Immunoprecipitation of metabolically radiolabeled infected-cell extracts by using specific sera demonstrated a 76-kDa HA polypeptide and gene products of 60, 44, and 23 kDa which correspond to a MV F precursor and cleavage products F0, F1, and F2, respectively. Neither recombinant induced cell fusion of Vero cells when inoculated individually, but efficient cell fusion was readily observed upon coinfection of cells with both recombinants. Inoculation of dogs with the vaccinia virus-MV F recombinant (VV-MVF) did not give rise to detectable MV-neutralizing antibody. Inoculation of dogs with the vaccinia virus-MV HA recombinant (VV-MVHA) or coinoculation with both recombinants (VV-MVF and VV-MVHA) induced significant MV-neutralizing titers that were increased following a booster inoculation. Inoculation of dogs with the vaccinia virus recombinants or with MV failed to induce canine distemper virus (CDV)-neutralizing antibodies. Upon challenge with a lethal dose of virulent CDV, signs of infection were observed in dogs inoculated with (VV-MVF). No symptoms of disease were observed in dogs that had been vaccinated with VV-MVHA or with VV-MVHA and VV-MVF and then challenged with CDV. All dogs vaccinated with the recombinant viruses as well as those inoculated with MV or a vaccine strain of CDV survived CDV challenge.
Increased Interleukin-1 and Interleukin-6 Serum Concentrations in Severe Primary Pulmonary Hypertension (1995)

Primary pulmonary hypertension (PPH) is characterized by the proliferation of smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with severe PPH referred to our center for lung transplantation. Results were compared with those obtained in 15 normal controls and nine patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF alpha serum levels were within the normal range in each group. This contrasted with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/- SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3 +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and suggests a role for proinflammatory cytokines in PPH.
Multiplex high-throughput solid-phase minisequencing by capillary electrophoresis and liquid core waveguide fluorescence detection (2002)

Minisequencing, solid-phase single-nucleotide primer extension reaction, is a robust method for performing multiplex single-nucleotide polymorphism (SNP) analysis. We have combined this technology with capillary gel electrophoresis in a multicapillary format, using liquid core waveguide (LCW) fluorescence detection. Polymerase chain reaction (PCR) amplification of multiple DNA targets is performed with one primer for each target biotinylated. Separation of the complementary strands, minisequencing and washing steps are carried out using streptavidin-coated magnetic beads. Dideoxynucleotides analogues labelled with different fluorophores are used for the extension of the minisequencing primers. The extended oligonucleotides, the length of which defines the position on the target and the color the identity of the polymorphism, are then separated in a gel-filled array of capillaries, coated on the outside with a layer of a fluoropolymer to provide the liquid core waveguide characteristics. The technology has a potential for extremely high throughputs when a combination of multiplex PCR-minisequencing is used together with a large array of capillaries, four-color detection and high-speed separation.
From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer (2006)

Cancer is a hyperproliferative disorder that involves transformation, dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. Extensive research during the last 30 years has revealed much about the biology of cancer. Drugs used to treat most cancers are those that can block cell signalling, including growth factor signalling (e.g., epidermal growth factor); prostaglandin production (e.g., COX-2); inflammation (e.g., inflammatory cytokines: NF-kappaB, TNF, IL-1, IL-6, chemokines); drug resistance gene products (e.g., multi-drug resistance); cell cycle proteins (e.g., cyclin D1 and cyclin E); angiogenesis (e.g., vascular endothelial growth factor); invasion (e.g., matrix metalloproteinases); antiapoptosis (e.g., bcl-2, bcl-X(L), XIAP, survivin, FLIP); and cellular proliferation (e.g., c-myc, AP-1, growth factors). Numerous reports have suggested that Ayurvedic plants and their components mediate their effects by modulating several of these recently identified therapeutic targets. However, Ayurvedic medicine requires rediscovery in light of our current knowledge of allopathic (modern) medicine. The focus of this review is to elucidate the Ayurvedic concept of cancer, including its classification, causes, pathogenesis and prevention; surgical removal of tumours; herbal remedies; dietary modifications; and spiritual treatments.
Immunophilin ligands demonstrate common features of signal transduction leading to exocytosis or transcription. (1991)

Investigations of the actions and interactions of the immunophilin ligands FK506, cyclosporin A (CsA), rapamycin, and 506BD suggest that complexes of FK506 with an FK506-binding protein or of CsA with a cyclophilin (CsA-binding protein) inhibit the T-cell receptor-mediated signal transduction that results in the transcription of interleukin 2. Now we report an identical spectrum of activities of FK506, CsA, rapamycin, and 506BD on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from the rat basophilic leukemia cell line RBL-2H3, a mast cell model. Both FK506 and CsA inhibit receptor-mediated exocytosis (CsA IC50 = 200 nM; FK506 IC50 = 2 nM) without affecting early receptor-associated events (hydrolysis of phosphatidylinositol, synthesis and release of eicosanoids, uptake of Ca2+). In contrast, rapamycin and 506BD, which share common structural elements with FK506, by themselves have no effect on IgE receptor-mediated exocytosis. Both compounds, however, prevent inhibition by FK506 but not by CsA. Affinity chromatography with FK506, CsA, and rapamycin matrices indicates that the same set of immunophilins present in RBL-2H3 cells have been found in Jurkat T cells and calf thymus; however, the relative amounts of these proteins differ in the two cell types. These results suggest the existence of a common step in cytoplasmic signaling in T cells and mast cells that may be part of a general signaling mechanism.
Building Blocks for N-Type Molecular and Polymeric Electronics. Perfluoroalkyl- versus Alkyl-Functionalized Oligothiophenes (nTs; n = 2−6). Systematic Synthesis, Spectroscopy, Electrochemistry, and Solid-State Organization (2004)

The synthesis, comparative physicochemical properties, and solid-state structures of five oligothiophene (nT) series differing in substituent nature and attachment, regiochemistry, and oligothiophene core length (n) are described. These five series include the following 25 compounds: (i) alpha,omega-diperfluorohexyl-nTs 1 (DFH-nTs, n = 2-6), (ii) beta,beta'-diperfluorohexyl-nTs 2 (isoDFH-nTs, n = 2-6), (iii) alpha,omega-dihexyl-nTs 3 (DH-nTs, n = 2-6), (iv) beta,beta'-dihexyl-nTs 4 (isoDH-nTs, n = 2-6), and (v) unsubstituted oligothiophenes 5 (alphanTs, n = 2-6). All new compounds were characterized by elemental analysis, mass spectrometry, and multinuclear NMR spectroscopy. To probe and address quantitatively how the chemistry and regiochemistry of conjugated core substitution affects molecular and solid-state properties, the entire 1-5 series was investigated by differential scanning calorimetry, thermogravimetric analysis, and optical absorption and emission spectroscopies. Single-crystal X-ray diffraction data for several fluorocarbon-substituted oligomers are also presented and compared. The combined analysis of these data indicates that fluorocarbon-substituted nT molecules strongly interact in the condensed state, with unit cell level phase separation between the aromatic core and fluorocarbon chains. Surprisingly, despite these strong intermolecular interactions, high solid-state fluorescence efficiencies are exhibited by the fluorinated derivatives. Insight into the solution molecular geometries and conformational behavior are obtained from analysis of optical and variable-temperature NMR spectra. Finally, cyclic voltammetry data offer a reliable picture of frontier MO energies, which, in combination with DFT computations, provide key information on relationships between oligothiophene substituent effects and electronic response properties.
The C Terminus of the Human Nicotinic α4β2 Receptor Forms a Binding Site Required for Potentiation by an Estrogenic Steroid (2001)

In addition to actions mediated by changes in gene expression, steroids can directly modulate several transmitter-gated and voltage-gated ion channels. Despite numerous studies showing that steroids enhance or reduce ion channel activity, the site(s) that mediates steroid recognition is not known. To identify the regions in which steroids bind and affect ion channel activity, we have taken advantage of the observation that human alpha4beta2 neuronal nicotinic receptors are potentiated by an estrogen steroid, 17beta-estradiol, whereas a rat alpha4beta2 receptor is not. Mutations indicate that a sequence (AGMI) at the end of the C terminus of the human alpha4 subunit forms a binding site required for 17beta-estradiol potentiation. In contrast, ethynyl beta-estradiol (an oral contraceptive) potentiates both human and rat alpha4beta2 receptors. A single tryptophan in the C terminus of both the rat and the human alpha4 subunit is sufficient for potentiation by ethynyl beta-estradiol, probably through a pi-pi interaction. Mutation of this tryptophan eliminates the ability of ethynyl beta-estradiol to potentiate rat receptors. However, in human receptors it was necessary to mutate both the AGMI sequence and the tryptophan to eliminate potentiation by ethynyl beta-estradiol. The findings that beta-estradiol requires the AGMI sequence but that a single C-terminal tryptophan is sufficient for potentiation by ethynyl beta-estradiol indicate that the C terminus forms a binding site for these steroids. The binding site(s) for block appears to differ from those involved in potentiation because the C-terminal sequence does not affect block by steroids such as progesterone, and progesterone does not competitively inhibit potentiation.
From Laboratory to Field. Using Information from Arabidopsis to Engineer Salt, Cold, and Drought Tolerance in Crops (2004)

After almost a century since its first appearance in the scientific literature, Arabidopsis has now been widely adopted as a model plant of choice for biological research ([Somerville and Koornneef, 2002][1]). Its many advantages include a small genome, short life cycle, small stature, prolific seed
Studies on Foliar Penetration (1970)

The evaluation of the factors controlling the penetration of 4-amino-3,5,6-trichloropicounic acid (picloram), containing 14C in the carboxyl group, into leaves of Phaseolus vulgaris is complicated by the ability of the leaf tissue to decarboxylate the compound rapidly. The degradation system becomes fully activated only after some hours following treatment with picloram while the capacity for decarboxylation declines with the age of the leaf. When allowance for decarboxylation is made, the pattern of penetration for picloram resembles in particular that of 2,2-dichloropropionic acid (dalapon). At the abaxial surface penetration continues over 24 h at a fairly constant rate but in light, which enhances penetration, a ‘surge’occurs between the second and sixth hour. Raising the external concentration promotes penetration and in light entry is directly proportional to concentration up to at least 2.5 × 10−l M. The response to varying light intensity resembles that of dalapon rather than 2,4-D. Even low intensities promote penetration; the effect is maximal at about 10 000 lx at the abaxial surface but continues at least up to 20 000 lx at the adaxial surface. Penetration is retarded at 4°C but the decarboxylation system remains functional. In light, but not in darkness, penetration is strikingly reduced by 3-(3,4-dichlorophenyl)-l,l-dimethylurea (DCMU). Raising the external pH from 4.2 to 7.2 retards entry. It is concluded that the factors which determine the penetration of picloram into Phaseolus leaves also control the entry of a wide range of organic compounds and inorganic ions.
Production of lycopene by the food yeast,Candida utilis that does not naturally synthesize carotenoid (1998)

The Erwinia uredovora crtE, crtB, and crtI genes, which are responsible for the synthesis of carotenoid lycopene from farnesyl pyrophosphate, were expressed in Candida utilis under the control of the promoters and terminators derived from the C. utilis GAP, PGK, and PMA genes, respectively. The yeast transformant carrying the carotenoid biosynthesis genes produced 758 microg/g dry weight of lycopene along with 407 microg/g dry weight of phytoene in the stationary phase. It was observed in the C. utilis transformant that ergosterol content was decreased to 65% of that in the parent strain that accumulated 6.04 mg/g dry weight of ergosterol. It is therefore possible that the carbon flux for the ergosterol biosynthesis has been branched at farnesyl pyrophosphate to generate a new pathway for the lycopene production in this yeast transformant.
Reproducible Measurement of Single-Molecule Conductivity (2001)

A reliable method has been developed for making through-bond electrical contacts to molecules. Current-voltage curves are quantized as integer multiples of one fundamental curve, an observation used to identify single-molecule contacts. The resistance of a single octanedithiol molecule was 900 +/- 50 megohms, based on measurements on more than 1000 single molecules. In contrast, nonbonded contacts to octanethiol monolayers were at least four orders of magnitude more resistive, less reproducible, and had a different voltage dependence, demonstrating that the measurement of intrinsic molecular properties requires chemically bonded contacts.
Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice (2004)

Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor-promoting effects. We first determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase-2. We also found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF-kappaB and IKKalpha and phosphorylation and degradation of IkappaBalpha. We next assessed the effect of skin application of PFE on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA-treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE-treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskin-tumor-promoting effects in CD-1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPA-induced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in-depth study to define active agent(s) in PFE capable of affording antitumor-promoting effect is warranted.
Substrate specificity of trypsin investigated by using a genetic selection. (1990)

The structural determinants of the primary substrate specificity of rat anionic trypsin were examined by using oligonucleotide-directed mutagenesis coupled to a genetic selection. A library was created that encoded trypsins substituted at amino acid positions 189 and 190 at the base of the substrate binding pocket. A genetic selection, with a dynamic range of 5 orders of proteolytic activity, was used to search 90,000 transformants of the library. Rapid screening for arginyl amidolysis and esterolysis confirmed the activity of the purified isolates. Trypsin and 15 mutant trypsins with partially preserved function were identified and characterized kinetically on arginyl and lysyl peptide substrates. Alternative arrangements of amino acids in the substrate binding pocket sustained efficient catalysis. A negative charge at amino acid position 189 or 190 was shown to be essential for high-level catalysis. With the favored aspartic acid residue at position 189, several amino acids could replace serine at position 190. Modulation of the specificity for arginine and lysine substrates was shown to depend on the amino acid at position 190. The regulatory effect of the amino acid side chain at position 190 on the substrate specificity is also reflected in substrate binding pockets of naturally occurring trypsin homologs.
Interferometric contrast between resonant coherent anti-Stokes Raman sattering and nonresonant four-wave mixing (2004)

Utilizing interferometry, we distinguish between resonant CARS and nonresonant four wave mixing, a pernicious problem of CARS microscopy. An optical parametric amplifier creates a coherent reference beam to demodulate the temporal CARS signal from acetone, sensitive to its concentration.
Identification of an Opioid κ Receptor Subtype-Selective N-Substituent for (+)-(3R,4R)-Dimethyl-4-(3-hydroxyphenyl)piperidine (1998)

A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-¿(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl¿-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor.
The DAWN (Diabetes Attitudes, Wishes and Needs) study (2002)

Abstract Interim report on a global diabetes psychosocial research initiative, organised by Novo Nordisk in collaboration with the International Diabetes Federation and under the supervision of an expert international Scientific Advisory Panel Copyright © 2002 John Wiley &amp; Sons, Ltd.
Disappointing Durable Remission Rates in Complex Crohnʼs Disease Fistula (2014)

Only the minority of CD complex perianal fistulas were in remission after conventional treatment strategies after a median follow-up of 10 years. Simple fistulas were more likely to heal than complex fistulas, and less of these healed fistulas relapsed. However, more than 3 quarters of the patients had complex perianal fistulas.
Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. (1995)

We investigated the role of gp39-CD40 interaction in the development of glomerulonephritis in lupus mice. In contrast to normal mice, lupus mice had much higher percentages of intensely gp39+ T cells in their spleens even at the preautoimmune age of 1 mo, and the further increase in gp39 expression by anti-CD3 Ab stimulation was markedly greater in lupus T cells. The pathogenic autoantibody-inducing ability of Th clones and splenic Th cells from lupus mice could be blocked in vitro by anti-gp39 Ab. Acceleration of lupus nephritis by the transfer of pathogenic autoantibody-inducing Th clones in vivo could also be completely blocked by anti-gp39 Ab. Surprisingly, a brief treatment of lupus mice with anti-gp39 Ab had a sustained beneficial effect on their spontaneous disease long after the Ab had been cleared from their systems. Only three injections of anti-gp39 Ab given to prenephritic lupus mice at 3 mo of age markedly delayed and reduced the incidence of lupus nephritis up to 12 mo of age by which time almost all the control mice had developed severe glomerulonephritis. Remarkably, pathogenic Th cells were left intact in these anti-gp39-treated mice but their B cells could not produce pathogenic autoantibodies even 9 mo after the therapy. Our studies suggest that blocking the interaction between gp39 on pathogenic Th cells and CD40 on lupus B cells at a crucial window of time delays the expansion autoimmune memory B cells resulting in long-term therapeutic benefits.