gebhart/patrepeval huggingface dataset:
Drug-Induced Headache: Long-Term Results of Stationary Versus Ambulatory Withdrawal Therapy (1999)

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 +/- 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p < 0.2). The main risk factors for a relapse were male sex (OR = 3.9, CI = 1.3-11.6), intake of combined analgesic drugs (OR = 3.8, CI = 1.4-10.3), administration of naturopathy (OR = 6.0, CI = 1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR = 1.9, CI = 0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.
Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors (2011)

National Institutes of Health (NIH)-sponsored screening centers provide academic researchers with a special opportunity to pursue small-molecule probes for protein targets that are outside the current interest of, or beyond the standard technologies employed by, the pharmaceutical industry. Here, we describe the outcome of an inhibitor screen for one such target, the enzyme protein phosphatase methylesterase-1 (PME-1), which regulates the methylesterification state of protein phosphatase 2A (PP2A) and is implicated in cancer and neurodegeneration. Inhibitors of PME-1 have not yet been described, which we attribute, at least in part, to a dearth of substrate assays compatible with high-throughput screening. We show that PME-1 is assayable by fluorescence polarization-activity-based protein profiling (fluopol-ABPP) and use this platform to screen the 300,000+ member NIH small-molecule library. This screen identified an unusual class of compounds, the aza-β-lactams (ABLs), as potent (IC(50) values of approximately 10 nM), covalent PME-1 inhibitors. Interestingly, ABLs did not derive from a commercial vendor but rather an academic contribution to the public library. We show using competitive-ABPP that ABLs are exquisitely selective for PME-1 in living cells and mice, where enzyme inactivation leads to substantial reductions in demethylated PP2A. In summary, we have combined advanced synthetic and chemoproteomic methods to discover a class of ABL inhibitors that can be used to selectively perturb PME-1 activity in diverse biological systems. More generally, these results illustrate how public screening centers can serve as hubs to create spontaneous collaborative opportunities between synthetic chemistry and chemical biology labs interested in creating first-in-class pharmacological probes for challenging protein targets.
Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (2014)

We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic acid receptor γ selective agonist), and the combination of these two drugs for the prevention of oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral-cavity and esophageal squamous-cell carcinoma previously generated in our laboratory. We observed decreased numbers of neoplastic tongue lesions and reduced lesion severity in the 4-NQO plus CD1530 (4N+C) and 4-NQO plus bexarotene plus CD1530 (4N+B+C) groups compared with the 4-NQO group. RNA-Seq analyses showed increases in transcripts in cell proliferation/cell cycle progression pathways in the 4-NQO vs. the untreated group. In addition, β-catenin and matrix metallopeptidase 9 (MMP9) protein levels and reactive oxygen species (ROS), as assessed by 4-hydroxynonenal (4-HNE) staining, were elevated in tongue tissues 17 wk after the termination of the 4-NQO treatment. The 4N+B, 4N+C, and 4N+B+C groups showed dramatically lower levels of β-catenin, MMP9, and 4-HNE staining compared with the 4-NQO group. The major reduction in 4-HNE staining in the retinoid treatment groups suggests a novel mechanism of action, reduction of ROS, by which bexarotene and CD1530 inhibit carcinogenesis.
The Linear Track Olfactometer : An Assay Device for Taxes of the German Cockroach, Blattella germanica (L.)(Dictyoptera : Blattellidae) toward Their Aggregation Pheromone (1985)

A T-shaped wind-tunnel olfactometer with a special wire pathway was designed and built to examine taxes of the German cockroach, Blattella germanica (L.) toward aggregation pheromonally odoured air or air current. Test animals were made to climb up to a T-junction on the wire and to choose a direction at one point. Chemotaxis and odour modulated anemotaxis were demonstrated in two different air-flow modes (C-mode and A-mode), respectively. Their shelter contaminated with their frass induced strong positive taxis in both modes in B. germanica nymphs. The preference toward the odour source was independent of the wind speed in the C-mode, whereas it correspondingly ascended with the increase of wind speed in the A-mode. The probit analysis on the excess proportion index and wind speed gave 0.86 cm/sec as the median effective stimulus level. Bilaterally antennectomized nymphs exhibited neither taxis, whereas those unilaterally antennectomized represented significant positive taxis toward the stimulus in both modes. The latter implied that besides tropotaxis, klinotaxis also participated in their orientation behaviour in both modes.
Reverse cholesterol transport (1991)

New research firmly establishes the reverse cholesterol transport pathway, which carries cholesterol through the high-density lipoprotein, as significant in normal cholesterol homeostasis. Modulation of this pathway by transgenic and pharmacological techniques indicates potential therapeutic functions for increased high-density lipoprotein levels in atherosclerosis.
Transmission and focusing of light in one-dimensional periodically nanostructured metals (2002)

In this paper we show how the optical properties of a metallic film can be tailored by one-dimensional periodically nanostructuring it which, in turn modifies the surface plasmon properties. The interaction of light with the surface plasmons can be used for two apparently opposite effects: trapping incident radiation into small volumes (in reflection gratings) and transmitting light very efficiently (in transmission gratings). A physical picture of the mechanisms involved, as well as dependences of the transmission and reflection spectra on wavelength, absorption and geometrical parameters of the grating, are provided.
Dynamic system representation of basic and nonlinear in parameters oscillatory motion gestures (2002)

We present a system for generation and recognition of oscillatory gestures. Inspired by gestures used in two representative human-to-human control areas, we consider a set of oscillatory (circular) motions and refine from them a 24 gesture lexicon. Each gesture is modeled as a dynamic system with added geometric constraints to allow for real time gesture recognition using a small amount of processing time and memory. The gestures are used to control a pan-tilt camera neck. The gesture lexicon is then enhanced to include nonlinear in parameter ("come here") gesture representations. An enhancement is suggested which would enable the system to be trained to recognized previously unidentified yet consistent human generated oscillatory motion gestures.
A metalevel architecture for knowledge-based neural network design (2002)

In this paper, the term knowledge-based neural network (NN) design is used to refer to all efforts at exploiting prior knowledge in neural network configuration and training. A variety of techniques have been proposed for this purpose; SCANDAL provides a workbench for evaluating and integrating these techniques. After a quick overview of three main approaches to NN design, we describe SCANDALS multi-agent, metalevel architecture as well as its strategies for maximizing the use of domain knowledge. To assess the impact of prior knowledge on NN performance, experiments were conducted comparing knowledge-based techniques with a search-based configuration algorithm. Results show that the use of prior knowledge in neural network design leads to both faster learning and improved generalization. More interestingly, this appears to hold even when domain knowledge and data are deficient; in such cases, knowledge is extracted from the available data and is used both to configure the network and to generate artificial training instances. This leads us to hope that time-consuming iterative search can be avoided even in knowledge-lean domains.
Detection of PCV3 in German wild boars (2019)

The data show a high prevalence of PCV3 and co-infections with PCV1 and PCV2 in German wild boars. The finding of PCV3 in both clusters suggests that the virus was introduced into the animal populations before Berlin was divided. Furthermore, the methods used will be indispensable for screening for circoviruses in pigs genetically modified for xenotransplantation.
Deleterious Effects of Hepatitis Delta Virus Replication on Host Cell Proliferation (2001)

Hepatitis delta virus (HDV) infection and spread in vivo are dependent upon coinfection by hepatitis B virus (HBV), and dual HDV/HBV infection is frequently more severe than HBV infection alone, raising the possibility that HDV infection may be deleterious to cells. Here we have examined the effects of HDV replication on the long-term growth of cultured cells. Our results show that most cells transfected with HDV cDNA do not give rise to stable cell lines expressing viral antigens or replicative intermediates; in addition, cotransfection of HDV replicons with a plasmid vector expressing a hygromycin resistance marker results in a dose-dependent impairment of hygromycin-resistant colony formation. When cells transfected with replication-competent HDV cDNA are followed prospectively, a progressive decline in viral RNA replication and a steady decrease in the proportion of cells expressing delta antigen are observed. However, in transient transfection assays, no evidence was found to link HDV replication to apoptosis or to cell cycle arrest, nor did HDV replication confer on host cells enhanced sensitivity to inducers of apoptosis. Thus, HDV replication does not appear to be acutely cytotoxic. However, in dividing cells HDV replication is associated with a subtler growth disadvantage, leading to selection in culture for cells displaying diminished HDV expression. This effect would not be expected to cause hepatitis in vivo but might contribute to impaired liver regeneration in the setting of ongoing hepatocellular injury.
Effect of Progesterone Supplementation on Pregnancy and Embryo Survival in Ewes (1989)

Two hundred eighteen ewes were used in experiments 1) to develop a progesterone supplementation regimen capable of sustaining serum concentrations of progesterone at about 2.0 ng/ml for a period of 50 d (Exp. 1) and 2) to determine the effects of progesterone supplementation (d 6 to 50 after mating) on pregnancy and embryo survival rates in mated ewes (Exp. 2). In ovariectomized ewes in Exp. 1, s.c. administration of four cylindrical (9.5 x 60 mm) silastic implants, containing 20% (1.1 g) progesterone by weight, sustained mean serum concentrations of progesterone of 1.9 +/- .07 ng/ml compared with 1.03 +/- .05 ng/ml in ewes bearing two implants. In Exp. 2 each ewe (n = 159) was mated to two fertile rams at a spontaneous estrus (d 0) during mid-breeding season. Mean ovulation rate, determined on a subgroup of 46 ewes, was 1.45 +/- .05. On d 6, ewes were assigned randomly to control (two implants containing no progesterone) or progesterone-treated (four implants similar to those used in Exp. 1) groups. From d 7 to 50 after mating, progesterone concentrations in serum were greater (P less than .001) in progesterone-treated (four implants similar to those used in Exp. 1) groups. From d 7 to 50 after mating, progesterone concentrations in serum were greater (P less than .001) in progesterone-treated (3.50 +/- .06) than in control (2.65 +/- .05) ewes. Pregnancy rates (86% and 83%) and calculated embryo survival rates (77% and 78%) were similar (P greater than .05) for the control and progesterone-treated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
What Is the Best Treatment for Hallux Valgus? (2009)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Nematode populations and their effects on herbage production in a volcanic plateau pasture (1986)

Abstract Insecticidal rates of carbofuran and oxamyl were applied to a trial at Wairakei to control Argentine stem weevil ( Listronotus bonariensis (Kuschel)) in ryegrass ( Lolium perenne L.), but herbage responses were greatest in the white clover ( Trifolium repens L.) component of the pasture. Autumn samples showed significant reductions in the populations of many nematodes, both vermiform and within roots. Nematodes likely to have been responsible for depressing white clover growth are Meloidogyne hapla, Heterodera trifolii, Paratrichodorus minor, Pratylenchus , and Paratylenchus . Because nematodes were probably largely responsible for the observed response to applied insecticide, care is needed in interpreting results of all such trials. It was not possible’ to partition the effects of the various nematodes on pasture production.
Calcium-induced protein folding. Structure-affinity relationships in synthetic analogs of the helix-loop-helix calcium binding unit. (1981)

Three peptide analogs of the helix-loop-helix Ca2+ binding unit, 21-, 26-, and 34-residues in length, similar in sequence to rabbit skeletal troponin C site III have been prepared by the solid-phase method. The CD spectra of the 21-residue fragment indicated very little secondary structure in aqueous medium in the absence of Ca2+. Addition of Ca2+ increased the secondary structure of the peptide but the KCa was very weak, 3.1 x 10(2) M-1. The same peptide in hydrophobic medium in the absence of Ca2+ had considerable secondary structure and the KCa value increased considerably, 3.5 x 10(5) M-1. The 26-residue peptide, containing 5 more residues on the NH2 terminus of the 21-residue peptide, showed slightly more secondary structure in aqueous medium in the absence of Ca2+. Addition of Ca2+ to this peptide raised the amount of secondary structure in the metal ion-peptide complex and resulted in a higher KCa value, 3.8 x 10(4) M-1. By assuming that the COOH-terminal region of the 26-residue peptide-metal ion complex assumes a structure similar to that of the 21-residue peptide-metal ion complex, one is able to assign the increase in structure to the NH2-terminal side of the Ca2+-binding loop. Hydrophobic medium further increased the secondary structure of this peptide and also increased the KCa value to 4.5 x 10(5) M-1, a value similar to that obtained for the 21-residue peptide. The 34-residue peptide contained a further 8 amino acid residues on the NH2 terminus of the 26-residue peptide. This peptide had considerable secondary structure in aqueous medium which increased in the presence of Ca2+. The peptide has a reasonable affinity for Ca2+ in aqueous medium, KCa = 2.6 x 10(5) M-1. Again, a hydrophobic medium increased both the amount of secondary structure and the Ca2+ affinity constant, KCa = 9.2 x 10(5) M-1. A model of Ca2+-induced folding of the three peptides under different conditions is described and results obtained from this model are used to describe Ca2+ binding to the four Ca2+ binding units in rabbit skeletal troponin C.
Highly stable expression of a foreign gene from rabies virus vectors. (1996)

A reverse genetics approach was applied to generate a chimeric nonsegmented negative strand RNA virus, rabies virus (RV) of the Rhabdoviridae family, that expresses a foreign protein. DNA constructs containing the entire open reading frame of the bacterial chloramphenicol acetyltransferase (CAT) gene and an upstream RV cistron border sequence were inserted either into the nontranslated pseudogene region of a full-length cDNA copy of the RV genome or exchanged with the pseudogene region. After intracellular T7 RNA polymerase-driven expression of full-length antigenome RNA transcripts and RV nucleoprotein, phosphoprotein and polymerase from transfected plasmids, RVs transcribing novel monocistronic mRNAs and expressing CAT at high levels, were recovered. The chimeric viruses possessed the growth characteristics of standard RV and were genetically stable upon serial cell culture passages. CAT activity was still observed in cell cultures infected with viruses passaged for more than 25 times. Based on the unprecedented stability of the chimeric RNA genomes, which is most likely due to the structure of the rhabdoviral ribonucleoprotein complex, we predict the successful future use of recombinant rhabdovirus vectors for displaying foreign antigens or delivering therapeutic genes.
Unraveling the Specificity of Heparanase Utilizing Synthetic Substrates (2010)

Heparanase is a promising anticancer target because of its involvement in cancer invasion and metastasis. Heparanase cleaves heparan sulfate (HS), a sulfated polysaccharide, and activates a series of HS-mediated cell proliferation and angiogenesis processes. Understanding the substrate specificity of heparanase will aid the discovery of heparanase inhibitors. Here, we sought to determine the specificity of heparanase using synthetic polysaccharide substrates. The substrates were prepared using purified HS biosynthetic enzymes. Using these substrates, we were able to dissect the structural moieties required for heparanase. Our data suggest that heparanase cleaves the linkage between a GlcA unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. In addition, heparanase cleaves the linkage of a GlcA unit and N-sulfo glucosamine unit with a 2-O-sulfated GlcA residue, not a 2-O-sulfated IdoA residue, in proximity. We also discovered that the polysaccharide with repeating disaccharide units of IdoA2S-GlcNS inhibits the activity of heparanase. Our findings advance the understanding of the substrate specificity of heparanase and identify a lead compound for developing polysaccharide-based heparanase inhibitors.
Specific inhibition of tissue kallikrein 1 with a human monoclonal antibody reveals a potential role in airway diseases (2009)

KLK1 (tissue kallikrein 1) is a member of the tissue kallikrein family of serine proteases and is the primary kinin-generating enzyme in human airways. DX-2300 is a fully human antibody that inhibits KLK1 via a competitive inhibition mechanism (Ki=0.13 nM). No binding of DX-2300 to KLK1 was observed in a surface-plasmon-resonance biosensor assay when KLK1 was complexed to known active-site inhibitors, suggesting that DX-2300 recognizes the KLK1 active site. DX-2300 did not inhibit any of the 21 serine proteases that were each tested at a concentration of 1 microM. We validated the use of DX-2300 for specific KLK1 inhibition by measuring the inhibition of KLK1-like activity in human urine, saliva and bronchoalveolar lavage fluid, which are known to contain active KLK1. In human tracheobronchial epithelial cells grown at the air/liquid interface, DX-2300 blocked oxidative-stress-induced epidermal-growth-factor receptor activation and downstream mucus cell proliferation and hypersecretion, which have been previously shown to be mediated by KLK1. In an allergic sheep model of asthma, DX-2300 inhibited both allergen-induced late-phase bronchoconstriction and airway hyper-responsiveness to carbachol. These studies demonstrate that DX-2300 is a potent and specific inhibitor of KLK1 that is efficacious in in vitro and in vivo models of airway disease.
Integrating Immune Checkpoint Blockade with Anti-Neo/Mutated Antigens Reactivity to Increase the Clinical Outcome of Immunotherapy (2015)

Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs) deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients.
Hemophilus Influenzae Type B Disease in Children Vaccinated with Type B Polysaccharide Vaccine (1986)

We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine. The geometric mean concentration of antibody to type b polysaccharide in convalescent-phase serum from 31 of the vaccinated patients who had hemophilus disease was significantly lower than that in serum from 25 patients of similar age with the disease who had never been vaccinated (0.59 vs. 3.46 micrograms per milliliter, P less than 0.001). However, only 3 of 46 patients in whom the vaccine failed and who were tested for hypogammaglobulinemia had this finding, and none of 33 children tested for IgG2 had low serum concentrations of this immunoglobulin subclass, which is thought to be important in the immune response to polysaccharide antigens. In addition, all but 1 of the 46 patients in whom the vaccine failed and who were tested for IgG antibody to tetanus toxoid protein, a thymic-dependent antigen, had normal values, and 19 of 20 tested for hemolytic complement activity had normal levels. In white children, the presence of the Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was associated with a sevenfold increase in the relative risk of vaccine failure (P less than 0.003). We conclude that vaccine failure may be related in part to genetic factors, and that most vaccinated children in whom Hemophilus influenzae disease develops have deficient antibody responses to the type b polysaccharide despite normal serum concentrations of immunoglobulin and normal antibody responses to tetanus toxoid.