gebhart/patrepeval huggingface dataset:
Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation (2006)

Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-alpha and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-alpha production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-alpha production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1-positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-alpha from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1-positive endosomes accompanied by the loss of IFN-alpha production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-alpha and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-alpha response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs.
Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice (2009)

Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.
Detection of Single Nucleotide Mismatches via Fluorescent Polymer Superquenching (2003)

An improved assay for the detection of a 20-mer DNA sequence coding for the Anthrax Lethal Factor sequence that utilizes fluorescence superquenching and peptide nucleic acids (PNAs) is reported. The basis for this assay is a microsphere sensor that is coated with both Neutravidin (a biotin-binding protein) and biotinylated poly(phenylene)ethynylene (a fluorescent conjugated polymer). A 15-mer PNA tethered through its N-terminus to a biotin serves as a capture ligand for DNA oligonucleotides. When mixed, the PNAs and microspheres form a strong complex through the biotin−avidin interaction, creating a sensor for DNA detection. The 20-mer DNA target strand and a 17-mer DNA-QTL (QTL = quencher tether ligand, where the quencher is a QSY-7 label at the 3‘-terminus of the DNA strand) of a similar sequence to the target strand are then used to develop an assay for DNA detection. A sequential addition of target, followed by DNA-QTL, yields a sensitive and selective assay for DNA detection. This study compares PNA to DNA in the ability to perform as a capture ligand, evaluates the importance of assay temperature, and illustrates resolution of single base-pair mismatches using this novel detection platform.
Your Best Self Helps Reveal Your True Self (2011)

How does trying to make a positive impression on others impact the accuracy of impressions? In an experimental study, the impact of positive self-presentation on the accuracy of impressions was examined by randomly assigning targets to either “put their best face forward” or to a control condition with low self-presentation demands. First, self-presenters successfully elicited more positive impressions from others, being viewed as more normative and better liked than those less motivated to self-present. Importantly, self-presenters were also viewed with greater accuracy than control targets, being perceived more in line with their self-reported distinctive personality traits and their IQ test scores. Mediational analyses were consistent with the hypothesis that self-presenters were more engaging than controls, which in turn led these individuals to be viewed with greater distinctive self–other agreement. In sum, positive self-presentation facilitates more accurate impressions, indicating that putting one’s best self forward helps reveal one’s true self.
Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma. (2002)

These results indicate that iNOS may not correlate with cancer cell-proliferative activity or apoptosis; survivin, however, may not only suppress apoptosis but also accelerate cancer cell-proliferative activity and play an important role in tumor progression in HCC.
Multiplex PCR for identification of methicillin-resistant staphylococci in the clinical laboratory (1994)

A multiplex PCR assay for detection of the staphylococcal mecA gene (the structural gene for penicillin-binding protein 2a) was compared with agar dilution and disk diffusion susceptibility test methods for identifying methicillin resistance. The multiplex PCR assay combined two primer sets (mecA and 16S rRNA) in a single reaction. A total of 500 staphylococcal isolates (228 isolates of Staphylococcus aureus and 272 isolates of coagulase-negative staphylococci) from clinical specimens were studied. For S. aureus, 40 of 40 mecA-positive isolates and 4 of 188 mecA-negative isolates were oxacillin resistant (positive and negative predictive values of 100 and 98%, respectively). In 3 of 4 discordant isolates, resistance was due to hyperproduction of beta-lactamase. For coagulase-negative staphylococci, 148 of 159 mecA-positive isolates and 0 of 113 mecA-negative isolates were oxacillin resistant (positive and negative predictive values of 93 and 100%, respectively). Twenty-six isolates were categorized as indeterminate because of the absence of a detectable 16S rRNA product. Four of these 26 isolates contained mecA when retested. The assay is designed to be incorporated into the work flow of the clinical microbiology laboratory and allows for the identification of intrinsic resistance in a timely and reliable manner.
Effect of methotrexate (MTX) on NAD(P)+ dehydrogenases of HeLa cells: malic enzyme, 2-oxoglutarate and isocitrate dehydrogenases (1997)

The effects of methotrexate (MTX) on oxygen uptake by permeabilized HeLa cells were evaluated. MTX did not inhibit state III respiration when the oxidizable substrate was succinate, but when the substrates were 2-oxoglutarate or isocitrate the respiration decreased about 50 per cent at 1.0 mM concentration of the drug. This effect was explained by inhibition of 2-oxoglutarate and isocitrate dehydrogenases by MTX. No effect was observed on succinate dehydrogenase. An evaluation of the effects of MTX on malic enzyme activity as measured by pyruvate plus lactate production in intact cells supplied with malate showed a decrease of about 40 per cent in metabolite production using 0.4 mM MTX. HeLa cell malic enzyme, as observed for other tumour cells, is compartmentalized in mitochondria and cytosol, and is another example of a dehydrogenase inhibited by MTX.
Understanding consequences of concurrent therapies (1993)

In 1989, the occurrence of a rare, life-threatening ventricular arrhythmia (torsades de pointes) in an otherwise healthy young woman led alert clinicians at the Naval Hospital in Bethesda, Md, to consider the possibility that the patient's near-fatal arrhythmia was triggered by a drug-drug interaction involving her antihistamine (terfenadine) and her antifungal (ketoconazole) medications.<sup>1</sup>Consulting clinical pharmacologists from the Uniformed Services University of the Health Sciences and the US Food and Drug Administration (FDA) suggested that ketoconazole inhibited the oxidative metabolism of terfenadine. Analysis of blood samples revealed that the patient had high levels of unmetabolized terfenadine, a compound not usually detectable in blood because it is metabolized so quickly. Review of reports to the FDA's spontaneous reporting system revealed that among additional cases of torsades de pointes in patients receiving terfenadine, many were also receiving ketoconazole. This evidence led the FDA to ask Marion Merrill Dow, Kansas City, Mo,
Echocardiographic Destruction of Albumin Microbubbles Directs Gene Delivery to the Myocardium (2000)

Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.
Infection by Influenza A Viruses of Tracheal Organ Cultures Derived from Homologous and Heterologous Hosts (1974)

Journal Article Infection by Influenza A Viruses of Tracheal Organ Cultures Derived from Homologous and Heterologous Hosts Get access R. C. Schmidt, R. C. Schmidt From the Department of Epidemiology, School of Public Health, The University of Michigan, Ann Arbor, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar H. F. Maassab, H. F. Maassab From the Department of Epidemiology, School of Public Health, The University of Michigan, Ann Arbor, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar F. M. Davenport F. M. Davenport From the Department of Epidemiology, School of Public Health, The University of Michigan, Ann Arbor, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 129, Issue 1, January 1974, Pages 28–36, https://doi.org/10.1093/infdis/129.1.28 Published: 01 January 1974 Article history Received: 12 February 1973 Revision received: 09 July 1973 Published: 01 January 1974
Synthesis of SnS nanocrystals by the solvothermal decomposition of a single source precursor (2007)

Abstract SnS nanocrystals (NCs) were synthesized from bis(diethyldithiocarbamato) tin(II) in oleylamine at elevated temperature. High-resolution transmission electron microscopy (HRTEM) investigation and X-ray diffraction (XRD) analysis showed that the synthesized SnS particles are monocrystalline with an orthorhombic structure. The shape and size tunability of SnS NCs can be achieved by controlling the reaction temperature and time, and the nature of the stabilizing ligands. The comparison between experimental optical band gap values shows evidence of quantum confinement of SnS NCs. Prepared SnS NCs display strong absorption in the visible and near-infrared (NIR) spectral regions making them promising candidates for solar cell energy conversion.
Efficacy of orally administered amphipathic polyaminocarboxylic acid chelators for the removal of plutonium and americium: Comparison with injected Zn-DTPA in the rat (2005)

Chelators are used to promote excretion of actinides and some other metals, but few are orally effective. The relative efficacies of orally administered triethylenetetraminepentaacetic acids (TT) with varying lipophilic properties on the removal of 241Am and 239Pu and comparison with parenteral Zn-DTPA was determined. The actinides were administered to adult rats 2 weeks prior to initiation of 30 d of chelation treatment. The TT compounds were given orally while Zn-DTPA was given twice weekly by injection. Total body content of 241Am was measured before and during the treatment period and organ contents of 241Am and 239Pu were measured at the end of the study. Significant reductions in 241Am occurred within the first week, with Zn-DTPA being the most effective. By 3 weeks, the most lipophilic chelator, C22TT was as effective as Zn-DTPA. After 30 d, reductions in organ content of 239Pu and 241Am directly correlated with increasing lipophilicity of the TT chelators. Oral C22TT was as effective as injected Zn-DTPA in liver and bone, the major organs of actinide deposition. The removal of 239Pu from the liver and reduction of redeposition of 239Pu in newly formed bone by C22TT was confirmed by neutron-induced autoradiographs. The amphipathic TT chelators may be useful as orally administered alternatives to current parenteral DTPA for the removal of actinide elements from the body, particularly for longer-term therapeutic applications.
Osteocartilaginous Allografts as Compared with Autografts in the Treatment of Knee Joint Osteocartilaginous Defects in Dogs (1978)

RODRIGO, JUAN J. M.D.*; SAKOVICH, LEO*; TRAVIS, CARYN*; SMITH, GAIL* Author Information
Treatment of acute myocardial infarction: does the type of hospital make a difference? PPAMI Study Group. (1999)

There is sparse data on the treatment practices being followed for acute myocardial infarction at various hospitals that differ in their financial infrastructure, availability of facilities and attachment to a medical college. In this prospective observational study, we evaluated the treatment practices for acute myocardial infarction, its appropriateness based on ACC/AHA guidelines and possible influence by type of hospital and certain patient characteristics. Thrombolysis, beta-blockers and angiotensin-converting enzyme-I inhibitors were used in 674 (63%), 506 (47%) and 413 (38%) respectively of 1072 patients. However, when evaluated according to ACC/AHA guidelines, appropriate use was noted in 83 percent, 78 percent and 99.3 percent, respectively. Thrombolysis was inappropriately denied to 14.7 percent patients whereas in 2.4 percent it was used contrary to recommendations. The most common reason for ineligibility for thrombolysis was late arrival. Beta-blockers were denied to 25.1 percent patients. Decision on use of angiotensin-converting enzyme-I was appropriate in most patients. Aspirin was used in 1027 (95.8%) patients. Government hospitals were least likely to thrombolyse a patient as compared to private, industrial and voluntary hospitals; however, this difference was not seen with the use of beta-blockers and angiotensin-converting enzyme-I. Hospitals attached to medical colleges follow guidelines for use of thrombolysis and beta-blockers more closely than non-teaching hospitals. To conclude, evaluation of appropriateness of a therapeutic modality is of greater clinical significance than mere absolute use. Benefits of thrombolytic therapy can be extended by minimising pre-hospital delay; and there is scope for improved utility of beta-blockers which are cost-effective. In addition, the hospital type also has an impact on the treatment practice being followed for acute myocardial infarction.
Cloning of an Avian Adeno-Associated Virus (AAAV) and Generation of Recombinant AAAV Particles (2003)

Recent studies have proposed that adeno-associated viruses (AAVs) are not evolutionarily linked to other mammalian autonomous parvoviruses but are more closely linked to the autonomous parvoviruses of birds. To better understand the relationship between primate and avian AAVs (AAAVs), we cloned and sequenced the genome of an AAAV (ATCC VR-865) and generated recombinant AAAV particles. The genome of AAAV is 4,694 nucleotides in length and has organization similar to that of other AAVs. The entire genome of AAAV displays 56 to 65% identity at the nucleotide level with the other known AAVs. The AAAV genome has inverted terminal repeats of 142 nucleotides, with the first 122 forming the characteristic T-shaped palindromic structure. The putative Rep-binding element consists of a tandem (GAGY)(4) repeat, and the putative terminal resolution site (trs), CCGGT/CG, contains a single nucleotide substitution relative to the AAV(2) trs. The Rep open reading frame of AAAV displays 50 to 54% identity at the amino acid level with the other AAVs, with most of the diversity clustered at the carboxyl and amino termini. Comparison of the capsid proteins of AAAV and the primate dependoviruses indicate that divergent regions are localized to surface-exposed loops. Despite these sequence differences, we were able to produce recombinant AAAV particles carrying a lacZ reporter gene by cotransfection in 293T cells and were able to examine transduction efficiency in both chicken primary cells and several cell lines. Our findings indicate that AAAV is the most divergent AAV described to date but maintains all the characteristics unique to the genera of dependovirus.
Prognostic factors for low birthweight repetition in successive pregnancies: a cohort study (2013)

Improved quality of antenatal care and adequate maternal weight gain during pregnancy may be feasible strategies to prevent LBW repetition in successive pregnancies.
Aberrant DNA Methylation at Genes Associated with a Stem Cell-like Phenotype in Cholangiocarcinoma Tumors (2013)

Genetic abnormalities of cholangiocarcinoma have been widely studied; however, epigenomic changes related to cholangiocarcinogenesis have been less well characterized. We have profiled the DNA methylomes of 28 primary cholangiocarcinoma and six matched adjacent normal tissues using Infinium's HumanMethylation27 BeadChips with the aim of identifying gene sets aberrantly and epigenetically regulated in this tumor type. Using a linear model for microarray data, we identified 1610 differentially methylated autosomal CpG sites, with 809 hypermethylated (representing 603 genes) and 801 hypomethylated (representing 712 genes) in cholangiocarcinoma versus adjacent normal tissues (false-discovery rate ≤ 0.05). Gene ontology and gene set enrichment analyses identified gene sets significantly associated with hypermethylation at linked CpG sites in cholangiocarcinoma including homeobox genes and target genes of PRC2, EED, SUZ12, and histone H3 trimethylation at lysine 27. We confirmed frequent hypermethylation at the homeobox genes HOXA9 and HOXD9 by bisulfite pyrosequencing in a larger cohort of cholangiocarcinoma (n = 102). Our findings indicate a key role for hypermethylation of multiple CpG sites at genes associated with a stem cell-like phenotype as a common molecular aberration in cholangiocarcinoma. These data have implications for cholangiocarcinogenesis, as well as possible novel treatment options using histone methyltransferase inhibitors.
A self-coherence based anti-jam GPS receiver (2004)

In this paper, we propose an anti-jam GPS receiver that is based on the self-coherence feature of the GPS signal. Due to the repetition of the spreading code within a navigation symbol, GPS signals exhibit strong self-coherence between the code chips separated by an integer multiple of the spreading gain. The proposed receiver utilizes the inherent self-coherence property of the GPS C/A-code to suppress interferers that have different structures from that of the GPS signal. The multi-antenna GPS receiver provides the optimum set of beamforming coefficients by maximizing the cross-correlation between the beamformer output and a reference signal.
Inactivation of Pasteurella ( Mannheimia ) haemolytica Leukotoxin Causes Partial Attenuation of Virulence in a Calf Challenge Model (2000)

The leukotoxin of Pasteurella (Mannheimia) haemolytica is believed to play a significant role in pathogenesis, causing cell lysis and apoptosis that lead to the lung pathology characteristic of bovine shipping fever. Using a system for Cre-lox recombination, a nonpolar mutation within the lktC transacylase gene of the leukotoxin operon was created. The lktC locus was insertionally inactivated using a loxP-aph3-loxP cassette, and then the aph3 marker was excised from the chromosome by Cre recombinase expressed from a P. haemolytica plasmid. The resulting lktC strain (SH2099) secretes inactive leukotoxin and carries no known antibiotic resistance genes. Strain SH2099 was tested for virulence in a calf challenge model. We inoculated 3 x 10(8) or 3 x 10(9) CFU of wild-type or mutant bacteria into the lungs of healthy, colostrum-deprived calves via transthoracic injection. Animals were observed for clinical signs and for nasal colonization for 4 days, after which they were euthanized and necropsied. The lower inoculum (3 x 10(8) CFU) caused significantly fewer deaths and allowed lung pathology to be scored and compared, while the 3 x 10(9) CFU dose of either the wild-type or mutant was lethal to >/=50% of the calves. The estimated 50% lethal dose of SH2099 was four times higher than that of the wild-type strain. Lung lesion scores were reduced twofold in animals inoculated with the mutant, while clinical scores were nearly equivalent for both strains. The wild-type and mutant strains were equally capable of colonizing the upper respiratory tracts of the calves. In this study, the P. haemolytica lktC mutant was shown to be less virulent than the parent strain.
Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. (2000)

Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid that is abundant in the fish-based diets of populations that exhibit a remarkably low incidence of cancer, exerts anticancer activity in vitro and in animal models of experimental cancer. Here we define the molecular basis for the anticancer effects of EPA. EPA inhibits cell division by inhibiting translation initiation. This is a consequence of the ability of EPA to release Ca2+ from intracellular stores while inhibiting their refilling via capacitative Ca2+ influx that results in partial emptying of intracellular Ca2+ stores and thereby activation of protein kinase R. Protein kinase R phosphorylates and inhibits eukaryotic initiation factor 2alpha, resulting in inhibition of protein synthesis at the level of translation initiation, preferentially reducing the synthesis and expression of growth-regulatory proteins, including G1 cyclins, and causes cell cycle arrest in G1. In a KLN-205 squamous cell carcinoma mouse model, daily oral administration of EPA resulted in a significant reduction of tumor size and expression of cyclin D1 in the tumor tissues. Furthermore, EPA-treated tumors showed a significant increase in the proportion of diploid cells, indicative of cell cycle arrest in G0-G1, and a significant reduction of malignant hypertetraploid cells. These results characterize EPA as a member of an emerging new class of anticancer compounds that inhibit translation initiaton.