gebhart/patrepeval huggingface dataset:
The Origin of the Synergistic Effect of Muramyl Dipeptide with Endotoxin and Peptidoglycan (2002)

Although the basis for the high mortality rate for patients with mixed bacterial infections is likely to be multifactorial, there is evidence for a synergistic effect of muramyldipeptide (MDP) with lipopolysaccharide (LPS) on the synthesis of proinflammatory cytokines by mononuclear phagocytes. In this study, co-incubation of human Mono Mac 6 cells with MDP and either LPS or peptidoglycan (PGN) resulted in an apparent synergistic effect on tumor necrosis factor-alpha (TNF-alpha) secretion. Although incubation of cells with MDP alone produced minimal TNF-alpha, it caused significant expression of TNF-alpha mRNA. These findings suggest that the majority of TNF-alpha mRNA induced by MDP alone is not translated into protein. Furthermore, simultaneous incubation of cells with MDP and either LPS or PGN resulted in TNF-alpha mRNA expression that approximated the sum of the amounts expressed in response to MDP, LPS, and PGN individually. These findings indicate that the apparent synergistic effect of MDP on TNF-alpha production induced by either LPS or PGN is due to removal of a block in translation of the mRNA expressed in response to MDP. In subsequent studies, the effects of MDP alone and its effect on the production of TNF-alpha by LPS and PGN were determined to be independent of CD14, Toll-like receptor 2, and Toll-like receptor 4. These findings indicate that MDP acts through receptor(s) other than those primarily responsible for transducing the effects of LPS and PGN. Successful treatment of patients having mixed bacterial infections is likely to require interventions that address the mechanisms involved in responses induced by a variety of bacterial cell wall components.
Generation of a monoclonal antibody to the carboxy-terminal domain of tau by immunization with the amino-terminal domain of the amyloid precursor protein (1996)

A fusion protein between beta-galactosidase and the amino-terminal domain of amyloid precursor protein (APP) was used as an immunogen for the production of monoclonal antibodies. One of these antibodies, the 5D12 monoclonal antibody, labeled the neurofibrillary tangles (NFT) by immunohistochemistry, as well as isolated paired helical filaments (PHF) in electron microscopy. In immunoassay, the ascitic fluid produced by the 5D12 clone was demonstrated to contain a high titer of antibodies to heat-stable microtubule associated proteins (MAPs). By immunoblotting, the proteins recognized in heat-stable MAPs were found to correspond to tau proteins. The 5D12 antibody recognized normal tau isolated from rat and human brain homogenates, and PHF-tau isolated from the brain of patients with Alzheimer's disease (AD). By immunoblotting, the 5D12 antibody also recognized the full-length recombinant tau protein but not the fusion protein used as an immunogen. The immunoreactivity of the 5D12 antibody with tau was completely abolished when the half-carboxy domain of tau, containing the tubulin-binding repeats, was removed. This study demonstrates that the use of the amino-terminal domain of APP as an immunogen led to the generation of a monoclonal antibody to the half-carboxy domain of tau.
Detection of immobilized amplicons by ELISA-like techniques (1996)

The NucleoLink surface is a physically modified, thermostable, optically clear resin. It allows the covalent binding of 5'-phosphorylated oligonucleotides. Target DNA amplification by polymerase chain reaction (PCR) is accomplished by asymmetric amplification on the covalently immobilized primer that develops into immobilized amplicons. A DNA fragment of bovine leukemia virus is used as a model system for the detection of immobilized amplicons by ELISA-like techniques. Covalently bound oligonucleotides are also utilized as capture probe in the hybridization-based signal amplification for detection of an infectious organism.
18O-Labeling of N-Glycosylation Sites To Improve the Identification of Gel-Separated Glycoproteins Using Peptide Mass Mapping and Database Searching (1999)

Peptide mass mapping using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry in conjunction with interrogation of sequence databases is a powerful tool for the identification of proteins. Glycosylated proteins often yield poor MALDI peptide maps due to shielding of proteolytic cleavage sites and the presence of modified peptides. Here we demonstrate that enzymatic removal of N-linked glycans with simultaneous partial (50%) 18O-labeling of glycosylated asparagine residues prior to proteolysis and MALDI peptide mass mapping can overcome these problems. As a result, more peptides are observed in MALDI spectra which, in turn, increases the specificity of subsequent database searches. Furthermore, the detection of a labeled peptide directly translates into partial sequence information as N-linked carbohydrates are exclusively attached to asparagine residues that form part of the NXS/T sequence. The mass of the formerly glycosylated peptide together with the NXS/T sequence pattern represents a discriminating criterion for database searching which, on average, increases the search specificity by a factor of 100. This procedure allows the unambiguous identification of glycoproteins that would otherwise require sequencing and, at the same time, enables the identification of N-glycosylation sites with higher sensitivity than previously possible.
Tissue distribution and antithrombotic activity of unlabeled or14C-labeled porcine intestinal mucosal heparin following administration to rats by the oral route (2000)

Distribution and antithrombotic activity of orally administered unfractionated porcine heparin were studied. [ 14 C]Heparin was prepared by de-N-acetylation of porcine mucosal heparin followed by re-N-acetylation, using [ 14 C]acetic anhydride. [ 14 C]Heparin and (or) cold heparin (60 mg/kg) were administered by stomach tube to male Wistar rats. Blood, all levels of gut and gut contents, liver, lung, spleen, kidney, and aortic and vena caval endothelium were collected under deep anesthesia at 3, 6, 15, 30, and 60 min and 4 and 24 h (6 rats/group) after administration. Urine and feces were collected at 24 h, using metabolic cages. In three additional rats, drugs were administered in gelatin capsules. Tissues listed above and tongue, esophagus, trachea, brain, heart, thymus, bile ducts, vena caval and aortic walls, ureters, bladder, samples of muscle, skin, hair, and bone marrow were collected at 24 h. Radioactivity and chemical heparin, measured by agarose gel electrophoresis, were observed in all tissues examined as well as gut washes, plasma, urine, and feces. Radiolabel recovered was confirmed to be heparin by autoradiograms of gradient polyacrylamide electrophoretic gels. [ 14 C]Heparin and chemical heparin in gut tissue suggest a transit time of 4 h. Porcine or bovine heparin (7.5 mg/kg), administered by stomach tube, decreased the incidence of thrombosis induced by applying 10% formalin in 65% methanol to the exposed jugular vein of rats. Heparin isolation from non-gut tissue, endothelium, urine, and plasma and the observed antithrombotic effect are consistent with oral bioavailability.Key words: heparin, [ 14 C]heparin, oral administration, distribution, radiolabel, thrombosis.
Identification and characterization of xpac protein, the gene product of the human XPAC (xeroderma pigmentosum group A complementing) gene. (1991)

We have cloned human xeroderma pigmentosum group A complementing (XPAC) cDNA that encodes a "zinc finger" protein with a predicted size of 31 kDa. To detect the xpac protein in cells, we raised antibody against a recombinant human xpac protein. Using this antibody, we identified the xpac protein in the nucleus of cells. In normal human cells, 40- and 38-kDa proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A reduced amount of the smaller protein was detected in XP 39OSSV cells, which show low UV sensitivity, and no xpac proteins were detected in XP 2OSSV cells, which show high UV sensitivity. These levels of xpac proteins in xeroderma pigmentosum cells were determinants of heterogeneity of the DNA repair defect in group A xeroderma pigmentosum. Synthesis of the xpac protein did not increase after UV irradiation.
Robust classification of bacterial and viral infections via integrated host gene expression diagnostics (2016)

Improved diagnostics for acute infections could decrease morbidity and mortality by increasing early antibiotics for patients with bacterial infections and reducing unnecessary antibiotics for patients without bacterial infections. Several groups have used gene expression microarrays to build classifiers for acute infections, but these have been hampered by the size of the gene sets, use of overfit models, or lack of independent validation. We used multicohort analysis to derive a set of seven genes for robust discrimination of bacterial and viral infections, which we then validated in 30 independent cohorts. We next used our previously published 11-gene Sepsis MetaScore together with the new bacterial/viral classifier to build an integrated antibiotics decision model. In a pooled analysis of 1057 samples from 20 cohorts (excluding infants), the integrated antibiotics decision model had a sensitivity and specificity for bacterial infections of 94.0 and 59.8%, respectively (negative likelihood ratio, 0.10). Prospective clinical validation will be needed before these findings are implemented for patient care.
CREB-binding protein activation by presenilin 1 but not by its M146L mutant (2006)

The transcriptional coactivator CREB-binding protein plays a key role in regulating gene expression in a number of different cell types. Recently, a report has suggested a link between CREB-binding protein and presenilins, which are mutated in many cases of early onset Alzheimer's disease. Thus, presenilin 1 and 2 double knockout mice showed reductions in CREB-binding protein levels and in cAMP response element-dependent gene expression in the cerebral cortex, which is likely to contribute to the subsequent neuronal degeneration. This suggests that the inactivation of CREB-binding protein caused by mutation in presenilin 1 may be involved in the disease process. We have shown that wild-type presenilin 1 stimulates the transcriptional activity ability of CREB-binding protein whereas presenilin 1 M146L mutant did not produce such an effect. The activation of CREB-binding protein by wild-type presenilin 1 involves the PI 3-kinase, p38 mitogen-activated protein kinase (MAPK) and p42/p44 MAPK pathways and targets primarily the C terminus of CREB-binding protein. To our knowledge, this is the first report that shows regulation of CREB-binding protein activity by wild-type presenilin 1 and not by its M146L mutant, and suggests a mechanism in which mutation of presenilin 1 may lead to neurodegeneration.
Optimum Design of Cavity Stabilized FET Oscillators (2006)

The optimum circuit topology of cavity stabilized FET oscillators is found out from comparing various circuit configurations. Output power, loaded Q-factor, stable tuning range, FM-noise and power dissipated in stabili- zing resistors are related by both a large-signal and a noise analysis.
Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases. (1993)

Little is known about the signaling pathways by which motoneurons induce synapses on muscle fibers, and no receptors for synapse-inducing signals have yet been identified. Because several other inductive events in development are mediated by receptor tyrosine kinases (RTKs), and because phosphotyrosine staining within muscle fibers is concentrated at synaptic sites, one possibility is that synapse-inducing signals are transduced by a RTK within the muscle fiber. We have used PCR to search for tyrosine kinases within the electric organ of the electric ray Torpedo californica, since this tissue is homologous to muscle but is much more densely innervated and is therefore a rich source of synaptic molecules. We have isolated a RTK that is specifically expressed in electric organ and skeletal muscle. The kinase domain of this receptor is related to the trk family of neurotrophin receptors, but unlike any previously described receptor, the extracellular region of this Torpedo RTK contains a kringle domain close to the transmembrane domain.
Characterization of the role of IL-6 in the progression of prostate cancer (1999)

IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype.
Drug rechallenge following drug‐induced liver injury (2017)

For critical medicines, drug rechallenge may be appropriate when 1) no safer alternatives are available, 2) the objective benefit exceeds the risk, and 3) patients are fully informed and consent, can adhere to follow-up, and alert providers to hepatitis symptoms. To better understand rechallenge outcomes and identify key risk factors for positive rechallenge, additional data are needed from controlled clinical trials, prospective registries, and large health care databases. (Hepatology 2017;66:646-654).
Identification of the Gene Encoding Sulfopyruvate Decarboxylase, an Enzyme Involved in Biosynthesis of Coenzyme M (2000)

The products of two adjacent genes in the chromosome of Methanococcus jannaschii are similar to the amino and carboxyl halves of phosphonopyruvate decarboxylase, the enzyme that catalyzes the second step of fosfomycin biosynthesis in Streptomyces wedmorensis. These two M. jannaschii genes were recombinantly expressed in Escherichia coli, and their gene products were tested for the ability to catalyze the decarboxylation of a series of alpha-ketoacids. Both subunits are required to form an alpha(6)beta(6) dodecamer that specifically catalyzes the decarboxylation of sulfopyruvic acid to sulfoacetaldehyde. This transformation is the fourth step in the biosynthesis of coenzyme M, a crucial cofactor in methanogenesis and aliphatic alkene metabolism. The M. jannaschii sulfopyruvate decarboxylase was found to be inactivated by oxygen and reactivated by reduction with dithionite. The two subunits, designated ComD and ComE, comprise the first enzyme for the biosynthesis of coenzyme M to be described.
Microflow devices and systems (1994)

Microflow devices including microvalves, micropumps and microflow sensors fabricated by micromachining are reviewed from the point of view of the actuating principle and structures. Integration of microflow control devices and microflow sensors allowed very precise control of small flow. High performance liquid dosing microsystems and sophisticated chemical analysing microsystems were demonstrated by the combination of microflow devices and microsensors. Applications of microflow devices and systems are also introduced.
Activities of 3'-azido-3'-deoxythymidine nucleotide dimers in primary lymphocytes infected with human immunodeficiency virus type 1 (1990)

The relative antiviral potencies of five nucleotide heterodimers of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-3'-deoxythymidilyl-(5',5')-2'-3'-dideoxy-5'-adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and the corresponding 2-cyanoethyl congeners AZT-P(CyE)-ddA and AZT-P(CyE)-ddI, were determined in primary human peripheral blood mononuclear cells infected with human immunodeficiency virus type 1. The homodimer 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxythymidilic acid (AZT-P-AZT) was also included for comparison. The potencies of the compounds were AZT-P-ddA greater than or equal to AZT-P-ddI greater than AZT-P(CyE)-ddA greater than or equal to AZT-P(CyE)-ddI greater than or equal to AZT greater than AZT-P-AZT. Whereas AZT-P-ddA and AZT-P-ddI had in vitro therapeutic indices greater than that of AZT, the homodimer of AZT had a low therapeutic index. AZT-P-ddI exhibited the lowest toxicity in peripheral blood mononuclear, Vero, or CEM cells. Combination studies between AZT and 2',3'-dideoxyinosine (ddI) at nontoxic concentrations indicated a synergistic interaction at a drug ratio of 1:100. At higher ratios (1:500 and 1:1,000), the interactions were synergistic only at concentrations that produced up to 75% virus inhibition. At higher levels of antiviral effects, this combination was antagonistic, as determined by the multiple drug effect analysis method. AZT-P-ddI was about 10-fold less toxic than AZT to human granulocyte-macrophage progenitor cells. However, no significant difference was apparent when the compounds were evaluated against cells of the erythroid lineage. The greater antiviral activity and lower toxicity of this compound could not be attributed to the extracellular decomposition of the dimer in media at physiological temperature and pH. However, in acidic solutions, AZT-P-ddI decomposed in a pH-dependent manner. Advanced preclinical studies with this heterodimer of two clinically effective antiretroviral agents should be considered.
Recombinant polyclonal antibodies: therapeutic antibody technologies come full circle. (2005)

Current antibody therapeutics can be grouped into two generations, each distinguished by a unique feature of the immune system: diversity and specificity. Antibodies from human blood (immunoglobulin) represent the first generation, and are characterized by the natural diversity of human antibody responses. The second generation consists of recombinant monoclonal antibodies (mAbs), which are characterized by high specificity toward a single, often well-described antigen. The natural immune response comprises a plurality of specificities, many of which do not compete for binding, whereas molecules in a mAb all compete for binding to the same epitope. Thus, the epitope is more likely to become a limiting factor for mAb binding to complex targets compared with a polyclonal antibody. Also, epitope-escape by mutation or natural variation is less likely to be a problem for polyclonal antibodies. Technologies attempting to develop truly human recombinant antigen-specific polyclonal antibodies, such as the Sympress technology, are closing a natural circle between the first generations of antibody technologies.
Sufficient condition on noise correlations for scalable quantum computing (2013)

I study the effectiveness of fault-tolerant quantum computation against correlated Hamiltonian noise, and derive a sufficient condition for scalability. Arbitrarily long quantum computations can be executed reliably provided that noise terms acting collectively on $k$ system qubits are sufficiently weak, and decay sufficiently rapidly with increasing $k$ and with increasing spatial separation of the qubits.
Suppression of Macrophage Activation with CNI-1493 Increases Survival in Infant Rats with Systemic Haemophilus influenzae Infection (2000)

CNI-1493, a potent macrophage deactivator, was used to treat infant rats systemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75 percent increased rate of survival compared to that for untreated controls. The effect of CNI-1493 on the inflammatory response was studied by immunohistochemical detection of individual tumor necrosis factor alpha (TNF-alpha)-, interleukin 1 beta (IL-1beta)-, and gamma interferon (IFN-gamma)-producing cells in the spleen. A significant reduction of the incidence of TNF-alpha- and IL-1beta-expressing cells was found for CNI-1493-treated animals. IFN-gamma expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly reduced the number of infiltrating granulocytes in the brain from that for controls. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats.
Measurements of particle size distribution parameters in ferrofluids (1978)

A method is presented by means of which (for a ferrofluid with a lognormal distribution of particle size) it is possible to determine the standard deviation (σ) and median particle diameter (D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">v</inf> ) from the room temperature magnetisation curve. The method has been applied to several commercial ferrofluids, containing ferrite particles, and to fluids consisting of cobalt particles in toluene prepared by the method of Hess and Parker. The particle size distributions have also been measured by using an electron microscope. It has been found that the magnetic data gives estimates of the 'magnetic size distribution' parameters D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vm</inf> and σ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</inf> , which differed from the 'physical size distribution' parameters D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vp</inf> and σ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</inf> obtained from electron microscope data. It is found that D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vp</inf> > D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vm</inf> , and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sigma_{p} &lt; \sigma_{m}</tex> . These observations are consistent with the results of Kaiser and Miskolczy and Granqvist and Buhrman.
Accurate and absolute quantitative measurement of gene expression by single-tube RT-PCR and HPLC. (1995)

We report a method that allows accurate, absolute quantification of gene expression in a single reverse transcriptase (RT)-PCR reaction. This method makes use of novel high-performance liquid chromatography (HPLC) technology to resolve and quantify the products of competitive, mutant RNA PCRs. The HPLC technique allows rapid, high resolution of reaction products. On-line UV detection eliminates the need for radiolabel or other tracers. The HPLC technique also demonstrates that these competition reactions readily generate heteroduplex products. The ability of HPLC to resolve and quantify heteroduplex products is fundamental to the accuracy of the technique. Accurate measurements of gene expression have been obtained over four orders of magnitude and experiments employing predetermined quantities of specific native RNA input have demonstrated the ability of the system to provide absolute estimates of gene expression. Large size differences between native and mutant RNA inputs affected reverse transcriptase (RT) efficiency, but not PCR amplification efficiency. However, the magnitude of the RT efficiency effect can be estimated, is reproducible, and can therefore be adjusted by a calculated correction factor. The RT efficiency difference can been eliminated by reduction in the magnitude of the sequence difference between native and mutant RNA so that no correction factor is required. The application of the technique to quantification of expression of the alpha 1 subunit of sodium, potassium-ATPase in microdissected nephron segments is demonstrated.