gebhart/patrepeval huggingface dataset:
Therapeutic potential of IFN- -modified dendritic cells in acute and chronic experimental allergic encephalomyelitis (2003)

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-specific IFN-gamma production, and induced apoptosis of CD4(+) T cells possibly through DC expressing indoleamine 2,3-dioxygenase and/or an IFN-gamma-dependent pathway. As a result, infiltration of macrophages and CD4(+) T cells within the spinal cords was dramatically reduced in animals injected with IFN-gamma-DC as compared to animals injected with PBS or naive DC. This approach may represent a novel possibility of individualized immunotherapy using autologous, in vitro modified DC as a complement to conventional therapy in multiple sclerosis and other diseases with an autoimmune background.
Prokaryotic Homologs of the Eukaryotic 3-Hydroxyanthranilate 3,4-Dioxygenase and 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase in the 2-Nitrobenzoate Degradation Pathway ofPseudomonas fluorescensStrain KU-7 (2003)

The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, respectively. The NbaC enzyme carries out the oxidation of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate-6-semialdehyde, while the NbaD enzyme catalyzes the decarboxylation of the latter compound to 2-aminomuconate-6-semialdehyde. The NbaC and NbaD proteins were overexpressed in Escherichia coli and characterized. The substrate specificity of the 23.8-kDa NbaC protein was found to be restricted to 3-hydroxyanthranilate. In E. coli, this enzyme oxidizes 3-hydroxyanthranilate with a specific activity of 8 U/mg of protein. Site-directed mutagenesis experiments revealed the essential role of two conserved histidine residues (His52 and His96) in the NbaC sequence. The NbaC activity is also dependent on the presence of Fe(2+) but is inhibited by other metal ions, such as Zn(2+), Cu(2+), and Cd(2+). The NbaD protein was overproduced as a 38.7-kDa protein, and its specific activity towards 2-amino-3-carboxymuconate-6-semialdehyde was 195 U/mg of protein. Further processing of 2-aminomuconate-6-semialdehyde to pyruvic acid and acetyl coenzyme A was predicted to proceed via the activities of NbaE, NbaF, NbaG, NbaH, NbaI, and NbaJ. The predicted amino acid sequences of these proteins are highly homologous to those of the corresponding proteins involved in the metabolism of 2-aminophenol (e.g., AmnCDEFGH in Pseudomonas sp. strain AP-3). The NbaR-encoding gene is predicted to have a regulatory function of the LysR family type. The function of the product of the small open reading frame, NbaX, like the homologous sequences in the nitrobenzene or 2-aminophenol metabolic pathway, remains elusive.
The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. (1996)

Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and glutathione peroxidase did not change in the transgenic mice. Electron microscopy revealed dose-dependent ultrastructural alterations with marked mitochondrial damage in nontransgenic mice treated with ADR, but not in the transgenic littermates. Biochemical analysis indicated that the levels of serum creatine kinase and lactate dehydrogenase in ADR-treated mice were significantly greater in nontransgenic than their transgenic littermates expressing a high level of human MnSOD after ADR treatment. These results support a major role for free radical generation in ADR toxicity as well as suggesting mitochondria as the critical site of cardiac injury.
Mechanical Ventilation with Heated Humidifiers or Heat and Moisture Exchangers: Effects on Patient Colonization and Incidence of Nosocomial Pneumonia (1995)

The contribution of ventilator circuit bacterial contamination to the occurrence of ventilator-associated pneumonia remains controversial. In a previous study, we found that the incidence of pneumonia was identical with ventilator circuit changes every 48 h and with no ventilator circuit changes. The present study prospectively assessed whether keeping ventilator circuits clean with a heat and moisture exchanger exhibiting antimicrobial barrier properties affects patient colonization and the incidence of nosocomial pneumonia in patients receiving mechanical ventilation for more than 48 h. Consecutive patients were randomly allocated to humidification with either a heat and moisture exchanger (Group 1, n = 61) or a heated humidifier (Group 2, n = 70). In both groups, no circuit changes were performed throughout ventilatory support. Duration of mechanical ventilation was identical in both groups (10 +/- 8.6 d (range: 2 to 47) in Group 1 and 12.5 +/- 14.2 d [range: 2 to 85] in Group 2). The incidence of pneumonia (positive quantitative culture of protected brush specimen) was similar in both groups (6/61 and 8/70 in Groups 1 and 2, respectively; p = 0.8), as was duration of ventilation prior to pneumonia (9 +/- 5.9 versus 8.2 +/- 5.7 d; p = 0.8). Ventilator tubing contamination was considerably reduced with the use of a heat and moisture exchanger. In contrast, bacterial colonization of the pharynx and trachea was identical in both groups. These results suggest that circuit colonization plays little or no role in the occurrence of ventilator-associated pneumonia, provided usual maintenance precautions are applied.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemical characterization of programmed cell death in NGF‐deprived sympathetic neurons (1992)

Young sympathetic neurons die when deprived of nerve growth factor (NGF). Under such circumstances, cell death is appropriate to the developing nervous system and requires RNA and protein synthesis. We have hypothesized the existence of an endogenous death program within neurons that is suppressed by trophic factors. The extent and timing of required changes in the synthetic events that comprise the death program are unknown. In an effort to characterize the biochemical events that mediate the death program further, we performed several experiments on embryonic rat sympathetic neurons in vitro. The death program was blocked with cycloheximide when total protein synthesis was inhibited > or = 80%. When protein synthesis was inhibited within 22 +/- 4 h of NGF deprivation, death was prevented in half the neurons. Hence, we define the commitment point for protein synthesis to be 22 +/- 4 h. Analogously, the commitment point for RNA synthesis was 26 +/- 4 h and that for NGF rescue, 24 +/- 4 h. We tested the ability of a wide variety of chemicals to interfere with the death program. Most compounds tested were unable to prevent neuronal death. Some treatments, however, did save NGF-deprived neurons and were subsequently characterized. These included ultraviolet light and agents that raise intracellular concentrations of cAMP. Finally, we looked for the neuronal expression in vitro and in vivo of genes that have been associated with programmed death in other cell types, including TRPM-2/SGP-2, polyubiquitin, TGF beta-1, c-fos, and c-myc. None of these genes showed significant activation associated with neuronal death.
Use of Insoluble Biodegradable Polymers in Ophthalmic Systems for the Sustained Release of Drugs (1995)

Biomaterials have made a great impact on medicine. However, numerous challenges remain. The eye presents special challenges for drug delivery in the treatment of various ocular diseases. Many of the conventional therapeutic modalities have not adequately solved these problems. Medicated biodegradable devices used for drug delivery may offer several advantages over conventional ocular drug delivery methods. In this review, we discuss firstly the different mechanisms of erosion leading to the dissolution of the polymeric drug delivery systems. The principal investigation using polymer exhibiting a biodegradation (erosion type Ill) characterized by the cleavage of the polymeric chain, and the formation of small molecules is presented. These biodegradable polymers discussed include poly(alkyl cyanoacrylates), poly(lactic acids), poly(glycolic acids) and their copolymers, polycaprolactones, polyanhydrides and poly(ortho esters). In the last part of this review the application of these biodegradable polymers to the treatment of glaucoma is presented.
Novel Imidazoles and Hydantoins Moderately Strained by Incorporation with 2-Azabicyclo[2.2.1]heptene Skeleton (1994)

Abstract The reactions of 3-acyl-2-azabicyclo[2.2.1]hept-5-enes with phenyl isocyanate, phenyl isothiocyanate, and ethoxycarbonyl isothiocyanate followed by cyclization reactions under basic conditions respectively provided a hydantoin, a thiohydantoin, and a 1,3-dihydro-2H-imidazole-2-thione incorporated with the azabicyclic skeleton. Treatment of the imidazolethione with Raney nickel gave a phenyl-substituted imidazole fused with 2-azabicyclo[2.2.1]hept-2-ene. The effect of annulation on the 13C NMR of the imidazole ring is discussed.
2,6,10-Tris(dialkylamino)trioxatriangulenium Ions. Synthesis, Structure, and Properties of Exceptionally Stable Carbenium Ions (1998)

A general synthetic route to a novel type of triamino-substituted planar carbenium ions (5) is reported. The synthetic method is based on a facile and selective nucleophilic aromatic substitution on the tris(2,4,6-trimethoxyphenyl)carbenium ion (1) with amines and gives access to a wide variety of more complex amino-substituted carbenium ions. X-ray crystallography shows that the 2,6,10-tris(N-pyrrolidinyl)-4,8,12-trioxatriangulenium ion (5b) is planar and forms segregated stacks of cations and PF6 anions in the solid phase. The stability of the 2,6,10-tris(diethylamino)-4,8,12-trioxatriangulenium ion 5a is expressed as the pKR+ value, which is determined in strongly basic nonaqueous solution on the basis of a new acidity function C_. The pKR+ value of 5a is measured to be 19.7, which is 10 orders of magnitude higher than the values found for the most stable carbenium ions previously reported. Electrochemical reduction of compound 5a leads to rapid dimerization. Two consecutive one-electron oxidations are identified by cyclic voltammetry.
Overview of beam steering technology based on rotational double prisms (2013)

The rotational-double-prism system can change the optical path by rotating separately the two prisms of a common axis,so that it can be used to steer the beams or the Line of Sight(LOS).Compared with the conventional two-axis or three-axis optical electro-optical gimbals,the rotational-double-prism-based beam or LOS steering devices offer tremendous advantages such as high accuracy,compactness and good dynamic performance,and have been proved to be the helpful complementarity for electro-optical gimbals.This paper analyzes the beam steering mechanism of the rotational-double-prism system,and introduces the key problems of the relevant theories for the beam steering,which focus on the beam deflection mechanism,beam scanning mode,prism rotation control,beam deformation,imaging aberration and the imaging distortion induced by a prism.It describes the research progress of engineering technology and gives several kinds of products based the rotational-double-prism system and their application to the laser beam steering and target searching,target recognition and traking imaging.Finally,the technical challenges concluded in scanning patterns,beam quality,chromatic aberration,image distortions and rotation control are discussed and the development trends are evaluated.
Heat-inducible vectors for use in gene therapy (2000)

The objectives of this study were to quantity and compare the activities of a minimal heat shock (HS) promoter and other promoters used in gene therapy applications, and to identify strategies to amplify the heat inducibility of therapeutic genes. Human tumour cells were transiently or stably transfected with the HS promoter driving expression of reporter genes. HS promoter activity was induced transiently, with maximum activity 16-24 h after HS, and was dependent on temperature. The activity of the minimal HS promoter was similar, after 42 degrees C HS for 1 h, to that of the cytomegalovirus (CMV) promoter. To determine if the HS promoter could be used to activate a second conditional promoter, cells were transiently transfected with vectors containing both the HS and human immunodeficiency virus type 1 (HIV1) promoters. When the IL-2 gene was placed downstream of the HIV1 promoter. IL-2 production was temperature-independent. The addition of the HIV tat gene downstream of the HS promoter caused IL-2 to be induced more than 3 fold after a single 42 degrees C HS. These data indicate that the minimal HS promoter, following activation by clinically attainable temperatures (< or = 42 degrees C), can drive expression of therapeutic genes at levels comparable to the CMV promoter and be used in conjunction with a second conditional promoter to drive temperature-dependent, gene expression.
Guided acoustic wave propagation for porcelain coating characterization (1997)

In this paper a measurement technique to obtain dispersion curves for guided acoustic modes in porcelain-coated steel is described. The measurement is performed with two angled ultrasonic longitudinal transducers in a pitch catch configuration by employing an immersion technique. Phase velocities for the guided modes are selected through the variation of the angle formed by the transmitter beam with the surface normal vector. The excitation signal of the transmitting transducer is a narrow band pulse. For each phase velocity, the guided mode frequencies are recovered by evaluating the frequency minima of the reflection coefficient.
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate. (1994)

In Drosophila, the proneural genes of the achaete-scute complex encode transcriptional activators that can commit cells to a neural fate. We have isolated cDNAs for two Xenopus achaete-scute homologs, ASH3a and ASH3b, which are expressed in a subset of central nervous system (CNS) neuroblasts during early neurogenesis. After expressing either ASH3 protein in developing Xenopus embryos, we find enlargement of the CNS at the expense of adjacent non-neural ectoderm. Analysis of molecular markers for neural, epidermal, and neural crest cells indicates that CNS expansion occurs as early as neural plate formation. ASH3-dependent CNS enlargement appears to require neural induction, as it does not occur in animal cap explants. Inhibition of DNA synthesis shows that additional CNS tissue does not depend on cell division--rather it reflects conversion of prospective neural crest and epidermal cells to a neural fate. The differentiation of the early forming primary neurons also seems to be prevented by ASH3 expression. This may be secondary to the observed activation of Xotch transcription by ASH3.
Carbon nanoparticles in lateral flow methods to detect genes encoding virulence factors of Shiga toxin-producing Escherichia coli (2010)

The use of carbon nanoparticles is shown for the detection and identification of different Shiga toxin-producing Escherichia coli virulence factors (vt1, vt2, eae and ehxA) and a 16S control (specific for E. coli) based on the use of lateral flow strips (nucleic acid lateral flow immunoassay, NALFIA). Prior to the detection with NALFIA, a rapid amplification method with tagged primers was applied. In the evaluation of the optimised NALFIA strips, no cross-reactivity was found for any of the antibodies used. The limit of detection was higher than for quantitative PCR (q-PCR), in most cases between 10(4) and 10(5) colony forming units/mL or 0.1-0.9 ng/μL DNA. NALFIA strips were applied to 48 isolates from cattle faeces, and results were compared to those achieved by q-PCR. E. coli virulence factors identified by NALFIA were in very good agreement with those observed in q-PCR, showing in most cases sensitivity and specificity values of 1.0 and an almost perfect agreement between both methods (kappa coefficient larger than 0.9). The results demonstrate that the screening method developed is reliable, cost-effective and user-friendly, and that the procedure is fast as the total time required is <1 h, which includes amplification.
Inability of Ixodes cookei and Amblyomma americanum Nymphs (Acari: Ixodidae) To Transmit Borrelia burgdorferi (1992)

The vector competency of Ixodes cookei Packard and Amblyomma americanum (L.) for Borrelia burgdorferi was studied using Syrian hamsters. Ixodes dammini Spielman, Clifford, Piesman & Corwin were used as controls. Darkfield and immunofluorescent examinations of midgut diverticula revealed B. burgdorferi spirochetes in 32 of 36 (88.9%) I. dammini larvae, 5 of 36 (13.9%) I. cookei larvae, and 7 of 36 (19.4%) A. americanum larvae within 48 h after feeding on infected Syrian hamsters. B. burgdorferi were also observed in the midguts of 94 of 107 (87.8%) I. dammini nymphs that developed from the fed larvae. However, none of 30 I. cookei nymphs was positive for spirochetes and only 1 of 60 (1.7%) A. americanum nymphs was found positive for B. burgdorferi. Nymphs of each tick species, reared from larvae that had fed on infected hamsters, were allowed to feed on uninfected hamsters to determine their ability to transmit B. burgdorferi. Transmission was demonstrated only by I. dammini nymphs.
Metabolism of organically bound tritium (1984)

The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables.
Structural and biochemical analyses of DNA and RNA binding by a bifunctional homing endonuclease and group I intron splicing factor (2003)

We determined the crystal structure of a bifunctional group I intron splicing factor and homing endonuclease, termed the I-AniI maturase, in complex with its DNA target at 2.6 A resolution. The structure demonstrates the remarkable structural conservation of the beta-sheet DNA-binding motif between highly divergent enzyme subfamilies. DNA recognition by I-AniI was further studied using nucleoside deletion and DMS modification interference analyses. Correlation of these results with the crystal structure provides information on the relative importance of individual nucleotide contacts for DNA recognition. Alignment and modeling of two homologous maturases reveals conserved basic surface residues, distant from the DNA-binding surface, that might be involved in RNA binding. A point mutation that introduces a single negative charge in this region uncouples the maturase and endonuclease functions of the protein, inhibiting RNA binding and splicing while maintaining DNA binding and cleavage.
Metabolic effects of antisickling amounts of nitrogen and nor-nitrogen mustard on rabbit and human erythrocytes (1975)

Nitrogen mustard (NH2) and Nor-nitrogen mustard (Nor-HN2) both inhibit the polymerization of deoxyhemoglobin S in solution and in intact erythrocytes. Metabolic studies were undertaken to determine the feasability of an extracorporeal treatment with these or related agents. Glucose utilization, hexose monophosphate shunt activity, methemoglobin reduction, and incubation with acetylphenylhydrazine for Heinz body formation were performed, as well as specific assays for hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glutathione reductase, ATP, reduced glutathione (GSH), and survival of autologous mustard-treated cells in rabbits. HN2 was found to enter red cells rapidly and bind to intracellular contents. Metabolic studies revealed no significant inhibition or alteration of function by Nor-HN2 at 10 mg/ml of whole blood. Rabbit red cell survival was also normal. HN2, however, inhibited glutathione reductase and blocked the free sulfhydryl group of GSH by forming serveral addition products of alkylated GSH. Heinz body test with acetylphenylhydrazine became positive in HN2-treated cells, and rabbit red cell survival was shortened considerably in the concentration range used to inhibit sickling. Ascorbic acid stimulation of the hexose shunt pathway was inhibited by HN2, but methylene blue stimulation remained unaffected. 14-C-HN2 remains bound to red cells in vivo, and the disappearance of radioactivity is similar to that found with 14-C-DFP (disopropylfluorophosphate). Oxygen affinity of both HN2 and Nor-HN2 treated human red cells remains virtually the same as that found in control samples. It is concluded that Nor-HN2 may be a suitable agent for an extracorporeal therapy, and that each mustard needs to be evaluated individually for its antisickling effects and its suitability for extracorporeal use.
Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes (2008)

The purpose of this study was to determine whether bile acids (BAs) modulate hepatic pro-protein convertase subtilisin/kexin 9 (PCSK9) gene expression. Immortalized human hepatocytes were treated with various BAs. Chenodeoxycholic acid (CDCA) treatment specifically decreased both PCSK9 mRNA and protein contents. Moreover, activation of the BA-activated farnesoid X receptor (FXR) by its synthetic specific agonist GW4064 also decreased PCSK9 expression. Of functional relevance, coadministration of CDCA counteracted the statin-induced PCSK9 expression, leading to a potentiation of LDL receptor activity. This study suggests that a transcriptional repression of PCSK9 by CDCA or FXR agonists may potentiate the hypolipidemic effect of statins.