gebhart/patrepeval huggingface dataset:
Expression of a T cell receptor-like molecule on normal and malignant murine T cells detected by rat monoclonal antibodies to nonclonotypic determinants. (1986)

A T cell receptor-like molecule with a dimer structure of 45 kilodaltons (Kd) under reducing and 90 Kd under nonreducing conditions was detected on the surface of two murine T lymphoma lines, EL-4 and MBL-2, by two rat monoclonal antibodies. The two antibodies seemed to react with different determinants on the same molecule. The antibodies did not react with the surface of normal T cells as tested by flow cytometric analysis of cell surface staining. Two-dimensional gel electrophoresis (IEF vs SDS-PAGE) and tryptic peptide analysis revealed the molecule to consist of two chains with different isoelectric points and different tryptic peptides. A conventional antiserum was raised against the heterodimer purified from EL-4 cells. The immune serum did not bind to the surface of normal T cells. However, the immune serum as well as the monoclonal antibodies immunoprecipitated the dimer molecules from detergent-solubilized normal thymocytes and spleen cells. The dimer molecule was detected on both immature and mature thymocytes. These results suggest that the antibodies detect non-clonotypic determinants on a T cell receptor-like protein. The determinants are masked on the surface of normal T cells, whereas they are exposed on the surface of at least two T lymphoma cell lines. Three polypeptides of 30 Kd, 25 Kd, and 15 Kd were also coprecipitated with the heterodimer from MBL-2 cells. These proteins may associate with the heterodimer and may be masking the antigenic determinants on normal T cells. The relationship between the heterodimer molecule described here and the T cell antigen receptor or the human T cell antigen 9.3 is still unknown.
Identification of functionally distinct domains of human granulocyte- macrophage colony-stimulating factor using monoclonal antibodies (1991)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is required for the survival, growth, and differentiation of hematopoietic progenitor cells. Although the primary structure of GM-CSF is known from cDNA cloning, the relationship between structure and function of GM-CSF is not fully understood. Fifteen different monoclonal antibodies (MoAbs) to human GM-CSF were generated to map immunologically distinct areas of the molecule. Each of the MoAbs was biotinylated and shown by enzyme-linked immunosorbent assay to bind to recombinant GM-CSF that had been affixed to a solid phase. Each of the 15 unconjugated MoAbs was then used to compete with each biotinylated MoAb for binding to GM-CSF. These cross-blocking studies identified eight distinct epitopes of native GM-CSF. Seven of these epitopes were also present in denatured GM-CSF by Western blotting, and four of the epitopes were at least partially conserved on GM-CSF that was reduced in beta-mercaptoethanol. MoAbs to four of eight epitopes neutralized both recombinant (glycosylated and nonglycosylated) and natural human GM-CSF in a GM colony-forming unit (CFU-GM) assay and blocked GM-CSF-induced activation of neutrophils. For most of the antibodies there was a good correlation between neutralizing activity and the capacity to block binding of 125I-GM-CSF to neutrophils or blasts. Non-neutralizing antibodies to one epitope partially blocked binding of 125I-GM-CSF to neutrophils. None of the MoAbs neutralized interleukin-3, G-CSF, or M-CSF. The locations of seven of the epitopes could be partially mapped with regard to the amino acid structure by determining reactivity to GM-CSF synthetic peptides or to human-mouse chimeric GM-CSFs. The neutralizing antibodies were found to map to amino acids 40–77, 78–94, or 110–127. Thus, these MoAbs are useful to identify functional domains of GM-CSF and in identifying regions that are likely to be involved in receptor interaction.
Generation of a catalytic sequence-specific hybrid DNase (1989)

Hybrid nucleases consisting of an oligonucleotide fused to a unique site on the relatively nonspecific phosphodiesterase staphylococcal nuclease have been shown to sequence specifically cleave DNA. We have introduced mutations into the binding pocket of the nuclease which lower the kcat/Km of the enzyme. Hybrid nucleases generated from these mutants sequence selectively hydrolyze single-stranded DNA in a catalytic fashion, and under a much wider range of conditions than was previously possible. One such hybrid nuclease (Y113A, K116C) was able to site selectively cleave single-stranded M13mp7 DNA (7214 nt), primarily at one phosphodiester bond. Another hybrid nuclease (Y113A, L37A, K116C) catalyzed the hydrolysis of a 78-nt DNA substrate with a kcat of 1.2 min-1 and a Km of 120 nM. The effects of variations in the length and sequence of the oligonucleotide binding region were examined, as were changes in the length of the tether between the oligonucleotide and the enzyme. Cleavage specificity was also assayed as a function of substrate DNA primary and secondary structure and added poly(dA).
A New Method for the Preparation of Minicells for Physiological Studies (1973)

Abstract A procedure has been developed for preparing minicells that does not rely on sucrose gradients in a rate-zone centrifuge. In the presence of low levels (10 units/ml) of penicillin, the contaminating bacteria present in minicell cultures after low-speed differential centrifugation are turned into long filamentous cells and can be killed by sonic treatment. An additional low-speed centrifugation (2, 000 g for 5 min) yields purified minicells with less than one contaminating cell per 10 minicells.
Studies in Owl Monkeys Leading to the Development of a Synthetic Vaccine against the Asexual Blood Stages of Plasmodium Falciparum (1990)

During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity. We determined the minimal infective dose of the P. falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P. falciparum strains. A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge. These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P. falciparum.
Anaerobic Fluidized Bed Membrane Bioreactor for Wastewater Treatment (2010)

Anaerobic membrane bioreactors have potential for energy-efficient treatment of domestic and other wastewaters, membrane fouling being a major hurdle to application. It was found that fouling can be controlled if membranes are placed directly in contact with the granular activated carbon (GAC) in an anaerobic fluidized bed bioreactor (AFMBR) used here for post-treatment of effluent from another anaerobic reactor treating dilute wastewater. A 120-d continuous-feed evaluation was conducted using this two-stage anaerobic treatment system operated at 35 °C and fed a synthetic wastewater with chemical oxygen demand (COD) averaging 513 mg/L. The first-stage was a similar fluidized-bed bioreactor without membranes (AFBR), operated at 2.0-2.8 h hydraulic retention time (HRT), and was followed by the above AFMBR, operating at 2.2 h HRT. Successful membrane cleaning was practiced twice. After the second cleaning and membrane flux set at 10 L/m(2)/h, transmembrane pressure increased linearly from 0.075 to only 0.1 bar during the final 40 d of operation. COD removals were 88% and 87% in the respective reactors and 99% overall, with permeate COD of 7 ± 4 mg/L. Total energy required for fluidization for both reactors combined was 0.058 kWh/m(3), which could be satisfied by using only 30% of the gaseous methane energy produced. That of the AFMBR alone was 0.028 kWh/m(3), which is significantly less than reported for other submerged membrane bioreactors with gas sparging for fouling control.
Site directed biotinylation of filamentous phage structural proteins (2011)

Filamentous bacteriophages have been used in numerous applications for the display of antibodies and random peptide libraries. Here we describe the introduction of a 13 amino acid sequence LASIFEAQKIEWR (designated BT, which is biotinylated in vivo by E. coli) into the N termini of four of the five structural proteins of the filamentous bacteriophage fd (Proteins 3, 7, 8 and 9). The in vivo and in vitro biotinylation of the various phages were compared. The production of multifunctional phages and their application as affinity reagents are demonstrated.
Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging (2003)

The presence of amyloid-beta (Abeta) plaques in the brain is a hallmark pathological feature of Alzheimer's disease (AD). Transgenic mice overexpressing mutant amyloid precursor protein (APP), or both mutant APP and presenilin-1 (APP/PS1), develop Abeta plaques similar to those in AD patients, and have been proposed as animal models in which to test experimental therapeutic approaches for the clearance of Abeta. However, at present there is no in vivo whole-brain imaging method to detect Abeta plaques in mice or men. A novel method is presented to detect Abeta plaques in the brains of transgenic mice by magnetic resonance microimaging (muMRI). This method uses Abeta1-40 peptide, known for its high binding affinity to Abeta, magnetically labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). Intraarterial injection of magnetically labeled Abeta1-40, with mannitol to transiently open the blood-brain barrier (BBB), enabled the detection of many Abeta plaques. Furthermore, the numerical density of Abeta plaques detected by muMRI and by immunohistochemistry showed excellent correlation. This approach provides an in vivo method to detect Abeta in AD transgenic mice, and suggests that diagnostic MRI methods to detect Abeta in AD patients may ultimately be feasible.
Spatial reconstruction of coronary arteries from angiographic images (1991)

A method for 3D reconstruction of coronary arteries from two angiographic projection views is presented (cinefilm 35 mm, 50 images/s). The geometric information defining the two projections is secured by filming a cube bearing 15 steel markers in the approximate location of the heart. For 3D reconstruction, a pair of images of the cube and two simultaneous images of the coronary tree are digitized on a computer assisted system. Two matrices describing the two projections are obtained from the 15 x 2 x 2 image coordinates of the cube markers. Next, the operator draws with a mouse the approximate centre lines of the coronary arteries to be 3D reconstructed. The program then determines the centre lines and the edges of the vessels in the two images accurately. The 3D centre lines are reconstructed and the true local vessel diameters determined. Intravascular volumes are obtained by summation of elementary volumes. The reconstructed arteries are visualized on a colour TV monitor. Measurements on various phantoms have shown that lengths of a few centimetres can be measured with typically 2% error. The accuracy of volume determination was somewhat less due to the inaccuracy of lumen determination. For real coronary arteries the volume error is estimated to be about 15% because of the poorer image quality.
PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes (2015)

PI3Ks regulate diverse immune cell functions by transmitting intracellular signals from Ag, costimulatory receptors, and cytokine receptors to control cell division, differentiation, survival, and migration. In this study, we report the effect of inhibiting the p110δ subunit of PI3Kδ on CD8(+) T cell responses to infection with the intracellular bacteria Listeria monocytogenes. A strong dependency on PI3Kδ for IFN-γ production by CD8(+) T cells in vitro was not recapitulated after Listeria infection in vivo. Inactivation of PI3Kδ resulted in enhanced bacterial elimination by the innate immune system. However, the magnitudes of the primary and secondary CD8 +: T cell responses were reduced. Moreover, PI3Kδ activity was required for CD8(+) T cells to provide help to other responding CD8(+) cells. These findings identify PI3Kδ as a key regulator of CD8(+) T cell responses that integrates extrinsic cues, including those from other responding cells, to determine the collective behavior of CD8(+) T cell populations responding to infection.
A lab-on-a-chip for detection of nerve agent sarin in blood (2008)

Sarin (C(4)H(10)FO(2)P,O-isopropyl methylphosphonofluoridate) is a colourless, odourless and highly toxic phosphonate that acts as a cholinesterase inhibitor and disrupts neuromuscular transmission. Sarin and related phosphonates are chemical warfare agents, and there is a possibility of their application in a military or terrorist attack. This paper reports a lab-on-a-chip device for detecting a trace amount of sarin in a small volume of blood. The device should allow early detection of sarin exposure during medical triage to differentiate between those requiring medical treatment from mass psychogenic illness cases. The device is based on continuous-flow microfluidics with sequential stages for lysis of whole blood, regeneration of free nerve agent from its complex with blood cholinesterase, protein precipitation, filtration, enzyme-assisted reaction and optical detection. Whole blood was first mixed with a nerve gas regeneration agent, followed by a protein precipitation step. Subsequently, the lysed product was filtered on the chip in two steps to remove particulates and fluoride ions. The filtered blood sample was then tested for trace levels of regenerated sarin using immobilised cholinesterase on the chip. Activity of immobilised cholinesterase was monitored by the enzyme-assisted reaction of a substrate and reaction of the end-product with a chromophore. Resultant changes in chromophore-induced absorbance were recorded on the chip using a Z-shaped optical window. Loss of enzyme activity obtained prior and after passage of the treated blood sample, as shown by a decrease in recorded absorbance values, indicates the presence of either free or regenerated sarin in the blood sample. The device was fabricated in PMMA (polymethylmethacrylate) using CO(2)-laser micromachining. This paper reports the testing results of the different stages, as well as the whole device with all stages in the required assay sequence. The results demonstrate the potential use of a field-deployable hand-held device for point-of-care triage of suspected nerve agent casualties.
MicroRNAs and Their Therapeutic Potential for Human Diseases: Aberrant MicroRNA Expression in Alzheimer’s Disease Brains (2010)

MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled manner. They play a key role in neuronal development, differentiation, and synaptic plasticity. However, at present, the pathological implications of deregulated miRNA expression in neurodegenerative diseases remain largely unknown. This review will briefly summarize recent studies that focus attention on aberrant miRNA expression in Alzheimer's disease brains.
Characterization and Subcellular Compartmentation of Recombinant 4-Hydroxyphenylpyruvate Dioxygenase from Arabidopsis in Transgenic Tobacco1 (1999)

4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and molecular oxygen. In plants this enzyme activity is involved in two distinct metabolic processes, the biosynthesis of prenylquinones and the catabolism of tyrosine. We report here the molecular and biochemical characterization of an Arabidopsis 4HPPD and the compartmentation of the recombinant protein in chlorophyllous tissues. We isolated a 1508-bp cDNA with one large open reading frame of 1338 bp. Southern analysis strongly suggested that this Arabidopsis 4HPPD is encoded by a single-copy gene. We investigated the biochemical characteristics of this 4HPPD by overproducing the recombinant protein in Escherichia coli JM105. The subcellular localization of the recombinant 4HPPD in chlorophyllous tissues was examined by overexpressing its complete coding sequence in transgenic tobacco (Nicotiana tabacum), using Agrobacterium tumefaciens transformation. We performed western analyses for the immunodetection of protein extracts from purified chloroplasts and total leaf extracts and for the immunocytochemistry on tissue sections. These analyses clearly revealed that 4HPPD was confined to the cytosol compartment, not targeted to the chloroplast. Western analyses confirmed the presence of a cytosolic form of 4HPPD in cultured green Arabidopsis cells.
IL‐12 as a therapeutic target for pharmacological modulation in immune‐mediated and inflammatory diseases: regulation of T helper 1/T helper 2 responses (1999)

Interleukin-12 (IL-12) is a pivotal cytokine in driving the immune system towards a T helper (Th)1 type response and preventing a Th2 type immune profile. Therefore, IL-12 is indispensable in the defense against certain, mainly intracellular pathogens, but overproduction of this cytokine is crucially involved in the etiology of several inflammatory and autoimmune diseases. Hence, IL-12 is an ideal target for pharmacological intervention in the therapy of autoimmune and inflammatory diseases. The production of IL-12 and a resultant Th1 type immune response can be suppressed with several pharmacological approaches including modulation of intracellular cyclic AMP levels, glucocorticoids and nuclear factor-kappaB inhibition. IL-12 responsiveness may be inhibited using anti-IL-12 antibodies, soluble IL-12 receptors or the IL-12 p40 homodimer. Exploitation of these approaches may provide novel means for the experimental therapy of a variety of pathophysiological states.
Optimization of HAART with genetic algorithms and agent-based models of HIV infection (2007)

A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html
The Pseudotypic Paradox (1982)

The assembly of virion surface glycoproteins by enveloped viruses appears to be both specific and non-specific. It is non-specific in the sense that, during a dual infection by various unrelated viruses, there is very common (if not universal) and efficient mixing of envelope glycoproteins from both genotypes in the progeny virions. However, it seems to be specific in the sense that non-viral, cell surface proteins are, in the main, recognized as alien and are excluded from incorporation into virions during budding. These findings suggest that all enveloped viruses may share an essentially common molecular mechanism for the specific assembly and budding of virus glycoproteins while at the same time incorporating a mechanism for the exclusion of glycoproteins of cellular origin. One of the simplest explanations for this phenomenon may be that virus envelope surface structures all evolved from a single ancestral virus.
Tissue-Selective Effects of Injected Deoxycholate (2010)

We report observations that provide a possible explanation for the in vivo preferential fat targeting by DC. Fat tissue, being deficient in cell-associated proteins and interstitial albumin, may be unable to sufficiently neutralize the detergent activity of DC, possibly making fat uniquely sensitive to DC.
Taurine provides antioxidant defense against NaF-induced cytotoxicity in murine hepatocytes (2008)

Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The present study was conducted to investigate the protective role of taurine (2-aminoethane sulphonic acid) against fluoride-induced cytotoxicity in murine hepatocytes. Sodium fluoride (NaF) was used as the source of fluoride for this particular study. Dose-dependent studies suggest that incubation of hepatocytes with NaF (100mM) for 1h significantly decreased the cell viability as well as intracellular antioxidant power. Increased activities of alanine transaminase (ALT) and alkaline phosphatase (ALP) due to the same dose of toxin exposure confirmed membrane damage. Toxin-induced increased level of intracellular reactive oxygen species (ROS) was confirmed by intracellular ROS production assay using a fluorescent probe 2',7'-dichlorofluorescein diacetate (DCF-DA). In addition, the activities of the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) were also decreased by toxin treatment at the previous dose. The same treatment also reduced the level of glutathione (GSH) and total thiols, elevated the level of oxidized glutathione (GSSG) and increased the level of lipid peroxidation end products, protein carbonyl content and extent of DNA fragmentation. Incubation of hepatocytes with taurine, both prior to and in combination with NaF, altered all the NaF-induced parameters. A known antioxidant, vitamin C was taken to compare the cytoprotective activity of taurine against fluoride poisoning. Combining all, the results suggest that taurine protects mouse hepatocytes against fluoride-induced cytotoxity.
Electron-rich, bulky PNN-type ruthenium complexes: synthesis, characterization and catalysis of alcohol dehydrogenation (2006)

Reaction of the electron-rich, bulky tridentate PNN ligand (PNN=2-di-tert-butylphosphinomethyl-6-diethylaminomethylpyridine) with Ru(PPh3)3Cl2 at 65 degrees C resulted in formation of the mononuclear dinitrogen complex (PNN)Ru(Cl)2N2 (minor) and the N2 bridged Ru(II) dinuclear complex [(PNN)Ru(Cl)2]2(micro-N2) (major). These complexes can be interconverted; passing argon through a solution of the mixture resulted in formation of pure . The cationic square-pyramidal [(PNN)Ru(PPh3)Cl]OTf was obtained by the reaction of complex with silver triflate followed by PPh3. Reaction of complex with CO yielded (PNN)Ru(CO)Cl2, which upon reaction with one equiv. of AgBF4 gave the cationic [(PNN)Ru(CO)Cl]BF4. The dicationic [(PNN)Ru(CO)(H2O)(acetone)](BF4)2 was obtained from with 2 equiv. of AgBF4 in acetone solution. Complexes , and were structurally characterized by X-ray crystallography. Complexes and upon addition of an equivalent of base, catalyzed the dehydrogenation of secondary alcohols to the corresponding ketones and primary alcohols to esters in good yields and high selectivity accompanied with the evolution of hydrogen gas.
Atomic Structure of a Lithium-Rich Layered Oxide Material for Lithium-Ion Batteries: Evidence of a Solid Solution (2011)

Li[Li0.2Ni0.2Mn0.6]O2, which is a cathode material for Li-ion batteries with enhanced capacity, has been examined, for the first time, with a combination of aberration-corrected scanning transmission electron microscopy (STEM), STEM computer simulations, and diffraction scanning transmission electron microscopy (D-STEM). These techniques, in combination with X-ray diffraction (XRD) and conventional electron diffraction (ED), indicate that this material is composed of a solid solution with C2/m monoclinic symmetry and multiple planar defects. In addition, we show that XRD and ED alone can give misleading information and cannot resolve the structure of these materials without the additional use of the aforementioned techniques.