gebhart/patrepeval huggingface dataset:
Increased CCT-eta expression is a marker of latent and active disease and a modulator of fibroblast contractility in Dupuytren’s contracture (2013)

Dupuytren's contracture (DC) is a fibroproliferative disorder of unknown etiology characterized by a scar-like contracture that develops in the palm and/or digits. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is increased in fibrotic wound healing, and is essential for the accumulation of α-smooth muscle actin (α-SMA) in fibroblasts. The purpose of this study was to determine if CCT-eta is similarly implicated in the aberrant fibrosis seen in DC and to investigate the role of CCT-eta in the behavior of myo/fibroblasts in DC. Fibroblasts were obtained from DC-affected palmar fascia, from adjacent phenotypically normal palmar fascia in the same DC patients (PF), and from non-DC palmar fascial tissues in patients undergoing carpal tunnel (CT) release. Inherent contractility in these three populations was examined using fibroblast-populated collagen lattices (FPCLs) and by cell traction force microscopy. Expression of CCT-eta and α-SMA protein was determined by Western blot. The effect of CCT-eta inhibition on the contractility of DC cells was determined by deploying an siRNA versus CCT-eta. DC cells were significantly more contractile than both matching palmar fascial (PF) cells and CT cells in both assays, with PF cells demonstrating an intermediate contractility in the FPCL assay. Whereas α-SMA protein was significantly increased only in DC cells compared to PF and CT cells, CCT-eta protein was significantly increased in both PF and DC cells compared to CT cells. siRNA-mediated depletion of CCT-eta inhibited the accumulation of both CCT-eta and α-SMA protein in DC cells, and also significantly decreased the contractility of treated DC cells. These observations suggest that increased expression of CCT-eta appears to be a marker for latent and active disease in these patients and to be essential for the increased contractility exhibited by these fibroblasts.
Messenger RNA-Electroporated Dendritic Cells Presenting MAGE-A3 Simultaneously in HLA Class I and Class II Molecules (2004)

An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th cells and CD8(+) CTLs. A promising tool in cancer immunotherapy is, therefore, the genetic modification of dendritic cells (DCs) by introducing the coding region of a tumor Ag, of which the antigenic peptides will be presented in both HLA class I and class II molecules. This can be achieved by linking the tumor Ag to the HLA class II-targeting sequence of an endosomal or lysosomal protein. In this study we compared the efficiency of the targeting signals of invariant chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP. Human DCs were electroporated before or after maturation with mRNA encoding unmodified enhanced green fluorescent protein (eGFP) or eGFP linked to various targeting signals. The lysosomal degradation inhibitor chloroquine was added, and eGFP expression was evaluated at different time points after electroporation. DCs were also electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA class I and class II molecules was investigated. Our data suggest that proteins linked to the different targeting signals are targeted to the lysosomes and are indeed presented in the context of HLA class I and class II molecules, but with different efficiencies. Proteins linked to the LAMP1 or DC-LAMP signal are more efficiently presented than proteins linked to the invariant chain-targeting signal. Furthermore, DCs electroporated after maturation are more efficient in Ag presentation than DCs electroporated before maturation.
G-quadruplex DNA Aptamers and their Ligands: Structure, Function and Application (2012)

Highly specific and tight-binding nucleic acid aptamers have been selected against a variety of molecular targets for over 20 years. A significant proportion of these oligonucleotides display G-quadruplex structures, particularly for DNA aptamers, that enable molecular recognition of their ligands. G-quadruplex structures couple a common scaffold to varying loop motifs that act in target recognition. Here, we review DNA G-quadruplex aptamers and their ligands from a structural and functional perspective. We compare the diversity of DNA G-quadruplex aptamers selected against multiple ligand targets, and consider structure with a particular focus on dissecting the thrombin binding aptamer - thrombin interaction. Therapeutic and analytical applications of DNA G-quadruplex aptamers are also discussed. Understanding DNA G-quadruplex aptamers carries implications not only for therapeutics and diagnostics, but also in the natural biochemistry of guanine-rich nucleic acids.
Conduction Velocity Restitution of the Human Atrium—An Efficient Measurement Protocol for Clinical Electrophysiological Studies (2011)

Conduction velocity (CV) and CV restitution are important substrate parameters for understanding atrial arrhythmias. The aim of this work is to (i) present a simple but feasible method to measure CV restitution in-vivo using standard circular catheters, and (ii) validate its feasibility with data measured during incremental pacing. From five patients undergoing catheter ablation, we analyzed eight datasets from sinus rhythm and incremental pacing sequences. Every wavefront was measured with a circular catheter and the electrograms were analyzed with a cosine-fit method that calculated the local CV. For each pacing cycle length, the mean local CV was determined. Furthermore, changes in global CV were estimated from the time delay between pacing stimulus and wavefront arrival. Comparing local and global CV between pacing at 500 and 300 ms, we found significant changes in seven of eight pacing sequences. On average, local CV decreased by 20 ± 15% and global CV by 17 ± 13%. The method allows for in-vivo measurements of absolute CV and CV restitution during standard clinical procedures. Such data may provide valuable insights into mechanisms of atrial arrhythmias. This is important both for improving cardiac models and also for clinical applications, such as characterizing arrhythmogenic substrates during sinus rhythm.
Requirement for Both the Cd3/T Cell Receptor Complex and the Cd2/Lymphocyte Function-Associated Antigen-3 Adhesion System in Monocyte-Independent T Cell Activation by Oxidized Erythrocytes (1989)

Recent reports have shown that human T lymphocytes can be activated in vitro by desialyzed oxidized erythrocytes (DOE) in a monocyte-independent fashion. These findings suggest that, in addition to providing the activating stimulus, DOE may also fulfill accessory cell roles normally supplied by monocytes in T cell activation. DOE may thus be a useful substitute for antigen-presenting accessory cells in studies of T cell activation. This report describes experiments conducted to determine if T cell activation by DOE involves cell surface structures known to play a role in antigen-induced T cell activation. T cell stimulation by DOE was blocked by anti-CD3 monoclonal antibody, suggesting that perturbation of the CD3/T cell antigen receptor complex on T cells is required for activation. Activation was also blocked by anti-CD2 monoclonal antibody, indicating involvement of the CD2/LFA-3 adhesion system. Since DOE and monocytes both express LFA-3, the role of LFA-3 on DOE in T cell activation was assessed. DOE pretreated with anti-LFA-3 monoclonal antibody induced markedly lower levels of T cell proliferation. As further evidence for LFA-3 involvement, DOE prepared from 5 patients with paroxysmal nocturnal hemoglobinuria (PNH), known to exhibit deficient LFA-3 expression, were also deficient in T-cell stimulatory activity. These findings illustrate that T cell activation by DOE requires many of the surface structures involved in activation by antigen-bearing accessory cells, and may thus serve as a useful model for studies of T cell activation.
Collagen, Human Collagen, and Fat: The Search for a Three-Dimensional Soft Tissue Filler (2001)

As the body ages, not only are the soft tissues of the face subject to gravity but they also may undergo progressive atrophy. Suspensory procedures may return the tissues to a more youthful position, but the atrophic changes are left uncorrected and produce an aged appearance. Three-dimensional (3-D) soft tissue fillers ideally would replace the bulk that was lost. Safety, persistence, and verisimilitude to the native tissues should be optimal in useful 3-D fillers. To date, no such material has been described, but there has been a resurgence in natural materials for this purpose. This article serves as an update on human-derived soft tissue fillers.
The proteasome (multicatalytic protease) is a component of the 1500-kDa proteolytic complex which degrades ubiquitin-conjugated proteins. (1990)

Mammalian cells contain two large proteolytic complexes, the 650-kDa proteasome (or multicatalytic protease) and the 1500-kDa (26 S) Ubiquitin-conjugate-degrading enzyme. Since the proteasome is also required for the ATP-dependent degradation of ubiquitinated proteins, we tested whether it may be a component of the larger complex. The proteasome normally is soluble in 38% ammonium sulfate. However, after preincubation of reticulocyte extracts with ATP, several proteasome activities appeared in the 38% ammonium sulfate pellet, including the ability to degrade hydrophobic peptides and 14C-casein. Also, following preincubation with ATP, the precipitable fraction could degrade 125I-lysozyme-ubiquitin (Ub) conjugates. The activities were not present after incubation without ATP or with a nonmetabolizable ATP analog. Nondenaturing gel electrophoresis indicated the ATP-dependent appearance of a new band which degraded proteasome substrates, and reacted with an anti-proteasome monoclonal antibody on Western blot. This new band appeared larger than the proteasome and migrated similarly to the larger Ub-conjugate-degrading complex. The formation of the larger complex required factor(s) present in the 38% ammonium sulfate pellet and either the 40-80% fraction or the purified proteasome from reticulocytes or muscle. After complex formation, hydrolysis of Ub-protein conjugates and also the non-ubiquitinated substrate, casein, was stimulated severalfold by ATP, but non-metabolizable ATP analogs had little or no effect. Thus, the proteasome corresponds to component CF-3 of Ganoth et al. (Ganoth, D., Leshinisky, E., Eytan, E., and Hershkov, A. (1989) J. Biol. Chem. 263 12412-12419) and undergoes an energy-dependent association with other factors to form the 1500-kDa, ATP-requiring proteolytic complex.
Innate Immune Recognition of Cancer (2015)

The observation that a subset of cancer patients show evidence for spontaneous CD8+ T cell priming against tumor-associated antigens has generated renewed interest in the innate immune pathways that might serve as a bridge to an adaptive immune response to tumors. Manipulation of this endogenous T cell response with therapeutic intent-for example, using blocking antibodies inhibiting PD-1/PD-L1 (programmed death-1/programmed death ligand 1) interactions-is showing impressive clinical results. As such, understanding the innate immune mechanisms that enable this T cell response has important clinical relevance. Defined innate immune interactions in the cancer context include recognition by innate cell populations (NK cells, NKT cells, and γδ T cells) and also by dendritic cells and macrophages in response to damage-associated molecular patterns (DAMPs). Recent evidence has indicated that the major DAMP driving host antitumor immune responses is tumor-derived DNA, sensed by the stimulator of interferon gene (STING) pathway and driving type I IFN production. A deeper knowledge of the clinically relevant innate immune pathways involved in the recognition of tumors is leading toward new therapeutic strategies for cancer treatment.
Solution for high-performance Schottky-source/drain MOSFETs: Schottky barrier height engineering with dopant segregation technique (2004)

A novel approach for achieving high-performance Schottky-source/drain MOSFETs (SBTs: Schottky Barrier Transistors) is proposed. The dopant segregation (DS) technique is employed and significant modulation of Schottky barrier height is demonstrated. The DS-SBT fabricated with the current CoSi/sub 2/ process show competitive drive current and better short-channel-effect immunity compared to the conventional MOSFET. In conclusion the DS-Schottky junction is useful for the source/drain of advanced MOSFETs.
Theory of double parasitic loop counterpoise antenna radiation patterns (1973)

Concepts of ray optics and the results of Sommerfeld's half-plane diffraction theory are applied to obtain theoretical expressions for the elevation plane radiation field produced by double parasitic loop counterpoise antennas. Theoretical results are compared with results obtained from model measurements. Within the range of approximation the agreement between theory and experiment has been found to be satisfactory. A method of designing the antenna for special application to air traffic control systems is also discussed briefly.
Non-invasive aneuploidy detection using free fetal DNA and RNA in maternal plasma: recent progress and future possibilities (2010)

The technical advances for non-invasive aneuploidy tests based on cff DNA and placental mRNA in maternal plasma have been enormous. Multimarker assays including genome-wide approaches with the option of qualitative information on variation (polymorphism or mutation) besides quantitative information are the preferred methods of choice. The time for population-based, double blind, large-scale clinical cohort trials has come.
Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis (1993)

The product of the vpr open reading frame of human immunodeficiency virus type 1 (HIV-1) is a 15-kDa, arginine-rich protein that is present in virions in molar quantities equivalent to that of Gag. We report here the results of our investigations into the mechanism by which Vpr is incorporated into virions during assembly in infected cells. For these studies we used an expression vector encoding a Vpr molecule fused at its amino terminus to a nine-amino-acid peptide from influenza virus hemagglutinin. The tagged Vpr expression vector and a vpr mutant HIV-1 provirus were used to cotransfect COS cells, and the resulting virions were tested for the presence of the tagged protein on immunoblots probed with monoclonal antibody against the hemagglutinin peptide. The COS-produced virions were found to contain readily detectable amounts of tagged Vpr and smaller amounts of a putative tagged Vpr dimer. Infectivity of the particles was not altered by incorporation of tagged Vpr. Our results using this system in combination with mutant HIV-1 proviruses suggested that incorporation of Vpr into virions requires the carboxy-terminal Gag protein of HIV-1 (p6) but not gp160, Pol, or genomic viral RNA. In addition, analysis of mutated, tagged Vpr molecules suggested that amino acids near the carboxy terminus (amino acids 84 to 94) are required for incorporation of Vpr into HIV-1 virions. The single cysteine residue near the carboxy terminus was required for production of a stable protein. Arginine residues tested were not important for incorporation or stability of tagged Vpr. These results suggested a novel strategy for blocking HIV-1 replication.
Analysis of Specific Proteins in Prostatic Fluid for Detecting Prostatic Malignancy (1979)

In an attempt to identify an indicator(s) specifically associated with prostatic cancer prostatic fluid was collected by rectal massage from patients with prostatic cancer, prostatitis, benign prostatic hyperplasia and from those without recognized prostatic lesions in order to measure various immunoproteins. The proteins examined were IgG, IgA, IgM, complements C3 and C4, and transferrin. Prostatic fluid samples were subjected first to immunoelectrophoresis. Distinct differences in C3, C4 and transferrin concentrations were noted between patients with prostatic cancer and other patients. These proteins were stained heavily in the electrophoresis gels of fluid from cancer patients but were either missing or lightly stained in all other groups. These qualitative determinations were replaced subsequently by a quantitative measurement using the radial immunodiffusion technique. Results of the latter study confirmed the aforementioned observations and indicated that the levels of C3, C4 and transferrin in the prostatic fluid of cancer patients were elevated significantly when compared to all other patient groups. These observations indicate that the measurement of complements C3 and C4, and transferrin in the prostatic fluid may assist in the identification of patients with a high risk of prostatic cancer.
Characterization of the promoter region of the Bacillus subtilis spoIIE operon (1988)

Mutations that define the spoIIE locus of Bacillus subtilis block sporulation at an early stage and recently were shown to prevent the proteolytic processing of sigma E (sigma 29) into its active form, an event that is believed to control critical changes in gene expression during the second hour of development. By taking advantage of two Tn917-mediated insertional mutations in spoIIE, we have cloned DNA spanning the locus. Gene disruption experiments with subcloned fragments transferred to integrational vectors revealed that the locus consisted of a single transcription unit about 2.5 kilobase pairs in size. Transcriptional lacZ fusions were used to show that expression of this transcription unit initiated at 1.5 h after the end of log-phase growth and depended upon the products of all spo0 loci. Expression was directed by a single promoter whose position was determined by high-resolution S1 protection mapping. A deletion analysis of the promoter region was also carried out, with novel integrational vectors based on derivatives of coliphage M13. The results indicated that a region of DNA extending from 183 to 118 base pairs upstream from the start point of transcription was required for full activity of the spoIIE promoter. The presumptive RNA polymerase-binding region of the promoter exhibited striking similarity to the spoIIG promoter and featured perfect but unusually spaced -10 and -35 consensus sequences for sigma A (sigma 43)-associated RNA polymerase.
Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. (1984)

A cDNA sequence coding for mouse mast-cell growth-factor (MCGF) has been cloned from a cDNA library prepared from mRNA derived from a concanavalin A-activated mouse T-cell clone. Cloning was achieved using the pcD vector that permits expression of cDNA inserts in mammalian cells. The DNA sequence codes for a polypeptide of 166 amino acid residues including a putative signal peptide. The supernatant fluid obtained after transfection of COS-7 monkey cells with the pcD-MCGF plasmid had mouse MCGF activity. The MCGF amino acid sequence between amino acids 33 and 41, deduced from the nucleotide sequence of its cDNA, is identical to the NH2-terminal sequence of the mouse lymphokine, interleukin 3, suggesting that MCGF is related to interleukin 3.
Porcine malignant hyperthermia susceptibility: erythrocytic osmotic fragility. (1985)

Erythrocyte osmotic fragility was determined in 27 Pietrain swine which were susceptible to malignant hyperthermia (MH), 29 Yorkshire swine which were resistant to MH (controls), and 50 crossbred swine (Pietrain x Yorkshire), half of which were MH susceptible. Halothane challenge tests and blood creatine kinase activity were used as criteria for determining MH susceptibility. Mean values for osmotic fragility of erythrocytes in concentrations of NaCl between 60 and 120 mM were significantly different for the 3 groups (P less than 0.001). Hemolysis (50%) of erythrocytes occurred at NaCl concentrations of 90 mM for Pietrains, 85 mM for crossbreds, and 78 mM for controls. Increased fragility values occurred in 96% of the Pietrains, 3% of the controls, and 42% of crossbred swine that were halothane test-positive, and 58% of halothane test-negative crossbreds (P less than 0.05). The mean time of onset of signs of MH in response to halothane challenge testing was twice as long in the crossbreds as in Pietrains (P less than 0.01). Reticulocyte counts were moderately high in blood samples from both the Pietrains (P less than 0.001) and the crossbreds (P less than 0.05). Of the swine which were tested for erythrocyte selenium-dependent glutathione peroxidase activity, values were within acceptable laboratory limits in 18 of 20 Pietrains, 14 of 14 halothane test-negative crossbreds, and 8 of 8 halothane test-positive crossbreds. In 2 of 20 Pietrains, a 35% deficiency of this enzyme was found. Heinz bodies were not detected in erythrocytes examined from 21 Pietrains, 20 crossbred swine (8 halothane test positives), and 12 controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative study of actin filament patterns in lens epithelial cells. Are these determined by the mechanisms of lens accommodation? (1989)

Actin filament patterns in lens epithelia from animals of various taxonomic groups were studied using rhodamine phalloidin fluorescence microscopy of epithelial whole mounts and transmission electron microscopy of tangential sections. The results were compared with the accommodative mechanism operating in each case as reported in the literature. Lenses that accommodate by deformation of the anterior surface, in squirrel, chipmunk, rabbit, monkey and human, showed polygonal arrays (PAs) at the apical end of the epithelial cells. Lenses that translate as a whole, in shark, bony fish and frog, showed stress fibers (SFs) at the basal or apical end of the cells. No specialized actin pattern was seen in turtle and bird, which have lenses that are squeezed into an anterior lenticonus; cat, where the lens is translated forward; or rat, cow and most mice, which have no defined accommodation. In exception, certain strains of laboratory mice did show sequestered actin bundles (SABs) and/or PAs. Based on our findings, we conclude that PAs, which resemble geodesic domes, do not take an active part in near-point accommodation; but like SFs, may serve to resist overextension by internal pressure of the fiber mass or by zonular tension.
Evidence for a tumour suppressive function of IGF1-binding proteins in human breast cancer. (2007)

This study supports the role of IGFBP-1, -3 and -7 as potential tumour suppressor genes in human breast cancer.