gebhart/patrepeval huggingface dataset:
Role of Regulatory T Cells for the Outcome of Allo- and Autoimmune Responses (2004)

Regulatory T (T<sub>R</sub>) cells provide one of the critical mechanisms for the maintenance of tolerance and immune homeostasis in vivo. Here, we present an overview of the current concepts of regulatory T-cell development and function in the context of autoimmunity and transplantation medicine. While naturally occurring CD4+CD25+ T<sub>R</sub> cells are generated in thymus and act in cell contact-dependent, cytokine-independent manner, the regulatory capacity of induced T<sub>R</sub> cells involves suppressive cytokines like IL-10 and TGFβ. New marker genes for these T<sub>R</sub> cells, including <i>foxp3, integrin α<sub>E</sub>β<sub>7</sub></i> and<i>neuropilin1</i>, that will facilitate our ability to develop better ways for controlling harmful immune responses to allo- and autoantigens are under discussion.
Grating couplers on porous silicon planar waveguides for sensing applications (2008)

We study the use of polymer gratings as light couplers into porous silicon planar waveguides for sensing applications. Experimental evidence of a guided mode in a grating-coupled porous silicon structure is presented, along with a study of its detuning due to waveguide infiltration with a chemical linker. All the measurements are in good agreement with simulations obtained by means of a Fourier modal method, where the porous silicon birefringence is considered. These results demonstrate that this system is potentially useful for chemical and biological sensing applications.
Protein‐Bound Acrolein (1999)

Several lines of evidence support the role of oxidative stress, including increased lipid peroxidation, in the pathogenesis of Alzheimer's disease (AD). Lipid peroxidation generates various reactive aldehydes, such as 4-hydroxynonenal (HNE), which have been detected immunochemically in AD, particularly in neurofibrillary tangles, one of the major diagnostic lesions in AD brains. A recent study demonstrated that acrolein, the most reactive among the alpha,beta-unsaturated aldehyde products of lipid peroxidation, could be rapidly incorporated into proteins, generating a carbonyl derivative, a marker of oxidative stress to proteins. The current studies used an antibody raised against acrolein-modified keyhole limpet hemocyanin (KLH) to test whether acrolein modification of proteins occurs in AD. Double immunofluorescence revealed strong acrolein-KLH immunoreactivity in more than half of all paired helical filament (PHF)-1-labeled neurofibrillary tangles in AD cases. Acrolein-KLH immunoreactivity was also evident in a few neurons lacking PHF-1-positive neurofibrillary tangles. Light acrolein-KLH immunoreactivity occurred in dystrophic neurites surrounding the amyloid-beta core, which itself lacked acrolein-KLH staining. The pattern of acrolein-KLH immunostaining was similar to that of HNE. Control brains did not contain any acrolein-KLH-immunoreactive structures. The current results suggest that protein-bound acrolein is a powerful marker of oxidative damage to protein and support the hypothesis that lipid peroxidation and oxidative damage to protein may play a crucial role in the formation of neurofibrillary tangles and to neuronal death in AD.
Wetting Transitions in Two-, Three-, and Four-Phase Systems (2011)

We discuss wetting of rough surfaces with two-phase (solid-liquid), three-phase (solid-water-air and solid-oil-water), and four-phase (solid-oil-water-air) interfaces mimicking fish scales. We extend the traditional Wenzel and Cassie-Baxter models to these cases. We further present experimental observations of two-, three-, and four-phase systems in the case of metal-matrix composite solid surfaces immersed in water and in contact with oil. Experimental observations show that wetting transitions can occur in underwater oleophobic systems. We also discuss wetting transitions as phase transitions using the phase-field approach and show that a phenomenological gradient coefficient is responsible for wetting transition, energy barriers, and wetting/dewetting asymmetry (hysteresis).
Membrane-proximal Ig-like domain of Fc gamma RIII (CD16) contains residues critical for ligand binding. (1994)

Ag-Ab complexes are cleared from the circulation through a complex system of receptors for the Fc portion of Ig (FcRs). Fc gamma RIII (CD16) is a low affinity FcR for IgG that is composed of two highly homologous Ig-like extracellular domains. Using secondary structure predictions, we located a strongly hydrophilic region in the second Ig-like domain of Fc gamma RIII that is predicted to lie between beta-strands C and C'. Substitutions of seven out of eight amino acids in this region abolished binding to IgG. Substitution of a conformationally adjacent amino acid in a bend just before beta-strand F and an amino acid in the B-C loop also affected ligand binding. However, amino acid substitutions in two different predicted loops in the second Ig-like domain as well as substitutions to three predicted loops in the first Ig-like domain had no effect on function. A chimeric Fc gamma RIII molecule lacking the second Ig-like domain was unable to bind IgG further, suggesting the presence of the binding site in the second domain. Neutralizing mAbs that inhibit Fc gamma RIII interaction with IgG were mapped to the E-F loop in the membrane proximal domain of Fc gamma RIII, providing further evidence of the importance of this region of the molecule in ligand interaction.
Structural Characteristics of Fluorophores That Form Intramolecular H-Type Dimers in a Protease Substrate (1997)

Recently, we designed and synthesized a new class of profluorescent protease substrates whose spectral properties fit the exciton model; more specifically, spectra of these polypeptides which were doubly labeled with rhodamines showed blue-shifted absorption peaks and fluorescence quenching, both indicators of H-dimer formation. In the work described here NorFES, an undecapeptide which is cleaved by the serine protease elastase, was homodoubly labeled on opposite sides of its cleavage site with six fluorophores in order to identify structural elements of dyes which influence intramolecular H-type dimer formation. Absorption and fluorescence spectra of these six substrates obtained before and after enzymatic cleavage indicate that the exciton band is strongest in the peptide doubly labeled with tetramethylrhodamine, followed by rhodamine-X, and then (diethylamino)coumarin. In contrast, spectra of NorFES homodoubly labeled with fluorescein, hydroxycoumarin, or pyrene do not exhibit exciton bands. These data suggest that factors significant in H-type dimerization are as follows (in decreasing order): delocalized charge, symmetry, and magnitude of the lowest energy electronic transition dipole. Surprisingly, in the group of fluorophores in this study, no evidence for hydrophobic interactions as an important influence was observed.
Accessory cells in murine Peyer's patch. I. Identification and enrichment of a functional dendritic cell. (1983)

Previous studies have suggested that in vitro and in vivo immune responses are defective in Peyer's patch (PP) as a result of a deficiency in accessory cell number or function. However, we report here that enzymatic dissociation of PP does release a cell population with accessory activity in oxidative mitogenesis, i.e., the proliferation of periodate-modified T cells. The accessory activity present in PP is quantitatively similar to that of spleen. Accessory function is mediated by a cell type(s) that has the following characteristics: low buoyant density, lack of adherence to plastic or glass surfaces, lack of Fc receptors, and presence of surface Ia and the 33D1 dendritic cell (DC)-specific determinants. This PP accessory cell was markedly enriched by a novel technique. PP cells formed large aggregates when cultured for 16 h with irradiated, periodate-treated spleen cells. From the clusters we obtained a low density cell population that was 60% Ia positive, 33D1 positive, non-T and non-B, Fc receptor-negative, and dendritic in morphology. The DC-enriched populations were 60-80-fold enriched in accessory function relative to unfractionated PP. We can now compare PP accessory cells with accessory cells from other organs, and try to determine how PP dendritic cells contribute to the unique functions of this lymphoid organ.
Characterization of Chemical Inhibitors of Brefeldin A-activated Mono-ADP-ribosylation (1997)

Brefeldin A, a toxin inhibitor of vesicular traffic, induces the selective mono-ADP-ribosylation of two cytosolic proteins, glyceraldehyde-3-phosphate dehydrogenase and the novel GTP-binding protein BARS-50. Here, we have used a new quantitative assay for the characterization of this reaction and the development of specific pharmacological inhibitors. Mono-ADP-ribosylation is activated by brefeldin A with an EC50 of 17.0 +/- 3.1 microg/ml, but not by biologically inactive analogs including a brefeldin A stereoisomer. Brefeldin A acts by increasing the Vmax of the reaction, whereas it does not influence the Km of the enzyme for NAD+ (154 +/- 13 microM). The enzyme is an integral membrane protein present in most tissues and is modulated by Zn2+, Cu2+, ATP (but not by other nucleotides), pH, temperature, and ionic strength. To identify inhibitors of the reaction, a large number of drugs previously tested as blockers of bacterial ADP-ribosyltransferases were screened. Two classes of molecules, one belonging to the coumarin group (dicumarol, coumermycin A1, and novobiocin) and the other to the quinone group (ilimaquinone, benzoquinone, and naphthoquinone), rather potently and specifically inhibited brefeldin A-dependent mono-ADP-ribosylation. When tested in living cells, these molecules antagonized the tubular reticular redistribution of the Golgi complex caused by brefeldin A at concentrations similar to those active in the mono-ADP-ribosylation assay in vitro, suggesting a role for mono-ADP-ribosylation in the cellular actions of brefeldin A.
Rescue of Severe Infantile Hypophosphatasia Mice by AAV-Mediated Sustained Expression of Soluble Alkaline Phosphatase (2011)

Hypophosphatasia (HPP) is an inherited disease caused by a deficiency of tissue-nonspecific alkaline phosphatase (TNALP). The major symptom of human HPP is hypomineralization, rickets, or osteomalacia, although the clinical severity is highly variable. The phenotypes of TNALP knockout (Akp2(-/-)) mice mimic those of the severe infantile form of HPP. Akp2(-/-) mice appear normal at birth, but they develop growth failure, epileptic seizures, and hypomineralization and die by 20 days of age. Previously, we have shown that the phenotype of Akp2(-/-) mice can be prevented by enzyme replacement of bone-targeted TNALP in which deca-aspartates are linked to the C-terminus of soluble TNALP (TNALP-D10). In the present study, we evaluated the therapeutic effects of adeno-associated virus serotype 8 (AAV8) vectors that express various forms of TNALP, including TNALP-D10, soluble TNALP tagged with the Flag epitopes (TNALP-F), and native glycosylphosphatidylinositol-anchored TNALP (TNALP-N). A single intravenous injection of 5×10(10) vector genomes of AAV8-TNALP-D10 into Akp2(-/-) mice at day 1 resulted in prolonged survival and phenotypic correction. When AAV8-TNALP-F was injected into neonatal Akp2(-/-) mice, they also survived without epileptic seizures. Interestingly, survival effects were observed in some animals treated with AAV8-TNALP-N. All surviving Akp2(-/-) mice showed a healthy appearance and a normal activity with mature bone mineralization on X-rays. These results suggest that sustained alkaline phosphatase activity in plasma is essential and sufficient for the rescue of Akp2(-/-) mice. AAV8-mediated systemic gene therapy appears to be an effective treatment for the infantile form of human HPP.
B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma (2013)

BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating multiple myeloma.
Acute myeloid leukemia and myelodysplastic syndrome in children treated for cancer: comparison with primary presentation (2002)

There has not been a reported series of children with therapy-induced myelodysplastic syndrome/acute myeloid leukemia (tMDS/tAML) who were treated systematically. This paper describes 24 children with tMDS/tAML who were assigned randomly to standard- or intensive-timing induction on protocol CCG 2891. Presenting features and outcomes of those children were compared with those of 960 patients with de novo MDS (62 patients) or AML (898 patients). Children with tMDS/tAML were older at presentation (P =.015), had lower white blood cell counts (P =.01), and were more likely to have MDS (21% vs 7%) (P =.02) and trisomy 8 (P =.06). Fewer had hepatomegaly (P =.02), splenomegaly (P =.03), hepatosplenomegaly (P =.02), or classic AML translocations [t(8;21), t(15;17), 16q22; P =.02]. They had a poorer induction rate (50% vs 72%, P =.016), overall survival (26% vs 47% at 3 years, P =.007), and event-free survival (21% vs 39% at 3 years, P =.023). Disease-free survival after achieving remission was similar (45% vs 53%, P =.868). Children with tMDS/tAML who received intensive-timing induction had better outcomes than those who received standard-timing induction (overall survival 32% vs 0%, P =.54). In this study, the latency period to development of tMDS/tAML was the same for presumed alkylator-induced as for topoisomerase-induced myeloid leukemia. The findings of this study confirm that most children with tMDS/tAML have disease resistant to current therapies. Standard-timing induction appears less effective for this population.
Human Anti-V3 HIV-1 Monoclonal Antibodies Encoded by the VH5-51/VL Lambda Genes Define a Conserved Antigenic Structure (2011)

Preferential usage of immunoglobulin (Ig) genes that encode antibodies (Abs) against various pathogens is rarely observed and the nature of their dominance is unclear in the context of stochastic recombination of Ig genes. The hypothesis that restricted usage of Ig genes predetermines the antibody specificity was tested in this study of 18 human anti-V3 monoclonal Abs (mAbs) generated from unrelated individuals infected with various subtypes of HIV-1, all of which preferentially used pairing of the VH5-51 and VL lambda genes. Crystallographic analysis of five VH5-51/VL lambda-encoded Fabs complexed with various V3 peptides revealed a common three dimensional (3D) shape of the antigen-binding sites primarily determined by the four complementarity determining regions (CDR) for the heavy (H) and light (L) chains: specifically, the H1, H2, L1 and L2 domains. The CDR H3 domain did not contribute to the shape of the binding pocket, as it had different lengths, sequences and conformations for each mAb. The same shape of the binding site was further confirmed by the identical backbone conformation exhibited by V3 peptides in complex with Fabs which fully adapted to the binding pocket and the same key contact residues, mainly germline-encoded in the heavy and light chains of five Fabs. Finally, the VH5-51 anti-V3 mAbs recognized an epitope with an identical 3D structure which is mimicked by a single mimotope recognized by the majority of VH5-51-derived mAbs but not by other V3 mAbs. These data suggest that the identification of preferentially used Ig genes by neutralizing mAbs may define conserved epitopes in the diverse virus envelopes. This will be useful information for designing vaccine immunogen inducing cross-neutralizing Abs.
Syntheses and Transformations of 4-Amino-2-methylthio- and 4-Amino-2-methoxypyrimidine-5-carboxamide Oximes (1985)

d e o x i m e s ( 2 a n d 14).
Accuracy and precision of volumetric determinations using two commercial CAD systems for prosthetics: a technical note. (1998)

The aim of this study was to evaluate the validity and reliability of volume determinations using the commercially available Seattle ShapeMaker CAD/CAM system for production of prosthetic sockets and to compare it with the commercially available CAPOD system. We used three types of reference objects for volumetric determinations: steel tubes, plaster of Paris casts, and residual limb models. Three different sizes were examined for each type of object. Volume measurements with the two CAD/CAM systems were compared with measurements obtained by water filling, water immersion, or mathematical calculation (tubes only). We found an inconsistent systematic error of less than 3.1% for ShapeMaker and no systematic error for CAPOD. Random errors, represented by the coefficient of variation, were below 1.3% for the ShapeMaker and, in most cases, below 0.4% for the CAPOD. Theoretical changes in volume of 2.6% and 0.8% are possible to detect with these CAD/CAM systems. In our opinion, both systems have sufficient precision for routine clinical use in prosthetics and orthotics. However, in our study, the ShapeMaker committed larger random and systematic errors than CAPOD. This means that, according to our study, CAPOD offers the best possibility to determine and detect small changes in residual limb volume as a function of time.
Mammalian tissue trypsin-like enzymes. Comparative reactivities of human skin tryptase, human lung tryptase, and bovine trypsin with peptide 4-nitroanilide and thioester substrates. (1983)

The subsite specificity of human lung and skin tryptase (trypsin-like enzyme) has been studied at pH 7.5 using 17 amino acid and dipeptide thioester substrates and 14 tripeptide 4-nitroanilide substrates. The reactivity and specificity of the human tryptases were compared with bovine trypsin and other trypsin-like enzymes. Neither tryptase was similar to either kallikrein or factor XIIa (Hageman factor). The skin enzyme was the most reactive as measured by the specificity constant kcat/KM. The best substrate was benzyloxycarbonyl(Z)-Lys-Arg-S-CH2CH(CH3)2 which had a kcat/KM value of 59,000,000 M-1 S-1. Only a single substrate, Z-Glu-Phe-Arg-4-nitroanilide, was slightly more reactive with the lung tryptase. Both enzymes have extended substrate-binding sites and proline residues at P3 substantially decrease kcat/KM. Both enzymes preferred the tripeptide 4-nitroanilides with a P2 Gly residue over Phe, and both favored the substrate Z-Lys-Gly-Arg-4-nitroanilide over similar substrates containing six other representative amino acid residues at P3. The lung enzyme was inhibited over three times faster by p-amidinophenylmethanesulfonyl fluoride than the skin enzyme. The preference of the skin tryptase for substrates with two terminal basic residues indicates that this enzyme could process prohormones and proproteins which contain this structural feature at the cleavage site. The substrates reported in this paper should be useful for the further characterization of the physiologic function of tryptases.
Molecular Characterization of a Phage-Encoded Resistance System in Lactococcus lactis (1999)

A specific fragment of the genome of Tuc2009, a temperate lactococcal bacteriophage, was shown to contain several open reading frames, whose deduced protein products exhibited similarities to proteins known to be involved in DNA replication and modification. In this way, a putative single-stranded binding protein, replisome organizer protein, topoisomerase I, and a methylase were identified. When the genetic information coding for the putative replisome organizer protein of Tuc2009, Rep2009, was supplied on a high-copy-number plasmid vector, it was shown to confer a phage-encoded resistance (Per) phenotype on its lactococcal host UC509.9. The presence of this recombinant plasmid was shown to cause a marked reduction in Tuc2009 DNA replication, suggesting that the observed phage resistance was due to titration of a factor, or factors, required for Tuc2009 DNA replication. Further experiments delineated the phage resistance-conferring region to a 160-bp fragment rich in direct repeats. Gel retardation experiments, which indicated a protein-DNA interaction between this 160-bp fragment and the Rep2009 protein, were performed. UC509.9 strains harboring plasmids with randomly mutated versions of this fragment were shown to display a variable phage resistance phenotype, depending on the position of the mutations.
Determining readiness for predoctoral internship training: the process of developing a screening measure (2010)

The purpose of this study was to illustrate the development of a screening measure to assess readiness for psychology internship training. The screening measure was comprised 13 items rated on a 4-point scale. Two program faculty members reviewed the application of each candidate independently. Psychologists were arbitrarily assigned to belong to reviewer group 1 or 2. Data from group 1 were subjected to exploratory factor analysis; data from group 2 were subjected to confirmatory factor analysis. Two factors were identified and confirmed: Factor I comprised 6 items referring to core competencies, and Factor II comprised 4 items referring to relevant background experiences. Correlations between raters at the factor and item level generally were in the moderate range. This study illustrates the process of developing a screening measure to help determine readiness for internship training.
Intermediates of adeno-associated virus type 2 assembly: identification of soluble complexes containing Rep and Cap proteins (1995)

The proteins encoded by the adeno-associated virus type 2 (AAV-2) rep and cap genes obtained during a productive infection of HeLa cells with AAV-2 and adenovirus type 2 were fractionated according to solubility, cellular localization, and sedimentation properties. The majority of Rep and Cap proteins accumulated in the nucleus, where they distributed into a soluble and an insoluble fraction. Analysis of the soluble nuclear fraction of capsid proteins by sucrose density gradients showed that they formed at least three steady-state pools: a monomer pool sedimenting at about 6S, a pool of oligomeric intermediates sedimenting between 10 and 15S, and a broad pool of assembly products with a peak between 60 and 110S, the known sedimentation positions of empty and full capsids. While the soluble nuclear monomer and oligomer pool contained predominantly only two capsid proteins, the 30 to 180S assembly products contained VP1, VP2, and VP3 in a stoichiometry similar to that of purified virions. They probably represent different intermediates in capsid assembly, DNA encapsidation, and capsid maturation. In contrast, the cytoplasmic fraction of capsid proteins showed a pattern of oligomers continuously increasing in size without a defined peak, suggesting that assembly of 60S particles occurs in the nucleus. Soluble nuclear Rep proteins were distributed over the whole sedimentation range, probably as a result of association with AAV DNA. Subfractions of the Rep proteins with defined sedimentation values were obtained in the soluble nuclear and cytoplasmic fractions. We were able to coimmunoprecipitate capsid proteins sedimenting between 60 and 110S with antibodies against Rep proteins, suggesting that they exist in common complexes possibly involved in AAV DNA packaging. Antibodies against the capsid proteins, however, precipitated Rep78 and Rep68 predominantly with a peak around 30S representing a second complex containing Rep and Cap proteins.
Optical photonic crystals synthesized from colloidal systems of polystyrene spheres and nanocrystalline titania (1999)

We have developed a novel ceramic processing technique to fabricate photonic crystals (PCs) with close-packed lattices of air pores in a dielectric background. The ordering of colloidal spheres and incorporation of the titania is performed simultaneously, in contrast to other approaches. Excellent ordering of the lattice of air pores is achieved over domains extending over 100 /spl mu/. The PCs exhibit a uniform color and a corresponding sharp peak in the reflectivity at the wavelength of the first stopband. The position of the reflectivity peak scales very well with the size of the air pores, providing strong evidence for photonic crystal effects.