gebhart/patrepeval huggingface dataset:
Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. (1987)

Macrophage interactions with extracellular matrix and other cells are important in phagocytosis, inflammation, and immunity. To learn more about the surface molecules involved in adhesion we compared the binding of murine macrophages and polymorphonuclear leukocytes (PMN) with artificial substrate in vitro. A distinctive type of adhesion of thioglycollate-elicited peritoneal macrophages (TPM) to bacteriologic plastic (BP) was defined, which was pronase-sensitive, Mg2+-dependent, and required cytoskeletal stabilization. A rat mAb designated 5C6 was isolated because it inhibited TPM attachment to BP, as well as mediating detachment of TPM adherent to that substratum. In addition, it inhibited the attachment of PMN to tissue culture plastic. This antiadhesive property of 5C6 mAb required intact IgG; the F(ab')2 fragment was partially effective and Fab was ineffective. 5C6 recognized the type 3 complement receptor, inhibiting rosetting of EAC3bi to TPM and immunoprecipitating a heterodimer of 160 and 95 kD that comigrated with the M1/70 immunoprecipitate. 5C6 recognized a pronase-stable epitope distinct from that of M1/70. Other mAbs, including M1/70 (CR3) and 2.4G2 (FcR), failed to have any antiadhesive effect in vitro. The inhibitory activity of 5C6 in short-term adhesion assays correlated with its inhibition of recruitment of myelomonocytic cells to a thioglycollate-elicited peritoneal exudate in vivo, after intravenous injection of mAb. 5C6 IgG inhibited recruitment of myelomonocytic cells by 84 +/- 3% at 1 d compared with saline-injected controls. The F(ab')2 fragment and a class-matched control IgG had little effect. Recruitment of TPM at 4 d was also efficiently inhibited by 5C6 IgG. 5C6 IgG was not cytotoxic, had no effect on marrow egress, did not cause increased phagocytic clearance of circulating neutrophils, and had no adverse effect on chemotaxis in vitro. We show that CR3 alone of the LFA-family is necessary for the recruitment of myelomonocytic cells to inflammatory stimuli such as thioglycollate broth. This strategy may be of general use in isolating reagents that inhibit the adhesive function of CR3 and provides a novel approach to antiinflammatory therapy.
Nanoparticle Polymer Composites: Where Two Small Worlds Meet (2006)

The mixing of polymers and nanoparticles is opening pathways for engineering flexible composites that exhibit advantageous electrical, optical, or mechanical properties. Recent advances reveal routes to exploit both enthalpic and entropic interactions so as to direct the spatial distribution of nanoparticles and thereby control the macroscopic performance of the material. For example, by tailoring the particle coating and size, researchers have created self-healing materials for improved sustainability and self-corralling rods for photovoltaic applications. A challenge for future studies is to create hierarchically structured composites in which each sublayer contributes a distinct function to yield a mechanically integrated, multifunctional material.
Labyrinth: a homogeneous computational medium (2002)

As a RAM-based reconfigurable logic array, Labyrinth provides the flexibility and malleability of software with the performance of a dedicated circuit. With a single bit register and a half adder per cell, the architecture is optimized for register intensive, massively parallel algorithms. The fine-grained, highly-symmetric architecture scales very naturally and facilitates compact circuit layouts. A 64-cell test chip has been successfully built and tested, and a 4096-cell chip is in the final stages of preparation for fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
On-focal-plane signal processing for current-mode active pixel sensors (1997)

On-focal-plane signal processing for current-mode active pixel sensors (APS), including fixed pattern noise (FPN) suppression and high-resolution analog-to-digital conversion (ADC), is presented. An FPN suppression circuit that removes the offset current variation between pixels by using a combination of an n-type and a p-type current copier cell is described. The FPN suppression circuit exhibits linear transfer characteristics in the input current range from 0 to 30 /spl mu/A. On-chip ADC is expected to improve imaging system performance and reliability, while reducing system size, weight, and cost. Operation and performance of a current-mode second-order incremental /spl Delta/-/spl Sigma/ A/D converter with column parallel architecture and for high-resolution and medium-slow-speed applications is presented. A 12-bit resolution with /spl plusmn/1.5 LSB accuracy at the conversion rate of 5.6 kHz was obtained. The LSB corresponds to less than twelve signal charges of current-mode 10-/spl mu/m pixel APS's. Based on the experimental results, a brief description of a possible image sensor with the on-chip signal processing is also described.
3′‐Hydroxymethyl 2′‐deoxynucleoside 5′‐triphosphates are inhibitors highly specific for reverse transcriptase (1986)

dNTP(3'-OCH3), a 3'-O-methyl derivative of dNTP, is a chain terminator substrate for DNA synthesis catalyzed by AMV reverse transcriptase. The enzyme seems to be the only DNA polymerase susceptible to the inhibitor while all the other DNA polymerases tested are fully resistant to the nucleotide analog. The resistant polymerases are: E. coli DNA polymerase I, Klenow's fragment of DNA polymerase I, phage T4 DNA polymerase, calf thymus DNA polymerase alpha, rat liver DNA polymerase beta and calf thymus terminal deoxyribonucleotidyl transferase.
Learning and Memory Functions of the Basal Ganglia (2002)

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.
Cloning of Antizyme Inhibitor, a Highly Homologous Protein to Ornithine Decarboxylase (1996)

The degradation of ornithine decarboxylase (ODC) catalyzed by the 26 S proteasome is accelerated by antizyme, an ODC inhibitory protein induced by polyamines. Previously, we have found another possible regulatory protein of ODC degradation, antizyme inhibitor. Antizyme inhibitor binds to the antizyme with a higher affinity than that of ODC, releasing ODC from ODC-antizyme complex. We report here the cDNA sequence of rat heart antizyme inhibitor. The deduced sequence of the protein is highly similar to, but distinct from, sequences of ODCs from various species. Antizyme inhibitor contains amino acid residues required for formation of active sites of ODC, but it completely lacks ODC activity. Antizyme inhibitor has no homology with peptide sequence in the mammalian ODC carboxyl terminus, which is needed for rapid turnover of ODC. It inhibits antizyme-dependent ODC degradation, but, unlike ODC, its degradation is not accelerated by antizyme.
Detection of cross‐reactive anti‐DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives (1985)

Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.
Overexpression of Androgen Receptor in Prostate Cancer (2012)

Kastraatioresistentti eturauhassyöpä (castration resistant prostate cancer, CRPC) on tappava tauti. CRPC:n kehittymismekanismit tunnetaan vain osittain. Parhaiten ymmärretty muutos CRPC:ssä on androgeenireseptorin (AR) yli-ilmentyminen. Eturauhassolut ovat riippuvaisia AR:sta kasvaakseen ja erilaistuakseen, samoin kuin eturauhassyöpäsolut ovat riippuvaisia AR:sta taudin etenemiseksi. Siten AR on yksi suurimmista CRPC:n kehityksen edistäjistä.\n\nTämä tutkimus pyrki selvittämään molekyylitason muutoksia androgeenireseptoria yli-ilmentävissä soluissa erityisesti transkriptionaalisella tasolla. Lisäksi tämä tutkimus pyrki tunnistamaan niitä AR:n kohdegeenejä, jotka ovat tärkeitä eturauhassyövän etenemiselle ja joita voitaisiin käyttää biomarkkereina tai lääkkeiden kohdemolekyyleinä.\n\nTulokset osoittivat, että AR:n yli-ilmentäminen tehostaa reseptorin sitoutumista kromatiiniin jo suhteellisen alhaisissa androgeenipitoisuuksissa. Samoissa olosuhteissa myös reseptorin ja muiden transkriptiokoneiston perusosien, kuten RNA polymeraasin, kromatiiniin sitoutumisen dynamiikka muuttui. Sitoutuminen tapahtui aiemmin ja voimakkaammin androgeenireseptoria yli-ilmentävissä soluissa. Tulosten perusteella kromatiini on avoimemmassa muodossa AR:a yli-ilmentävissä soluissa jo vähähormonisissa olosuhteissa. Siten AR yli-ilmentyminen suosii kromatiinin saavutettavuutta, mikä johtaa tehostettuun transkriptioon. AR:n sitoutuminen kromatiiniin ja transkription tehostuminen ovat erilaiset eri geeneillä.\n\nTutkimuksessa tunnistettiin ja karakterisoitiin myös uusia AR kohdegeenejä. SKP2, ZWINT ja FEN1 yli-ilmentyivät CRPC:ssa, kun taas SNAI2:n ilmentyminen oli vähentynyt. Funktionaaliset kokeet osoittivat, että ZWINT, SNAI2 ja FEN1 voivat olla tärkeitä eturauhassyövän kasvulle. FEN1:n ilmentyminen assosioitui myös syövän uusiutumiseen. FEN1 voi siis olla merkittävä tekijä syövän etenemisessä kastraatioresistenttiin vaiheeseen ja mahdollinen lääkekohde. Kaiken kaikkiaan nämä tulokset tarjoavat mekanismin AR yli-ilmentymisen aiheuttamalle kastraatioresistenssille.
Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies (2011)

The hypothesis is that the mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 min under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 µm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite.
Evaluation of T-cell responses to peptides with MHC class I-binding motifs derived from PE_PGRS 33 protein of Mycobacterium tuberculosis (2007)

The PE and PPE proteins of Mycobacterium tuberculosis form a source of antigenic variation among different strains of M. tuberculosis. One of the PE_PGRS proteins, Rv1818c, plays a role in the pathogenesis of mycobacterial infection and specifically influences host-cell responses to tuberculosis infection. Although little is known about these two classes of protein, an immunoinformatics approach has indicated the possibility of their participation in eliciting a major histocompatibility complex (MHC) class I-mediated immune response against tuberculosis, as peptides derived from Rv1818c are predicted to bind to MHC class I molecules with high affinity. In the present work, a DNA vaccine was constructed encoding the full-length Rv1818c protein of M. tuberculosis and its immunogenicity was analysed in BALB/c mice. Immunization with Rv1818c DNA induced a strong CD8+ cytotoxic lymphocyte and Th1-type response, with high levels of gamma interferon (IFN-gamma) and low levels of interleukin-4. Two nonameric peptides (Peptide(6-14) and Peptide(385-393)) from Rv1818c were identified by their ability to induce the production of IFN-gamma by CD8+ T cells in mice immunized with Rv1818c DNA. An epitope-specific response was demonstrated by the lysis of peptide-pulsed antigen-presenting cells, release of cytotoxic granules and IFN-gamma production. These peptides bound with high affinity to MHC H-2K(d) and showed low dissociation rates of peptide-MHC complexes. These results could form the basis for testing the identified T-cell epitopes of PE_PGRS proteins in the induction of protective immunity against M. tuberculosis challenge in the mouse model.
Plasminogen activator inhibitor (PAI‐1) in plasma and platelets (1988)

The distribution of PAI-1 in the plasma and platelets of normal individuals and of patients with platelet abnormalities was studied. An ELISA, capable of measuring PAI-1 in plasma at 1.5 ng/ml, and a functional assay of t-PA inhibition were used to assay platelet-free plasma (PFP), platelet-rich plasma in which the platelets were lysed (PRP) and serum. The PAI-1 concentration of normal PFP was 21.0 +/- 7.2 ng/ml (mean +/- SD) and those of PRP and serum were 282.6 +/- 68.0 and 270.3 +/- 71.9 ng/ml. The concentration of PAI-1 in PRP was proportional to the platelet count with 0.67 +/- 0.18 ng/10(6) platelets. Patients with thrombocytopenia had approximately normal PAI-1 concentrations in PFP; the extremely low concentrations in serum or PRP reflected the platelet count. A patient with grey platelet syndrome showed a comparable pattern, confirming that PAI-1 occurs in the platelet alpha-granules and indicating that the plasma concentration of PAI-1 is independent of the platelet pool of PAI-1. The median inhibitory activities towards t-PA were 1.6, 8.7 and 8.3 units/ml in normal PFP, PRP and serum respectively. PAI-1 in PFP had a median specific activity (units/mg PAI-1) about 5-fold higher than platelet PAI-1. Plasma and platelets represent two distinct pools of PAI-1, both of which should be considered in studies on the relationship between circulating PAI-1 and thrombotic disease.
Detecting and Reacting to Changes in Sensing Units: The Active Classifier Case (2014)

The ability to detect concept drift, i.e., a structural change in the acquired datastream, and react accordingly is a major achievement for intelligent sensing units. This ability allows the unit, for actively tuning the application, to maintain high performance, changing online the operational strategy, detecting and isolating possible occurring faults to name a few tasks. In the paper, we consider a just-in-time strategy for adaptation; the sensing unit reacts exactly when needed, i.e., when concept drift is detected. Change detection tests (CDTs), designed to inspect structural changes in industrial and environmental data, are coupled here with adaptive k-nearest neighbor and support vector machine classifiers, and suitably retrained when the change is detected. Computational complexity and memory requirements of the CDT and the classifier, due to precious limited resources in embedded sensing, are taken into account in the application design. We show that a hierarchical CDT coupled with an adaptive resource-aware classifier is a suitable tool for processing and classifying sequential streams of data.
Essential Role of Growth Hormone in Ischemia-Induced Retinal Neovascularization (1997)

Retinal neovascularization is the major cause of untreatable blindness. The role of growth hormone (GH) in ischemia-associated retinal neovascularization was studied in transgenic mice expressing a GH antagonist gene and in normal mice given an inhibitor of GH secretion (MK678). Retinal neovascularization was inhibited in these mice in inverse proportion to serum levels of GH and a downstream effector, insulin-like growth factor–I (IGF-I). Inhibition was reversed with exogenous IGF-I administration. GH inhibition did not diminish hypoxia-stimulated retinal vascular endothelial growth factor (VEGF) or VEGF receptor expression. These data suggest that systemic inhibition of GH or IGF-I, or both, may have therapeutic potential in preventing some forms of retinopathy.
Globalization, Innovation, and Regional Development (1998)

Contemporary theoretical and empirical analysis of globalization and regionalization have remained relatively separate from each other: globalization is assumed precisely to transcend nation-state and region while industrial districts are presumed to be relatively self-contained. In contrast to these views, this paper examines the changing dynamics and new reciprocal interdependence of regional and innovation networks in Silicon Valley: integration with global networks has become essential to the long-term viability of regional innovation processes within the infamous region. The paper also summarizes how structural transformations have led to a new understanding of internationalization, transnationalization, and globalization in the world economy, and describes the problems with prevailing state-led counter movements to these processes. It then introduces a new model of problem-solving growth in a context of globalization, and suggests the need for the facilitative state whose role will be a new form of interstitial participation.
Optimization of Inhibitors of the Tyrosine Kinase EphB4. 2. Cellular Potency Improvement and Binding Mode Validation by X-ray Crystallography (2012)

Inhibition of the tyrosine kinase erythropoietin-producing human hepatocellular carcinoma receptor B4 (EphB4) is an effective strategy for the treatment of solid tumors. We have previously reported a low nanomolar ATP-competitive inhibitor of EphB4 discovered in silico by fragment-based high-throughput docking combined with explicit solvent molecular dynamics simulations. Here we present a second generation of EphB4 inhibitors that show high inhibitory potency in both enzymatic and cell-based assays while preserving the appealing selectivity profile exhibited by the parent compound. In addition, respectable levels of antiproliferative activity for these compounds have been obtained. Finally, the binding mode predicted by docking and molecular dynamics simulations is validated by solving the crystal structures of three members of this chemical class in complex with the EphA3 tyrosine kinase whose ATP-binding site is essentially identical to that of EphB4.
Therapeutic Effect of a Retroviral Wild-Type p53 Expression Vector in an Orthotopic Lung Cancer Model (1994)

Development of gene-replacement treatment strategies based on the type of mutations found in target cancers is warranted and may lead to the development of new adjunctive therapies and gene-specific prevention strategies for lung cancer.
Hair Cells and Supporting Cells Share a Common Progenitor in the Avian Inner Ear (1998)

Sensory organs of the vertebrate inner ear contain two major cell types: hair cells (HCs) and supporting cells (SCs). To study the lineage relationships between these two populations, replication-defective retroviral vectors encoding marker genes were delivered to the otic vesicle of the chicken embryo. The resulting labeled clones were analyzed in the hearing organ of the chicken, called the basilar papilla (BP), after cellular differentiation. BPs were allowed to develop for 2 weeks after delivery of the retrovirus, were removed, and were processed histochemically as whole mounts to identify clones of cells. Clusters of labeled cells were evident in the sensory epithelium, the nonsensory epithelium, and in adjacent tissues. Labeled cell types included HCs, two morphologically distinct types of SCs, homogene cells, border cells, hyaline cells, ganglion cells, and connective tissue cells. Each clone was sectioned and cell-type identification was performed on sensory clones expressing retrovirally transduced beta-galactosidase. Cell composition was determined for 41 sensory clones, most of which contained both HCs and SCs. Clones containing one HC and one SC were observed, suggesting that a common progenitor exists that can remain bipotential up to its final mitotic division. The possibility that these two cell types may also arise from a mitotic precursor during HC regeneration in the mature basilar papilla is consistent with their developmental history.
Empirical Parameters for Solvent Acidity, Basicity, Dipolarity, and Polarizability of the Ionic Liquids [BMIM][BF4] and [BMIM][PF6] (2015)

The empirical solvent scales for polarizability (SP), dipolarity (SdP), acidity (SA), and basicity (SB) have been successfully used to interpret the solvatochromism of compounds dissolved in organic solvents and their solvent mixtures. Providing that the published solvatochromic parameters for the ionic liquids 1-(1-butyl)-3-methylimidazolium tetrafluoroborate, [BMIM][BF4] and 1-(1-butyl)-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], are excessively widespread, their SP, SdP, SA, and SB values are measured herein at temperatures from 293 to 353 K. Four key points are emphasized herein: (i) the origin of the solvatochromic solvent scales--the gas phase, that is the absence of any medium perturbation--; (ii) the separation of the polarizability and dipolarity effects; (iii) the simplification of the probing process in order to obtain the solvatochromic parameters; and (iv) the SP, SdP, SA, and SB solvent scales can probe the polarizability, dipolarity, acidity, and basicity of ionic liquids as well as of organic solvents and water-organic solvent mixtures. From the multiparameter approach using the four pure solvent scales one can draw the conclusion that (a) the solvent influence of [BMIM][BF4] parallels that of formamide at 293 K, both of them miscible with water; (b) [BMIM][PF6] shows a set of solvatochromic parameters similar to that of chloroacetonitrile, both of them water insoluble; and (c) that the corresponding solvent acidity and basicity of the ionic liquids can be explained to a great extent from the cation species by comparing the empirical parameters of [BMIM](+) with those of the solvent 1-methylimidazole. The insolubility of [BMIM][PF6] in water as compared to [BMIM][BF4] is tentatively connected to some extent to the larger molar volume of the anion [PF6](-), and to the difference in basicity of [PF6](-) and [BF4](-).