gebhart/patrepeval huggingface dataset:
Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. (1994)

Knowledge of the pathogenetic mechanisms responsible for the activation of the coagulation system associated with endotoxemia is important for the development of improved modalities for prevention and treatment. We analyzed the appearance in plasma of TNF, IL-6, and indices of coagulation and fibrinolytic system activation in normal chimpanzees after intravenous infusion of endotoxin. Endotoxin infusion elicited reproducible and dose-dependent elevations in serum TNF and IL-6, as well as marked increases in thrombin generation in vivo as measured by immunoassays for prothrombin activation fragment F1 + 2, thrombin-antithrombin III complexes, and fibrinopeptide A. Activation of the fibrinolytic mechanism was monitored with assays for plasminogen activator activity and plasmin-alpha 2-antiplasmin complexes. To potentially intervene in the molecular pathways elicited by endotoxin, pentoxifylline, an agent that interrupts "immediate early" gene activation by monocytes, or a potent monoclonal antibody that neutralizes tissue factor-mediated initiation of coagulation, were infused shortly before endotoxin. Pentoxifylline markedly inhibited increases in the levels of TNF and IL-6, as well as the effects on coagulation and fibrinolysis. In contrast, the monoclonal antibody to tissue factor completely abrogated the augmentation in thrombin generation, but had no effect on cytokine levels or fibrinolysis. We conclude that the endotoxin-induced activation of coagulation appears to be mediated by the tissue factor-dependent pathway, the fibrinolytic response triggered by endotoxin is not dependent on the generation of thrombin, and that the release of cytokines may be important in mediating the activation of both the coagulation and the fibrinolytic mechanisms in vivo.
Determination of cavities using electrical resistivity tomography (2012)

Abstract Geophysical surveys for cavity detection are one of the most common nearsurface applications. The usage of resistivity methods is also very straightforward for the air-filled underground voids, which should have theoretically infinite resistivity in the ERT image. In the first part of the paper, we deal with the comparison of detectability of the cavity by several types of the electrode arrays, the second part discusses the effect of a thin layer around the cavity itself, by means of 2D modelling. The presence of this layer deforms the resistivity image significantly as the resistive anomaly could be turned into a conductive one, in the case when the thin layer is more conductive than the background environment. From the electrical array analysis for the model situation a dipole-dipole and combined pole-dipole shows the best results among the other involved electrical arrays.
A Genomic Regulatory Element That Directs Assembly and Function of Immune-Specific AP-1–IRF Complexes (2012)

Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given the absence of specific Ets partners. Chromatin immunoprecipitation sequencing in T helper 17 (T(H)17) cells reveals that IRF4 targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements (AICEs) that are co-bound by BATF, an AP-1 factor required for T(H)17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T(H)2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.
Surface characterization of nanomaterials and nanoparticles: Important needs and challenging opportunities (2013)

This review examines characterization challenges inherently associated with understanding nanomaterials and the roles surface and interface characterization methods can play in meeting some of the challenges. In parts of the research community, there is growing recognition that studies and published reports on the properties and behaviors of nanomaterials often have reported inadequate or incomplete characterization. As a consequence, the true value of the data in these reports is, at best, uncertain. With the increasing importance of nanomaterials in fundamental research and technological applications, it is desirable that researchers from the wide variety of disciplines involved recognize the nature of these often unexpected challenges associated with reproducible synthesis and characterization of nanomaterials, including the difficulties of maintaining desired materials properties during handling and processing due to their dynamic nature. It is equally valuable for researchers to understand how characterization approaches (surface and otherwise) can help to minimize synthesis surprises and to determine how (and how quickly) materials and properties change in different environments. Appropriate application of traditional surface sensitive analysis methods (including x-ray photoelectron and Auger electron spectroscopies, scanning probe microscopy, and secondary ion mass spectroscopy) can provide information that helps address several of the analysis needs. In many circumstances, extensions of traditional data analysis can provide considerably more information than normally obtained from the data collected. Less common or evolving methods with surface selectivity (e.g., some variations of nuclear magnetic resonance, sum frequency generation, and low and medium energy ion scattering) can provide information about surfaces or interfaces in working environments (<i>operando</i> or <i>in situ</i>) or information not provided by more traditional methods. Although these methods may require instrumentation or expertise not generally available, they can be particularly useful in addressing specific questions, and examples of their use in nanomaterial research are presented.
Correlation of Fc? Receptor Expression of Monocytes with Clearance Function by Macrophages in Systemic Lupus erythematosus (1998)

The expression of Fc gamma receptor II (Fc gammaRII) and Fc gammaRIII on monocytes in peripheral blood and the clearance of immunoglobulin (Ig)G-sensitized erythrocytes (EA) by tissue macrophages were investigated in parallel in patients with systemic lupus erythematosus (SLE). The relationship between receptor expression and the rate of clearance of EA (half-time) was analyzed. The detected decrease in mean fluorescence intensity of both FcR gammaII and Fc gammaRIII of patients' monocytes stained with specific monoclonal antibodies (IV.3 and 3G8) was inversely correlated with the prolonged clearance half-time of 51Cr-labelled and anti-D IgG-sensitized autologous erythrocytes in these patients. A correlation was found between the impaired clearance function and the severity of the disease manifestation expressed by either clinical activity or renal involvement in our SLE patients. From these results it can be concluded that the in-vitro determination of monocyte Fc gammaRII and Fc gammaRIII expression may predict the in-vivo macrophage function via the same Fc receptors.
Effects of Three-Dimensional Culture and Growth Factors on the Chondrogenic Differentiation of Murine Embryonic Stem Cells (2005)

Embryonic stem (ES) cells have the ability to self-replicate and differentiate into cells from all three germ layers, holding great promise for tissue regeneration applications. However, controlling the differentiation of ES cells and obtaining homogenous cell populations still remains a challenge. We hypothesize that a supportive three-dimensional (3D) environment provides ES cell-derived cells an environment that more closely mimics chondrogenesis in vivo. In the present study, the chondrogenic differentiation capability of ES cell-derived embryoid bodies (EBs) encapsulated in poly(ethylene glycol)-based (PEG) hydrogels was examined and compared with the chondrogenic potential of EBs in conventional monolayer culture. PEG hydrogel-encapsulated EBs and EBs in monolayer were cultured in vitro for up to 17 days in chondrogenic differentiation medium in the presence of transforming growth factor (TGF)-beta1 or bone morphogenic protein-2. Gene expression and protein analyses indicated that EB-PEG hydrogel culture upregulated cartilage-relevant markers compared with a monolayer environment and induction of chondrocytic phenotype was stimulated with TGF-beta1. Histology of EBs in PEG hydrogel culture with TGF-beta1 demonstrated basophilic extracellular matrix deposition characteristic of neocartilage. These findings suggest that EB-PEG hydrogel culture, with an appropriate growth factor, may provide a suitable environment for chondrogenic differentiation of intact ES cell-derived EBs.
Antisense Ablation of Type I Metabotropic Glutamate Receptor mGluR1Inhibits Spinal Nociceptive Transmission (1998)

Electrophysiological and behavioral studies point to a role of group I metabotropic glutamate receptors (mGluR1 and mGluR5) in mediating spinal nociceptive responses in rats. However, antagonists with a high degree of specificity for each of these sites are not yet available. We, therefore, examined the effects of antisense deletion of spinal mGluR1 expression in assays of behavioral analgesia and of electrophysiological responses of dorsal horn neurons. Rats treated with an mGluR1 antisense oligonucleotide reagent, delivered continuously to the intrathecal space of the lumbar spinal cord, developed marked analgesia as measured by an increase in the latency to tail-flick (55 degreesC) over a period of 4-7 d. This correlated with a selective reduction in mGluR1, but not mGluR5, immunoreactivity in the superficial dorsal horn compared with untreated control rats, in parallel with a significant reduction in the proportion of neurons activated by the mGluR group I agonist 3, 5-dihydroxyphenylglycine (DHPG), whereas the proportion of cells excited by the mGluR5 agonist, trans-azetidine-2,4-dicarboxylic acid (t-ADA) remained unaffected. In contrast, rats treated with mGluR1 sense or mismatch probes showed none of these changes compared with untreated, control rats. Furthermore, multireceptive dorsal horn neurons in mGluR1 antisense-treated rats were strongly excited by innocuous stimuli to their peripheral receptive fields, but showed severe reductions in their sustained excitatory responses to the selective C-fiber activator mustard oil and in responses to DHPG.
A regulatory role of activated T‐lymphocytes on human megakaryocytopoiesis in vitro (1985)

Cellular interactions responsible for regulating in vitro megakaryocytopoiesis were studied using a microagar culture system which permits the simultaneous proliferation of human megakaryocytic progenitor cells (CFU-M) and T-lymphocytic colonies (CFU-TL). The proliferation of these colony types depends mainly on two factors: phytohaemagglutinin (PHA) and erythropoietin (EP). The direct addition of increasing PHA concentrations to the liquid overlayer resulted in a parallel increase of CFU-M and CFU-TL. If the T-lymphocytes were removed by an E-rosetting technique a marked diminution of CFU-M and CFU-TL numbers was observed. However, monocyte depletion resulted in a marked augmentation of CFU-M proliferation compared to unfractionated mononuclear cells. In order to confirm that the reduction of CFU-M proliferation observed after T-depletion was primarily mediated by the absence of T-lymphocytes, we have co-cultured different concentrations of previously removed autologous T-lymphocytes with a constant number of T-depleted bone marrow cells. A parallel increase of CFU-TL and CFU-M was found if 0.75 - 7.5 X 10(4) T-lymphocytes were added to the culture. In conclusion, our results indicate that activated T-lymphocytes augment proliferation of human bone marrow CFU-M and that monocytes are less important for the growth of megakaryocytic colonies.
Non–invasive measurements of breast tissue optical properties using frequency–domain photon migration (1997)

A multiwavelength, high bandwidth (1 GHz) frequency-domain photon migration (FDPM) instrument has been developed for quantitative, non-invasive measurements of tissue optical and physiological properties. The instrument produces 300 kHz to 1 GHz photon density waves (PDWs) in optically turbid media using a network analyser, an avalanche photodiode detector and four amplitude-modulated diode lasers (674 nm, 811 nm, 849 nm, and 956 nm). The frequency of PDW phase and amplitude is measured and compared to analytically derived model functions in order to calculate absorption, mu a, and reduced scattering, mu s, parameters. The wavelength-dependence of absorption is used to determine tissue haemoglobin concentration (total, oxy- and deoxy- forms), oxygen saturation and water concentration. We present preliminary results of non-invasive FDPM measurements obtained from normal and tumour-containing human breast tissue. Our data clearly demonstrate that physiological changes caused by the presence of small (about 1 cm diameter) palpable lesions can be detected using a handheld FDPM probe.
Discriminant-function-based minimum recognition error rate pattern-recognition approach to speech recognition (2000)

A discriminant function-based minimum recognition error rate pattern recognition approach is described and studied for various applications in speech processing. This approach departs from the conventional paradigm, which links a classification/recognition task to the problem of distribution estimation. Instead, it takes a discriminant function based statistical pattern recognition approach. The suitability of this approach for classification error rate minimization is established through a special loss function. It is meaningful even when the model correctness assumption is known to be not valid. We study the theoretical basis of this approach and compare it with various criteria used in speech recognition. We differentiate the method of classifier design by way of distribution estimation and the discriminant function methods of minimizing classification error rate, based on the fact that in many realistic applications, such as speech recognition, the true distribution form of the source is rarely known precisely, and without model correctness assumption, the classical optimality theory of the distribution estimation approach cannot be applied directly. We discuss issues in this new classifier design paradigm and present various extensions of this approach to classifier design applications in speech processing.
Green Tea Extracts for the Prevention of Metachronous Colorectal Adenomas: A Pilot Study (2008)

GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas.
The P2 Receptors and Congenital Platelet Function Defects (2005)

Platelets possess three P2 receptors: two (P2Y (1) and P2Y (12)) are receptors for adenosine diphosphate (ADP), and one (P2X1) is a receptor for adenosine triphosphate (ATP). The P2Y (1) receptor, which is coupled to Gq and phospholipase C-beta, is responsible for mobilization of ionized calcium from internal stores and mediates the ADP-induced platelet shape change and initial wave of rapidly reversible aggregation. The other ADP receptor, P2Y (12), is negatively coupled to adenylyl cyclase through Gi and mediates a progressive and sustained ADP-induced aggregation not preceded by shape change. In addition, this receptor plays an important role in the potentiation of platelet secretion induced by several platelet agonists. The combined action of P2Y (1) and P2Y (12) is necessary for the full platelet aggregation response to ADP. Four patients with severe deficiency of P2Y (12) have been described so far. Sequence analysis of the P2Y (12) locus of three of these patients revealed homozygous mutations that produced a frame shift mutation and premature truncation of the protein. The fourth patient had an allele with a frame shift mutation and a normal allele, which could be silenced by an additional, as yet unknown, mutation. More recently, we described a patient with a congenital bleeding disorder and a dysfunctional P2Y (12). The patient is a compound heterozygote, in whom one allele contained a G to A transition resulting in an Arg (256) to Gln codon substitution (R256Q) and the other allele contained a C to T transition resulting in an Arg (265) to Trp codon substitution (R265W). The two substitutions are located in TM6 and EL3 of the receptor. Stable Chinese hamster ovaries (CHO) cell lines were established expressing either wild-type P2Y (12) and P2Y (12)(R256Q) or P2Y (12)(R265W). Neither mutation blocked the ability of the P2Y (12) receptor to translocate to the CHO cell surface. ADP at all tested concentrations (0.1 to 10 muM) greatly inhibited the forskolin-induced increase of cyclic adenosine monophosphate (cAMP) in CHO cells transfected with wild-type P2Y (12), whereas CHO cells transfected with either mutant protein were only partially inhibited by ADP. Thus, the molecular basis for the patient's dysfunctional platelet phenotype is explained by missense mutations and the expression of a dysfunctional P2Y (12) receptor. The localization of both mutations in TM6 and EL3 identifies this region of P2Y (12) as a structurally and functionally critical region of the receptor.
Human Adipose-Derived Mesenchymal Stem Cells Modulate Experimental Autoimmune Arthritis by Modifying Early Adaptive T Cell Responses (2015)

Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunosuppressive properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Recent data have identified that GM-CSF-expressing CD4 T cells and Th17 cells have critical roles in the pathogenesis of arthritis and other inflammatory diseases. Although many studies have demonstrated that MSCs can either prevent or suppress inflammation, no studies have addressed their modulation on GM-CSF-expressing CD4 T cells and on the plasticity of Th17 cells. To address this, a single dose of human expanded adipose-derived mesenchymal stem cells (eASCs) was administered to mice with established collagen-induced arthritis. A beneficial effect was observed soon after the infusion of the eASCs as shown by a significant decrease in the severity of arthritis. This was accompanied by reduced number of pathogenic GM-CSF(+) CD4(+) T cells in the spleen and peripheral blood and by an increase in the number of different subsets of regulatory T cells like FOXP3(+) CD4(+) T cells and IL10(+) IL17(-) CD4(+) T cells in the draining lymph nodes (LNs). Interestingly, increased numbers of Th17 cells coexpressing IL10 were also found in draining LNs. These results demonstrate that eASCs ameliorated arthritis after the onset of the disease by reducing the total number of pathogenic GM-CSF(+) CD4(+) T and by increasing the number of different subsets of regulatory T cells in draining LNs, including Th17 cells expressing IL10. All these cellular responses, ultimately, lead to the reestablishment of the regulatory/inflammatory balance in the draining LNs.
Synthesis of a Series of 4-Benzyloxyaniline Analogues as Neuronal N-Type Calcium Channel Blockers with Improved Anticonvulsant and Analgesic Properties (1999)

In this article, the rationale for the design, synthesis, and biological evaluation of a series of N-type voltage-sensitive calcium channel (VSCC) blockers is described. N-Type VSCC blockers, such as ziconotide, have shown utility in several models of stroke and pain. Modification of the previously reported lead, 1a, led to several 4-(4-benzyloxylphenyl)piperidine structures with potent in vitro and in vivo activities. In this series, the most interesting compound, (S)-2-amino-1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-p iperidin-1-yl}-4-methyl-pentan-1-one (11), blocked N-type calcium channels (IC(50) = 0.67 microM in the IMR32 assay) and was efficacious in the audiogenic DBA/2 seizure mouse model (ED(50) = 6 mg/kg, iv) as well as the antiwrithing model (ED(50) = 6 mg/kg, iv). Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca(2+) channels and Na(+) channels in superior cervical ganglion neurons at similar concentrations. Compound 11, which showed superior in vivo efficacy, stands out as an interesting lead for further development of neurotherapeutic agents in this series.
Active Site Binding Modes of HIV-1 Integrase Inhibitors (2000)

Using the crystal structure of the first complex of the HIV-1 integrase catalytic core domain with an inhibitor bound to the active site, structural models for the interaction of various inhibitors with integrase were generated by computational docking. For the compound of the crystallographic study, binding modes unaffected by crystal packing have recently been proposed. Although a large search region was used for the docking simulations, the ligands investigated here are found to bind preferably in similar ways close to the active site. The binding site is formed by residues 64-67, 116, 148, 151-152, 155-156, and 159, as well as by residue 92 in case of the largest ligand of the series. The coherent picture of possible interactions of small-molecule inhibitors at the active site provides an improved basis for structure-based ligand design. The recurring motif of tight interaction with the two lysine residues 156 and 159 is suggested to be of prime importance.
Self-Limited Nanosoldering of Silver Nanowires for High-Performance Flexible Transparent Heaters (2019)

Silver nanowires (Ag NWs) are key materials to fabricate next-generation flexible transparent electrodes (FTEs). Currently, the applications of Ag NWs are impeded by the large wire-wire contact resistance. Herein, a self-limited nanosoldering method is proposed to reduce the contact resistance by epitaxially depositing silver nanosolders at the Ag NW junctions, which have a negligible effect on the optical transparency, while decreasing the sheet resistance of the Ag NW film from 18.6 to 7.7 Ω/sq at a transmittance of 90%. In addition, the deposited nanosolders at the junctions remarkably improve the electrical and mechanical stabilities of the Ag NW electrodes. Notably, this simple nanosoldering process can be rapidly conducted under room temperature and ambient conditions and is free of any technical support or specific equipment. This technique is easily applied to the nanosoldering of 210 × 297 mm FTEs. Based on these FTEs, a high-performance flexible transparent heater with a sheet resistance 3.7 Ω/sq at a transmittance of 82.5% is constructed. Because of the high heating rate (4.8 °C/s), the heater can produce uniform heating (145 °C) at a short response time (30 s) and low input voltage (6 V).
Antimetabolites: A Convenient Synthesis Of Mercaptopurine and Thioguanine Analogues (1994)

Abstract A novel synthesis of 7-mercaptomethylpyrazolo[1,5-a]pyrimidines and pyrazolo[4,3:6′,7′]pyrazolo[1,5-a]pyrimidines utilizing ketene dithioacetals and 5-aminopyrazoles as starting components is described.
Comparative analysis of amino acid distributions in integral membrane proteins from 107 genomes (2005)

We have performed a comparative analysis of amino acid distributions in predicted integral membrane proteins from a total of 107 genomes. A procedure for identification of membrane spanning helices was optimized on a homology-reduced data set of 170 multi-spanning membrane proteins with experimentally determined topologies. The optimized method was then used for extraction of highly reliable partial topologies from all predicted membrane proteins in each genome, and the average biases in amino acid distributions between loops on opposite sides of the membrane were calculated. The results strongly support the notion that a biased distribution of Lys and Arg residues between cytoplasmic and extra-cytoplasmic segments (the positive-inside rule) is present in most if not all organisms.