gebhart/patrepeval huggingface dataset:
Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis (2013)

The addition of blood leucocyte gene expression to FEV(1) and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.
cGMP-Mediated Inhibition of TNF-α Production by the Atrial Natriuretic Peptide in Murine Macrophages (2000)

The atrial natriuretic peptide (ANP) is suggested to regulate inflammatory response by alteration of macrophage functions. The aim of this study was to investigate whether ANP influences production of TNF-alpha. TNF-alpha production in murine bone marrow-derived macrophages was induced by LPS, and TNF-alpha secretion (+/-ANP) was determined by L929 bioassay. ANP dose dependently (10-8-10-6 M) inhibited TNF-alpha release by up to 95%. The effect was mediated via the guanylate cyclase-coupled A receptor, as was shown by employing dibutyryl-cGMP, the cGMP-inhibitory compound Ly-83583, and the A receptor antagonist HS-142-1. A specific ligand of the natriuretic peptide "clearance" receptor inhibited TNF-alpha production only at 10-7 and 10-8 M, but not at 10-6 M. The B receptor ligand C-type natriuretic peptide showed no TNF-alpha-inhibitory effect. To investigate the underlying mechanism of ANP-mediated TNF-alpha inhibition, Northern blot was performed. ANP-treated macrophages displayed decreased TNF-alpha-mRNA levels. Besides the known inhibition of NF-kappaB activation, in this study we demonstrated that ANP also attenuates the activation of the proinflammatory transcription factor AP-1 (gel shift assay). ANP did not alter subunit composition of AP-1 complexes, as was shown by supershift assays applying anti-c-jun and anti-c-fos Abs. To get information on the ANP effect for human inflammatory processes, we investigated cytokine production in human LPS-activated blood. ANP significantly attenuated production of TNF-alpha and IL-1beta without affecting production of IL-10 and IL-1ra. In summary, ANP was shown to attenuate TNF-alpha production of LPS-activated macrophages via cGMP. The inhibition is suggested to involve transcriptional processes that are the result of reduced activation of responsible transcription factors.
Nociceptors Are Interleukin-1β Sensors (2008)

A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E(2), bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1beta (IL-1beta), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1beta acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1beta sensor, nociceptors can directly signal the presence of ongoing tissue inflammation.
Universal Sensing by Transduction of Antibody Binding with Backscattering Interferometry (2010)

All binding events induce a change in refractive index, and antibody–antigen interactions are no exception. We describe the use of backscattering interferometry to quantify antibody binding without labels and with high sensitivity. As a broad range of antibodies are available, this method represents a general way to selectively detect a wide variety of trace molecules in simple or complex mixtures. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Image Completion Using Efficient Belief Propagation Via Priority Scheduling and Dynamic Pruning (2007)

In this paper, a new exemplar-based framework is presented, which treats image completion, texture synthesis, and image inpainting in a unified manner. In order to be able to avoid the occurrence of visually inconsistent results, we pose all of the above image-editing tasks in the form of a discrete global optimization problem. The objective function of this problem is always well-defined, and corresponds to the energy of a discrete Markov random field (MRF). For efficiently optimizing this MRF, a novel optimization scheme, called priority belief propagation (BP), is then proposed, which carries two very important extensions over the standard BP algorithm: "priority-based message scheduling" and "dynamic label pruning." These two extensions work in cooperation to deal with the intolerable computational cost of BP, which is caused by the huge number of labels associated with our MRF. Moreover, both of our extensions are generic, since they do not rely on the use of domain-specific prior knowledge. They can, therefore, be applied to any MRF, i.e., to a very wide class of problems in image processing and computer vision, thus managing to resolve what is currently considered as one major limitation of the BP algorithm: its inefficiency in handling MRFs with very large discrete state spaces. Experimental results on a wide variety of input images are presented, which demonstrate the effectiveness of our image-completion framework for tasks such as object removal, texture synthesis, text removal, and image inpainting.
Radiation and scattering from electrically small conducting bodies of arbitrary shape (1986)

A simple moment solution is given for low frequency electromagnetic scattering and radiation problems. The problem is reduced to the corresponding electrostatic and magnetostatic problems. Each static problem is solved using the Method of Moments. The surface of the perfectly conducting scatterer is modeled by a set of planar triangular patches. Pulse expansion functions and point matching testing are used to compute the charge density in the electrostatic problem. For the magnetostatic current a set of charge-free vector expansion functions is used. The problem is formulated assuming the scatterer to be in an unbounded homogeneous region. Scatterers of various shapes, such as the circular disc, the sphere, and the cube are studied. Special attention is paid to a conducting box with a narrow slot. The computed results are the scattered fields, the induced charge and current distributions, and the induced electric and magnetic dipole moments. These are in close agreement with whatever published data are available.
Mitogen-Activated Protein Kinase Inhibition Induces Translocation of Bmf to Promote Apoptosis in Melanoma (2009)

Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway is implicated in the development and progression of many human cancers, including melanoma. Mutually exclusive activating mutations in NRAS or BRAF have been identified in approximately 85% of melanomas, and components of this pathway have been developed as molecular targets for therapeutic intervention. We and others have shown that inhibition of this pathway with specific small molecule MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitors induces a wide range of apoptotic responsiveness in human melanoma cells both in vitro and in vivo. To define the molecular mechanism underlying variable apoptotic sensitivity of melanoma cells to MEK inhibition, we examined the expression and subcellular localization of Bcl-2 family members in a comprehensive set of human melanoma cell lines. Whereas the proapoptotic protein Bim was activated and localized to the mitochondrial membrane in all cell lines regardless of apoptotic sensitivity, Bmf activation and cytosolic translocation was exclusive to sensitive cells. In resistant cells, Bmf remained sequestered to the cytoskeleton through dynein light chain 2 (DLC2) binding. Overexpression of Bmf in resistant cells did not enhance apoptosis, whereas expression of mutant BmfA69P, which has decreased binding to DLC2, promoted cell death. Expression of BmfA69P mutants possessing the Bcl-2 homology 3 (BH3) domain mutation L138A, which impairs BH3 interactions, did not enhance apoptosis in resistant cells. RNA interference targeting Bim and Bmf provided protection from apoptosis induced by MEK inhibition. These results show a novel role for Bmf in promoting apoptosis and provide insight into the mechanism of apoptotic resistance to MEK inhibition in melanoma.
The Mengovirus Leader Protein Suppresses Alpha/Beta Interferon Production by Inhibition of the Iron/Ferritin-Mediated Activation of NF-κB (2002)

In our studies on the biological function of the mengovirus leader protein, we identified a casein kinase II (CK-2) phosphorylation site in the protein. Here we report that the mengovirus leader protein can be phosphorylated by CK-2 in vitro. Expression of a recombinant leader protein in which the consensus CK-2 sequence around threonine 47 was disturbed resulted in a mutant protein that could no longer be phosphorylated. The CK-2 consensus sequence was modified by site-directed mutagenesis and subsequently introduced into a mengovirus cDNA clone to investigate the effect of the phosphorylation of the leader protein on virus replication and on the host cell response. Modifications by which the CK-2 consensus sequence was disturbed resulted in mutant viruses with reduced growth kinetics. We demonstrated that the integrity of the CK-2 phosphorylation site of the mengovirus leader protein was specifically related to the suppression of NF-kappa B activation and subsequent suppression of alpha/beta interferon production in infected cells. We also found that the integrity of the CK-2 phosphorylation site of the leader protein coincided with an increase of ferritin expression in the infected cell. These data indicate that the leader protein suppresses the iron-mediated activation of NF-kappa B and thereby inhibits alpha/beta interferon expression in the infected cell.
Hematoxylin and Eosin Staining of Tissue and Cell Sections (2008)

INTRODUCTIONHematoxylin and eosin (H&E) stains have been used for at least a century and are still essential for recognizing various tissue types and the morphologic changes that form the basis of contemporary cancer diagnosis. The stain has been unchanged for many years because it works well with a variety of fixatives and displays a broad range of cytoplasmic, nuclear, and extracellular matrix features. Hematoxylin has a deep blue-purple color and stains nucleic acids by a complex, incompletely understood reaction. Eosin is pink and stains proteins nonspecifically. In a typical tissue, nuclei are stained blue, whereas the cytoplasm and extracellular matrix have varying degrees of pink staining. Well-fixed cells show considerable intranuclear detail. Nuclei show varying cell-type- and cancer-type-specific patterns of condensation of heterochromatin (hematoxylin staining) that are diagnostically very important. Nucleoli stain with eosin. If abundant polyribosomes are present, the cytoplasm will have a distinct blue cast. The Golgi zone can be tentatively identified by the absence of staining in a region next to the nucleus. Thus, the stain discloses abundant structural information, with specific functional implications. A limitation of hematoxylin staining is that it is incompatible with immunofluorescence. It is useful, however, to stain one serial paraffin section from a tissue in which immunofluorescence will be performed. Hematoxylin, generally without eosin, is useful as a counterstain for many immunohistochemical or hybridization procedures that use colorimetric substrates (such as alkaline phosphatase or peroxidase). This protocol describes H&E staining of tissue and cell sections.
Design and synthesis of unprecedented cyclic γ-AApeptides for antimicrobial development (2012)

Antimicrobial drug resistance is one of the greatest threats facing mankind. Antimicrobial peptides (AMPs) can potentially circumvent drug resistance, probably through a bacterial membrane-disruption mechanism. However, they suffer from low in vivo stability, potential immunogenicity, and difficulty in optimization. The development of antimicrobial peptidomimetics is therefore an emerging research area as they avoid the potential disadvantages of AMPs. Cyclic peptidomimetics are of significant interest since constraints induced by cyclization are expected to further improve their antimicrobial activity. Nonetheless, the report of cyclic oligomeric peptidomimetics for antimicrobial development is rare. Herein, for the first time, we report the design and synthesis of cyclic γ-AApeptides via an on-resin cyclization. These cyclic γ-AApeptides are potent and broad-spectrum active against fungus and multi-drug resistant Gram-positive and Gram-negative bacterial pathogens. Our results demonstrate the potential of cyclic γ-AApeptides as a new class of antibiotics to circumvent drug resistance by mimicking the bactericidal mechanism of AMPs. Meanwhile, the facile synthesis of cyclic γ-AApeptides may further expand the applications of γ-AApeptides in biomedical sciences.
A DNAzyme Catalytic Beacon Sensor for Paramagnetic Cu2+ Ions in Aqueous Solution with High Sensitivity and Selectivity (2007)

Copper is a key metal ion both in environment monitoring and in biology, and exposure to high concentration of copper can cause adverse health effects. Although significant progresses have been made in designing fluorescent sensors for diamagnetic metal ions, few effective Cu2+ sensors are known because of the paramagnetic nature of the metal ion. We herein report a highly sensitive and selective “turn-on” fluorescent Cu2+ sensor based on an in vitro selected DNAzyme (also known as catalytic DNA or deoxyribozyme). The substrate strand of the DNAzyme was labeled with a fluorophore on the 3‘-end and a quencher on the 5‘-end, and the enzyme strand was labeled with a second quencher on the 5‘-end. Initially, the fluorescence was quenched. Addition of Cu2+ induced oxidative cleavage of the substrate, and the fluorescence intensity increased by 13-fold. The sensor has a detection limit of 35 nM and a dynamic range up to 20 μM. The sensor selectivity is more than 2000-fold for Cu2+ over Fe2+ and UO22+ and more than 10 000-fold over any other metal ions. The DNAzyme catalytic beacon method demonstrated here can be applied to designing turn-on fluorescent sensors for other paramagnetic metal ions.
Immunogenetic control of experimental type ii collagen‐induced arthritis (1981)

Seven inbred rat strains were tested for susceptibility to experimental type II collagen-induced arthritis and for development of cellular immunity to type II collagen by delayed hypersensitivity skin testing. WF (RT1u), LEW (RT1l), and DA (RT1a) were the most susceptible of the strains tested with respect to incidence (greater than 95%) and severity of disease. LEW and DA were strongly skin test reactive to calf type II collagen. BUF (RT1b) developed moderate skin test responses to calf type II collagen and showed low susceptibility to collagen arthritis (1/8). MAXX (RT1n), LEW.B3 (RT1nvl), and AUG (RT1c) were not susceptible to collagen arthritis and showed negative to very weak skin test responses to type II collagen. Disease susceptibility was inherited as a dominant trait in the F1 progeny of (WF X LEW.B3) matings. These data suggest that clinical expression of experimental collagen-induced arthritis and immune responsiveness to type II collagen are controlled in part by genes within or closely linked to the rat major histocompatibility complex--RT1.
Anti-HIV-1 Protease Triterpenoid Saponins from the Seeds of Aesculus chinensis (1999)

Eight bioactive triterpenoid saponins (1-8) were isolated from the seeds of Aesculus chinensis, four of which are novel compounds. The major saponins were identified as escin Ia (1), Ib (2), isoescin Ia (3) and Ib (4), while the new compounds were identified as 22alpha-tigloyl-28-acetylprotoaescigenin-3beta-O-¿beta -D-glucopyranos yl (1-2) ¿beta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVc, 5), 22alpha-angeloyl-28-acetylprotoaescigenin-3beta-O-¿bet a-D-glucopyrano syl (1-2) ¿beta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVd, 6), 28-tigloylprotoaescigenin-3beta-O-¿beta-D-glucopyranosyl (1-2) ¿beta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVe, 7), and 28-angeloylprotoaescigenin-3beta-O-¿beta-D-glucopyranosyl (1-2) ¿beta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVf, 8). The structures were determined by chemical and spectroscopic methods. All the above compounds were evaluated for their inhibitory activity against HIV-1 protease.
New Trends for the Nonlinear Measurement and Modeling of High-Power RF Transistors and Amplifiers With Memory Effects (2012)

Power amplifier (PA) behavior is inextricably linked to the characteristics of the transistors underlying the PA design. All transistors exhibit some degree of memory effects, which must therefore be taken into account in the modeling and design of these PAs. In this paper, we will present new trends for the characterization, device modeling, and behavioral modeling of power transistors and amplifiers with strong memory effects. First the impact of thermal and electrical memory effects upon the performance of a transistor will be revealed by comparing continuous wave and pulsed RF large-signal measurements. Pulsed-RF load-pull from the proper hot bias condition yields a more realistic representation of the peak power response of transistors excited with modulated signals with high peak-to-average power ratio. Next, an advanced device modeling method based on large-signal data from a modern nonlinear vector network analyzer instrument, coupled with modeling approaches based on advanced artificial neural network technology, will be presented. This approach enables the generation of accurate and robust time-domain nonlinear simulation models of modern transistors that exhibit significant memory effects. Finally an extension of the X-parameter (X-parameter is a trademark of Agilent Technologies Inc.) behavioral model to account for model memory effects of RF and microwave components will be presented. The approach can be used to model hard nonlinear behavior and long-term memory effects and is valid for all possible modulation formats for all possible peak-to-average ratios and for a wide range of modulation bandwidths. Both the device and behavioral models have been validated by measurements and are implemented in a commercial nonlinear circuit simulator.
OX40L blockade and allergen‐induced airway responses in subjects with mild asthma (2013)

Pharmacological activity of anti-OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post-dosing, but there was no effect on allergen-induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses.
Young S. Kwon (1998)

As it gets easier to access information at home through networks, it becomes the user’s responsibility to formulate an effect query for his information search. One of the difficulties in using the current information retrieval systems is that it is hard for a user, especially a novice, to formulate a query effectively. Often they get overwhelmed by a large amount of information retrieved or get nothing; most users continue to reformulate queries until they get what they want or exhausted. One solution to this problem is to automate the process of query reformulation using the relevance feedback from the previous search. In this research, a Boolean query is viewed as a classifier and a decision tree classifier, ID3 is revised to act as a query in information retrieval (call it ID3-IR). The current emphasis in our experiments is to analyze the changes in the retrieval performance (measured by recall, precision, and E) of the ID3-IR using a different number of relevant input documents. Based on the test set, MEDLARS, it is shown that an input set with more relevant documents achieves higher recall and lower precision. In overall performance analysis measured by E, an input set with more relevant documents is superior to one with less relevant documents after the second reformulation.
Inhibitory Effect of a Novel Anticomplementary Agent, K-76COONa, on the Release of Histamine Induced by Zymosan and Compound 48/80 (1985)

A novel sesquiterpene anticomplementary agent, K-76COONa, if locally applied, was revealed to have an activity to prevent histamine release from rat connective tissue mast cells not only in a zymosan-induced inflammation of the air pouch type (zymosan-air-pouch inflammation) but also in compound 48/80-induced air-pouch inflammation. Moreover, K-76COONa inhibited in vitro histamine release from rat peritoneal mast cells induced by compound 48/80.
Noninvasive Assessment of Gastric Emptying by Near-Infrared Fluorescence Ref lectance Imaging in Mice: Pharmacological Validation with Tegaserod, Cisapride, and Clonidine (2004)

Noninvasive near-infrared fluorescence reflectance imaging (FRI) is an in vivo technique to assess physiological and molecular processes in the intact organism. Here we describe a method to assess gastric emptying in mice. TentaGel beads with covalently bound cyanine dye (Cy5.5) conjugates as fluorescent probe were administered by oral gavage. The amount of intragastric beads/label was derived from the fluorescence signal intensity measured in a region of interest corresponding to the mouse stomach. The FRI signal intensity decreased as a function of time reflecting gastric emptying. In control mice, the gastric half-emptying time was in agreement with literature data. Pharmacological modulation of gastric motility allowed the evaluation of the sensitivity of the FRI-based method. Gastric emptying was either stimulated or inhibited by treatment with the 5-HT(4) receptor agonists tegaserod (Zelnorm) and cisapride or the alpha(2)-receptor agonist clonidine, respectively. Tegaserod and cisapride dose-dependently accelerated gastric emptying. In contrast, clonidine dose-dependently delayed gastric emptying. In conclusion, FRI using fluorescently labeled beads allows the reliable determination of gastric emptying as well as the assessment of pharmacological interventions. The technique thus offers the potential to characterize molecular targets and pathways involved in physiological regulation and pharmacological modulation of gastric emptying.
MAINTENANCE OF SERUM ANTIBODY LEVELS (2004)

In vertebrates, serum antibodies are an essential component of innate and adaptive immunity and immunological memory. They also can contribute significantly to immunopathology. Their composition is the result of tightly regulated differentiation of B lymphocytes into antibody-secreting plasma blasts and plasma cells. The survival of antibody-secreting cells determines their contribution to the immune response in which they were generated and to long-lasting immunity, as provided by stable serum antibody levels. Short-lived plasma blasts and/or plasma cells secrete antibodies for a reactive immune response. Short-lived plasma blasts can become long-lived plasma cells, probably by competition with preexisting plasma cells for occupation of a limited number of survival niches in the body, in a process not yet fully understood. Limitation of the number of long-lived plasma cells allows the immune system to maintain a stable humoral immunological memory over long periods, to react to new pathogenic challenges, and to adapt the humoral memory in response to these antigens.