gebhart/patrepeval huggingface dataset:
Tumor Necrosis Factor α Suppresses the Induction of Connective Tissue Growth Factor by Transforming Growth Factor-β in Normal and Scleroderma Fibroblasts (2000)

Connective tissue growth factor (CTGF) is overexpressed in a variety of fibrotic disorders, presumably secondary to the activation and production of transforming growth factor-beta (TGF-beta), a key inducer of fibroblast proliferation and matrix synthesis. The CTGF gene promoter has a TGF-beta response element that regulates its expression in fibroblasts but not epithelial cells or lymphocytes. Recent studies have shown that the macrophage-produced cytokine tumor necrosis factor alpha (TNFalpha) is necessary to promote inflammation and to induce genes, such as matrix metalloproteinases, involved with the early stages of wound healing. In this study, we examined the ability of TNFalpha to modulate CTGF gene expression. TNFalpha was found to suppress the TGF-beta-induced expression of CTGF protein in cultured normal fibroblasts. The activity of TNFalpha was blocked by NF-kappaB inhibitors. We showed that sequences between -244 and -166 of the CTGF promoter were necessary for both TGF-beta and TNFalpha to modulate CTGF expression. There was a constitutive expression of CTGF by scleroderma fibroblasts that was increased by TGF-beta treatment. Although TNFalpha was able to repress TGF-beta-induced CTGF and collagen synthesis both in normal and scleroderma skin fibroblasts, fibroblasts cultured from scleroderma patients were more resistant to TNFalpha as TNFalpha was unable to suppress the basal level of CTGF expression in scleroderma fibroblasts. Thus, we suspect that the high level of constitutive CTGF expression in scleroderma fibroblasts and its inability to respond to negative regulatory cytokines may contribute to the excessive scarring of skin and internal organs in patients with scleroderma.
Nanobeam Mechanics: Elasticity, Strength, and Toughness of Nanorods and Nanotubes (1997)

The Young's modulus, strength, and toughness of nanostructures are important to proposed applications ranging from nanocomposites to probe microscopy, yet there is little direct knowledge of these key mechanical properties. Atomic force microscopy was used to determine the mechanical properties of individual, structurally isolated silicon carbide (SiC) nanorods (NRs) and multiwall carbon nanotubes (MWNTs) that were pinned at one end to molybdenum disulfide surfaces. The bending force was measured versus displacement along the unpinned lengths. The MWNTs were about two times as stiff as the SiC NRs. Continued bending of the SiC NRs ultimately led to fracture, whereas the MWNTs exhibited an interesting elastic buckling process. The strengths of the SiC NRs were substantially greater than those found previously for larger SiC structures, and they approach theoretical values. Because of buckling, the ultimate strengths of the stiffer MWNTs were less than those of the SiC NRs, although the MWNTs represent a uniquely tough, energy-absorbing material.
Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. (2007)

In this study of patients who had active PsA and a previous, inadequate response to DMARD therapy, adalimumab was well tolerated and significantly reduced the signs, symptoms, and disability of PsA during 12 weeks of blinded and 12 weeks of open-label therapy. Adalimumab also improved psoriasis in these patients.
Composting for Avian Influenza Virus Elimination (2012)

Effective sanitization is important in viral epizootic outbreaks to avoid further spread of the pathogen. This study examined thermal inactivation as a sanitizing treatment for manure inoculated with highly pathogenic avian influenza virus H7N1 and bacteriophages MS2 and 6. Rapid inactivation of highly pathogenic avian influenza virus H7N1 was achieved at both mesophilic (35°C) and thermophilic (45 and 55°C) temperatures. Similar inactivation rates were observed for bacteriophage 6, while bacteriophage MS2 proved too thermoresistant to be considered a valuable indicator organism for avian influenza virus during thermal treatments. Guidelines for treatment of litter in the event of emergency composting can be formulated based on the inactivation rates obtained in the study.
Do Patent Pools Encourage Innovation? Evidence from the 19th-Century Sewing Machine Industry (2009)

Members of a patent pool agree to use a set of patents as if they were jointly owned by all members and license them as a package to other firms. Regulators favor pools as a means to encourage innovation: Pools are expected to reduce litigation risks for their members and lower license fees and transactions costs for other firms. This paper uses the example of the first patent pool in U.S. history, the Sewing Machine Combination (1856-1877) to perform the first empirical test of the effects of a patent pool on innovation. Contrary to theoretical predictions, the sewing machine pool appears to have discouraged patenting and innovation, in particular for the members of the pool. Data on stitches per minute, as an objectively quantifiable measure of innovation, confirm these findings. Innovation for both members and outside firms slowed as soon as the pool had been established and resumed only after it had dissolved.
Virtual network computing (1998)

VNC is an ultra thin client system based on a simple display protocol that is platform independent. It achieves mobile computing without requiring the user to carry any hardware. VNC provides access to home computing environments from anywhere in the world, on whatever computing infrastructure happens to be available-including, for example, public Web browsing terminals in airports. In addition, VNC allows a single desktop to be accessed from several places simultaneously, thus supporting application sharing in the style of computer supported cooperative work (CSCW). The technology underlying VNC is a simple remote display protocol. It is the simplicity of this protocol that makes VNC so powerful. Unlike other remote display protocols such as the X Window System and Citrix's ICA, the VNC protocol is totally independent of operating system, windowing system, and applications. The VNC system is freely available for download from the ORL Web site at http://www.orl.co.uk/vnc/. We begin the article by summarizing the evolution of VNC from our work on thin client architectures. We then describe the structure of the VNC protocol, and conclude by discussing the ways we use VNC technology now and how it may evolve further as new clients and servers are developed.
Crosstalk between Gα i - and Gα q -coupled receptors is mediated by Gβγ exchange (1999)

Activation of Galpha(i)-coupled receptors often causes enhancement of the inositol phosphate signal triggered by Galpha(q)-coupled receptors. To investigate the mechanism of this synergistic receptor crosstalk, we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2) resulted in a similar increase in potency and efficacy of bradykinin or UTP. In contrast, these stimuli did not affect the potency of direct activators of Galpha(q); a truncated Gbeta(3) mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level were still enhanced. This suggests that the Gbetagamma-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were equally effective in enhancing the signals of the B(2) and a UTP-preferring P2Y receptor, indicating a very broad specificity of this synergism. The enhancement of the bradykinin signal by (i) Galpha(i)-activating receptor ligands or (ii) cotransfection of Gbetagamma was suppressed when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein. Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins as determined by GTPgammaS-induced decrease in high affinity agonist binding and by B(2) receptor-enhanced [(35)S]GTPgammaS binding. These findings support the concept that Gbetagamma exchange between Galpha(i)- and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.
Nitrosative Stress-induced Apoptosis through Inhibition of NF-κB (2002)

Nitrosative stress produced by cytokines predisposes to apoptotic cell death. However, the molecular mechanism by which this occurs is not well understood. We have shown previously that nitric oxide (NO) regulates the activity of the anti-apoptotic transcription factor NF-kappaB. Here we demonstrate that the inhibition of NF-kappaB by NO sensitizes A549 and Jurkat T cells to tumor necrosis factor-alpha (TNFalpha)-induced apoptosis. The molecular basis of NF-kappaB inhibition is different in the two cell types. In A549 cells, NO functions at the nuclear level to inhibit NF-kappaB by S-nitrosylation. In Jurkat cells, NO inhibits the NF-kappaB activating pathway in the cytoplasm at a step proximal to the degradation of IkappaBalpha. The inhibition of NF-kappaB is reflected in the level of intracellular S-nitrosothiols, which are constitutively metabolized. These data suggest that NO can influence cell death by modulating NF-kappaB activity with the sites of inhibition being cell type-specific. The data also show that NO bioactivity regulates tumor necrosis factor-alpha signaling.
Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy (1995)

Anthracyclines entrapped in small-sized, sterically stabilized liposomes have the advantage of long circulation time, reduced systemic toxicity, increased uptake into systemic tumors, and gradual release of their payload. To date, there is no information on the behavior of these liposomes in brain tumors. The objective of this study was to compare the biodistribution and clinical efficacy of free doxorubicin (F-DOX) and stealth liposome-encapsulated DOX (SL-DOX) in a secondary brain tumor model. Nine days after tumor inoculation Fischer rats with a right parietal malignant sarcoma received an intravenous dose of 6 mg/kg of either F-DOX or SL-DOX for evaluation of drug biodistribution. For therapeutic trials a single dose of 8 mg/kg was given 6 or 11 days after tumor induction, or alternatively, weekly doses (5 mg/kg) were given on Days 6, 13, and 20. Liposome-encapsulated DOX was slowly cleared from plasma with a t1/2 of 35 hours. Free-DOX maximum tumor drug levels reached a mean value of 0.8 microgram/g and were identical in the adjacent brain and contralateral hemisphere. In contrast, SL-DOX tumor levels were 14-fold higher at their peak levels at 48 hours, declining to ninefold increased levels at 120 hours. A gradual increase in drug levels in the brain adjacent to tumor was noted between 72 and 120 hours (up to 4 micrograms/g). High-performance liquid chromatography analysis identified a small amount of aglycone metabolites within the tumor mass from 96 hours and beyond, after SL-DOX injection. Cerebrospinal fluid levels were barely detectable in tumor-bearing rats treated with F-DOX up to 120 hours after drug injection (< or = 0.05 microgram/ml), whereas the levels found after SL-DOX were 10- to 30-fold higher. An F-DOX single-dose treatment given 6 days after tumor inoculation increased the rats' life span (ILS) by 135% over controls (p < 0.05) but was not effective if given on Day 11. In contrast, SL-DOX treatment resulted in an ILS of 168% (p < 0.0003) with no difference when given after 6 or 11 days. Treatment with three weekly doses of SL-DOX produced an ILS of 189% compared to 126% by F-DOX (p < 0.0002). The authors conclude that the use of long-circulating liposomes as cytotoxic drug carriers in brain tumor results in enhanced drug exposure and improved therapeutic activity, with equal effectiveness against early small- and large-sized brain tumors.
Cyclic activity of the receptors of cobalamin bound to transcobalamin II (1987)

The activity of receptors specific for human transcobalamin II-Cobalamin (TC II-Cbl) were measured in virus-transformed lymphoblasts, hepatocytes (hepatoma) and diploid fibro lasts. In all three types of human cells the receptor activity increased as cells went from a resting phase to the most actively dividing phase. Receptor activity declined as cell division slowed. The changes in activity of lymphoblasts and hepatocytes were produced by changes in receptor number and not by changes in affinity between receptors and TC II-Cbl. The basis of the change in fibroblasts was not clear. The Cbl-dependent methionine synthetase activity of fibroblasts, in contrast, tended to be greatest when the cultures were confluent and replication had slowed. As the fibroblasts became senescent the receptor activity for TC II-Cbl declined and the fluctuations with the phase of the cell were blunted. However, the release of apo TC II from the cells was maintained. These observations must be taken into consideration when the respective cells are used as models. Even more important are the implications of the observations of the changes in receptor activity for TC II-Cbl for the regulation of the entry of Cbl into cells.
Surface‐Enhanced Raman Scattering of Small Molecules from Silver‐Coated Silicon Nanopores (2003)

New ways of detecting low concentrations of analytes , which could be used as part of integrated on‐chip devices, are offered by surface‐enhanced Raman‐scattering substrates fabricated on the nanoscale. The ability of metal surfaces to amplify a Raman‐scattering signal (see Figure) is combined with an enlarged substrate surface area, allowing orders of magnitude enhancement for the detection of rhodamine 6G and adenine.
Different DNA Polymerases Are Involved in the Short- and Long-Patch Base Excision Repair in Mammalian Cells (1998)

Mammalian cells possess two distinct pathways for completion of base excision repair (BER): the DNA polymerase beta (Pol beta)-dependent short-patch pathway (replacement of one nucleotide), which is the main route, and the long-patch pathway (resynthesis of 2-6 nucleotides), which is PCNA-dependent. To address the issue of how these two pathways share their role in BER the ability of Pol beta-defective mammalian cell extracts to repair a single abasic site constructed in a circular duplex plasmid molecule was tested in a standard in vitro repair reaction. Pol beta-deficient extracts were able to perform both BER pathways. However, in the case of the short-patch BER, the repair kinetics was significantly slower than with Pol beta-proficient extracts, while the efficiency of the long-patch synthesis was unaffected by the loss of Pol beta. The repair synthesis was fully dependent on PCNA for the replacement of long patches. These data give the first evidence that in cell extracts DNA polymerases other than Pol beta are specifically involved in the long-patch BER. These DNA polymerases are also able to perform short-patch BER in the absence of PCNA, although less efficiently than Pol beta. These findings lead to a novel model whereby the two BER pathways are characterized by different protein requirements, and a functional redundancy at the level of DNA polymerases provides cells with backup systems.
Light‐Directed Activation of Human T‐Cells (2007)

Anti-human CD3 antibodies are rendered inert with a coating of photolabile 2-nitrobenzyl groups until their activity is restored by irradiation with UVA light, at which point the antibodies are free to bind and activate T-cells. Such antibodies should enable the regulation of cytotoxic T-cell activity at required times and locations in the body. This would have widespread medical application, particularly in the treatment of cancer. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2007/z700200_s.pdf or from the author. 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.
Stretchable tracks for laser-machined neural electrode arrays (2009)

An easy and fast method for fabrication of neural electrode arrays is the patterning of platinum foil and spin-on silicone rubber using a laser. However, the mechanical flexibility of such electrode arrays is limited by the integrated tracks that connect the actual electrode sites and the contacts to which wires are welded. Changing the design from straight lines to meanders, the tracks can be stretched to a certain extend defined by the shape of the meanders. Horse-shoe-like designs described by an opening angle theta = 60 degrees and ratio between curvature radius r and track width w of r/w = 3.6 permitted stretching of 14.4% before track breakage. For r/w = 11.7 a maximum elongation at break of 19.7% was measured. Larger opening angles theta provided even better flexibility but with increasing theta, the tensile strength and the electrical conductance of a single track is compromised and the maximum integration density (tracks per area) decreases.
Polypyrrole-heparin composites as stimulus-responsive substrates for endothelial cell growth (1999)

Heparin is a potent anticoagulant which can be immobilized on biomaterial surfaces to increase their hemocompatability. In the present work, we have electrochemically synthesized composites comprising heparin and the electrically conducting polymer polypyrrole. The incorporation and exposure of heparin were controlled by varying key conditions of polymer synthesis (i.e., applied current and synthesis time). The resulting composite polymers were electroactive after synthesis and the amount of heparin exposed in the polymer could be increased (up to threefold) by switching the polymers from their oxidized to reduced states. Polymer reduction was achieved by either application of negative potentials (-0.4 to -0.7 V for 90 s) or exposure to aqueous reductant (0.1M sodium dithionite for 30 min). Heparin-polypyrrole composites remained stable after autoclaving, displaying no significant loss of electroactivity, and had a shelf life of at least 2 years postautoclaving. Finally, the composites were found to be excellent substrates for the growth of human endothelial cells.
Data Mining and Predictive Modeling of Biomolecular Network from Biomedical Literature Databases (2007)

In this paper, we present a novel approach Bio-IEDM (Biomedical Information Extraction and Data Mining) to integrate text mining and predictive modeling to analyze biomolecular network from biomedical literature databases. Our method consists of two phases. In phase 1, we discuss a semisupervised efficient learning approach to automatically extract biological relationships such as protein-protein interaction, protein-gene interaction from the biomedical literature databases to construct the biomolecular network. Our method automatically learns the patterns based on a few user seed tuples and then extracts new tuples from the biomedical literature based on the discovered patterns. The derived biomolecular network forms a large scale-free network graph. In phase 2, we present a novel clustering algorithm to analyze the biomolecular network graph to identify biologically meaningful subnetworks (communities). The clustering algorithm considers the characteristics of the scale-free network graphs and is based on the local density of the vertex and its neighborhood functions that can be used to find more meaningful clusters with different density level. The experimental results indicate our approach is very effective in extracting biological knowledge from a huge collection of biomedical literature. The integration of data mining and information extraction provides a promising direction for analyzing the biomolecular network.
Intranasal ketamine (2010)

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Purine metabolism in Neisseria gonorrhoeae: the requirement for hypoxanthine (1980)

Strains isolated from disseminated gonococcal infections often require hypoxanthine for growth. The biochemical bases for the requirement for hypoxanthine in strains isolated from both disseminated (Ile-Val-Arg-Hyx-Ura-phenotype) and non-disseminated (Hyx-phenotype) infections were compared. The requirement for hypoxanthine was dependent upon the composition of the growth medium. In a complete defined medium, hypoxanthine was replaced by a mixture of adenine and guamine but not by either purine alone. The addition of adenine along inhibited gonococcal growth. This inhibition was reversed by the addition of guanine and most likely resulted from an inhibition of de novo purine biosynthesis. In a histidine-free medium, adenine replaced the hypoxanthine requirement in Ile-Val-Arg-Hyx-Ura-strains. Adenine did not replace the hypoxanthine requirement in Hyx- strains. The Ile-Val-Arg-Hyx-Ura- strains exhibited a markedly reduced rate of the novo purine biosynthesis while Hyx- strains were blocked in this pathway. In vivo concentrations of purines are important factors which may limit the intracellular or extracellular growth of these strains.
The Crystal Structure of Recombinant Human Neutrophil-activating Peptide-2 (M6L) at 1.9-Å Resolution (1995)

Neutrophil-activating peptide-2 (NAP-2) is a 70-residue carboxyl-terminal fragment of platelet basic protein, which is found in the alpha-granules of human platelets. NAP-2, which belongs to the CXC family of chemokines that includes interleukin-8 and platelet factor 4, binds to the interleukin-8 type II receptor and induces a rise in cytosolic calcium, chemotaxis of neutrophils, and exocytosis. Crystals of recombinant NAP-2 in which the single methionine at position 6 was replaced by leucine to facilitate expression belong to space group P1 (unit cell parameters a = 40.8, b = 43.8, and c = 44.7 A and alpha = 98.4 degrees, beta = 120.3 degrees, and gamma = 92.8 degrees), with 4 molecules of NAP-2 (Mr = 7600) in the asymmetric unit. The molecular replacement solution calculated with bovine platelet factor 4 as the starting model was refined using rigid body refinement, manual fitting in solvent-leveled electron density maps, simulated annealing, and restrained least squares to an R-factor of 0.188 for 2 sigma data between 7.0- and 1.9-A resolution. The final refined crystal structure includes 265 solvent molecules. The overall tertiary structure, which is similar to that of platelet factor 4 and interleukin-8, includes an extended amino-terminal loop, three strands of antiparallel beta-sheet arranged in a Greek key fold, and one alpha-helix at the carboxyl terminus. The Glu-Leu-Arg sequence that is critical for receptor binding is fully defined by electron density and exhibits multiple conformations.