gebhart/patrepeval huggingface dataset:
Redox-regulated Signaling by Lactosylceramide in the Proliferation of Human Aortic Smooth Muscle Cells (1997)

Previously, our laboratory reported that lactosylceramide (LacCer) stimulated human aortic smooth muscle cell proliferation via specific activation of p44 mitogen-activated protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and induced expression of the transcription factor c-fos downstream to the p44 MAPK signaling cascade (Bhunia A. K., Han, H., Snowden, A., and Chatterjee S. (1996) J. Biol. Chem. 271, 10660-10666). In the present study, we explored the role of free oxygen radicals in LacCer-mediated induction of cell proliferation. Superoxide levels were measured by the lucigenin chemiluminescence method, MAPK activity was measured by immunocomplex kinase assays, and Western blot analysis and c-fos expression were measured by Northern blot assay. We found that LacCer (10 microM) stimulates endogenous superoxide production (7-fold compared with control) in human aortic smooth muscle cells specifically by activating membrane-associated NADPH oxidase, but not NADH or xanthine oxidase. This process was inhibited by an inhibitor of NADPH oxidase, diphenylene iodonium (DPI), and by antioxidants, N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate. NAC and DPI both abrogated individual steps in the signaling pathway leading to cell proliferation. For example, the p21(ras).GTP loading, p44 MAPK activity, and induction of transcription factor c-fos all were inhibited by NAC and DPI as well as an antioxidant pyrrolidine dithiocarbamate or reduced glutathione (GSH). In contrast, depletion of GSH by L-buthionine (S, R)-sulfoximine up-regulated the above described signaling cascade. In sum, LacCer, by virtue of activating NADPH oxidase, produces superoxide (a redox stress signaling molecule), which mediates cell proliferation via activation of the kinase cascade. Our findings may explain the potential role of LacCer in the pathogenesis of atherosclerosis involving the proliferation of aortic smooth muscle cells.
Molecular modeling and mutagenesis studies of the N-terminal domains of galectin-3: evidence for participation with the C-terminal carbohydrate recognition domain in oligosaccharide binding (2000)

A model structure (Henrick,K., Bawumia,S., Barboni,E.A.M., Mehul,B. and Hughes, R.C. (1998) Glycobiology:, 8, 45-57) of the carbohydrate recognition domain (CRD, amino acid residues 114-245) of hamster galectin-3 has been extended to include N-terminal domain amino acid residues 91-113 containing one of the nine proline-rich motifs present in full-length hamster galectin-3. The modeling predicts two configurations of the N-terminal tail: in one the tail turns toward the first (SI) and last (S12) beta-strands of the CRD and lies at the apolar dimer interface observed for galectins -1 and -2. In the second folding arrangement the N-terminal tail lies across the carbohydrate-binding pocket of the CRD where it could participate in sugar-binding: in particular tyrosine 102 and adjacent residues may interact with the partly solvent exposed nonreducing N-acetylgalactosamine and fucose substituents of the A-blood group structure GalNAcalpha1,3 [Fucalpha1,2]Galbeta1,4GlcNAc-R. Binding studies using surface plasmon resonance of a recombinant fragment Delta1-93 protein containing residues 94-245 of hamster galectin-3 and a collagenase-derived fragment Delta1-103 containing residues 104-245, as well as alanine mutagenesis of residues 101-105 in Delta1-93 protein, support the prediction that Tyr102 and adjacent residues make significant contributions to oligosaccharide binding.
Fast and efficient lossless image compression (2002)

A new method gives compression comparable with the JPEG lossless mode, with about five times the speed. FELICS is based on a novel use of two neighboring pixels for both prediction and error modeling. For coding, the authors use single bits, adjusted binary codes, and Golomb or Rice codes. For the latter they present and analyze a provably good method for estimating the single coding parameter.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. (2001)

The epidermal growth factor receptor (EGFR) autocrine pathway contributes to a number of processes important to cancer development and progression, including cell proliferation, apoptosis, angiogenesis, and metastatic spread. The critical role the EGFR plays in cancer has led to an extensive search for selective inhibitors of the EGFR signaling pathway. The results of a large body of preclinical studies and the early clinical trials thus far conducted suggest that targeting the EGFR could represent a significant contribution to cancer therapy. A variety of different approaches are currently being used to target the EGFR. The most promising strategies in clinical development include monoclonal antibodies to prevent ligand binding and small molecule inhibitors of the tyrosine kinase enzymatic activity to inhibit autophosphorylation and downstream intracellular signaling. At least five blocking monoclonal antibodies have been developed against the EGFR. Among these, IMC-225 is a chimeric human-mouse monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy to enter clinical evaluation in cancer patients in Phase II and III studies, alone or in combination with conventional therapies, such as radiotherapy and chemotherapy. A number of small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity is also in development. OSI-774 and ZD1839 (Iressa) are currently in Phase II and III development, respectively. ZD1839, a p.o. active, selective quinazoline derivative has demonstrated promising in vitro and in vivo antitumor activity. Preliminary results from Phase I and II trials in patients with advanced disease demonstrate that ZD1839 and OSI-774 have an acceptable tolerability profile and promising clinical efficacy in patients with a variety of tumor types. This mini-review describes the EGFR inhibitors in clinical development.
Conformational Changes in BID, a Pro-apoptotic BCL-2 Family Member, upon Membrane Binding (2004)

The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. We applied the site-directed spin labeling method of electron paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation. Our study presents a more detailed model for the reorganization of the structure of tBID on membranes.
Inhibition of transforming growth factor ? production by nitric oxide-treated chondrocytes: Implications for matrix synthesis (1999)

Objective Nitric oxide (NO) is generated copiously by articular chondrocytes activated by interleukin-1β (IL-1β). If NO production is blocked, much of the IL-1β inhibition of proteoglycan synthesis is prevented. We tested the hypothesis that this inhibitory effect of NO on proteoglycan synthesis is secondary to changes in chondrocyte transforming growth factor β (TGFβ). Methods Monolayer, primary cultures of lapine articular chondrocytes and cartilage slices were studied. NO production was determined as nitrite accumulation in the medium. TGFβ bioactivity in chondrocyte- and cartilage-conditioned medium (CM) was measured with the mink lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35S-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. Results IL-1β increased active TGFβ in chondrocyte CM by 12 hours; by 24 hours, significant increases in both active and latent TGFβ were detectable. NG-monomethyl-L-arginine (L-NMA) potentiated the increase in total TGFβ without affecting the early TGFβ activation. IL-1β stimulated a NO-independent, transient increase in TGFβ3 at 24 hours; however, TGFβ1 was not changed. When NO synthesis was inhibited with L-NMA, IL-1β increased CM concentrations of TGFβ1 from 24–72 hours of culture. L-arginine (10 mM) reversed the inhibitory effect of L-NMA on NO production and blocked the increases in TGFβ1. Anti-TGFβ1 antibody prevented the restoration of proteoglycan synthesis by chondrocytes exposed to IL-1β + L-NMA, confirming that NO inhibition of TGFβ1 in IL-1β–treated chondrocytes effected, in part, the decreased proteoglycan synthesis. Furthermore, the increase in TGFβ and proteoglycan synthesis seen with L-NMA was reversed by the NO donor S-nitroso-N-acetylpenicillamide. Similar results were seen with cartilage slices in organ culture. The autocrine increase in CM TGFβ1 levels following prior exposure to TGFβ1 was also blocked by NO. Conclusion NO can modulate proteoglycan synthesis indirectly by decreasing the production of TGFβ1 by chondrocytes exposed to IL-1β. It prevents autocrine-stimulated increases in TGFβ1, thus potentially diminishing the anabolic effects of this cytokine in chondrocytes.
The NLRP3 inflammasome, a target for therapy in diverse disease states (2010)

A role for NLRP3 inflammasome in recurrent and chronic inflammation was initially described in a group of rare autoinflammatory conditions, termed cryopyrin-associated periodic syndrome. Subsequently, inflammasomes have been implicated in the pathology of many common diseases, including cancer, gout and diabetes. Despite diverse pathologies, the central role of the inflammasome in innate defences and tumour elimination suggests common therapeutic approaches to reduce inflammation where appropriate.
Regulation by Adrenocorticotropic Hormone of the in Vivo Expression of Scavenger Receptor Class B Type I (SR-BI), a High Density Lipoprotein Receptor, in Steroidogenic Cells of the Murine Adrenal Gland (1996)

The class B, type I scavenger receptor, SR-BI, binds high density lipoprotein (HDL) and can mediate selective uptake of HDL cholesteryl esters by cultured cells. The high levels of expression of SR-BI in steroidogenic tissues and the importance of selective uptake from HDL as a source of cholesterol for steroidogenesis raised the possibility that SR-BI may participate in cholesterol delivery to steroidogenic tissues in vivo. We have used immunoblotting and immunohistochemical methods to show that SR-BI is specifically expressed in a distinctive pattern on the surfaces of steroid-producing cells in the murine adrenal gland's cortex and that its expression in vivo is induced by adrenocorticotropic hormone and suppressed by glucocorticoids. Thus, expression of SR-BI protein is coordinately regulated with adrenal steroidogenesis. These data provide strong support for the hypothesis that SR-BI is a physiologically relevant HDL receptor that provides substrate cholesterol for steroid hormone synthesis.
Gardnerella vaginalis: characteristics, clinical considerations, and controversies (1992)

The clinical significance, Gram stain reaction, and genus affiliation of Gardnerella vaginalis have been controversial since Gardner and Dukes described the organism as the cause of "nonspecific vaginitis," a common disease of women which is now called bacterial vaginosis. The organism was named G. vaginalis when taxonomic studies showed that it was unrelated to bacteria in various genera including Haemophilus and Corynebacterium. Electron microscopy and chemical analyses have elucidated the organism's gram-variable reaction. Controversy over the etiology of bacterial vaginosis was largely resolved by (i) studies using improved media and methods for the isolation and identification of bacteria in vaginal fluids and (ii) standardization of criteria for clinical and laboratory diagnosis. Besides G. vaginalis, Mobiluncus spp., Mycoplasma hominis, and certain obligate anaerobes are now acknowledged as participants in bacterial vaginosis. The finding that G. vaginalis, Mobiluncus spp., and M. hominis inhabit the rectum indicates a potential source of autoinfection in addition to sexual transmission. Extravaginal infections with G. vaginalis are increasingly recognized, especially when the toxic anticoagulant polyanetholesulfonate is omitted from blood cultures and when urine cultures are incubated anaerobically for 48 h. The finding that mares harbor G. vaginalis suggests that an equine model can be developed for studies of Gardnerella pathogenesis.
MicroRNAs as targets for antisense-based therapeutics (2007)

MicroRNAs (miRNAs) are a novel class of endogenous non-coding single-stranded RNAs, which regulate gene expression post-transcriptionally by base pairing with their target mRNAs. So far > 5000 miRNA entries have been registered and miRNAs have been implicated in most, if not all, central cellular processes and several diseases. As the mechanism of action for miRNA regulation of target mRNAs is mediated by Watson-Crick base pairing, antisense oligonucleotides targeting the miRNAs appear as an obvious choice to specifically inhibit miRNA function. Indeed, miRNAs can be antagonized in vivo by oligonucleotides composed of high-affinity nucleotide mimics. Lessons learned from traditional antisense strategies and small-interfering RNA approaches, that is from potent nucleotide mimics, design rules, pharmacokinetics, administration and safety issues, are likely to pave the way for future clinical trials of miRNA-antagonizing oligonucleotides.
Enrichment of progenitor cells from human marrow. (1987)

Suspensions enriched for myeloid and erythroid colony-forming cells were prepared from human marrow by simultaneous treatment of low-density cells with the monoclonal antibodies Campath-1 and 80H.3, followed by immune-rosetting; lymphocytes and monocytes were successfully removed by this method. The final suspension contained 22% of blasts and 70% primitive myeloid-monocytic cells. GM-CFCs, counted after 14 days of culture, were enriched 21-fold. Of all cells present in the final suspension, 10.8% were day 8 GM cluster-forming cells, 2.3% were day 8 GM colony-forming cells, 2.4% were day 7 CFU-E, 0.9% were day 14 GM cluster-forming cells, 1.1% were day 14 GM colony-forming cells, and 0.6% were day 14 BFU-E. After enrichment, BFU-E became markedly more dependent on the addition of 5637-conditioned medium as a source of growth factors, suggesting that lymphocytes and/or monocytes support erythroid progenitor growth in cultures of unfractionated marrow. By removing these cells, we obtained a sensitive assay for burst-promoting activities in conditioned media. This procedure can be used to study the roles of marrow lymphocytes and monocytes in hemopoiesis as well as providing a basis for the purification of normal and aberrant progenitors.
Hanging on the ‘wire (1997)

The primary focus of this article is an analysis of an audio-only media space from a computer-supported cooperative work (CSCW) perspective. To explore whether audio by itself is suitable for shared media systems, we studied a workgroup using an audio-only media space. This media space, called Thunderwire, combined high-quality audio with open connec-tions to create a shared space for its users. The two-month field study provided a richly nuanced understanding of this audio spaces social use. The system afforded rich sociable interactions. As well, users were able to create a useful, usable social space; however, through an analysis of the social norms that the participants formulated, we show that they had to take into account being in an audio-only environment. Within the field study, then, audio by itself was sufficient for a usable media space and a useful social space, but users were forced to adapt to many audio-only and system conditions. The article also considers audios implications for privacy.
Efficient LBM Visual Simulation on Face-Centered Cubic Lattices (2009)

The Lattice Boltzmann method (LBM) for visual simulation of fluid flow generally employs cubic Cartesian (CC) lattices such as the D3Q13 and D3Q19 lattices for the particle transport. However, the CC lattices lead to suboptimal representation of the simulation space. We introduce the face-centered cubic (FCC) lattice, fD3Q13, for LBM simulations. Compared to the CC lattices, the fD3Q13 lattice creates a more isotropic sampling of the simulation domain and its single lattice speed (i.e., link length) simplifies the computations and data storage. Furthermore, the fD3Q13 lattice can be decomposed into two independent interleaved lattices, one of which can be discarded, which doubles the simulation speed. The resulting LBM simulation can be efficiently mapped to the GPU, further increasing the computational performance. We show the numerical advantages of the FCC lattice on channeled flow in 2D and the flow-past-a-sphere benchmark in 3D. In both cases, the comparison is against the corresponding CC lattices using the analytical solutions for the systems as well as velocity field visualizations. We also demonstrate the performance advantages of the fD3Q13 lattice for interactive simulation and rendering of hot smoke in an urban environment using thermal LBM.
Serum eosinophil peroxidase (EPO) levels in asthmatic patients (1997)

Eosinophil granular proteins are a useful eosinophilic activation marker in asthmatic patients. In this study, the eosinophil peroxidase (EPO) levels were assessed in different stages of bronchial asthma, in 123 patients suffering from asthma, classified as mild (n =49), moderate (n = 49), and severe (n = 25), according to the International Consensus Report of Diagnosis and Treatment of Asthma, as well as in 27 healthy controls, with the aim of evaluating the importance of this protein as a severity marker in bronchial asthma, and its possible correlation with parameters such as anamnesis, respiratory function tests, and peripheral blood eosinophil count, and also with some allergologic diagnostic tests, both in vivo and in vitro. The geometric mean serum level of EPO was 9.3 +/- 11.3 ng/ml (median +/- SD) in controls, 28 +/- 37.8 ng/ml in the asthmatic patients. Depending on the asthma severity, the EPO levels were 25 +/- 30.5; 29 +/- 37.1, and 41 +/- 47.3 ng/ml in mild, moderate, and severe asthmatics, respectively, being the significant differences between the group of patients with mild and severe asthma (P < 0.001). The number of eosinophils (eos) in peripheral blood was 157 +/- 20 eos/mm3 in the controls, 334/35 eos/mm3 in mild asthmatics, 510 +/- 87 eos/mm3 in moderate asthmatics, and 658 +/- 72 eos/mm3 in severe asthmatics, with significant differences between all groups (from P < 0.05 to P < 0.001). Both the serum levels of EPO and the number of eosinophils were greater in patients with active asthma patients with inactive asthma (P < 0.001). Significant negative correlations (P < 0.001) were found between serum levels of EPO and FEV1 (rs = 0.30), MEF25-75 (rs = -0.33) and MEF50 (rs = -0.34), and a good positive correlation (rs = 0.80, P < 0.001) was found between EPO levels and the number of eosinophils in peripheral blood. We also found a significant positive correlation between eosinophil number and clinical score (rs = 0.54, P < 0.001) and between EPO levels and the mentioned score (rs = 0.46, P < 0.001).
Evaluation of a Multisensor Armband in Estimating Energy Expenditure in Obese Individuals (2006)

The SWA is an easy to handle, practical, new portable device for measuring energy expenditure. The accuracy of the SWA appeared to be poor in the obese subjects we examined, especially those with high REE both in rest and exercise. We believe that it is necessary to incorporate new, obesity-specific algorithms in the relative software.
A cDNA for a Protein That Interacts with the Human Immunodeficiency Virus Tat Transactivator (1990)

The human immunodeficiency virus (HIV) tat protein (Tat) is a positive regulator of virus gene expression and replication. Biotinylated Tat was used as a probe to screen a lambda gt11 fusion protein library, and a complementary DNA encoding a protein that interacts with Tat was cloned. Expression of this protein, designated TBP-1 (for Tat binding protein-1), was observed in a variety of cell lines, with expression being highest in human cells. TBP-1 was localized predominantly in the nucleus, which is consistent with the nuclear localization of Tat. In cotransfection experiments, expression of TBP-1 was able to specifically suppress Tat-mediated transactivation. The strategy described may be useful for direct identification and cloning of genes encoding proteins that associate with other proteins to modulate their activity in a positive or negative fashion.
Protective Effects of Necrostatin-1 against Concanavalin A-Induced Acute Hepatic Injury in Mice (2013)

These results demonstrate that Nec-1 prevents ConA-induced liver injury via RIP1-related and autophagy-related pathways.
Chaperones Hsp70 and Hsp40 Suppress Aggregate Formation and Apoptosis in Cultured Neuronal Cells Expressing Truncated Androgen Receptor Protein with Expanded Polyglutamine Tract (2000)

Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. We have previously demonstrated that the SBMA gene product, the androgen receptor protein, is toxic and aggregates when truncated. Heat shock proteins function as molecular chaperones, which recognize and renaturate misfolded protein (aggregate). We thus assessed the effect of a variety of chaperones in a cultured neuronal cell model of SBMA. Overexpression of chaperones reduces aggregate formation and suppresses apoptosis in a cultured neuronal cell model of SBMA to differing degrees depending on the chaperones and their combinations. Combination of Hsp70 and Hsp40 was the most effective among the chaperones in reducing aggregate formation and providing cellular protection, reflecting that Hsp70 and Hsp40 act together in chaperoning mutant and disabled proteins. Although Hdj2/Hsdj chaperone has been previously reported to suppress expanded polyglutamine tract-formed aggregate, Hsdj/Hdj2 showed little effect in our system. These findings indicate that chaperones may be one of the key factors in the developing of CAG repeat disease and suggested that increasing expression level or enhancing the function of chaperones will provide an avenue for the treatment of CAG repeat disease.