gebhart/patrepeval huggingface dataset:
Stat3 Activation Is Required for Cellular Transformation by v- src (1998)

Stat3 activation has been associated with cytokine-induced proliferation, anti-apoptosis, and transformation. Constitutively activated Stat3 has been found in many human tumors as well as v-abl- and v-src-transformed cell lines. Because of these correlations, we examined directly the relationship of activated Stat3 to cellular transformation and found that wild-type Stat3 enhances the transforming potential of v-src while three dominant negative Stat3 mutants inhibit v-src transformation. Stat3 wild-type or mutant proteins did not affect v-ras transformation. We conclude that Stat3 has a necessary role in v-src transformation.
Inhibition of complement-mediated cytolysis by the terminal complement inhibitor of herpesvirus saimiri (1994)

Herpesvirus saimiri (HVS) is a lymphotropic herpesvirus that induces T-cell transformation in vitro and causes lymphomas and leukemias in New World primates other than its natural host, the squirrel monkey. Nucleotide sequence analysis of the HVS genome revealed two open reading frames with significant homology to genes for human complement regulatory molecules. One of these genes encodes a predicted protein (designated HVSCD59) with 48% amino acid sequence identity to the human terminal complement regulatory protein CD59 (HuCD59). The CD59 homolog from squirrel monkey (SMCD59) was cloned, and the corresponding amino acid sequence showed 69% identity with HVSCD59. BALB/3T3 cells stably expressing HVSCD59, SMCD59, or HuCD59 were equally protected from complement-mediated lysis by human serum. However, only HVSCD59-expressing cells were effectively protected from complement-mediated lysis when challenged with rat serum, suggesting that HVSCD59 was less species restrictive. The complement regulatory activity of HVSCD59 and SMCD59 occurred after C3b deposition, indicating terminal complement inhibition. Treatment of BALB/3T3 stable transfectants with phosphatidylinositol-specific phospholipase C prior to complement attack decreased the complement regulatory function of HVSCD59, suggesting cell surface attachment via a glycosyl-phosphatidylinositol anchor. Cells expressing HVSCD59 effectively inhibited complement-mediated lysis by squirrel monkey serum in comparison with SMCD59-expressing cells. Finally HVSCD59-specific transcripts were detected in owl monkey cells permissive for lytic HVS replication but not in T cells transformed by HVS, which failed to produce virions. These data are the first to demonstrate a functional, virally encoded terminal complement inhibitor and suggest that HVSCD59 represents a humoral immune evasion mechanism supporting the lytic life cycle of HVS.
Lipoprotein-Associated Phospholipase A2 Interacts with Phospholipid Vesicles via a Surface-Disposed Hydrophobic α-Helix (2011)

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) plays important roles in both the inhibition and promotion of inflammation in human disease. It catalyzes the hydrolytic inactivation of plasma platelet activating factor (PAF) and is also known as PAF acetylhydrolase. High levels of PAF are implicated in a variety of inflammatory diseases such as asthma, necrotizing enterocolitis, and sepsis. Lp-PLA(2) also associates with lipoproteins in human plasma where it hydrolyzes oxidized phospholipids to produce pro-inflammatory lipid mediators that can promote inflammation and the development of atherosclerosis. Lp-PLA(2) plasma levels have recently been identified as a biomarker of vascular inflammation, atherosclerotic vulnerability, and future cardiovascular events. The enzyme is thus a prominent target for the development of inflammation and atherosclerosis-modulating therapeutics. While the crystallographically determined structure of the enzyme is known, the enzyme's mechanism of interaction with PAF and the function-modulating lipids in lipoproteins is unknown. We have employed peptide amide hydrogen-deuterium exchange mass spectrometry (DXMS) to characterize the association of Lp-PLA(2) with dimyristoylphosphatidylcholine (DMPC) vesicles and found that specific residues 113-120 in one of the enzyme's surface-disposed hydrophobic α-helices likely mediate liposome binding.
Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins. (1994)

Herbimycin A, a benzoquinoid ansamycin, is widely used as an inhibitor of tyrosine kinases. We have examined the effects of herbimycin A and several analogues on p185, the tyrosine kinase encoded by the erbB2 gene in human breast cancer cells. Exposure to 0.35 microM herbimycin A reduced tyrosine phosphorylation of p185 in SKBr3 cells by 80% after 2 h, and the p185 protein level was reduced by 90% after 6 h. The reduction of p185 resulted primarily from increased degradation of p185; cellular protein synthesis was reduced only 16% in SKBr3 cells treated with herbimycin A, RNA synthesis was inhibited only 10%, and erbB2 mRNA levels were unchanged. Examination of the major cellular glycoproteins indicated that most glycoproteins were unaffected under conditions that substantially depleted p185. Studies with cell lines transfected with erbB2 containing defined deletions indicated that susceptibility to the depletion of p185 by herbimycin and its analogues required the domain encoded by amino acids 751-971. The benzoquinoid ansamycins therefore initiate a process of specific degradation of tyrosine kinases by a mechanism that remains unknown.
Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. (1988)

The polyamine-biosynthetic pathway represents an inviting target for the development of agents inhibiting carcinogenesis and tumor growth. Polyamines play an essential role in the proliferation and development of mammalian cells. Deranged polyamine metabolism may be an important factor in carcinogenesis. Depletion of polyamines inhibits growth of neoplastic cells in vitro and in animal models. Several different classes of other anticancer agents may under some conditions exert enhanced effects when polyamine levels are depleted. Some suitable inhibitors of polyamine production are currently available and other promising compounds are presently being tested. It should soon prove possible to block polyamine biosynthesis at every step in the pathway. The use of these inhibitors alone and combined either with each other or with other antitumor agents will enable a full examination of the potential of this approach.
Seasonal Variation in the Skin Transcriptome of Common Bottlenose Dolphins (Tursiops truncatus) from the Northern Gulf of Mexico (2015)

As long-lived predators that integrate exposures across multiple trophic levels, cetaceans are recognized as sentinels for the health of marine ecosystems. Their utility as sentinels requires the establishment of baseline health parameters. Because cetaceans are protected, measurements obtained with minimal disruption to free ranging animals are highly desirable. In this study we investigated the utility of skin gene expression profiling to monitor health and contaminant exposure in common bottlenose dolphins (Tursiops truncatus). Remote integument biopsies were collected in the northern Gulf of Mexico prior to the Deepwater Horizon oil spill (May 2010) and during summer and winter for two years following oil contamination (2010-2011). A bottlenose dolphin microarray was used to characterize the skin transcriptomes of 94 individuals from three populations: Barataria Bay, Louisiana, Chandeleur Sound, Louisiana, and Mississippi Sound, Mississippi/Alabama. Skin transcriptomes did not differ significantly between populations. In contrast, season had a profound effect on gene expression, with nearly one-third of all genes on the array differing in expression between winter and the warmer seasons (moderated T-test; p<0.01, fold-change≥1.5). Persistent organic pollutants (POPs) in blubber changed concurrently, reaching >two-fold higher concentrations in summer compared to winter, due to a seasonal decrease in blubber thickness and loss of stored lipid. However, global gene expression did not correlate strongly with seasonally changing contaminant concentrations, most likely because the refractory, lipid-stored metabolites are not substrates for phase I or II xenobiotic detoxification pathways. Rather, processes related to cell proliferation, motility, and differentiation dominated the differences in expression in winter and the warmer seasons. More subtle differences were seen between spring and summer (1.5% of genes differentially expressed). However, two presumed oil-exposed animals from spring presented gene expression profiles more similar to the summer animals (presumed exposed) than to other spring animals. Seasonal effects have not previously been considered in studies assessing gene expression in cetaceans, but clearly must be taken into account when applying transcriptomic analyses to investigate their contaminant exposure or health status.
Construction of Vectors Expressing Bioactive Heterodimeric and Single-Chain Murine Interleukin-12 for Gene Therapy (1998)

It has been well demonstrated that interleukin-12 (IL-12) could be useful to defend against a variety of pathogens, to suppress tumor growth and metastasis, and even to be employed as an adjuvant of vaccines to enhance beneficial type 1 T helper (Th1) cell response over detrimental type 2 T helper (Th2) cell responses. To apply IL-12 genes in gene therapy such as a DNA vaccine, a pIL-12 vector was constructed that contained two cytomegalovirus (CMV) promoters to drive the expression of p35 and p40 subunits, respectively. In addition, a pscIL-12 vector was designed with a linker to fuse p35 cDNA with p40 cDNA to produce a single-chain IL-12 protein, ensuring not only that the expression of p35 and p40 subunits was equally expressed, but also that no free p40 subunits interfered with IL-12 activity. The data suggested pIL-12 could produce a rather high level of biologically active IL-12 after transfection of COS cell lines as well as C2C12 muscle cell lines, as measured by both concanavalin A blast proliferation assay and enzyme-linked immunosorbent assay. Interestingly, the pscIL-12 vector could also express a bioactive murine IL-12 fusion protein in vitro. Furthermore, in vivo functional studies also demonstrated that mice co-immunized with a pS vector expressing the major envelope protein of hepatitis B virus (HBV) and IL-12 vectors encoding native IL-12 or single-chain IL-12 fusion protein elicited higher levels of IgG2a anti-HBs antibody and of Th1-related cytokine. Because p35 and p40 genes can be expressed in a vector by using a single promoter, pscIL-12 should be useful in future applications for nucleic acid vaccination or for gene therapy against diseases.
The Airy fiber: an optical fiber that guides light diffracted by a circular aperture (2016)

In theory, no more than 80% of the light diffracted by a circular aperture can be directly coupled into one mode of an ordinary optical fiber. To improve coupling efficiency, and illustrate an inverse method for designing optical fibers with a desired mode shape, we have made an optical fiber that guides an approximate Airy pattern as one of its modes. The fiber’s attenuation was 11.0 dB/km at a 1550 nm wavelength, the match between the fiber’s mode and the ideal infinite Airy pattern was 93.7%, and the far field resembled a top-hat beam. The guidance mechanism has strong similarities to photonic bandgap guidance.
Human immunodeficiency virus envelope glycoprotein/CD4-mediated fusion of nonprimate cells with human cells (1990)

Human immunodeficiency virus (HIV) infects human cells by binding to surface CD4 molecules and directly fusing with the cell membrane. Although mouse cells expressing human CD4 bind HIV, they do not become infected, apparently because of a block in membrane fusion. To study this problem, we constructed a recombinant vaccinia virus that can infect and promote transient expression of full-length CD4 in mammalian cells. This virus, together with another vaccinia recombinant encoding biologically active HIV envelope glycoprotein gp160, allowed us to study CD4/gp160-mediated cell-cell fusion in a wide variety of human and nonhuman cells in the absence of other HIV proteins. By using syncytium formation assays in which a single cell type expressed both CD4 and gp160, we demonstrated membrane fusion in lymphoid and nonlymphoid human cells but not in any of the 23 tested nonhuman cell types, derived from African green monkey, baboon, rabbit, hamster, rat, or mouse. However, in mixing experiments with one cell type expressing CD4 and the other cell type expressing gp160, all of these nonhuman cells could form CD4/gp160-mediated syncytia when mixed with human cells; in 20 of 23 cases, membrane fusion occurred only if the CD4 molecule was expressed on the human cells whereas in the other three cases, CD4 could be expressed on either one of the fusing partners. Interestingly, in one mouse cell line, CD4-dependent syncytia formed without a human partner, but only if a C-terminally truncated form of the HIV envelope glycoprotein was employed. Our results indicate that nonhuman cells are intrinsically capable of undergoing CD4/gp160-mediated membrane fusion, but this fusion is usually prevented by the lack of helper or the presence of inhibitory factors in the nonhuman cell membranes.
A sampling technique and its CMOS implementation with 1 Gb/s bandwidth and 25 ps resolution (1994)

This paper presents a technique and circuitry for high-resolution sampling of a digital waveform. Very fine sampling resolution is achieved by simultaneously propagating both data and clock signals through delay elements in such a way that resolution is controlled by the difference in the delay of clock and data signals. Delay units were designed using biased CMOS and differential CMOS inverters. A sampler circuit with 64 stages has been fabricated in 1.2 /spl mu/m CMOS technology, and test results show a bandwidth of up to 1 Gb/s for the input data and a sampling resolution externally adjustable between 25 and 250 ps. The fabricated circuit has shown sampling stability, monotonicity in sampling, and uniformity in sampling resolution. >
Abnormal Lignin in a Loblolly Pine Mutant (1997)

Novel lignin is formed in a mutant loblolly pine (Pinus taeda L.) severely depleted in cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), which converts coniferaldehyde to coniferyl alcohol, the primary lignin precursor in pines. Dihydroconiferyl alcohol, a monomer not normally associated with the lignin biosynthetic pathway, is the major component of the mutant's lignin, accounting for approximately 30 percent (versus approximately 3 percent in normal pine) of the units. The level of aldehydes, including new 2-methoxybenzaldehydes, is also increased. The mutant pines grew normally indicating that, even within a species, extensive variations in lignin composition need not disrupt the essential functions of lignin.
OX40 blockade inhibits house dust mite driven allergic lung inflammation in mice and in vitro allergic responses in humans (2014)

The costimulatory receptor OX40 is expressed on activated T cells and regulates T-cell responses. Here, we show the efficacy and mechanism of action of an OX40 blocking antibody using the chronic house dust mite (HDM) mouse model of lung inflammation and in vitro HDM stimulation of cells from HDM allergic human donors. We have demonstrated that OX40 blockade leads to a reduction in the number of eosinophils and neutrophils in the lavage fluid and lung tissue of HDM sensitized mice. This was accompanied by a decrease in activated and memory CD4(+) T cells in the lungs and further analysis revealed that both the Th2 and Th17 populations were inhibited. Improved lung function and decreased HDM-specific antibody responses were also noted. Significantly, efficacy was observed even when anti-OX40 treatment was delayed until after inflammation was established. OX40 blockade also inhibited the release of the Th2 cytokines IL-5 and IL-13 from cells isolated from HDM allergic human donors. Altogether, our data provide evidence of a role of the OX40/OX40L pathway in ongoing allergic lung inflammation and support clinical studies of a blocking OX40 antibody in Th2 high severe asthma patients.
Theromin, a Novel Leech Thrombin Inhibitor (2000)

We purified the most potent thrombin inhibitor described to date from the rhynchobdellid leech Theromyzon tessulatum. Designated theromin, it was purified to apparent homogeneity by gel permeation and anion exchange chromatography followed by two reverse-phase steps of high performance liquid chromatography. The primary sequence of theromin (a homodimer of 67 amino acid residues including 16 cysteine residues) was determined by a combination of reduction and s-beta-pyridylethylation, Edman degradation, trypsin enzymatic digestion, and matrix-assisted laser desorption mass spectrometry measurement. Theromin exhibits no sequence homology with any other thrombin inhibitors. Furthermore, theromin significantly diminishes, in a dose-dependent manner, the level of human granulocyte and monocyte activation induced by lipopolysaccharides. In summary, this potent thrombin inhibitor promises to have high biomedical significance.
Phosphatidylinositol 3-Kinase Is an Early Intermediate in the Gβγ-mediated Mitogen-activated Protein Kinase Signaling Pathway (1996)

The beta gamma-subunit of Gi mediates mitogen-activated protein (MAP) kinase activation through a signaling pathway involving Shc tyrosine phosphorylation, subsequent formation of a multiprotein complex including Shc, Grb2, and Sos, and sequential activation of Ras, Raf, and MEK. The mechanism by which G beta gamma mediates tyrosine phosphorylation of Shc, however, is unclear. This study assesses the role of phosphatidylinositol 3-kinase (PI-3K) in G beta gamma-mediated MAP kinase activation. We show that Gi-coupled receptor- and G beta gamma-stimulated MAP kinase activation is attenuated by the PI-3K inhibitors wortmannin and LY294002 or by over expression of a dominant negative mutant of the p85 subunit of PI-3K. Wortmannin and LY294002 also inhibit Gi-coupled receptor-stimulated Ras activation. The PI-3K inhibitors do not affect MAP kinase activation stimulated by over-expression of Sos, a constitutively active mutant of Ras, or a constitutively active mutant of MEK. These results demonstrate that PI-3K activity is required in the G beta gamma-mediated MAP kinase signaling pathway at a point upstream of Sos and Ras activation.
SMARCC1 expression is upregulated in prostate cancer and positively correlated with tumour recurrence and dedifferentiation. (2008)

All benign specimens showed no or minimal staining for SMARCC1. In contrast, 20% of the specimens from patients with non-metastatic and non-recurrent disease showed moderate to marked staining. In 31% of the patients with recurrent disease and in 31% of the patients with metastatic disease we found moderate to strong SMARCC1 immunostaining. In total, 23% of lymph node metastases expressed SMARCC1. SMARCC1 expression was also positively correlated to Gleason score (p<0.05), clinical T stage (p<0.01) and time to recurrence (p<0.001). In a logistic regression analysis, patients with a marked SMARCC1 immunostaining had a significantly elevated odds ratio (OR) of 16 for recurrent cancer and an OR of 4.5 for metastatic disease. Conclusions. Our present results demonstrate an increased expression of SMARCC1 protein in prostate cancer and reveal a positive correlation with tumour dedifferentiation, progression, metastasis and time to recurrence.
The FLORES Evaluation Datasets for Low-Resource Machine Translation: Nepali–English and Sinhala–English (2019)

Francisco Guzmán, Peng-Jen Chen, Myle Ott, Juan Pino, Guillaume Lample, Philipp Koehn, Vishrav Chaudhary, Marc’Aurelio Ranzato. Proceedings of the 2019 Conference on Empirical Methods in Natural Language Processing and the 9th International Joint Conference on Natural Language Processing (EMNLP-IJCNLP). 2019.
Expression of large tenascin‐C splice variants in synovial fluid of patients with rheumatoid arthritis (2007)

Tenascin-C (TN-C) is a hexameric glycoprotein component of extracellular matrix, and alternative RNA splicing creates two major TN-C size variants (the small and large variants). The large TN-C variants play key roles in many pathologic conditions in adults, including tumorigenesis, regeneration, and inflammation. This cross-sectional study compared levels of large TN-C variants in synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial fluid samples were obtained from knees of 26 patients with advanced RA and 79 with advanced OA. Expression of TN-C splice variants was examined using Western blotting. The levels of large TN-C variants in synovial fluid were determined by an enzyme-linked immunosorbent assay. Synovium were analyzed for TN-C by immunohistochemistry. Immunoblotting showed the presence of large TN-C variants in synovial fluid from patients with RA and OA. However, levels of large TN-C variants were fourfold higher in RA samples compared with OA samples (p < 0.01). Synovial fluid levels of TN-C in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA samples than in OA samples. These results indicate that local synthesis of TN-C is increased during rheumatic disease.
SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma (2003)

The suppressor of cytokine signaling (SOCS) family of proteins has been implicated in the negative regulation of several cytokine pathways, particularly the receptor-associated tyrosine kinase/signal transducer and activator of transcription (Jak/STAT) pathways of transcriptional activation. SOCS-1 (also known as JAB and SSI-1) inhibits signaling by many cytokines. Because of the previously observed hypermethylation-associated inactivation of SOCS-1 in hepatocellular carcinoma and the critical role of interleukin-6 (IL-6) as a survival factor in multiple myeloma (MM), we examined CpG island methylation of the SOCS-1 gene in MM cell lines and primary MM samples. Aberrant SOCS-1 methylation was found in the IL-6-dependent MM cell lines U266 and XG1, which correlated with transcriptional silencing. Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine (DAC) up-regulated SOCS-1 expression. Methylation-associated inactivation of SOCS-1 in hematopoietic cell lines correlated with greater sensitivity to the chemical JAK inhibitor AG490. Using methylation-specific polymerase chain reaction (MSP), we found that SOCS-1 is hypermethylated in 62.9% (23/35) of MM patient samples. In contrast, methylation analysis of malignant lymphomas of various histologies revealed SOCS-1 hypermethylation in only 3.2% (2/62), and there was no methylation of SOCS-1 in normal peripheral blood leukocytes or bone marrow cells. We conclude that SOCS-1 is frequently inactivated by hypermethylation in MM patients. Silencing of the SOCS-1 gene may impair negative regulation of the Jak/STAT pathway and therefore result in greater responsiveness to cytokines, thus supporting survival and expansion of MM cells.
Functionalization of substituted 2(1H)‐ and 4(1H)‐pyridones. III. The preparation of substituted 6‐Vinyl‐1,2‐dihydro‐2‐oxo‐ and 1,4‐dihydro‐4‐oxo‐3‐pyridinecarboxylic acids through the chemistry of pyridone dianions (1983)

Abstract The synthesis of various substituted 6‐vinyl‐1,2‐dihydro‐2‐oxo‐3‐pyridinecarboxylic acids from the dianions of 1,2‐dihydro‐6‐methyl‐2‐oxo‐3‐pyridinecarbonitrile and the corresponding 3‐ t ‐butyl ester is reported. The dianions were generated with LDA in THF at low temperature and reacted with various carbonyl substrates. Several conditions for the dehydration and hydrolysis of these adducts to the vinyl pyridone acids are discussed. Employing the conditions used for the 2‐pyridone analogs, a series of substituted 6‐vinyl‐1,4‐di‐hydro‐4‐oxo‐3‐pyridinecarboxylic acids was prepared through the new dianion of 1,4‐dihydro‐6‐methyl‐4‐oxo‐3‐pyridinecarboxylic acid, t ‐butyl ester.