gebhart/patrepeval huggingface dataset:
Context Effects on Misreading and Suppression at UAG Codons in Human Cells (1995)

The effect of the 3' codon context on the efficiency of nonsense suppression in mammalian tissue culture cells has been tested. Measurements were made following the transfection of cells with a pRSVgal reporter vector that contained the classical Escherichia coli lacZ UAG allele YA559. The position of this mutation was mapped by virtue of its fortuitous creation of a CTAG MaeI restriction enzyme site. Determination of the local DNA sequence revealed a C-->T mutation at codon 600 of the lacZ gene: CAG-->TAG. Site-directed mutagenesis was used to create a series of vectors in which the base 3' to the nonsense codon was either A, C, G, or U. Suppression of the amber-containing reporter was achieved by cotransfection with genes for human tRNA(Ser) or tRNA(Gln) UAG nonsense suppressors and by growth in the translational error-promoting aminoglycoside drug G418. Nonsense suppression was studied in the human cell lines 293 and MRC5V1 and the simian line COS-7. Overall, the rank order for the effect of changes to the base 3' to UAG was C < G = U < A. This study confirms and extends earlier findings that in mammalian cells 3' C supports efficient nonsense suppression while 3' A is unsympathetic for read-through at nonsense codons. The rules for the mammalian codon context effect on nonsense suppression are therefore demonstrably different from those in E. coli.
Kinetics of microbial growth on mixtures of pentachlorophenol and chlorinated aromatic compounds (1988)

Batch experiments were conducted to examine the effects of several substrate analogs on the degradation of pentachlorophenol by an enrichment culture of pentachlorophenol-utilizing bacteria. The presence of substrate analogs which were unable to serve as a carbon source for growth of the culture (e.g., 3,5,6,-trichloro-2-pyridinol, 2,4-dichlorophenoxyacetic acid) decreased the rate of pentachlorophenol degradation. The presence of a utilizable substrate analog (e.g., phenol, 2,4,5-trichlorophenol) also inhibited the initial rate of pentachlorophenol degradation; however, the overall removal rate was accelerated due to an increase in cell mass concentration as a result of simultaneous growth on both substrates. These effects were shown to be predicted by a mathematical model based on a modified Monod equation. Kinetic parameters obtained from the results of laboratory studies can be used for further process analysis to define the optimal conditions for the biological treatment of complex mixtures of phenolic compounds.
IL-33 Reduces Macrophage Foam Cell Formation (2010)

The development of atherosclerosis, a chronic inflammatory disease characterized by the formation of arterial fibrotic plaques, has been shown to be reduced by IL-33 in vivo. However, whether IL-33 can directly affect macrophage foam cell formation, a key feature of atherosclerotic plaques, has not been determined. In this study, we investigated whether IL-33 reduces macrophage foam cell accumulation in vivo and if IL-33 reduces their formation in vitro using THP-1 and primary human monocyte-derived macrophages. In Apolipoprotein E(-/-) mice fed on a high fat diet, IL-33 treatment significantly reduced the accumulation of macrophage-derived foam cells in atherosclerotic plaques. IL-33 also reduced macrophage foam cell formation in vitro by decreasing acetylated and oxidized low-density lipoprotein uptake, reducing intracellular total and esterified cholesterol content and enhancing cholesterol efflux. These changes were associated with IL-33-mediated reduction in the expression of genes involved in modified low-density lipoprotein uptake, such as CD36, and simultaneous increase in genes involved in cholesterol efflux, including Apolipoprotein E, thereby providing a mechanism for such an action for this cytokine. IL-33 also decreased the expression of key genes implicated in cholesterol esterification and triglyceride storage, including Acyl-CoA:cholesterol acyltransferase 1 and Adipocyte differentiation-related protein. Furthermore, using bone marrow-derived macrophages from ST2(-/-) mice, we demonstrate that the IL-33 receptor, ST2, is integral to the action of IL-33 on macrophage foam cell formation. In conclusion, IL-33 has a protective role in atherosclerosis by reducing macrophage foam cell formation suggesting that IL-33 maybe a potential therapeutic agent against atherosclerosis.
T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions (1982)

The development of T lymphocytes in 34 patients engrafted with allogeneic bone marrow was studied by indirect immunofluorescence using mouse monoclonal antibodies. Two antibodies, termed anti-Leu-1 and anti-Leu-4, react with distinct membrane components expressed by all peripheral T cells, whereas two other antibodies, termed anti-Leu-2a and anti-Leu-3a. react with complementary subsets of Leu-1 + and Leu-4+ lymphocytes. The Leu-2a + 3a– (Leu-2) subset contains suppressor/cytotoxic T cells, and the Leu-2a – 3a+ (Leu-3) subset contains helper T cells. The ratio of Leu-2/Leu-3 T cells was elevated in nearly all patients studied during the first month of engraftment, but this ratio subsequently returned to normal in patients with an uncomplicated course or with solved acute GVHD. In contrast, a deficiency of helper T cells with a resultant preponderance of suppressor/ cytotoxic T cells persisted in all patients studied with both acute and chronic GVHD after the first month. The implications of these findings in regard to the functions of these cells in vitro are discussed.
Mechanisms of Enzymatic Degradation of Amyloid β Microfibrils Generating Nanofilaments and Nanospheres Related to Cytotoxicity (2010)

Amyloid beta (Abeta) fibrils are found in the brain tissue of persons with Alzheimer's disease (AD), where they accumulate as plaques. One way to reduce the level of accumulation of Abeta in the brain and potentially treat AD is with Abeta-degrading enzymes such as neprilysin (NEP) and insulin-degrading enzyme (IDE). However, enzymatic responses and degradation mechanisms of Abeta fibrils (crystalline-state Abeta) have not been investigated, particularly with respect to how to avoid cytotoxicity of the degradation products to neuronal cells. Thus, insight into mechanisms of enzymatic degradation of Abeta fibrils would be instructive as a route to elucidating different structural features related to degradation and to cytotoxicity. We report mechanisms of enzymatic degradation of Abeta with cross-beta structures and show the series of steps involved in the digestion of Abeta microfibrils to nanospheres or nanofilaments by protease XIV or alpha-chymotrypsin, respectively. These degradation products, which contained almost the same secondary structures, exhibited different cytotoxicities, indicating that relationships between nanoassembled structures and cytotoxicity of Abeta peptides are more significant than the beta-sheet content. In addition, the enzymatic digestion at the Lys28 loop region linking the two beta-sheets in Abeta fibrils is suggested as a key target related to cytotoxicity, a feature that can be selectively targeted on the basis of the choice of protease.
NOVEL PHOTOCLEAVABLE PROTEIN CROSSLINKING REAGENTS AND THEIR USE IN THE PREPARATION OF ANTIBODY‐TOXIN CONJUGATES (1985)

Abstract— Two photolabile heterobifunctional protein crosslinking reagents have been synthesized and used for the conjugation of a protein toxin to an antibody. o‐Nitrobenzyl alcohol derivatives containing protected sulfhydryl groups were converted to o‐nitrobenzyloxycarbonyl chlorides and covalently attached to pokeweed antiviral protein (PAP‐S) obtained from the seeds of Phytolacca americana. The sulfhydryl groups were deprotected and the modified toxins were reacted with J5 antibody (specific for the common acute lymphoblastic leukemia antigen, CALLA) that had been functionalized with maleimido groups. Antibody‐toxin conjugates were formed predominantly in the ratio of 1:1, and were purified from unconjugated antibody and PAP‐S. Irradiation of the conjugates with light having a peak intensity at 365 nm effected photolytic fragmentation, and PAP‐S was released in fully active form. The methods described here may prove useful for the release of drugs or toxins at sites accessible to light.
UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein. (1989)

UV irradiation of human and murine cells enhances the transcription of several genes. Here we report on the primary target of relevant UV absorption, on pathways leading to gene activation, and on the elements receiving the UV-induced signal in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, in the gene coding for collagenase, and in the cellular oncogene fos. In order to induce the expression of genes. UV radiation needs to be absorbed by DNA and to cause DNA damage of the kind that cannot be repaired by cells from patients with xeroderma pigmentosum group A. UV-induced activation of the three genes is mediated by the major enhancer elements (located between nucleotide positions -105 and -79 of HIV-1, between positions -72 and -65 of the collagenase gene, and between positions -320 and -299 of fos). These elements share no apparent sequence motif and bind different trans-acting proteins; a member of the NF kappa B family binds to the HIV-1 enhancer, the heterodimer of Jun and Fos (AP-1) binds to the collagenase enhancer, and the serum response factors p67 and p62 bind to fos. DNA-binding activities of the factors recognizing the HIV-1 and collagenase enhancers are augmented in extracts from UV-treated cells. The increase in activity is due to posttranslational modification. While AP-1 resides in the nucleus and must be modulated there, NF kappa B is activated in the cytoplasm, indicating the existence of a cytoplasmic signal transduction pathway triggered by UV-induced DNA damage. In addition to activation, new synthesis of AP-1 is induced by UV radiation.
Altered MicroRNA Expression in Cervical Carcinomas (2008)

Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, they may offer new candidate targets to be exploited for both prognostic and therapeutic strategies in patients with cervical cancer.
Specificity of mood stabilizer action on neuronal growth cones (2007)

These results show that lithium, VPA and CBZ are unique in causing altered neuronal morphology via myo-inositol depletion.
A Digital-Microfluidic Approach to Chip Cooling (2008)

Thermal management has emerged as an increasingly important aspect of IC design. Elevated die temperatures are detrimental to circuit performance and reliability. Furthermore, hot spots due to spatially nonuniform heat flux in ICs can cause physical stress that further reduces reliability. The authors of this article review various chip-cooling techniques that have been proposed in the literature. They then present an alternative approach based on a recently invented digital-microfluidic platform that enables an adaptive cooling technique. This novel digital-fluid-handling platform uses a phenomenon known as electrowetting so that a vast array of discrete droplets of liquid, ranging from microliters to nanoliters and potentially to picoliters, can be independently moved along a substrate. Although this technology was originally developed for a biological and chemical lab on a chip, the authors show how it can be adapted for use as a fully reconfigurable, adaptive cooling platform.
Comparison of the Immediate Early Polypeptides of Human Cytomegalovirus Isolates (1981)

SUMMARY The in vivo and in vitro synthesized immediate early (IE) polypeptides of three isolates of human cytomegalovirus (CMV) have been compared by SDS-polyacrylamide gel electrophoresis. Of the 11 IE polypeptides detected early in infection, one was very abundant and had a different apparent mol. wt. depending on the isolate. This difference may be useful in the classification of CMV into strains.
PPAR Regulation of Inflammatory Signaling in CNS Diseases (2008)

Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that regulate immune and inflammatory responses. Specific ligands for PPARalpha, gamma, and delta isoforms have proven effective in the animal models of multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, and trauma/stroke, suggesting their use in the treatment of neuroinflammatory diseases. The activation of NF-kappaB and Jak-Stat signaling pathways and secretion of inflammatory cytokines are critical in the pathogenesis of CNS diseases. Interestingly, PPAR agonists mitigate CNS disease by modulating inflammatory signaling network in immune cells. In this manuscript, we review the current knowledge on how PPARs regulate neuroinflammatory signaling networks in CNS diseases.
Interleukin-8 induces neutrophil transendothelial migration. (1991)

Interleukin-8 (IL-8) is a potent neutrophil chemotactic stimulant. We have used chemically synthesized IL-8 to investigate its role in human neutrophil adhesion and transendothelial migration. IL-8 enhanced the adhesiveness of human neutrophils to plastic, and to both unstimulated and tumour necrosis factor (TNF)-stimulated endothelial monolayers in vitro. Using a two-compartment model separated by a confluent endothelial monolayer, we have shown that IL-8 chemotactic stimulation induced transmigration across the monolayer of up to 87.4 +/- 2.1% of added neutrophils (compared to random unstimulated transmigration of 2.2 +/- 0.7%), while chemokinetic stimulation led to transmigration of 21 +/- 3.8% of neutrophils. Preincubation of endothelium with TNF also induced transmigration in this model, and was additive when combined with an IL-8 chemotactic stimulus. Endothelial permeability was increased at maximal rates of chemotactic transmigration, which may correlate with increased permeability of vessels at inflammatory sites in vivo. The property of IL-8 to stimulate movement of neutrophils across endothelial monolayers in vitro supports the concept of a central role for this molecule in the accumulation of neutrophils at inflammatory lesions in vivo.
Regulation of inducible nitric oxide synthase messenger RNA expression and nitric oxide production by lipopolysaccharide in vivo: the roles of macrophages, endogenous IFN-γ, and TNF receptor-1-mediated signaling (1997)

To evaluate potential roles for macrophages, IFN-gamma, and TNF receptor 1 (TNFR1) in the regulation of LPS-induced inducible nitric oxide synthase (iNOS) mRNA expression, we used a model of macrophage depletion as well as IFN-gamma (GKO) and TNFR1 (TNFR1 -/-) knockout mice. LPS-induced iNOS mRNA in spleen was ablated in both macrophage-depleted and GKO mice. In livers of macrophage-depleted mice, LPS-induced iNOS mRNA was reduced by 55 to 85%, with the most profound reductions detected 6 and 8 h after LPS injection. In GKO mice, peak iNOS mRNA expression in liver (3 h) was unaffected by the loss of endogenous IFN-gamma. By 6 to 12 h after LPS challenge, however, hepatic LPS-induced iNOS mRNA and serum nitrate/nitrite levels were reduced substantially in GKO mice. Residual LPS-induced iNOS mRNA in livers of GKO mice was nearly ablated by macrophage depletion, indicating that induction of iNOS mRNA in liver requires both endogenous IFN-gamma and either macrophages and/or macrophage-derived factors. TNFR1-mediated signaling was involved in the induction of LPS-induced iNOS mRNA in liver at 3 and 6 h, but not in its maintenance at 8 h. Conversely, induction of iNOS mRNA in spleen by LPS was independent of TNFR1-mediated signaling. Our results indicate that macrophages and/or their secreted products, endogenous IFN-gamma production, and TNFR1-mediated signaling play key roles in the in vivo regulation of iNOS mRNA expression and that the extent of their involvement is both time and organ specific.
Thioredoxin Reductase Deficiency Potentiates Oxidative Stress, Mitochondrial Dysfunction and Cell Death in Dopaminergic Cells (2012)

Mitochondria are considered major generators of cellular reactive oxygen species (ROS) which are implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). We have recently shown that isolated mitochondria consume hydrogen peroxide (H₂O₂) in a substrate- and respiration-dependent manner predominantly via the thioredoxin/peroxiredoxin (Trx/Prx) system. The goal of this study was to determine the role of Trx/Prx system in dopaminergic cell death. We asked if pharmacological and lentiviral inhibition of the Trx/Prx system sensitized dopaminergic cells to mitochondrial dysfunction, increased steady-state H₂O₂ levels and death in response to toxicants implicated in PD. Incubation of N27 dopaminergic cells or primary rat mesencephalic cultures with the Trx reductase (TrxR) inhibitor auranofin in the presence of sub-toxic concentrations of parkinsonian toxicants paraquat; PQ or 6-hydroxydopamine; 6OHDA (for N27 cells) resulted in a synergistic increase in H₂O₂ levels and subsequent cell death. shRNA targeting the mitochondrial thioredoxin reductase (TrxR2) in N27 cells confirmed the effects of pharmacological inhibition. A synergistic decrease in maximal and reserve respiratory capacity was observed in auranofin treated cells and TrxR2 deficient cells following incubation with PQ or 6OHDA. Additionally, TrxR2 deficient cells showed decreased basal mitochondrial oxygen consumption rates. These data demonstrate that inhibition of the mitochondrial Trx/Prx system sensitizes dopaminergic cells to mitochondrial dysfunction, increased steady-state H₂O₂, and cell death. Therefore, in addition to their role in the production of cellular H₂O₂ the mitochondrial Trx/Prx system serve as a major sink for cellular H₂O₂ and its disruption may contribute to dopaminergic pathology associated with PD.
High-sulphur proteins in mammalian keratins: a possible aid in classification (1977)

A study has been made of the high-sulphur proteins isolated from keratins to determine the value of using their electrophoretic patterns as an aid in studying the classification of closely related animals. The high-sulphur proteins of 35 different species covering nine orders of the class Mammalia have been examined after electrophoresis in polyacrylamide gels at pH 2.6. From this study it can be concluded that keratin samples which have different electrophoretic patterns can be tentatively judged as coming from animals of different species, although identical patterns do not necessarily mean identity of animal source. The ease of keratin sampling and of electrophoretic analysis could make the method useful as an aid in classification.
The Essential Piaget. Edited by Howard E. Gruber and J. Jacques Vonèche. New York: Basic Books, 1977. xlii + 881 pages. $35.00. - Jean Piaget: Psychologist of the Real. By Brian Rotman. Ithaca, NY: Cornell University Press, 1977. 200 pages. $14.50. (1980)

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Stimulation of Megakaryocyte and Platelet Production by a Single Dose of Recombinant Human Thrombopoietin in Patients with Cancer (1997)

Background: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. Objective: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. Design: Phase I and II clinical cohort study. Setting: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Patients: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. Intervention: A single intravenous dose of thrombopoietin (0.3 to 2.4 µg/kg of body weight) 3 weeks before chemotherapy. Measurements: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. Results: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. Conclusions: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.
Definition of the Opus Audio Codec (2012)

This document defines the Opus interactive speech and audio codec. Opus is designed to handle a wide range of interactive audio applications, including Voice over IP, videoconferencing, in-game chat, and even live, distributed music performances. It scales from low bitrate narrowband speech at 6 kbit/s to very high quality stereo music at 510 kbit/s. Opus uses both Linear Prediction (LP) and the Modified Discrete Cosine Transform (MDCT) to achieve good compression of both speech and music. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the
AZT: A Biochemical Response Modifier of Methotrexate and 5-Fluorouracil Cytotoxicity in Human Ovarian and Pancreatic Carcinoma Cells (1991)

In ovarian and pancreatic carcinoma cell lines, the activity of the salvage enzyme, thymidine kinase (EC 2.7.1.21), was 2- to 13-fold higher than that of the key enzyme of thymidylate de novo biosynthesis, thymidylate synthase (dTMP synthase, EC 2.1.1.45). AZT (3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited thymidine kinase activity in extracts of human ovarian and pancreatic carcinoma cells, with Dixon plots yielding Ki = 1.1 microM in both cell lines. AZT (20 microM) yielded synergistic cytotoxicity with methotrexate (0.4 microM) in human pancreatic carcinoma cells in clonogenic assay and also with methotrexate (0.02 microM) in human ovarian carcinoma cells, as measured by cell counts. Thymidine (10 microM) and hypoxanthine (100 microM) reversed these inhibitions. AZT (20 or 40 microM) also provided synergistic cytotoxicity with 5-fluorouracil (0.5 and 1.0 microM) in human pancreatic carcinoma cells in clonogenic assay. These studies suggest a new role for AZT, which, as an inhibitor of thymidine salvage, should be useful as a biochemical response modifier to provide a synergistic clinical anticancer impact on de novo biosynthesis of thymidylates in conjunction with methotrexate or 5-fluorouracil.