gebhart/patrepeval huggingface dataset:
Diverse Gene Sequences Are Overexpressed in Werner Syndrome Fibroblasts Undergoing Premature Replicative Senescence (1991)

Genes that play a role in the senescent arrest of cellular replication are likely to be overexpressed in human diploid fibroblasts (HDF) derived from subjects with Werner syndrome (WS) because these cells have a severely curtailed replicative life span. To identify some of these genes, a cDNA library was constructed from WS HDF after they had been serum depleted and repleted (5 days in medium containing 1% serum followed by 24 h in medium containing 20% serum). Differential screening of 7,500 colonies revealed 102 clones that hybridized preferentially with [32P]cDNA derived from RNA of WS cells compared with [32P]cDNA derived from normal HDF. Cross-hybridization and partial DNA sequence determination identified 18 independent gene sequences, 9 of them known and 9 unknown. The known genes included alpha 1(I) procollagen, alpha 2(I) procollagen, fibronectin, ferritin heavy chain, insulinlike growth factor-binding protein-3 (IGFBP-3), osteonectin, human tissue plasminogen activator inhibitor type I, thrombospondin, and alpha B-crystallin. The nine unknown clones included two novel gene sequences and seven additional sequences that contained both novel segments and the Alu class of repetitive short interspersed nuclear elements; five of these seven Alu+ clones also contained the long interpersed nuclear element I (KpnI) family of repetitive elements. Northern (RNA) analysis, using the 18 sequences as probes, showed higher levels of these mRNAs in WS HDF than in normal HDF. Five selected mRNAs studied in greater detail [alpha 1(I) procollagen, fibronectin, insulinlike growth factor-binding protein-3, WS3-10, and WS9-14] showed higher mRNA levels in both WS and late-passage normal HDF than in early-passage normal HDF at various intervals following serum depletion/repletion and after subculture and growth from sparse to high-density confluent arrest. These results indicate that senescence of both WS and normal HDF is accompanied by overexpression of similar sets of diverse genes which may play a role in the senescent arrest of cellular replication and in the genesis of WS, normal biological aging, and attendant diseases.
LYAR, a novel nucleolar protein with zinc finger DNA-binding motifs, is involved in cell growth regulation. (1993)

A cDNA encoding a novel zinc finger protein has been isolated from a mouse T-cell leukemia line on the basis of its expression of a Ly-1 epitope in a lambda gt11 library. The putative gene was mapped on mouse chromosome 1, closely linked to Idh-1, but not linked to the Ly-1 (CD5) gene. The cDNA is therefore named Ly-1 antibody reactive clone (LYAR). The putative polypeptide encoded by the cDNA consists of 388 amino acids with a zinc finger motif and three copies of nuclear localization signals. Antibodies raised against a LYAR fusion protein reacted with a protein of 45 kD on Western blots and by immunoprecipitation. Immunolocalization indicated that LYAR was present predominantly in the nucleoli. The LYAR mRNA was not detected in brain, thymus, bone marrow, liver, heart, and muscle. Low levels of LYAR mRNA were detected in kidney and spleen. However, the LYAR gene was expressed at very high levels in immature spermatocytes in testis. The LYAR mRNA is present at high levels in early embryos and preferentially in fetal liver and fetal thymus. A number of B- and T-cell leukemic lines expressed LYAR at high levels, although it was not detectable in bone marrow and thymus. During radiation-induced T-cell leukemogenesis, high levels of LYAR were expressed in preleukemic thymocytes and in acute T leukemia cells. Fibroblast cells overexpressing the LYAR cDNA from a retrovirus vector, though not phenotypically transformed in vitro, had increased ability to form tumors in nu/nu mice. Therefore, LYAR may function as a novel nucleolar oncoprotein to regulate cell growth.
THE EFFECTS OF EXTRACELLULAR MATRIX AND OSTEOGENIC PROTEIN‐1 ON THE MORPHOLOGICAL DIFFERENTIATION OF RAT SYMPATHETIC NEURONS (1996)

The growth patterns of axons and dendrites differ with respect to their number, length, branching, and spatial orientation; therefore, it is likely that these processes differ in their growth requirements. To examine this hypothesis, we have been analyzing the responses of cultured rat sympathetic neurons to three types of stimuli: large structural proteins of the extracellular matrix, matrix-associated growth factors, and neurotrophins. Purified structural proteins such as laminin and collagen IV have been found to promote only axonal growth; whereas the matrix associated growth factor, osteogenic protein-1, selectively stimulates dendritic growth. In contrast, nerve growth factor modulates the growth of both types of processes. These data suggest that process-specific interactions with the extracellular environment may be critical determinants of cell shape in neurons. Perinatal rat sympathetic neurons grown in culture in the absence of serum or glial cells extend a single process which is axonal in nature. Exposure to osteogenic protein-1 causes the formation of additional processes which express the morphological, cytoskeletal, and ultrastructural characteristics of dendrites. Consistent with observations on the regulation of dendritic growth in sympathetic neurons in situ, the dendrite-promoting activity of osteogenic protein-1 is independent of synaptic or electrical activity, but is modulated by nerve growth factor. In the presence of optimal concentrations of osteogenic protein-1 and nerve growth factor, the size of the dendritic arbor extended by cultured sympathetic neurons approximates that seen in situ at comparable developmental stages. Osteogenic protein-1 does not promote dendritic growth in cultured neurons obtained from embryonic ciliary, dorsal root, trigeminal or nodose ganglia, suggesting that its morphogenetic effects are cell selective. Since mRNA for osteogenic protein-1 is expressed in mature as well as embryonic target tissues of the sympathetic nervous system, we also examined the effects of osteogenic protein-1 on cultures of sympathetic neurons derived from adult rats. Consistent with results obtained with perinatal neurons, osteogenic protein-1 selectively promoted dendritic growth in adult neurons. These data suggest that this matrix-associated growth factor could play a role not only in the morphogenesis of the developing nervous system, but also in the maintenance and remodeling of dendritic structures in the mature animal.
CYTOKINE AND CYTOTOXIC MOLECULE GENE EXPRESSION DETERMINED IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN THE DIAGNOSIS OF ACUTE RENAL REJECTION (2000)

We have shown that acute rejection episodes in renal transplant recipients were associated with an increase in mRNA expression of cytokines in mitogen-induced peripheral blood mononuclear cells. The evaluation of pro-inflammatory cytokines and cytotoxic molecules prove useful in the clinical identification of acutely rejecting transplant recipients and in the justification of concomitant antirejection therapy before histological diagnosis confirmation.
Cytotoxic T lymphocytes from HLA-A2 transgenic mice specific for HLA-A2 expressed on human cells. (1988)

CTL clones were derived from HLA-A2.1 transgenic mice by immunization with a human cell expressing HLA-A2.1. None of these clones lysed murine transfectants, and only 3 of 23 lysed monkey transfectants expressing HLA-A2. In contrast, all of these clones lysed a wide variety of human cells expressing HLA-A2.1. These results demonstrate the existence of species-specific epitopes on the HLA-A2.1 molecule, and suggest that these epitopes are formed by the association of class I MHC products with one or more endogenous species-specific molecules. These results provide an explanation for the frequently observed failure of HLA class I-specific CTL to recognize these antigens on murine transfectants. These results also suggest that such endogenous proteins may also contribute to the formation of epitopes recognized by allospecific CTL.
Allergen‐Induced Synthesis of Interleukin‐5, but not of IgE, is a Key Mechanism Linked to Symptomatic Episodes of Seasonal Allergic Rhinitis in Sensitized Individuals (1998)

Some individuals with detectable levels of Japanese cedar (Criptomeria japonica) pollen-specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms during the pollen season. The response of CD4+ T-helper (Th) cells to the pollen allergen might differ fundamentally between asymptomatic and symptomatic individuals who are already sensitized to the pollen. The aim of this study was to discern the possible differences in responses of peripheral blood mononuclear cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic subjects who have been sensitized to the pollen. This study included 20 non-atopic healthy volunteers (non-atopic group) and 48 patients who had detectable levels of the pollen-specific IgE before the pollen season in 1997. In the review of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms of seasonal allergic rhinitis (symptomatic group), and the remainder had no seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood mononuclear cells (1.0 x 10(7) cells/well) were obtained from each individual during the pollen season and cultured in the absence or presence of 12.5 microg of Cry j 1 for 4 days. The concentrations of IgE, interleukin-5 (IL-5), and interferon-gamma (IFN-gamma) in the culture supernatants were measured. The levels of IgE produced by Cry j 1-stimulated PBMCs of the asymptomatic and symptomatic groups were significantly higher than those of the non-atopic group, but did not differ between the asymptomatic and symptomatic groups. The levels of IL-5 produced by Cry j 1-stimulated PBMCs did not differ significantly between the non-atopic group and the asymptomatic group, but the levels of IL-5 were significantly higher in the symptomatic group than in the asymptomatic group as well as the non-atopic group. The levels of IFN-gamma produced by Cry j 1-stimulated PBMCs did not differ significantly among the three groups. In conclusion, our study has suggested that Japanese cedar pollen-induced synthesis of IL-5, but not of IgE or IFN-gamma, is likely to be a key mechanism linked to the symptomatic episode of seasonal allergic rhinitis in individuals sensitized to the pollen.
Mutations in the promoter spacer region and early transcribed region increase expression of staphylococcal enterotoxin A (1993)

The mechanism leading to increased production of staphylococcal enterotoxin type A (SEA) in mutant Staphylococcus aureus FRI722 compared within its wild-type parent strain, FRI100, was examined. Sequence analysis revealed two mutations in the upstream promoter region of FRI722 at nucleotides -28 and +3 with respect to the transcriptional initiation site at An sea translational fusion of the upstream region of FRI722 to the structural gene from FRI100 showed an increase in sea expression by Northern (RNA) analysis and in SEA production by Western (immunoblot) analysis. To independently evaluate the effect of each mutation, site-directed mutagenesis was done and revealed that each mutation was responsible for an increase in SEA production.
Isolation and characterization of a urokinase-type plasminogen activator (Mr = 54,000) from cultured human endothelial cells indistinguishable from urinary urokinase. (1984)

A urokinase-type plasminogen activator secreted by subcultured normal human umbilical vein endothelial cells was purified and compared to urinary urokinase (Mr = 54,000). The enzyme was isolated from serum-free conditioned medium in the presence of 0.1% (v/v) Triton X-100 by p-aminobenzamidine-agarose affinity chromatography, followed by Sephacryl S-200 gel filtration, followed by immunoadsorption chromatography on affinity purified specific anti-urokinase IgG-Sepharose CL-4B. This plasminogen activator form was obtained from the culture medium with a yield of about 47% and specific activity of about 93,000 IU/mg of protein, and represented approximately 18% of the total multiple molecular plasminogen activator activity forms present in endothelial cell conditioned medium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single band of plasminogen activator activity with an estimated molecular weight of about 54,000 that was completely inhibited by diisopropyl fluorophosphate (DFP) as well as a single band of radioactivity with similar molecular weight for both the isolated L-[4,5-3H]leucine and [3H]DFP-labeled enzyme. The radiolabeled protein focused as a single major band with a pI value of pH 8.5. The endothelial cell activator and urokinase appeared to be identical in terms of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, location of the [3H]DFP-labeled active site in the Mr = 33,000 heavy chain and [3H]DFP-labeled active site tryptic peptide, and two-dimensional 125I-labeled tryptic peptide maps. In quenching experiments of the fibrinolytic activities using affinity purified specific anti-urokinase IgG the endothelial cell-derived activator and urokinase appeared to be immunochemically identical, but unrelated to tissue plasminogen activator. These results indicate that the Mr = 54,000 urokinase-type plasminogen activator from cultured normal human endothelial cells is similar to, or identical with, Mr = 54,000 urinary urokinase.
Naltrexone as an Adjunctive Treatment for Older Patients With Alcohol Dependence (1997)

The authors examined the efficacy of naltrexone as an adjunctive treatment for alcohol dependence in older adults. Forty-four veterans over 50 years of age were enrolled in a 12-week, double-blind, placebo-controlled efficacy study of naltrexone (the equivalent of 50 mg per day). There were no differences in the frequency of any self-reported adverse effects or in liver enzyme values between the placebo- and naltrexone-treated groups. There were no differences between the treatment groups in the number of subjects remaining abstinent or in the number of subjects who relapsed. However, all placebo-treated subjects relapsed after sampling alcohol, whereas only three of six naltrexone-treated subjects met relapse criteria after alcohol exposure (P = 0.024). The authors conclude that naltrexone was well tolerated and efficacious in preventing relapse in subjects who drank.
Monoclonal antibody targeting of the EphA2 receptor tyrosine kinase in cancer (2003)

EphA2 is a transmembrane receptor tyrosine kinase that is upregulated on a large number of aggressive carcinomas. Despite its overexpression, the EphA2 on malignant cells fails to bind its ligand, ephrinA1, which is anchored to the membrane of adjacent cells. Unlike other receptor tyrosine kinases, EphA2 demonstrates kinase activity independent of ligand binding. However, ligand binding causes EphA2 to negatively regulate tumor cell growth and migration. Herein, we translate knowledge of EphA2 into strategies that selectively target malignant cells. We generated monoclonal antibodies that bind epitopes on the extracellular domains of EphA2. EphA2 antibodies were screened for their capabilities to mimic the biochemical and biological consequences of ligand binding. A subset of EphA2 monoclonal antibodies was found able to induce EphA2 autophosphorylation and subsequent degradation. These EphA2 agonistic antibodies inhibited anchorage-independent growth by MDA-MB-231 breast cancer cells but did not affect monolayer growth. Antibody targeting of EphA2 decreased tumor cell growth and extended survival as measured using xenograft tumor models. Moreover, we demonstrated that EphA2 antibodies inhibit tumor progression by inducing apoptosis. Investigation of the cellular basis of EphA2 antibody activity revealed that the EphA2 in malignant cells causes fibronectin production and that EphA2 antibodies prevent fibronectin production. We further showed that fibronectin regulates the ability of malignant cells to colonize an inhospitable microenvironment. We also identified certain antibodies that may distinguish the EphA2 on malignant versus non-transformed cells. The differential binding arises as a result of steric occlusion of the EphA2 on normal cells by stable cell-cell adhesions. Consequently, antibodies that recognize these epitopes should be able to selectively target malignant cells without inducing toxicities to normal cells. These results suggest an opportunity for antibody-based targeting of the many cancers that overexpress EphA2.
The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. (1988)

The role of recombinant B cell stimulatory factor 2 (BSF-2/IL-6) in the regulation of growth and differentiation of B cells was investigated. rBSF-2 at 200 pg/ml could induce 50% of the maximum Ig production in B lymphoblastoid cell lines, the specific activity being estimated as 5 X 10(6) U/mg. rBSF-2 augmented PWM-induced IgM, IgG, and IgA production in mononuclear cells (MNC); the effect was exerted by directly acting on PWM-induced B blast cells to induce Ig production. However, rBSF-2 did not induce any growth of activated B cells. In contrast, rBSF-2 showed a potent growth activity on a murine hybridoma clone, MH60.BSF2. The concentration required for half-maximal [3H]TdR uptake was approximately 5 pg/ml, which was 40 times less than that required for Ig induction in a B cell line. Anti-BSF-2 antibody inhibited PWM-induced Ig production in MNC, but not PWM-induced proliferation. The antibody was effective even when added on day 4 of an 8-d culture, indicating that BSF-2 is one of the essential late-acting factors in PWM-induced Ig production.
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A (2016)

Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations in human cancer, but therapeutic approaches that target these defects are not yet clinically available. We demonstrate that defects in ARID1A sensitize tumour cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. Mechanistically, ARID1A deficiency results in topoisomerase 2A and cell cycle defects, which cause an increased reliance on ATR checkpoint activity. In ARID1A mutant tumour cells, inhibition of ATR triggers premature mitotic entry, genomic instability and apoptosis. The data presented here provide the pre-clinical and mechanistic rationale for assessing ARID1A defects as a biomarker of single-agent ATR inhibitor response and represents a novel synthetic lethal approach to targeting tumour cells.
A flyback-type single phase utility interactive inverter with low-frequency ripple current reduction on the DC input for an AC photovoltaic module system (2003)

In recent years, interest in natural energy has grown because of increased environmental concerns. Many kinds of inverter circuits and their control schemes for photovoltaic (PV) power generation systems have been studied. In a conventional system, the PV array in which many PV modules are connected in series is used to obtain sufficient DC-bus voltage for generating an AC utility line voltage from an inverter circuit. However, the total power generation of the PV array is sometimes decreased remarkably when a few modules are partially covered by shadows, thereby decreasing its inherent current generation, and preventing the generation current attaining its maximum value on the array. To overcome this drawback, an AC module strategy has been proposed. In this system, a small power DC-AC utility interactive inverter is mounted on each PV module individually. This inverter operates so as to generate the maximum power from its corresponding PV module. This paper proposes a novel flyback-type utility interactive inverter circuit suitable for AC module systems. The features of the proposed system are that it: (1) is small in volume and lightweight; (2) allows stable AC current injection into the utility line; (3) enables the stable parallel operation without AC current sharing control; and (4) enables the capacitance of the DC capacitor to be small. The effectiveness of the proposed system is clarified through simulation and experiments.
A novel low-power FPGA routing switch (2004)

We propose a new programmable FPGA routing switch that can operate in three different modes: high-speed, low-power or sleep. High-speed mode offers similar power and performance to a traditional routing switch. In low-power mode, power is reduced at the expense of speed. Leakage power is reduced by 36-40% in low-power vs. high-speed mode (on average); dynamic power is reduced by up to 28%. Leakage power in sleep mode is 61% lower than in high-speed mode. The applicability of the new switch is motivated through an analysis of timing slack in industrial FPGA designs. Specifically, we show that a considerable fraction of routing switches may be slowed down (operate in low-power mode), without impacting overall design performance.
Anti-inflammatory activity of macrolide antibiotics. (2000)

The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity.
pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy (2012)

The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.