gebhart/patrepeval huggingface dataset:
VIRAL LOAD CHANGES IN PATIENTS UNDERGOING CHEMOTHERAPY FOR AIDS-KS (1997)

Manome et al (JAIDS 11:109-116, 1996) showed several chemotherapy agents in common use, including anthracyclines, can activate HIV long terminal repeat (LTR). Doxorubicin at concentrations of 5 ng/ml and 30 ng/mg can increase LTR-driven CAT activity by 1.6 fold and 4.1 fold, respectively. Liposomal doxorubicin given at 20 mg/m2 achieves a peak plasma concentration of 8.34 µg/ml and area under the curve (AUC) of 590± 58.7 µg/ml•h which are much higher than the concentration used by Manome et al. Increase production of HIV virus was further demonstrated in chronically as well as in acutely HIV-infected T -cell lines treated with cisplatin and mitomycin C. We therefore conducted this pilot study to evaluate HIV viral load changes in patients with AIDS-KS receiving chemotherapy. Plasma samples for HIV RNA PCA by Roche method were collected before each treatment. All viral load assessments were performed in the UCLA Virology Research Laboratory using the same quantitative methods. Six patients who were being treated with systemic chemotherapy for their AIDS-KS were evaluated. Patients received chemotherapy every two to four weeks. While the antiviral therapy differed among the patients, treatment regimen for individual patients was not changed during the care of chemotherapy administration. All subjects were male. All but one patient had CD4+ cell counts less than 200. Patients 1, 2 and 3 were treated with Liposomal doxorubicin at 20 mg/m2. Patient 4 was treated with Taxol at 125 mg/m2. Patients 5 and 6 were treated with a combination of liposomal doxorubicin at 20 mg/m2, bleomycin 10 units/m2, and vincristine I mg. All but patient 2 are alive at this time. Both increases and decrease in HIV viral load were seen in these patients over the first 305 courses of chemotherapy. These data do not indicated a significant increase in HIV viral load in patients undergoing chemotherapy for AIDS-KS. No consistent trends in changes in plasma HIV viral loads were seen in this small sample of patients. Increased HIV replication as observed by Manome et al in vitro may have little clinical effect in patients receiving antiviral therapy.
Data from HSulf-1 Modulates FGF2- and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;HSulf-1 modulates the sulfation states of heparan sulfate proteoglycans critical for heparin binding growth factor signaling. In the present study, we show that HSulf-1 is transcriptionally deregulated under hypoxia in breast cancer cell lines. Knockdown of HIF-1α rescued HSulf-1 downregulation imposed by hypoxia, both at the RNA and protein levels. Chromatin immunoprecipitation with HIF-1α and HIF-2α antibodies confirmed recruitment of HIF-α proteins to the two functional hypoxia-responsive elements on the native HSulf-1 promoter. HSulf-1 depletion in breast cancer cells resulted in an increased and sustained bFGF2 (basic fibroblast growth factor) signaling and promoted cell migration and invasion under hypoxic conditions. In addition, FGFR2 (fibroblast growth factor receptor 2) depletion in HSulf-1–silenced breast cancer cells attenuated hypoxia-mediated cell invasion. Immunohistochemical analysis of 53 invasive ductal carcinomas and their autologous metastatic lesions revealed an inverse correlation for the expression of HSulf-1 to CAIX in both the primary tumors (&lt;i&gt;P&lt;/i&gt; ≥ 0.0198) and metastatic lesions (&lt;i&gt;P&lt;/i&gt; ≥ 0.0067), respectively, by χ&lt;sup&gt;2&lt;/sup&gt; test. Finally, HSulf-1 expression levels in breast tumors by RNA &lt;i&gt;in situ&lt;/i&gt; hybridization showed that high HSulf-1 expression is associated with increased disease-free and overall survival (&lt;i&gt;P&lt;/i&gt; ≥ 0.03 and &lt;i&gt;P&lt;/i&gt; ≥ 0.0001, respectively). Collectively, these results reveal an important link between loss of HSulf-1 under hypoxic microenvironment and increased growth factor signaling, cell migration, and invasion. &lt;i&gt;Cancer Res; 71(6); 2152–61. ©2011 AACR.&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Optical Energy Transfer from Relative Motion (2016)

By intersecting a moving optical potential, a small particle may gain or loss kinetic energy. We describe this energy transfer for a Gaussian beam gradient potential and a Rayleigh particle smaller than the beam radius.
Effect of Fixation Method for Moving Sheet on Joining Property in Sheets Welded by Magnetic Pulse Welding (2021)

In this paper, we describe magnetic pulse welding for two sheets with a gap (before welding) and the effect of the fixation method on the joining property in seam-welded sheets. The gap is a deformation space of a moving sheet placed on a welding coil. The way of setting the gap is related to the fixation method for the moving sheet. There are three types of fixation: two places, one place, and without fixing. Two-places fixing is generally used, but the overlapping width of the two sheets is wide, leading to a loss of materials. The moving sheet is deformed into a convex shape. Therefore, the welded sheet is joined by two lines regardless of the fixation method. The joining width of the two lines in the sheet welded by two-places fixing is the same. The joining widths in the sheet welded by one-place fixing differ slightly, but the overlapping width of the two sheets can be reduced. Joined interfaces in the welded sheets consist of both parts in contact with each base metal and parts of an intermediate layer. One-place fixing can be adopted in joining an aluminum alloy sheet to a high-strength steel sheet (SPFH), for example, A6061-T6/SPFH.
Sub‐salt overpressure detection before drilling using wave equation migration technologies (2009)

Unexpected zones of high pore pressure present the most significant risk—financial and health—to sub‐salt drilling operations in the Gulf of Mexico. Below‐trend P‐wave velocity is an imperfect, but oft‐used pore pressure attribute. We present two technologies to measure velocity under salt. The first infers sub‐salt sediment velocity from normalized base of salt (BoS) amplitude. The second computes time‐shift focusing information from a wave equation depth migration (WEM) and converts the focusing information to deviations from the migration velocity. Both techniques are tested successfully on the BP Velocity Benchmark Model, providing quasi‐independent verification of the low‐velocity zones under salt.
Synthesis and Crystal Structure of 1-(Cyano(4-methoxyphenyl)methyl)cyclohexyl Acetate (2007)

The title compound, C17H21NO3, was synthesized by the acetylation of the hydroxy group of 1-(cyano(4-methoxyphenyl)methyl)cyclohexanol, which was formed by the reaction of 4-methoxyphenyl acetonitrile with cyclohexanone. The compound was characterized spectroscopically, and the structure was investigated by X-ray crystallography. The compound crystallizes in the orthorhombic crystal class in the space group Pbca with cell parameters a = 13.412(6) Å, b = 12.398(14) Å, c = 19.026(19) Å and V = 3164(5) Å 3 Fatiadi , A. J. ( 1983 ). In: The Chemistry of Functional Groups, Supplement , Patai , S. & Rappoport Z. (Eds.), John Wiley and Sons : New York , 1057 – 1303 . [Google Scholar] for Z = 8. The cyclohexane ring is in a chair conformation. The structure exhibits intermolecular hydrogen bonds of the type C–H…N and C–H…O.
Global enhancement of nuclear localization‐dependent nuclear transport in transformed cells (2011)

Fundamental to eukaryotic cell function, nucleocytoplasmic transport can be regulated at many levels, including through modulation of the importin/exportin (Imp/Exp) nuclear transport machinery itself. Although Imps/Exps are overexpressed in a number of transformed cell lines and patient tumor tissues, the efficiency of nucleocytoplasmic transport in transformed cell types compared with nontransformed cells has not been investigated. Here we use quantitative live cell imaging of 3 isogenic nontransformed/transformed cell pairs to show that nuclear accumulation of nuclear localization signal (NLS)-containing proteins, but not their NLS-mutated derivatives, is increased up to 7-fold in MCF10CA1h human epithelial breast carcinoma cells and in simian virus 40 (SV40)-transformed fibroblasts of human and monkey origin, compared with their nontransformed counterparts. The basis for this appears to be a significantly faster rate of nuclear import in transformed cell types, as revealed by analysis using fluorescence recovery after photobleaching for the human MCF10A/MCF10CA1h cell pair. Nuclear accumulation of NLS/nuclear export signal-containing (shuttling) proteins was also enhanced in transformed cell types, experiments using the nuclear export inhibitor leptomycin B demonstrating that efficient Exp-1-mediated nuclear export was not impaired in transformed compared with nontransformed cells. Enhanced nuclear import and export efficiencies were found to correlate with 2- to 4-fold higher expression of specific Imps/Exps in transformed cells, as indicated by quantitative Western blot analysis, with ectopic expression of Imps able to enhance NLS nuclear accumulation levels up to 5-fold in nontransformed MCF10A cells. The findings indicate that transformed cells possess altered nuclear transport properties, most likely due to the overexpression of Imps/Exps. The findings have important implications for the development of tumor-specific drug nanocarriers in anticancer therapy.
Determination of oxalate by FIA with electrogenerated chemiluminescence detection. (1990)

シュウ酸(Ox)-tris(2,2'-bipyridine)ruthenium(II) {Ru(bpy)32+}電解化学発光系を利用したFIA法を作成し,実試料への適用例として尿中シュウ酸の定量に応用した.キャリヤーに蒸留水を用いる2流路FIAで,試薬溶液は10mM硫酸にRu(bpy)3Cl2を溶解して0.12mMとした.試薬溶液は電解反応器(electrochemical reactor, ECR)を通過した後,フローセルの直前でキャリヤーと合流し,混合した後,排出する.このとき生ずる光量を測定する.本法によれば0～400pmolの範囲で発光強度と良好な直線関係を示し,検出下限(S/N=3)は0.3pmolであった.相対標準偏差(n=5, 5pmol)は2.3%であった.尿中のOxは尿を1%アセトニトリル溶液で1000～2000倍に希釈し,Sep-Pak C18で前処理することによって定量できた.
[RETRACTED] UNBS CBD Gummies Shocking Facts Revealed? v1 (2021)

[RETRACTED] UNBS CBD Gummies has assured that the product has been thoroughly tested and is safe to use. You are guaranteed to get the best results.
On the Influence of the C2−O2 and C3−O3 Bonds in 4,6-O-Benzylidene-Directed β-Mannopyranosylation and α-Glucopyranosylation (2006)

The synthesis of 4,6-O-benzylidene-protected 2-deoxyarabino-, 3-deoxyarabino-, and 3-deoxyribothioglycosides is described and their glycosylation reactions, with activation by either 1-benzenesulfinyl piperidine/trifluoromethansulfonic anhydride or diphenyl sulfoxide/trifluoromethanesulfonic anhydride, studied. In contrast to the corresponding 4,6-O-benzylidene-protected glucosyl and mannosyl donors, which are alpha- and beta-selective, respectively, poor diastereoselectivity is observed in all cases. The reasons for this poor selectivity are discussed in terms of the interaction between the C2-O2 and C3-O3 bonds in the glucosyl and mannosyl donors and of the influence of this interaction on the ease of formation of the intermediate glycosyl oxacarbenium ions.
Antibacterial activities of polyunsaturated fatty acid extracts from Sardinella longiceps and Sardinella fimbriata (2011)

Polyunsaturated fatty acids (PUFA) content of two species of fishes Sardinella fimbriata and Sardinella longiceps was examined and their antibacterial activities were compared. PUFA isolated from the tissue extracts were used to conduct Antibacterial Sensitivity Tests on pathogenic bacterial strains like Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pnuemoniae, Enterobacter aerogenes, Proteus vulgaris, Salmonella enterica and Pseudomonas aeruginosa. These extracts were subjected to Gas Chromatography for the quantitative analysis of PUFA. Extracts from both species showed inhibitory effects on the strains of S. aureus, E. faecalis, E. coli and P. aeruginosa. No inhibitory activities were observed on the strains of K. pnuemoniae, E. aerogenes, P. vulgaris and S. enterica. S. fimbriata extract showed a higher inhibitory effect on all the inhibited bacterial strains. Gas Chromatography analysis revealed higher concentrations of docosahexaenoic acid (DHA) in the extracts from S. fimbriata as compared to S. longiceps. The differences between the antibacterial activities of the two extracts could be attributed to the disparity in DHA content.
Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction (2014)

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.
Improvement of bioavailability of poorly absorbed drugs. III. Oral acute toxicity and local irritation of medium chain glyceride. (1985)

Oral acute toxicity of medium chain glyceride (MCG) was studied in mice and rats. In mice and rats, clinical signs such as irregular respiration, laxity of movement, staggering gait and loss of righting reflex appeared after single oral administration of MCG at a relatively large dose. The LD50 values determined in male and female mice were 26.9 and 28.5 ml/kg, and in male and female rats were 27.4 and 26.7 ml/kg, respectively. In order to evaluate the biological safety of MCG suppository of cefmetazole sodium (CMZ), its local irritation on the mucous membrane was studied. Primary eye irritation of MCG suppository of CMZ was studied in rabbits. Although mild irritation was seen in conjunctivae, no remarkable changes were observed in cornea and iris. Furthermore, primary effect of MCG suppository of CMZ on the rectal mucous membrane was studied macro- and microscopically. It was observed that remarkable histological changes of rectal mucous membrane by MCG suppository of CMZ were not observed in all animals used.
Non-Phosphorylatable PEA-15 Sensitises SKOV-3 Ovarian Cancer Cells to Cisplatin (2020)

The efficacy of cisplatin-based chemotherapy in ovarian cancer is often limited by the development of drug resistance. In most ovarian cancer cells, cisplatin activates extracellular signal-regulated kinase1/2 (ERK1/2) signalling. Phosphoprotein enriched in astrocytes (PEA-15) is a ubiquitously expressed protein, capable of sequestering ERK1/2 in the cytoplasm and inhibiting cell proliferation. This and other functions of PEA-15 are regulated by its phosphorylation status. In this study, the relevance of PEA-15 phosphorylation state for cisplatin sensitivity of ovarian carcinoma cells was examined. The results of MTT-assays indicated that overexpression of PEA-15AA (a non-phosphorylatable variant) sensitised SKOV-3 cells to cisplatin. Phosphomimetic PEA-15DD did not affect cell sensitivity to the drug. While PEA-15DD facilitates nuclear translocation of activated ERK1/2, PEA-15AA acts to sequester the kinase in the cytoplasm as shown by Western blot. Microarray data indicated deregulation of thirteen genes in PEA-15AA-transfected cells compared to non-transfected or PEA-15DD-transfected variants. Data derived from The Cancer Genome Atlas (TCGA) showed that the expression of seven of these genes including <i>EGR1</i> (early growth response protein 1) and <i>FLNA</i> (filamin A) significantly correlated with the therapy outcome in cisplatin-treated cancer patients. Further analysis indicated the relevance of nuclear factor erythroid 2related factor 2/antioxidant response element (Nrf2/ARE) signalling for the favourable effect of PEA-15AA on cisplatin sensitivity. The results warrant further evaluation of the PEA-15 phosphorylation status as a potential candidate biomarker of response to cisplatin-based chemotherapy.
A Cancer Cell–Intrinsic GOT2–PPARδ Axis Suppresses Antitumor Immunity (2022)

Abstract Despite significant recent advances in precision medicine, pancreatic ductal adenocarcinoma (PDAC) remains near uniformly lethal. Although immune-modulatory therapies hold promise to meaningfully improve outcomes for patients with PDAC, the development of such therapies requires an improved understanding of the immune evasion mechanisms that characterize the PDAC microenvironment. Here, we show that cancer cell–intrinsic glutamic-oxaloacetic transaminase 2 (GOT2) shapes the immune microenvironment to suppress antitumor immunity. Mechanistically, we find that GOT2 functions beyond its established role in the malate–aspartate shuttle and promotes the transcriptional activity of nuclear receptor peroxisome proliferator–activated receptor delta (PPARδ), facilitated by direct fatty acid binding. Although GOT2 is dispensable for cancer cell proliferation in vivo, the GOT2–PPARδ axis promotes spatial restriction of both CD4+ and CD8+ T cells from the tumor microenvironment. Our results demonstrate a noncanonical function for an established mitochondrial enzyme in transcriptional regulation of immune evasion, which may be exploitable to promote a productive antitumor immune response. Significance: Prior studies demonstrate the important moonlighting functions of metabolic enzymes in cancer. We find that the mitochondrial transaminase GOT2 binds directly to fatty acid ligands that regulate the nuclear receptor PPARδ, and this functional interaction critically regulates the immune microenvironment of pancreatic cancer to promote tumor progression. See related commentary by Nwosu and di Magliano, p. 2237.. This article is highlighted in the In This Issue feature, p. 2221
Interleukin-4 inhibits interleukin-1 alpha-induced granulocyte- macrophage colony-stimulating factor gene expression in a murine B- lymphocyte cell line via downregulation of RNA precursor (1992)

Interleukin-4 (IL-4) regulates the growth of B cells. When combined with colony-stimulating factors (CSFs) and selected cytokines, IL-4 has a synergistic effect on the clonal growth of bone marrow cells. Recently, we have shown that IL-1 alpha and lipopolysaccharide induce expression of the granulocyte-macrophage CSF (GM-CSF) gene in murine B-cell lines. In the present study, we show that IL-4 inhibits the production of GM-CSF in the IL-1 alpha-stimulated murine B-cell line M12.4.1. IL-4 did not change the transcription rate of the GM-CSF gene, and caused only a slight decrease in cytoplasmic GM-CSF messenger RNA (mRNA) half-life in cells treated with IL-1 alpha. PCR analysis of nuclear RNA with probes specific for GM-CSF intron sequences suggests that IL-1 alpha enhances accumulation of nuclear precursor RNA and that decreased GM-CSF expression after IL-4 treatment is mainly due to intranuclear destabilization of the primary transcript. Under the same experimental conditions, IL-4 did not affect expression of the IL-4 receptor mRNA and did increase the mRNA concentration of the low-affinity receptor for IgE (Fc epsilon RII). These data suggest that the suppressive effect of IL-4 is specific for GM-CSF mRNA expression, and thus provide evidence for an additional role of IL-4 in the regulation of GM-CSF expression in B cells.
RF36 | PSUN77 Female Dexras1 WT & KO Mice Fed a High Fat Diet Do Not Have Different Body Compositions nor Bone Densities (2022)

Abstract Glucocorticoids are a frequently prescribed class of medications, widely used for their anti-inflammatory and immunosuppressive effects. However, long term usage of glucocorticoids is associated with a variety of adverse effects, including adrenal suppression, increased adiposity, and decreased bone density. DEXRAS1, also known as RASD1, is a member of the Ras family of GTPases that is upregulated by glucocorticoids. In in vitro experiments, DEXRAS1 has been shown to promote differentiation of adipocytes and decrease differentiation of osteoblasts. Studies conducted in male Dexras1 knockout (KO) and wild type (WT) mice treated with dexamethasone found decreased body weight and visceral fat, and increased bone density in KO mice when compared to WT mice; together, these experiments suggest that the removal of the Dexras1 gene can prevent glucocorticoid-induced osteoporosis and fat-accumulation.A major limitation of the aforementioned studies is that they were performed using only male mice, despite well-known sex related differences in body composition and bone density. On average, females have a higher percentage of body fat and lower bone density. While obesity is prevalent across all sexes, osteoporosis is 4 times more common in females. Therefore, in order to better understand sex as a biological variable on the effects of the Dexras1 gene, we compared female Dexras1 KO and WT mice fed a high-fat diet (HFD) containing 45 kcal% fat over the course of 14 weeks. Body composition was assessed by quantitative magnetic resonance. Bone morphometry was analyzed with micro-CT, and bone density was analyzed with micro-CT and dual-energy x-ray absorptiometry (DXA) scans of female murine femurs. Interestingly, there were no differences in the overall body weight, fat mass, nor lean mass over this period between WT and KO female mice. Similarly, the female Dexras1 KO and WT mice mice showed no differences in their bone density, cortical thickness, and average trabecular separation. Since there was no difference in the fat mass, it is not surprising that there was also no difference in bone density, as they are often inversely related. These data in conjunction with previous experiments on male mice suggest that sex strongly impacts the phenotype observed as a result of knocking out the Dexras1 gene. The mechanisms underlying differential regulation between the sexes is unclear, and could include differences in sex hormones, the presence of estrus cycle in females, differences in stress response, or even differences in microbiome. Consequently, more studies are necessary to fully understand the function and regulation of Dexras1. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.