gebhart/patrepeval huggingface dataset:
Induction of Differentiation in Acute Promyelocytic Leukemia Cells by 9-cis Retinoic Acid α-Tocopherol Ester (9-cisTretinoin Tocoferil) (1998)

Acute promyelocytic leukemia (APL) has a specific genetic rearrangement between the retinoic acid receptor (RAR)-α gene and the pml nuclear protein gene. All-trans retinoic acid (ATRA) induces granulocytic differentiation of APL-derived cells and is used to treat APL patients. However, ATRA interacts with normal cells with RAR throughout the entire body, and when used at high doses or over a long duration, it induces several adverse effects. The development of drugs that selectively act on APL cells may contribute to increasing the therapeutic efficacy of APL treatment as well as elucidating the mechanisms of response to ATRA. In this study, 9-cis retinoic acid α-tocopherol ester (9CTT) inhibited the proliferation of APL-derived NB4 and HT93 cells and induced differentiation markers, such as granulocytic maturation, nitroblue tetrazolium reduction, and CD11b expression, in these cells. The effects of 9CTT on non-APL cells, including HL-60 and U937 cells, were much weaker than those on APL cells, and tretinoin tocoferil (TT), which is an α-tocopherol ester of ATRA, did not induce the differentiation of APL cells as effectively as 9CTT. The differentiation-inducing effects of 9CTT were inhibited by RAR antagonists. 9CTT and TT similarly induced the transactivating activity of RARs, but were not effective on RXRs. 9CTT downregulated the expression of PML/RAR-α protein more effectively than TT, which suggests that it may be involved in the selectivity of 9CTT against APL cells. Interestingly, 9CTT enhanced the differentiation of APL cells induced by ATRA, 9-cis retinoic acid, and synthetic retinobenzoic acids. Combined with 1α,25-dihydroxyvitamin D3 (VD3), 9CTT also more than additively induced the differentiation of APL cells. Thus, 9CTT, alone or in combination with other retinoids or VD3, may be useful for the treatment of APL.
Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders (1991)

Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence, the relapse rate observed after autologous BMT in malignant hematologic disorders is higher than that observed after allogeneic BMT. Autologous BMT represents a much safer medical procedure available for many patients in need in situations where allogeneic BMT is not feasible or risky. The present experiments were designed to investigate whether it might be possible to combine the therapeutic benefits of autologous BMT with additional immunotherapy after BMT. The tumor model used for investigating GVL effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1, +7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic BMT indicated a steep increase in the absolute number of peripheral blood lymphocytes on days 17 through 24. All experimental groups were observed for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50 days after BMT, whereas mice receiving rIL-2 showed long-term disease-free survival. Optimal time for administration of rIL-2 was noted at 3 weeks post-BMT, with 90% of the mice surviving with no evidence of disease for more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after syngeneic BMT to simulate minimal residual disease after syngeneic BMT, rIL-2 therapy administered at 14 days post-BMT seemed effective in prolonging disease-free survival in contrast to the same regimen given at 1 day after BMT. Our data suggest that immunotherapy with rIL-2 should be further investigated as a new immunotherapeutic tool for decreasing the relapse rate after BMT for hematologic malignancies.
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression (2007)

We have categorized smoking-related changes in airway gene expression by their degree of reversibility upon smoking cessation. Our findings provide insights into the mechanisms leading to reversible and persistent effects of tobacco smoke that may explain former smokers increased risk for developing tobacco-induced lung disease and provide novel targets for chemoprophylaxis. Airway gene expression may also serve as a sensitive biomarker to identify individuals with past exposure to tobacco smoke.
Stoichiometric Synthesis of Pure MFe2O4(M = Mg, Co, and Ni) Spinel Ferrites from Tailored Layered Double Hydroxide (Hydrotalcite-Like) Precursors (2004)

In this paper a novel synthetic route of pure MFe2O4 (M = Mg, Co, and Ni) spinel ferrites is reported. The key feature of this method is using a single molecular precursor. The pure spinel ferrites can be obtained by calcination of tailored hydrotalcite-like layered double hydroxides (LDHs) of the type [M1-X-YFe2+YFe3+X(OH)2]X+(SO42-)X/2·mH2O (M = Mg, Co, and Ni) precursors at 900 °C for 2 h, in which the molar ratio of M2+/(Fe2+ + Fe3+) is adjusted to the same value as that in single spinel ferrite itself. The structural characteristics of the as-synthesized LDHs and their resulting calcined products are obtained by powder X-ray diffraction (XRD), chemical analysis, Fourier transform infrared spectroscopy (FT-IR), simultaneous thermogravimetric and differential thermal analysis (TG-DTA), and Mössbauer spectroscopy. The saturation magnetizations of the materials produced by calcinations of LDHs are higher than those of the spinel ferrites produced by the conventional ceramic and wet chemical routes, although the compositions of the materials are similar. The major advantage of the new method is that it affords uniform distribution of all metal cations on an atomic level in the LDH precursors; hence, the formation of spinel ferrites starting from the LDHs requires a much lower temperature and shorter time, leading to a lower chance of side-reactions occurring.
In vivo methylation in Escherichia coli by the Bacillus subtilis phage phi 3T I methyltransferase to protect plasmids from restriction upon transformation of Clostridium acetobutylicum ATCC 824 (1993)

The restriction endonuclease Cac824I has been shown to be a major barrier to electrotransformation of Clostridium acetobutylicum ATCC 824 (L. D. Mermelstein, N. E. Welker, G. N. Bennett, and E. T. Papoutsakis, Bio/Technology 10:190-195, 1992). Methylation by the phi 3T I methyltransferase encoded by Bacillus subtilis phage phi 3T was shown to protect plasmid DNA from restriction by Cac824I. Expression in Escherichia coli of the phi 3tI gene (which encodes the phi 3T I methyltransferase) from pAN1, which replicates via the p15A origin of replication, was sufficient to completely methylate coresident E. coli-C. acetobutylicum shuttle vectors with ColE1 origins of replication. Three shuttle vectors (pIMP1, pSYL2, and pSYL7) methylated in this manner were used to efficiently electrotransform strain ATCC 824. These vectors could not be introduced into strain ATCC 824 when unmethylated because the E. coli portions of the plasmids contain a large number of Cac824I sites. This method obviates the need to use B. subtilis-C. acetobutylicum shuttle vectors with few Cac824I sites to introduce DNA into C. acetobutylicum ATCC 824.
79. Quinoxaline derivatives. Part IV. Dihydro-oxo-1 : 4 : 5-triazanaphthalenecarboxyureides and related spirohydantoins (1957)

J. W. Clark-Lewis and M. J. Thompson, J. Chem. Soc., 1957, 430 DOI: 10.1039/JR9570000430
Synthesis and Structure—Activity Relationships of 3,5‐Diarylisoxazoles and 3,5‐Diaryl‐1,2,4‐oxadiazoles, Novel Classes of Small Molecule Interleukin‐8 (IL‐8) Receptor Antagonists. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
FTY720 Prevents Development of Experimental Autoimmune Myocarditis Through Reduction of Circulating Lymphocytes (2000)

FTY720 is a new immunosuppressant agent and selectively decreases the number of circulating lymphocytes. In this study, we compared the effects of FTY720 with those of tacrolimus on experimental autoimmune myocarditis (EAM) in rats. A significant decrease in circulating lymphocyte counts was noted after a single administration of FTY720 in normal rats. At day 0, 7-week-old male Lewis rats were immunized with purified porcine cardiac myosin emulsified in complete Freund's adjuvant. FTY720 or tacrolimus was administered intraperitoneally daily. The number of myocarditis-affected areas in the FTY720 treatment groups with doses of 0.1 mg/kg/ day was significantly lower than those in control groups at days 14 and 28. In addition, at day 28, the myocarditis-affected areas in the FTY720 treatment group were significantly smaller than those in the tacrolimus treatment group receiving the same dose. Effects of early administration (days 0-10) and delayed administration (days 11-20) of FTY720 also were examined. At day 28, the myocarditis-affected areas in the early therapy group were significantly lower than those in the control group. In conclusion, we demonstrated that the development of EAM could be prevented by FTY720. These data also indicated that lymphocyte-mediated immunity is critically involved in the development of EAM.
Advances and pitfalls in the analysis and interpretation of resting-state FMRI data (2010)

The last 15 years have witnessed a steady increase in the number of resting-state functional neuroimaging studies. The connectivity patterns of multiple functional, distributed, large-scale networks of brain dynamics have been recognised for their potential as useful tools in the domain of systems and other neurosciences. The application of functional connectivity methods to areas such as cognitive psychology, clinical diagnosis and treatment progression has yielded promising preliminary results, but is yet to be fully realised. This is due, in part, to an array of methodological and interpretative issues that remain to be resolved. We here present a review of the methods most commonly applied in this rapidly advancing field, such as seed-based correlation analysis and independent component analysis, along with examples of their use at the individual subject and group analysis levels and a discussion of practical and theoretical issues arising from this data 'explosion'. We describe the similarities and differences across these varied statistical approaches to processing resting-state functional magnetic resonance imaging signals, and conclude that further technical optimisation and experimental refinement is required in order to fully delineate and characterise the gross complexity of the human neural functional architecture.
Subsurface Tissue Lesions Created Using an Nd:YAG Laser and Cryogen Cooling (2003)

This technique may prove useful to target subsurface anatomic structures in urology.
Monitoring conformational dynamics of a single molecule by selective fluorescence spectroscopy (1998)

A recently developed, real-time spectroscopic technique, burst-integrated fluorescence lifetime (BIFL), is shown to be well suited for monitoring the individual molecular conformational dynamics of a single molecule diffusing through the microscopic, open measurement volume (approximately 10 fl) of a confocal epi-illuminated set-up. In a highly diluted aqueous solution of 20-mer oligonucleotide strand of DNA duplex labeled with the environment-sensitive fluorescent dye tetramethylrhodamine (TMR), fluorescence bursts indicating traces of individual molecules are registered and further subjected to selective burst analysis. The two-dimensional BIFL data allow the identification and detection of different temporally resolved conformational states. A complementary autocorrelation analysis was performed on the time-dependent fluctuations in fluorescence lifetime and intensity. The consistent results strongly support the hypothesized three-state model of the conformational dynamics of the TMR-DNA duplex with a polar, a nonpolar, and a quenching environment of TMR.
Laminar Shear Stress (1998)

Mechanical forces are important modulators of cellular function in many tissues and are particularly important in the cardiovascular system. The endothelium, by virtue of its unique location in the vessel wall, responds rapidly and sensitively to the mechanical conditions created by blood flow and the cardiac cycle. In this study, we examine data which suggest that steady laminar shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. We explore the ability of shear stress to modulate atherogenesis via its effects on endothelial-mediated alterations in coagulation, leukocyte and monocyte migration, smooth muscle growth, lipoprotein uptake and metabolism, and endothelial cell survival. We also propose a model of signal transduction for the endothelial cell response to shear stress including possible mechanotransducers (integrins, caveolae, ion channels, and G proteins), intermediate signaling molecules (c-Src, ras, Raf, protein kinase C) and the mitogen activated protein kinases (ERK1/2, JNK, p38, BMK-1), and effector molecules (nitric oxide). The endothelial cell response to shear stress may also provide a mechanism by which risk factors such as hypertension, diabetes, hypercholesterolemia, and sedentary lifestyle act to promote atherosclerosis.
CCL9/MIP‐1γ and its receptor CCR1 are the major chemokine ligand/receptor species expressed by osteoclasts (2002)

Although much has been learned recently of the mechanisms by which the differentiation of osteoclasts is induced, less is known of the factors that regulate their migration and localization, and their interactions with other bone cells. In related cell types, chemokines play a major role in these processes. We therefore systematically tested the expression of RNA for chemokines and their receptors by osteoclasts. Because bone is the natural substrate for osteoclasts and may influence osteoclast behavior, we also tested expression on bone slices. Quantitative RT-PCR using real-time analysis with SYBR Green was therefore performed on RNA isolated from bone marrow cells after incubation with macrophage-colony stimulating factor (M-CSF) with/without receptor-activator of NFkappaB ligand (RANKL), on plastic or bone. We found that RANKL induced expression of CCL9/MIP-1gamma to levels comparable to that of tartrate-resistant acid phosphatase (TRAP), a major specialized product of osteoclasts. CCL22/MDC, CXCL13/BLC/BCA-1, and CCL25/TECK were also induced. The dominant chemokine receptor expressed by osteoclasts was CCR1, followed by CCR3 and CX3CR1. Several receptors expressed on macrophages and associated with inflammatory responses, including CCR2 and CCR5, were down-regulated by RANKL. CCL9, which acts through CCR1, stimulated cytoplasmic motility and polarization in osteoclasts, identical to that previously observed in response to CCL3/MIP-1alpha, which also acts through CCR1 and is chemotactic for osteoclasts. These results identify CCL9 and its receptor CCR1 as the major chemokine and receptor species expressed by osteoclasts, and suggest a crucial role for CCL9 in the regulation of bone resorption.
The thymidylate synthase inhibitor, ICI D1694, overcomes translational detainment of the enzyme (1993)

We have investigated the mechanism of inactivation of thymidylate synthase (TS) by ICI D1694 (a folate-based quinazoline) in normal versus tumor-derived human mammary epithelial cells. ICI D1694 is a very potent cytotoxic agent against these cells with IC50 values of 1-2 nM. Its growth inhibitory activity was completely reversed by the addition of thymidine, confirming that TS is its sole target in these cells. Remarkably, TS protein levels rose by 10-40-fold following treatment with ICI D1694, depending on cell type, while TS mRNA levels remained constant. The mechanism appears to be a release of "detainment" of TS translation, since addition of cycloheximide, a translational inhibitor, blocked the TS protein levels from rising. But coadministration of 5,6-dichlorobenzimidazole, a transcriptional inhibitor, did not overcome protein accumulation, nor did thymidine which overcomes growth inhibition by ICI D1694. 5,10-Methylenetetrahydrofolate (via folinic acid), however, did block the effects of ICI D1694, showing that the drug has its effect upon both detainment and enzyme inhibition by binding to the folate substrate site of TS. In addition, in the presence of ICI D1694, TS protein was no longer cell cycle-regulated as evident by its constitutive expression in synchronized cells. This accumulation and constitutive expression of TS induced by D1694 should increase drug resistance under a clinical setting. We suggest that an ideal inhibitor of TS would target the TS allosteric site that binds to TS mRNA, responsible for specific translation of the protein, thereby complimenting inactivation of the enzyme.
Characterization of yeast iso-1-cytochrome c mRNA. (1980)

The iso-1-cytochrome c mRNA has been identified by hybridization of a 32P probe prepared from a plasmid containing the iso-1-cytochrome c gene to RNA size-fractionated on agarose gels and transferred to paper. A hybridization band was visible with RNA prepared from wild type cells, but not with RNA prepared from an iso-1-cytochrome c deletion mutant. RNA prepared from cells containing a nonsense mutation in the iso-1-cytochrome c gene showed reduced levels of hybridization. The RNA that hybridized to the probe was 700 +/- 50 nucleotides in length and was polyadenylated. The cellular levels of this RNA were repressed by glucose, and this repression was achieved within 5 min after glucose addition to a derepressed culture. No precursors of this RNA were detected in wild type cells or in an RNA1 mutant, temperature-sensitive for RNA metabolism. The length of the 3' noncoding region of this RNA was determined to be 200 +/- 25 nucleotides (excluding the poly(A) tail) and the 5' noncoding region was estimated to be about 120 nucleotides in length.
Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity (2011)

The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Elements) to map "open chromatin." Over 870,000 DNaseI or FAIRE sites, which correspond tightly to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and to be coincident with CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites and contained DNA motifs recognized by regulators of cell-type identity. We show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying noncoding DNA sequence variants that are causally linked to human disease.
Conformationally Restricted Analogues of 1N,12N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines (1998)

Eight analogues of 1N,12N-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1, 2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained (three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). 1N,12N-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the 4N, 9N-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1, 2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.
Organic electroluminescent devices based on molecularly doped polymers (1992)

Electroluminescent devices were fabricated using poly(methyl methacrylate) (PMMA) molecularly doped with triphenyldiamine derivative and tris(8-quinolinolato)aluminum(III) complex (Alq). A cell structure of glass substrate/indium–tin–oxide/doped PMMA/Mg:Ag was employed. Carrier injection from the electrodes to the doped PMMA layer through the dopants and concomitant electroluminescence from Alq were observed. Green emission with luminance of 920 cd/m2 was achieved at a drive voltage of 17 V.
A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5 (2002)

Here we report the cloning of a novel type I cytokine receptor, gp130-like monocyte receptor (GLM-R), with homology to the interleukin-6 receptor signal transducing chain, gp130, and granulocyte colony-stimulating factor receptor. Human and murine GLM-R cDNAs encode open reading frames of 732 and 716 amino acids, respectively, and the corresponding genes are located in close proximity to gp130 genes on human chromosome 5 and mouse chromosome 13. GLM-R is specifically expressed on CD14-positive cells and is up-regulated more than 50-fold upon activation of those cells. To address the question of whether GLM-R is a signaling receptor, we constructed a chimeric molecule, consisting of the extracellular domain of human growth hormone (hGH) receptor, and the intracellular domain of GLM-R. When transfected into factor-dependent 32D cells, this chimeric molecule could signal for proliferation and activate signal transducer and activator of transcription (STAT)-3 and STAT-5 upon stimulation with hGH. Thus, GLM-R is a novel signaling receptor chain potentially involved in the development and function of monocytes and macrophages.