gebhart/patrepeval huggingface dataset:
Inactivation of the Moloney murine leukemia virus long terminal repeat in murine fibroblast cell lines is associated with methylation and dependent on its chromosomal position (1991)

The expression of a retroviral vector with the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) promoter after integration into the genome of murine fibroblast cell lines was monitored with the Escherichia coli-derived beta-galactosidase (beta-gal) gene as the reporter. Monoclonal cell lines derived after retroviral infection exhibited a marked heterogeneity in their expression of the reporter gene. We studied two monoclonal cell lines with a single unrearranged copy of the vector provirus integrated into their genome. The first, BB10, expressed the marker enzyme in only 8% of its cell population, whereas in the second, BB16, beta-gal expression could be detected in over 98% of the cells. Treatment of BB10 with the DNA-demethylating agent 5-azacytidine raised the number of beta-gal-positive cells to over 60%. Transfection experiments showed that the Mo-MuLV LTR promoter-enhancer is potentially fully functional in both the BB10 and BB16 cell lines. The inactivated provirus from BB10 cells was cloned and subsequently used to generate retrovirus stocks. The promoter-enhancer activity of its LTR after infection with these BB10-derived viruses showed a variation similar to that of the original virus stocks. Our data showed that (1) inactivation of the Mo-MuLV LTR is a frequent event in murine fibroblast cell lines, (2) inactivation is associated with de novo methylation of cytidine residues, (3) the frequency of inactivation of the provirus must be determined by its chromosomal position, (4) the process of methylation of sequences within the LTR is not necessarily the same as the transcription-repression mechanism that is operating in undifferentiated embryonal carcinoma cells.
Application of Gold Nanoparticles for Targeted Therapy in Cancer (2008)

Cancer is a major public health problem worldwide. Some of the key challenges in cancer are early detection, diagnosis, and targeted therapy. Most of the patients are usually diagnosed in the late stage of the disease causing immunity to therapeutic intervention. Another major challenge in the therapeutic intervention of cancer is the toxicity of the anti-cancer drugs. When administered, these drugs are not only toxic towards malignant cells, but also towards normal cells. Nanotechnology can play a pivotal role in changing the very foundation of cancer treatment and diagnosis. At the heart of the nanotechnology are the nanoparticles and they can be synthesized in different shapes and sizes with tailor able optoelectronic and physico-chemical properties. Due to very high surface area of these nanoparticles, a number of biomolecules can be loaded to create a nanobioconjugate with multifunctional capabilities. Such a bi-functional nanobioconjugate containing a targeting agent and a drug would lead to targeted delivery of the drug to the malignant cells with better therapeutic efficacy and with reduced systemic toxicity. In a similar fashion targeted delivery of an imaging agent could lead to early detection of cancer. The design and development of nanoparticles and its nanobioconjugates in conjunction with the development of genomics and proteomics to identify biomarkers raise exciting opportunities for personalized treatment. In this particular review, we have discussed application of gold nanoparticles (AuNPs) in cancer and the current standing with respect to nanotechnology.
A remarkable epoxide opening. An expeditious synthesis of vernolepin and vernomenin (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA remarkable epoxide opening. An expeditious synthesis of vernolepin and vernomeninSamuel Danishefsky, Takeshi Kitahara, Paul F. Schuda, and Sarah J. EtheredgeCite this: J. Am. Chem. Soc. 1976, 98, 10, 3028–3030Publication Date (Print):May 1, 1976Publication History Published online1 May 2002Published inissue 1 May 1976https://pubs.acs.org/doi/10.1021/ja00426a066https://doi.org/10.1021/ja00426a066research-articleACS PublicationsRequest reuse permissionsArticle Views1373Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Use of Dissolved H2 Concentrations To Determine Distribution of Microbially Catalyzed Redox Reactions in Anoxic Groundwater (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUse of Dissolved H2 Concentrations To Determine Distribution of Microbially Catalyzed Redox Reactions in Anoxic GroundwaterDerek R. Lovley, Francis H. Chapelle, and Joan C. WoodwardCite this: Environ. Sci. Technol. 1994, 28, 7, 1205–1210Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/es00056a005https://doi.org/10.1021/es00056a005research-articleACS PublicationsRequest reuse permissionsArticle Views994Altmetric-Citations179LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity (2004)

Tissue factor pathway inhibitor (TFPI) is the major physiologic inhibitor of the extrinsic coagulation pathway. We have previously shown that TFPI is also a potent inhibitor of endothelial proliferation in vitro and of primary and metastatic tumor growth in vivo. Surprisingly, the antitumor activity of TFPI was demonstrated to be independent of its anticoagulant activity, suggesting a possible nonhemostatic mechanism of action for TFPI in these models. This antitumor mechanism may involve the very low density lipoprotein (VLDL) receptor because the in vitro antiproliferative activity of TFPI is mediated through interaction with the VLDL receptor. In the current study, we identify a 23-amino acid fragment of TFPI (TFPIc23) localized to the C-terminus, which mediates binding to the VLDL receptor. The TFPIc23 peptide inhibits endothelial cell proliferation through an apoptotic mechanism and blocks vessel outgrowth in the in vitro assays, and this activity is mediated through interaction with the VLDL receptor. In vivo, this peptide potently inhibits angiogenesis in Matrigel and chick chorioallantoic membrane models and also inhibits metastatic tumor growth. Our data demonstrate that this VLDL receptor-binding fragment of the TFPI molecule has apoptotic, antiangiogenic, and antitumor activity and suggests a possible mechanism whereby TFPI can regulate angiogenesis and tumor growth independently of its anticoagulant activity.
Measurement of fractional esterification rate of cholesterol in plasma depleted of apoprotein B containing lipoprotein: methods and normal values. (1996)

The distribution of differently sized HDL particles in the plasma can be assessed by measurement of the fractional rate of cholesterol esterification (FERHDL). We have characterized the isotopic assay and compared it to the enzymatic measurement of the decrease in HDL free cholesterol (mass assay). The normal values of FERHDL were established in 116 apparently healthy individuals. The isotopic assay is particularly sensitive to changes in the incubation temperature above 37 degrees C. The reproducibility of the assay in aliquots of plasma stored at -20 degrees C and -70 degrees C for 3 months and even up to 2 years was high. Intraindividual variability of FERHDL is low. In the subjects in whom FERHDL was measured over a 3-month and 2-5 years' period, FERHDL showed a low variability (97.5 +/- 2.6% and 101 +/- 6.0% respectively in a paired t-test). Comparison of the isotopic assay and the mass assay revealed that the isotopic assay was much more reproducible. Normal values of FERHDL and the HDL subspecies distribution (using gradient gel electrophoresis) were established in 63 men and 56 women. The average values of FERHDL were significantly higher in men (16.8 +/- 4.5%/h) than in women (10.6 +/- 3.6%/h) and correlated well with the distribution of the HDL subspecies. FERHDL radioassay as a highly reproducible method for the assessment of HDL subspecies distribution which may be suitable for both retrospective and prospective studies of diseases of atherogenous origin.
Expression of cadherin-11 delineates boundaries, neuromeres, and nuclei in the developing mouse brain (1996)

Cadherin-11 (cad11 or OB-cadherin) was previously identified as a mesenchymal cell-cell adhesion molecule. Here we studied the expression of cad11 transcripts in developing brains derived from E11.5 to E16.5 mouse embryos. In the brains at these stages, cad11 was expressed in various patterns, which could be grouped into three categories. First, cad11 expression occurred along boundaries between certain brain subdivisions, including those between the ventral and dorsal thalamus and between the mesencephalon and metencephalon. At these boundaries, cad11-positive cells were localized in a narrow, columnar compartment of the neuroepithelium. Second, cad11 expression delineated particular neuromeric compartments at the ventricular zone of the neuroepithelium. A typical example of this pattern was observed in the hypothalamus. Third, cad11 was expressed in differentiating or differentiated brain nuclei. The former included the thalamus, epithalamus, and pretectum; the latter included the mammillary, red, trigeminal motor, facial motor, prepositus hypoglossal, and inferior olive nuclei, as well as the substantia nigra. Furthermore, developing nuclei and the superficial zone of the cerebellum expressed cad11, and the cortical plate of the developing cerebrum also did so. We compared the expression pattern of cad11 with that of R-cadherin in the diencephalon and found that each cadherin delineated a unique set of diencephalic subdivisions. These findings suggest that cad11-mediated specific cell-cell adhesion plays roles in segmentation or compartmentalization of the developing brain in various ways. We also discussed the possibility that cad11 might be involved in neuronal connections between specific nuclei.
The Transmembrane Mutation G380R in Fibroblast Growth Factor Receptor 3 Uncouples Ligand-Mediated Receptor Activation from Down-Regulation (2000)

A point mutation, Gly380Arg, in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) leads to achondroplasia, the most common form of genetic dwarfism in humans. This substitution was suggested to enhance mutant receptor dimerization, leading to constitutive, ligand-independent activation. We found that dimerization and activation of the G380R mutant receptor are predominantly ligand dependent. However, using both transient and stable transfections, we found significant overexpression only of the mutant receptor protein. Metabolic pulse-chase experiments, cell surface labeling, and kinetics of uptake of radiolabeled ligand demonstrated a selective delay in the down-regulation of the mutant receptor. Moreover, this receptor was now resistant to ligand-mediated internalization, even at saturating ligand concentrations. Finally, transgenic mice expressing the human G380R mutant receptor under the mouse receptor transcriptional control demonstrated a markedly expanded area of FGFR3 immunoreactivity within their epiphyseal growth plates, compatible with an in vivo defect in receptor down-regulation. We propose that the achondroplasia mutation G380R uncouples ligand-mediated receptor activation from down-regulation at a site where the levels and kinetics of FGFR3 signals are crucial for chondrocyte maturation and bone formation.
Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21 (2006)

These results suggest that fibroblasts are a potential target of IL21 in the gut and that IL21 controls MMP secretion by fibroblasts.
Role of Substance P on Histamine H3 Antagonist-Induced Scratching Behavior in Mice (2006)

The purpose of the present study was to investigate the involvement of chemical mediators, other than histamine, in the scratching behavior induced by H(3) antagonists. Scratching behavior was induced by the histamine H(3) antagonists iodophenpropit and clobenpropit (10 nmol/site) when they were injected intradermally into the rostral part of the back of mast-cell-deficient (WBB6F1 W/W(v)) and wild-type (WBB6F1 +/+) mice. Subsequently, the effect of spantide, a tachykinin NK(1) antagonist, was measured for 60 min. The effects of the H(3) antagonists on in vitro histamine release from rat peritoneal mast cells were also investigated. When spantide was injected intradermally at a dose of 0.5 nmol/site, it significantly inhibited the response. Furthermore, iodophenpropit and clobenpropit (10(-6)-10(-8) M) did not induce histamine release in isolated rat peritoneal mast cells. Our results indicate that substance P is involved in the skin responses elicited by the histamine H(3) antagonists. Moreover, the fact that these histamine H(3) antagonists did not induce significant increases in the histamine release from rat peritoneal mast cells suggests that the histamine H(3) receptor may not be present in the peripheral cells considered in this study.
Zero total dispersion in step-index monomode fibres at 1.30 and 1.55 μm (1979)

The total dispersion of monomode fibres is resolved into its constituent parts. The use of waveguide dispersion to shift the zero dispersion point to longer wavelengths is described. The range of fibre parameters that give zero total dispersion at 1.3 or 1.55 μm are evaluated numerically for germania-doped silica. Comments are made on the consequences for jointing and microbending losses.
Detection of DNA Adducts in Human Breast Tissue. (1999)

Abstract : The purpose of this project is to optimize and apply new methodology for the detection of unknown DNA adducts in breast and, for comparison, other human tissues. In this methodology the DNA adducts are labeled with a fluorescent dye to enhance their detection. Although the first dye tested (IMI1) was not fully stable, this problem was overcome by preparing IMI2. High dye Purity is required, and this was accomplished for IMI2 by means of flash chromatography/submarine gel electrophoresis, which brought the purity to 99.9998%. A basic protocol has been set up for the entire method, starting with human cell culture or human autopsy tissue samples, including breast samples and finishing with detection by capillary electrophoresis with laser induced fluorescence detection (CE-LIF). Standard adducts, after labeling with IMI2, were detected by matrix assisted laser desorption ionization mass spectrometry (MALDI-MS), with 300 fmol in the laser beam. Thus, the methodology is emerging as planned.
Reconstitution of the Functional Mouse Oncostatin M (OSM) Receptor: Molecular Cloning of the Mouse OSM Receptor β Subunit (1999)

Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines that share the gp130 receptor subunit. Of these family members, leukemia inhibitory factor (LIF) is most closely related to OSM, and various overlapping biologic activities have been described between human LIF and OSM (hLIF and hOSM). Two types of functional hOSM receptors are known: the type I OSM receptor is identical to the LIF receptor that consists of gp130 and the LIF receptor β subunit (LIFRβ), and the type II OSM receptor consists of gp130 and the OSM receptor β subunit (OSMRβ). It is thus conceivable that common biologic activities between hLIF and hOSM are mediated by the shared type I receptor and OSM-specific activities are mediated by the type II receptor. However, in contrast to the human receptors, recent studies have demonstrated that mouse OSM (mOSM) does not activate the type I receptor and exhibits unique biologic activity. To elucidate the molecular structure of the functional mOSM receptor, we cloned a cDNA encoding mOSMRβ, which is 55.5% identical to the hOSMRβ at the amino acid level. mOSM-responsive cell lines express high-affinity mOSM receptors, as well as mOSMRβ, whereas embryonic stem cells, which are responsive to LIF but not to mOSM, do not express mOSMRβ. mOSMRβ alone binds mOSM with low affinity (kd = 13.0 nmol/L) and forms a high-affinity receptor (kd = 606 pmol/L) with gp130. Ba/F3 transfectants expressing both mOSMRβ and gp130 proliferated in response to mOSM, but failed to respond to LIF and human OSM. Thus, the cloned mOSMRβ constitutes an essential and species-specific receptor component of the functional mOSM receptor. Reminiscent of the colocalization of the mOSM and mLIF genes, the mOSMRβ gene was found to be located in the vicinity of the LIFRβ locus in the proximal end of chromosome 15.
Applications of stable, nonradioactive isotope tracers in in vivo human metabolic research (2016)

The human body is in a constant state of turnover, that is, being synthesized, broken down and/or converted to different compounds. The dynamic nature of in vivo kinetics of human metabolism at rest and in stressed conditions such as exercise and pathophysiological conditions such as diabetes and cancer can be quantitatively assessed with stable, nonradioactive isotope tracers in conjunction with gas or liquid chromatography mass spectrometry and modeling. Although measurements of metabolite concentrations have been useful as general indicators of one's health status, critical information on in vivo kinetics of metabolites such as rates of production, appearance or disappearance of metabolites are not provided. Over the past decades, stable, nonradioactive isotope tracers have been used to provide information on dynamics of specific metabolites. Stable isotope tracers can be used in conjunction with molecular and cellular biology tools, thereby providing an in-depth dynamic assessment of metabolic changes, as well as simultaneous investigation of the molecular basis for the observed kinetic responses. In this review, we will introduce basic principles of stable isotope methodology for tracing in vivo kinetics of human or animal metabolism with examples of quantifying certain aspects of in vivo kinetics of carbohydrate, lipid and protein metabolism.
Shared mechanisms in affective illness, epilepsy, and migraine. (1994)

For a specific subgroup of patients with migraine or affective illness who experience illness progression and drug tolerance, the amygdala kindling paradigm can be a useful, but nonhomologous, model. Although these patients do not have a seizure or seizure-like disorder, kindling has been used to examine the types of memory-like mechanisms that could underlie syndrome evolution in both migraine and affective illness. While the precipitants, symptomatology, duration of attack, and aura symptoms differ among epilepsy, migraine, and the affective disorders, all are paroxysmal dysregulations that partially share effective drug treatment. The principles of seizure progression presented here may apply to affective and migraine patients whose episodes progress from isolated and intermittent to more chronic or daily. These patients may also develop tolerance to long-term prophylactic treatments.
Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer (2019)

First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).
Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection (2008)

This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1-9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.