gebhart/patrepeval huggingface dataset:
L-asparaginase-induced modulation of methotrexate polyglutamylation in murine leukemia L5178Y. (1987)

The modulation of methotrexate polyglutamylation by L-asparaginase has been examined in mice bearing sublines of leukemia L5178Y that have different sensitivities to asparaginase. A single i.p. injection of 200 IU/kg of asparaginase completely inhibited ascites tumor cell growth in the parental L5178Y/S+ tumor for 120 h compared to 72 and 30 h in the L5178Y/S and L5178Y/S+/- sublines, respectively. Similarly, DNA and protein synthesis were completely inhibited by asparaginase for 96 h in L5178Y/S+ cells, but only for 72 and 24 h in L5178Y/S and L5178Y/S+/- cells. In each tumor the temporal patterns of depletion and recovery of S-phase cells were similar to the patterns of suppression and recovery of DNA and protein synthesis observed in that tumor. When methotrexate was administered at either 96 or 24 h after asparaginase during the asparaginase-induced S-phase nadirs of L5178Y/S+ and L5178Y/S+/- cells, respectively, subsequent methotrexate polyglutamylation was inhibited 83 and 92% compared to tumor cells exposed to methotrexate only. Recovery of methotrexate polyglutamylation in both tumors following L-asparaginase pretreatment coincided in time with the return in the fraction of S-phase cells towards the pretreatment values. The inhibition of methotrexate polyglutamate accumulation by asparaginase was associated with decreased retention of methotrexate in tumor cells. In contrast, asparaginase had no significant effect on methotrexate polyglutamate accumulation and methotrexate retention when administered after methotrexate. These data indicated that the asparaginase-induced modulation of methotrexate polyglutamylation in mice was directly related to the time course of inhibition and recovery of tumor cell proliferation by asparaginase, and thus varied with the intrinsic sensitivity of the individual tumor to the enzyme.
Multiple forms of the 20 S multicatalytic and the 26 S ubiquitin/ATP-dependent proteases from rabbit reticulocyte lysate. (1992)

We have used native gel electrophoresis followed by fluorogenic peptide overlay to identify multiple forms of rabbit reticulocyte multicatalytic protease (MCP) or 20 S protease, and two forms of rabbit 26 S ubiquitin/ATP-dependent protease. An abundant, fast-migrating 20 S complex (20 SF) possesses modest ability to hydrolyze the fluorogenic peptide succinyl-Leu-Leu-Val-Tyr-4-methyl-coumaryl-7-amide. In contrast, two minor, slower migrating species cleave the peptide at high rates. A unique 30-kDa polypeptide is associated with one of the active MCPs, and a 160-kDa subunit is associated with the other. Two electrophoretically distinct 26 S proteases can also be isolated from rabbit reticulocyte lysate. The faster migrating form, 26 SF, is more resistant to inactivation by ATP depletion. Despite the differential response to nucleotides and the distinctive electrophoretic mobilities of 26 SF and 26 SS, we have not identified any subunit differences between the two enzymes. In addition to active 26 S proteases, we have discovered and purified a proteolytically inactive particle that contains subunits characteristic of the 26 S protease (e.g. molecular masses between 30 and 110 kDa). Incubation of this protein complex with purified MCP and ATP results in the formation of the 26 S proteases.
4'-Substituted nucleosides. 3. Synthesis of some 4'-fluorouridine derivatives (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT4'-Substituted nucleosides. 3. Synthesis of some 4'-fluorouridine derivativesGeoffrey R. Owen, Julien P. H. Verheyden, and John G. MoffattCite this: J. Org. Chem. 1976, 41, 18, 3010–3017Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://doi.org/10.1021/jo00880a018RIGHTS & PERMISSIONSArticle Views449Altmetric-Citations53LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Loss and spectral control in fused tapered couplers (1994)

The loss and spectral characteristics of fused tapered coupiers depend, respectively, on the taper transition rate and on the size, shape, and length of the coupler waist region. We show how the choice of the fusing and tapering burner is critical in optimizing the behavior of three different coupler types: the single-wavelength splitter, the wavelength division multiplexer, and the wavelength-independent coupler.
Global mapping functions for the atmosphere delay at radio wavelengths (1996)

I have developed expressions for calculating the ratios (mapping functions) of the “line of sight” hydrostatic and wet atmospheric path delays to their corresponding zenith delays at radio wavelengths for elevation angles down to 3°. The coefficients of the continued fraction representation of the hydrostatic mapping function depend on the latitude and height above sea level of the observing site and on the day of the year; the dependence of the wet mapping function is only on the site latitude. By comparing with mapping functions calculated from radiosonde profiles for sites at latitudes between 43°S and 75°N, the hydrostatic mapping function is seen to be more accurate than, and of comparable precision to, mapping functions currently in use, which are parameterized in terms of local surface meteorology. When the new mapping functions are used in the analysis of geodetic very long baseline interferometry (VLBI) data, the estimated lengths of baselines up to 10,400 km long change by less than 5 mm as the minimum elevation of included data is reduced from 12° to 3°. The independence of the new mapping functions from surface meteorology, while having comparable accuracy and precision to those that require such input, makes them particularly valuable for those situations where surface meteorology data are not available.
[Contribution of polysomnography in the assessment of patients with chronic obstructive bronchopneumopathy]. (1991)

15 COPD patients underwent a polysomnographic study demonstrating poor quality of sleep, a mean of SAO2 of 88.8 +/- 3.9% and a apneic-hypopnea index (AHI) of 5.7 +/- 11.8. AHI was higher in sleep stages I and II than in REM sleep. SAO2 showed a progressive drop when going from an awake stage to REM sleep. Respiratory events responsible for the most important desaturation where mostly observed in REM sleep and corresponded in 8 patients to obstructive events (overlap syndrome). The lower mean SAO2 in REM probably explains the best the importance in desaturation related to the respiratory events (Hb dissociation curve). Ear oximetry recordings however interesting are not able to quantify and recognise correctly the respiratory events. Therefore a polysomnographic study remains necessary in order to diagnose adequately the overlap syndrome.
Competitive Reactions in Solutions of Poly-l-histidine, Calf Thymus DNA, and Synthetic Polyanions:  Determining the Binding Constants of Polyelectrolytes (2003)

The physicochemical characteristics of a nonviral gene delivery system will govern its functional bioactivity; however, empiricism dominates the literature in this field, and a significant deficiency of quantitative investigation and evaluation of nonviral gene delivery vehicles remains. Herein, we derive a physical model and experimental method to quantitatively determine the binding constants between a model polycationic nonviral gene delivery vehicle poly-L-histidine (PLH) and calf thymus DNA. The approach has utility to a variety of systems and is not limited to the described polymer model. The interaction of PLH with DNA was monitored by fluorescence quenching of an ethidium bromide probe in the pH range 4 to 8. The interaction increased with pH decrease with the most pronounced change between pH 6 and 7. The obtained pH-dependence of fraction of salt bonds formed between PLH and DNA was used to estimate pK(a) of PLH in the presence of DNA, which equaled 6.24. The interaction of PLH with DNA in the presence of added synthetic polyanions was studied by the same approach and found to be controlled by pH, nature of the charge groups of the polyanion, and its degree of polymerization. In the mixture with sodium poly(styrenesulfonate) the interaction was negligible in the whole studied pH range, whereas in the mixtures with sodium poly(acrylate) (PA) or sodium poly(methacrylate), DNA was able to compete effectively for the binding with PLH. For PA samples with degree of polymerization higher than degree of polymerization of PLH, DP(PA) > DP(PLH), the fraction of polycation bound to DNA was constant regardless of DP(PA.) In contrast, at DP(PA) < DP(PLH), a pronounced increase in the bound fraction was observed. It substantiates the notion that the binding energy of two polymers is mainly controlled by the DP of the shorter component of polyelectrolyte complex. The data on PLH distribution between DNA and added polyanion with different values of DP were treated according to the developed procedure to yield the effective binding constants of PLH with DNA and polyanion-competitor, calculated both per mole of interacting units K(1) and mole of interacting chains K(n). In all cases, K(1) had similar numerical values reflecting common type of interaction stabilizing the complexes, i.e., electrostatics. Slight variation of K(1) yielded in drastic changes in K(n) and alteration of dominance of PLH interaction with DNA or synthetic polyanion. The results of the study can have a high impact in deriving the correlation between the binding constant of a polycation to DNA and its ability to serve as gene delivery vehicle.
Endosomal release and intracellular delivery of anticancer drugs using pH-sensitive PEGylated nanogels (2007)

A pH-sensitive PEGylated nanogel was prepared by emulsion copolymerization of 2-(N,N-diethylamino)ethyl methacrylate (EAMA) with heterobifunctional poly(ethylene glycol) bearing a 4-vinylbenzyl group at the α-end and a carboxylic acid group at the ω-end (CH2CH–Ph–PEG–COOH; Mn = 8000) in the presence of potassium persulfate and ethylene glycol dimethacrylate (1.0 mol%) as cross-linker. The loading of the anticancer drug doxorubicin (DOX) into the pH-sensitive PEGylated nanogel was carried out by means of a solvent evaporation method, and the amount of DOX loaded into the PEAMA core was found to be 26 wt%. Furthermore, the DOX-loaded, pH-sensitive PEGylated nanogel showed almost no initial burst release of the DOX under physiological pH, whereas significant release of DOX from the pH-sensitive PEGylated nanogel was observed at the endosomal pH. The antitumor activity of the DOX-loaded, pH-sensitive, PEGylated nanogel against the human breast cancer cell line MCF-7 was lower than that of free DOX. On the other hand, the antitumor activity of the DOX-loaded, pH-sensitive, PEGylated nanogel against the human hepatoma cell line HuH-7, which is a natural drug-resistant tumor line, was superior to that of both free DOX and the DOX-loaded, pH-insensitive, PEGylated nanogel. Using fluorescence microscopy, pH-sensitive PEGylated nanogel in HuH-7 cells was found to be initially localized within the endosome and/or lysosome, with subsequent release of DOX from the nanogel in response to the endosomal pH, and ultimately, diffusion via the cytoplasm into the cell nucleus. These findings suggest that the pH-sensitive PEGylated nanogel represents a promising nano-sized carrier for anticancer drug delivery systems in vivo.
<b>EFFECTS OF SPECIFIC COMPETITIVE INHIBITORS OF SWEET TASTE RESPONSE ON GLUCOSE-INDUCED INSULIN </b><b>RELEASE </b> (1993)

The effects of specific competitive inhibitors of sweet taste response on insulin release and glucose oxidation were studied using isolated rat pancreatic islets. The 0: anomers of pnitrophenyl-D-glucopyranoside (PNP-Glu) and p-nitrophenyl-D-mannopyranoside (PNP-Man) dose-dependently (-5 mM) inhibited insulin release induced by l0 mM D-glucose without affecting glucose oxidation in the islets, while the [i anomers were ineffective, as reported in the gustatory cell. The inhibitory effect of the 0: anomers of these compounds, at 5 mM, were surmounted by increasing the concentration of D-glucose to 20 mM. Either anomer of p-nitrophenyl-1)-galactopyranoside (PNP-Gal) had no effect on insulin release.
Tilted femtosecond pulses for velocity matching in gas-phase ultrafast electron diffraction (2014)

Recent advances in pulsed electron gun technology have resulted in femtosecond electron pulses becoming available for ultrafast electron diffraction experiments. For experiments investigating chemical dynamics in the gas phase, the resolution is still limited to picosecond time scales due to the velocity mismatch between laser and electron pulses. Tilted laser pulses can be used for velocity matching, but thus far this has not been demonstrated over an extended target in a diffraction setting. We demonstrate an optical configuration to deliver high-intensity laser pulses with a tilted pulse front for velocity matching over the typical length of a gas jet. A laser pulse is diffracted from a grating to introduce angular dispersion, and the grating surface is imaged on the target using large demagnification. The laser pulse duration and tilt angle were measured at and near the image plane using two different techniques: second harmonic cross correlation and an interferometric method. We found that a temporal resolution on the order of 100 fs can be achieved over a range of approximately 1mm around the image plane.
A novel mechanism for the acquisition of virulence by a human influenza A virus (1998)

Cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for the infectivity of influenza A viruses. Here, we describe a novel mechanism of HA cleavage for a descendant of the 1918 pandemic strain of human influenza virus. We demonstrate that neuraminidase, the second major protein on the virion surface, binds and sequesters plasminogen, leading to higher local concentrations of this ubiquitous protease precursor and thus to increased cleavage of the HA. The structural basis of this unusual function of the neuraminidase molecule appears to be the presence of a carboxyl-terminal lysine and the absence of an oligosaccharide side chain at position 146 (N2 numbering). These findings suggest a means by which influenza A viruses, and perhaps other viruses as well, could become highly pathogenic in humans.
Isolation, Characterization, and Expansion Methods for Defined Primary Renal Cell Populations from Rodent, Canine, and Human Normal and Diseased Kidneys (2010)

Chronic kidney disease (CKD) is a global health problem; the growing gap between the number of patients awaiting transplant and organs actually transplanted highlights the need for new treatments to restore renal function. Regenerative medicine is a promising approach from which treatments for organ-level disorders (e.g., neurogenic bladder) have emerged and translated to clinics. Regenerative templates, composed of biodegradable material and autologous cells, isolated and expanded ex vivo, stimulate native-like organ tissue regeneration after implantation. A critical step for extending this strategy from bladder to kidney is the ability to isolate, characterize, and expand functional renal cells with therapeutic potential from diseased tissue. In this study, we developed methods that yield distinct subpopulations of primary kidney cells that are compatible with process development and scale-up. These methods were translated to rodent, large mammal, and human kidneys, and then to rodent and human tissues with advanced CKD. Comparative in vitro studies demonstrated that phenotype and key functional attributes were retained consistently in ex vivo cultures regardless of species or disease state, suggesting that autologous sourcing of cells that contribute to in situ kidney regeneration after injury is feasible, even with biopsies from patients with advanced CKD.
Gene targeting and gene transfer to unravel the molecular basis of the formation and disorders of blood vessels. (2000)

Novel gene technologies have allowed to manipulate the genetic balance of candidate molecules in mice in a controllable manner. Homologous or site-specific recombination in embryonic stem cells allows to study the consequences of deficiencies, mutations, conditional or tissue specific expression of gene products in transgenic mice. These technological breakthroughs have significantly advanced biomedical research and our understanding of the pathophysiological role of candidate disease genes. In addition, gene transfer allows to test the possible therapeutic use of gene products for gene therapy. With the advent of genome sequencing programs, these gene technologies provide means to study gene function in a conclusive manner. Furthermore, disease models can be generated which can be used as testmodels for (gene) therapy or for discovery of novel genes using differential gene profiling techniques. The present review will focus on the use of these technologies to study the molecular basis of how blood vessels form (angiogenesis) and how vessels can become affected by disorders. A selected number of molecules that have been studied in our laboratory will be reviewed in particular.
Recommending and evaluating choices in a virtual community of use (1995)

Article Recommending and evaluating choices in a virtual community of use Share on Authors: Will Hill Bellcore, 445 South Street, Morristown, NJ Bellcore, 445 South Street, Morristown, NJView Profile , Larry Stead Bellcore, 445 South Street, Morristown, NJ Bellcore, 445 South Street, Morristown, NJView Profile , Mark Rosenstein Bellcore, 445 South Street, Morristown, NJ Bellcore, 445 South Street, Morristown, NJView Profile , George Furnas Bellcore, 445 South Street, Morristown, NJ Bellcore, 445 South Street, Morristown, NJView Profile Authors Info & Claims CHI '95: Proceedings of the SIGCHI Conference on Human Factors in Computing SystemsMay 1995 Pages 194–201https://doi.org/10.1145/223904.223929Online:01 May 1995Publication History 590citation5,263DownloadsMetricsTotal Citations590Total Downloads5,263Last 12 Months235Last 6 weeks30 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Inorganic Luminescent Materials: 100 Years of Research and Application (2003)

Abstract Up until approximately 80 years ago, only black‐body radiation (including natural sources) was available to illuminate our environment. To realise state‐of‐the‐art lamps, TV sets, monitors, and medical scanners, took an enormous scientific and technical effort. Inorganic luminescent materials are key components, which were, are, and will be prerequisite to the functionality and success of many lighting and display systems. In this Highlight, a hundred years of inorganic luminescent material research are reviewed.
Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate (1979)

The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the DNA polymerase of the host cell, that the inhibition was dependent upon the base composition of the template, and that the triphosphate was a better substrate for the virus-induced polymerases than for the alpha cellular DNA polymerases.
Factors Influencing Adeno-Associated Virus-Mediated Gene Transfer to Human Cystic Fibrosis Airway Epithelial Cells: Comparison with Adenovirus Vectors (1998)

Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to airway epithelial cells are not well understood. We compared the transduction efficiencies of AAV vectors and adenovirus (Ad) vectors in immortalized cell lines from CF patients and in nasal epithelial primary cultures from normal humans and CF patients. Similar dose-dependent relationships between the vector multiplicities of infection and the efficiencies of lacZ gene transfer were observed. However, levels of transduction for both Ad and recombinant AAV (rAAV) were significantly lower in the airway epithelial cell than in the control cell lines HeLa and HEK 293. Transduction efficiencies differed among cultured epithelial cell types, with poorly differentiated cells transducing more efficiently than well-differentiated cells. A time-dependent increase in gene expression was observed after infection for both vectors. For Ad, but not for AAV, this increase was dependent on prolonged incubation of cells with the vector. Furthermore, for rAAV (but not for rAd), the delay in maximal transduction could be abrogated by wild-type Ad helper infection. Thus, although helper virus is not required for maximal transduction, it increases the kinetics by which this is achieved. Expression of Ad E4 open reading frame 6 or addition of either hydroxyurea or camptothecin resulted in increased AAV transduction, as previously demonstrated for nonairway cells (albeit to lower final levels), suggesting that second-strand synthesis may not be the sole cause of inefficient transduction. Finally, the efficiency of AAV-mediated ex vivo gene transfer to lung cells was similar to that previously described for Ad vectors in that transduction was limited to regions of epithelial injury and preferentially targeted basal-like cells. These studies address the primary factors influencing rAAV infection of human airway cells and should impact successful gene delivery in CF patients.