gebhart/patrepeval huggingface dataset:
ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1 (2012)

The epithelial Na(+) channel (ENaC) is a key transporter participating in the fine tuning of Na(+) reabsorption in the nephron. ENaC activity is acutely upregulated by epidermal growth factor (EGF), insulin, and insulin-like growth factor-1 (IGF-1). It was also proposed that reactive oxygen species (ROS) have a stimulatory effect on ENaC. Here we studied whether effects of EGF, insulin, and IGF-1 correlate with ROS production in the mouse cortical collecting duct (mpkCCD(c14)) cells. Western blotting confirmed the expression of the NADPH oxidase complex subunits in these cells. Treatment of mpkCCD(c14) cells with EGF, insulin, or IGF-1 evoked an increase in ROS production as measured by CM-H(2)DCF-DA fluorescence. ROS production caused by a xanthine-xanthine oxidase reaction also resulted in a significant elevation in short-circuit current through the mpkCCD(c14) monolayer. Transepithelial current measurements showed an acute increase of amiloride-sensitive current through the mpkCCD(c14) monolayer in response to EGF, insulin, or IGF-1. Pretreatment with the nonselective NADPH oxidase activity inhibitor apocynin blunted both ROS production and increase in ENaC-mediated current in response to these drugs. To further test whether NADPH oxidase subunits are involved in the effect of EGF, we used a stable M-1 cell line with a knockdown of Rac1, which is one of the key subunits of the NADPH oxidase complex, and measured amiloride-sensitive currents in response to EGF. In contrast to control cells, EGF had no effect in Rac1 knockdown cells. We hypothesize that EGF, insulin, and IGF-1 have a common stimulatory effect on ENaC mediated by ROS production.
Building a scaleable geo-spatial DBMS (1997)

This paper presents a number of new techniques for parallelizing geo-spatial database systems and discusses their implementation in the Paradise object-relational database system. The effectiveness of these techniques is demonstrated using a variety of complex geo-spatial queries over a 120 GB global geo-spatial data set.
Association Between Circulating Oxidized Low-Density Lipoprotein and Incidence of the Metabolic Syndrome (2008)

Higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of abdominal obesity, hyperglycemia, and hypertriglyceridemia.
Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore (2011)

Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment.
A reproducible grading scale for histological assessment of inflammation in ulcerative colitis (2000)

A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts (2013)

Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids.
Electrostatically-Induced Inclusion of Anions in Cyclodextrin Monolayers on Electrodes (1999)

Oxidative mercury−thiolate bond formation accounts for the assembly of densely packed monolayers of per-2,3-methylated per-6-thiolated α-, β-, and γ-cyclodextrins on the hanging mercury drop electrode. Inclusion of inorganic ions and uncharged hydrophobic guests into these monolayers was investigated by capacitance measurements. In the range of potentials where the electrode is positively charged, the interfacial capacitance depends on the type of electrolyte anions and on the applied potential. This can be explained with electrostatic double-layer forces. Whereas the smaller and less well solvated anions Cl-, NO3-, and ClO4- are included in the cyclodextrin cavities of these monolayers, the larger and more strongly solvated anions F-, SO42-, and H2PO4- are excluded. Anion inclusion constants can be obtained from the dependence of the interfacial capacitance on the anion concentration. The potential dependence of these inclusion constants shows that the nonelectrostatic contribution to the driving force for NO3- inclusion is negligibly small. Competitive binding of hydrophobic guest molecules decreases the interfacial capacitance. Fitting Langmuir isotherms to the plots of the interfacial capacitance as a function of adamantanol concentration yielded the binding constants 1.0 × 104 and 2.6 × 104 M-1 for the β- and γ-cyclodextrin monolayers, respectively. Binding of adamantanol to α-cyclodextrin monolayers could not be observed, apparently because this guest is too large for the internal cavity of the α-cyclodextrin receptor. In contrast, 1-hexanol binds to α-cyclodextrin monolayers with the binding constant 8.9 × 104 M-1. This shows that changes in the capacitance can serve as a general signal transduction mode to monitor interactions between cyclodextrin monolayers and charged or neutral guests. Also, the extension of these types of measurements into solid electrodes and the application to other guest-selective host monolayers open the possibility of designing a novel type of electrochemical sensors for electroinactive analytes.
A mechanism-based fluorogenic probe for the cytochrome P-450 cholesterol side chain cleavage enzyme (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA mechanism-based fluorogenic probe for the cytochrome P-450 cholesterol side chain cleavage enzymeDaniel J. Simpson, Clifford J. Unkefer, Thomas W. Whaley, and Babetta L. MarroneCite this: J. Org. Chem. 1991, 56, 18, 5391–5396Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/jo00018a036https://doi.org/10.1021/jo00018a036research-articleACS PublicationsRequest reuse permissionsArticle Views261Altmetric-Citations20LEARN 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
Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts1 (2006)

Despite multimodal treatment options, the response and survival rates for patients with malignant gliomas remain dismal. Clinical trials with convection-enhanced delivery (CED) have recently opened a new window in neuro-oncology to the direct delivery of chemotherapeutics to the CNS, circumventing the blood-brain barrier and reducing systemic side effects. Our previous CED studies with liposomal chemotherapeutics have shown promising antitumor activity in rodent brain tumor models. In this study, we evaluated a combination of nanoliposomal topotecan (nLs-TPT) and pegylated liposomal doxorubicin (PLD) to enhance efficacy in our brain tumor models, and to establish a CED treatment capable of improving survival from malignant brain tumors. Both liposomal drugs decreased key enzymes involved in tumor cell replication in vitro. Synergistic effects of nLs-TPT and PLD on U87MG cell death were found. The combination displayed excellent efficacy in a CED-based survival study 10 days after tumor cell implantation. Animals in the control group and those in singleagent groups had a median survival of less than 30 days, whereas the combination group experienced a median survival of more than 90 days. We conclude that CED of two liposomal chemotherapeutics (nLs-TPT and PLD) may be an effective treatment option for malignant gliomas.
Antibody-Based Bio-Nanotube Membranes for Enantiomeric Drug Separations (2002)

Synthetic bio-nanotube membranes were developed and used to separate two enantiomers of a chiral drug. These membranes are based on alumina films that have cylindrical pores with monodisperse nanoscopic diameters (for example, 20 nanometers). Silica nanotubes were chemically synthesized within the pores of these films, and an antibody that selectively binds one of the enantiomers of the drug was attached to the inner walls of the silica nanotubes. These membranes selectively transport the enantiomer that specifically binds to the antibody, relative to the enantiomer that has lower affinity for the antibody. The solvent dimethyl sulfoxide was used to tune the antibody binding affinity. The enantiomeric selectivity coefficient increases as the inside diameter of the silica nanotubes decreases.
Selectively-Permeable Ultrathin Film Composite Membranes Based on Molecularly-Imprinted Polymers (1998)

Membrane-based chemical separations constitute an emerging research area and industrial technology. The objective is to develop membranes that selectively transport a particular target molecule and reject (or transport at much lower rates) other molecules that might be present in the feed solution. This paper describes a new approach for preparing highly selective composite membranes for pharmaceutical or biomedical separations. This approach entails photopolymerization of a “molecularly-imprinted polymer film” across the surface of a microporous support to form a new type of ultrathin film composite membrane. Composite membranes based on polymers that were imprinted on the bronchodilator theophylline were prepared. The rate and selectivity of theophylline transport across these ultrathin film composites were investigated.
Association of the Homeobox Transcription Factor Gene ENGRAILED 2 with Autistic Disorder in Chinese Children (2008)

Both the allelic and genotypic distributions of the 2 polymorphisms were concordant with Hardy-Weinberg equilibrium. Significant differences were found for cases versus community and overall controls. By using the UNPHASE and PHASE programs, the 2-marker haplotype A-C of EN2 was identified to have a protective effect for autism, indicating that the ethnic difference might confound the EN2 association with autism. Therefore, more EN2 gene association studies of Han Chinese populations are warranted to confirm this finding.
Bone engineering by controlled delivery of osteoinductive molecules and cells (2004)

Bone regeneration can be enhanced or accelerated by the delivery of osteogenic signalling factors or bone forming cells. These factors have commonly provided benefit when retained at the defect site with a delivery vehicle formed from natural or synthetic materials. Growth factors can be directly delivered as recombinant proteins or expressed by genetically modified cells to induce bone formation. Furthermore, bone regeneration has been achieved with the transplantation of various cell types that can participate in bone healing. Carriers utilised for the delivery of osteoinductive material allow for a prolonged presentation at the repair site and the timing of presentation can be readily adjusted to correspond to the extent necessary for bone regeneration. This review examines some of the recent developments in delivery systems used to manage the presentation of these factors at the desired site. Moreover, the authors provide suggestions for continued progress in bone regeneration.
Ultra fast miniaturized real-time PCR: 40 cycles in less than six minutes (2006)

We have designed, fabricated and tested a real-time PCR chip capable of conducting one thermal cycle in 8.5 s. This corresponds to 40 cycles of PCR in 5 min and 40 s. The PCR system was made of silicon micromachined into the shape of a cantilever terminated with a disc. The thin film heater and a temperature sensor were placed on the disc perimeter. Due to the system's thermal constant of 0.27 s, we have achieved a heating rate of 175 degrees C s(-1) and a cooling rate of -125 degrees C s(-1). A PCR sample encapsulated with mineral oil was dispensed onto a glass cover slip placed on the silicon disc. The PCR cycle time was then determined by heat transfer through the glass, which took only 0.5 s. A real-time PCR sample with a volume of 100 nl was tested using a FAM probe. As the single PCR device occupied an area of only a few square millimeters, devices could be combined into a parallel system to increase throughput.
Transforming Growth Factor-α: a More Potent Angiogenic Mediator than Epidermal Growth Factor (1986)

Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are structurally related peptides. Purified human TGF-alpha produced in Escherichia coli and pure natural mouse EGF were compared for their ability to bind to target cells in vitro and to promote angiogenesis in the hamster cheek pouch bioassay. Both polypeptides were found to bind in vitro to several target cells, including endothelial cells, and to stimulate their DNA synthesis in an equipotent fashion. In vivo, however, TGF-alpha was more potent than EGF in promoting angiogenesis and, because TGF-alpha is known to be secreted by a variety of human tumors, it is suggested that this growth factor may contribute to tumor-induced angiogenesis.
In Vivo Functioning and Transplantable Mature Pancreatic Islet-Like Cell Clusters Differentiated from Embryonic Stem Cell (2003)

Our results provide evidence that ES cells could differentiate to functioning and transplantable mature pancreatic islet-like cell clusters using our newly developed differentiation method without employing gene transfer technique. This study may lead to a basis for production of indefinite sources of islets that could be applicable for future clinical trial.
Calibration of Solid Phase Microextraction for Air Analyses Based on Physical Chemical Properties of the Coating (1997)

Solid phase microextraction (SPME) with poly(dimethylsiloxane) (PDMS) is used to sample dynamic hydrocarbon standard gas mixtures with calibration for temperature, relative humidity, gas velocities, and gas concentrations. Equilibration times were found to vary from 15 to 450 s depending on the compound. Relative humidity greater than 90% at various temperatures was found to decrease analyte mass loading by 10%. Investigation of linearity with PDMS showed all of the analytes had a linear relationship between mass loaded at equilibrium and the gas concentrations studied. Analyte detection limits are better than those for conventional grab sampling (concentration with adsorbent tubes and analysis by gas chromatography and flame ionization detection). Partition coefficients (K) were established at various temperatures, yielding a linear relationship between log K and T-1. The linear expression has a slope that is a function of the gas constant and the analyte heat of vaporization (ΔH v) and a y-intercept that is a combination of terms among which include the gas constant, analyte ΔH v, and activity coefficient; therefore, K values can be estimated using literature ΔH v and ascertained at temperatures for which a K was not determined. This removes the restriction that calibration and air sampling must be carried out at the same temperature. A comparison of PDMS (100 μm) fiber lengths (n = 13) revealed an average fiber length of 1.02 ± 0.03 cm. An interfiber estimation of method precision (n = 10) yielded less than 9% RSD for all the test analytes. When a correction for fiber lengths was applied, the differences between the means of area counts for the individual fibers was statistically insignificant. SPME was successfully field tested as a grab sampler and an integrated sampler to analyze air at an industrial site, with excellent agreement to traditional air sampling methods. This work suggests that ambient and industrial air sampling with SPME is possible with essentially no calibration of the sampling device. It is only necessary to know the analyte's K to the fiber at various temperatures which is based on defined and empirically determinable physical constants.
The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. (1994)

LPS stimulates human monocytes and neutrophils to produce IL-1 beta and IL-1 receptor antagonist (IL-1ra). IL-10 has been shown to inhibit LPS-induced IL-1 beta production in human monocytes. The objective of these studies was to examine the effects of IL-10 on human monocyte and neutrophil IL-1ra protein and mRNA production and compare it to IL-1 beta. IL-10 markedly inhibited LPS-induced IL-1 beta mRNA and protein production in both cell types. IL-10 alone induced IL-1ra mRNA production in monocytes with a low level of protein production. Furthermore, IL-10 led to enhanced levels of IL-1ra mRNA in LPS-induced monocytes at 2 to 6 h and of IL-1ra protein at 4-16 h, but there was no increase in levels of IL-1ra protein at 24 h or later. In neutrophils IL-10 alone did not stimulate IL-1ra protein or mRNA production and did not augment LPS-induced IL-1ra mRNA. These net effects of IL-10 resulted in an increase in the ratio of IL-1ra to IL-1 beta in both neutrophils and monocytes. The net effects of IL-10 on inflammatory cells may be important in modulation of biologic responses to IL-1.
In vivo Na‐23 MR imaging and spectroscopy of rat brain during TmDOTP5− infusion (1992)

In vivo sodium-23 and hydrogen-1 magnetic resonance (MR) imaging and spectroscopy of the rat brain during infusion of the shift reagent thulium DOTP5- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra[methylene phosphonate] was performed to assign the various peaks observed during infusion and to evaluate the shift reagent in discriminating tissue compartments. Na-23 spectra collected during the infusion showed two shifted peaks that were assigned to intravascular Na+ and extracellular muscle Na+, respectively, and one unshifted peak assigned to intra- and extracellular brain Na+ and cerebrospinal fluid Na+. These assignments were validated with H-1 and Na-23 MR imaging and Na-23 chemical shift imaging (CSI). The H-1 and Na-23 images showed that a surface coil placed on a rat head can detect a substantial amount of signal from muscle surrounding the skull. Na-23 CSI spectra from successive 1-mm-thick coronal sections indicated that the shift reagent did not cross the blood-brain barrier. The study also showed that bulk susceptibility shifts are quite small with Tm-DOTP5-. This reagent may be useful in determining compartmental Na+ concentrations and blood flow kinetics in brain and in examining the integrity of the blood-brain barrier.
Assumptions in the radiotherapy of glioblastoma (1980)

In the light of advances in computerized tomography (CT), we have retrospectively evaluated the assumptions that underlie the radiation therapy of glioblastoma: (1) No neuroradiologic technique provides an accurate delineation of tumor bulk and location, (2) glioblastoma is commonly multicentric, and (3) a major source of therapeutic failure is recurrence beyond radiotherapy fields. CT scans, performed on glioblastoma patients within 2 months of postmortem examination, defined both gross and microscopic tumor extent (within a 2-cm margin) in all but 6 of 35 patients evaluated. The major source of error was subependymal spread (four patients). Multicentricity occurred in only 4% of untreated and 6% of treated (radiotherapy with or without chemotherapy) patients. All multicentric lesions were identified on CT scans. Serial CT scans on 42 patients revealed that glioblastoma recurred within a 2-cm margin of the primary site in 90%. Occurrences outside this margin were accurately delineated by CT in all instances. Because most patients show recurrence within or in close proximity to the original site, current radiation doses would appear to be inadequate for therapy of the primary tumor. CT scan accuracy may permit smaller-field and higher-dose irradiation therapy for glioblastoma.