gebhart/patrepeval huggingface dataset:
Pharmacokinetics of tobramycin and gentamicin in abusers of intravenous drugs (1985)

The kinetics of aminoglycoside elimination were determined in 18 hospitalized narcotics abusers receiving gentamicin or tobramycin for treatment of severe infection. Rapid aminoglycoside elimination (requiring doses of greater than 5 mg/kg per day to maintain adequate drug levels) was noted in 12 of the 18 patients (18 of 27 clearance studies). Patients found to have rapid elimination were younger (P less than 0.01) and had larger drug distribution volumes (P less than 0.005), greater measured creatinine clearances (P less than 0.05), and lower creatinine levels in serum (P less than 0.001) than those with normal elimination. Nevertheless, by regression analysis, age, creatinine levels in serum, creatinine clearances, and drug distribution volumes proved to be unreliable predictors of individual aminoglycoside clearance. Measured drug half-life in serum appeared to be the only reliable predictor of drug clearance (r = 0.93). Patients with rapid drug elimination had aminoglycoside clearances 16 to 43% greater than measured creatinine clearances, suggesting an extraglomerular route of drug elimination. We conclude that in drug abuse patients a significant and clinically unpredictable interpatient variation occurs in aminoglycoside elimination and that accurate serum kinetics are needed to determine therapeutic dosing. In addicts younger than 35 years, with a creatinine level of less than 1.0 mg/100 ml in serum, the risk of inadequate therapy is high if standard dosing guidelines are followed. For this group, initial dosing of 8 mg/kg per day, with a drug half-life determination on the first dose, is recommended. Pharmacokinetic analysis is critical for all drug abusers treated with aminoglycosides for serious infection.
The Termite Gut Microflora as an Oxygen Sink: Microelectrode Determination of Oxygen and pH Gradients in Guts of Lower and Higher Termites (1995)

Clark-type oxygen microelectrodes and glass pH microelectrodes, each with a tip diameter of <=10 (mu)m, were used to obtain high-resolution profiles of oxygen concentrations and pH values in isolated termite guts. Radial oxygen profiles showed that oxygen penetrated into the peripheral hindgut contents up to about 150 to 200 (mu)m below the epithelial surface in both the lower termite Reticulitermes flavipes (Kollar) and the higher termite Nasutitermes lujae (Wasmann). Only the central portions (comprising less than 40% of the total volume) of the microbe-packed, enlarged hindgut compartments ("paunches") were completely anoxic, indicating that some members of the hindgut microbiota constitute a significant oxygen sink. From the slopes of the oxygen gradients, we estimated that the entire paunches (gut tissue plus resident microbiota) of R. flavipes and N. lujae accounted for 21 and 13%, respectively, of the respiratory activity of the intact animals. Axial oxygen profiles also confirmed that in general, only the paunches were anoxic in their centers, whereas midguts and posterior hindgut regions contained significant amounts of oxygen (up to about 50 and 30% air saturation, respectively). A remarkable exception to this was the posterior portion of an anterior segment (the P1 segment) of the hindgut of N. lujae, which was completely anoxic despite its small diameter ((apprx=)250 (mu)m). Axial pH profiles of the guts of Nasutitermes nigriceps (Haldeman) and Microcerotermes parvus (Haviland) revealed that there were extreme shifts as we moved posteriorly from the midgut proper (pH (apprx=)7) to the P1 segment of the hindgut (pH >10) and then to the P3 segment (paunch; pH (apprx=)7). The latter transition occurred at the short enteric valve (P2 segment) and within a distance of less than 500 (mu)m. In contrast, R. flavipes, which lacks a readily distinguishable P1 segment, did not possess a markedly alkaline region, and the pH around the midgut-hindgut junction was circumneutral. The oxic status of the peripheral hindgut lumen and its substantial oxygen consumption, together with previous reports of large numbers of aerobic and facultatively anaerobic bacteria in the hindgut microflora, challenge the notion that termite hindguts are a purely anoxic environment and, together with the steep axial pH gradients in higher termites, refine our concept of this tiny microbial habitat.
Carbonic Anhydrase Inhibitors (2001)

CAs (EC 4.2.1.1) are wide-spread zinc enzymes, present in mammals in at least 14 different isoforms. Some of these isozymes are cytosolic (CA I, CA II, CA III, CA VII), others are membrane-bound (CA IV, CA IX, CA XII and CA XIV), CA V is mitochondrial and CA VI is secreted in the saliva. Three acatalytic forms are also known (CARP VIII, CARP X and CARP XI). Several important physiological and physio-pathological functions are played by many CA isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides. The catalytic and inhibition mechanisms of these enzymes are understood in great detail, and this greatly helped the design of potent inhibitors, some of which possess important clinical applications. The use of such enzyme inhibitors as antiglaucoma drugs will be discussed in detail, together with the recent developments that led to isozyme-specific and organ-selective inhibitors. A recent discovery is connected with the involvement of CAs and their sulfonamide inhibitors in cancer several potent sulfonamide inhibitors inhibited the growth of a multitude of tumor cells in vitro and in vivo, constituting thus interesting leads for developing novel antitumor therapies. Furthermore, some other classes of compounds that interact with CAs have recently been discovered, some of which possess modified sulfonamide or hydroxamate moieties. Some sulfonamides have also applications as diagnostic tools, in PET and MRI. Future prospects for drug design applications for inhibitors of these ubiquitous enzymes will also be discussed. Keywords: Carbonic Anhydrase Inhibitors, tumorigenicity, crystallographic data, zinc bound water, zinc hydroxide species, nanomolar range, aspartic protease, pharmacological agents, dorzolamide, antiglaucoma, ophthalmologic solutions, proton shuttle
Cytokine Response of Cultured Skeletal Muscle Cells Stimulated with Proinflammatory Factors Depends on Differentiation Stage (2013)

Myoblast proliferation and myotube formation are critical early events in skeletal muscle regeneration. The attending inflammation and cytokine signaling are involved in regulation of skeletal muscle cell proliferation and differentiation. Secretion of muscle-derived cytokines upon exposure to inflammatory factors may depend on the differentiation stage of regenerating muscle cells. Cultured human myoblasts and myotubes were exposed to 24-hour treatment with tumor necrosis factor (TNF)- α or lipopolysaccharide (LPS). Secretion of interleukin 6 (IL-6), a major muscle-derived cytokine, and interleukin 1 (IL-1), an important regulator of inflammatory response, was measured 24 hours after termination of TNF- α or LPS treatment. Myoblasts pretreated with TNF- α or LPS displayed robustly increased IL-6 secretion during the 24-hour period after removal of treatments, while IL-1 secretion remained unaltered. IL-6 secretion was also increased in myotubes, but the response was less pronounced compared with myoblasts. In contrast to myoblasts, IL-1 secretion was markedly stimulated in LPS-pretreated myotubes. We demonstrate that preceding exposure to inflammatory factors stimulates a prolonged upregulation of muscle-derived IL-6 and/or IL-1 in cultured skeletal muscle cells. Our findings also indicate that cytokine response to inflammatory factors in regenerating skeletal muscle partially depends on the differentiation stage of myogenic cells.
White-light supercontinuum generation in normally dispersive optical fiber using original multi-wavelength pumping system (2004)

We report on the experimental demonstration of a white-light supercontinuum generation in normally dispersive singlemode air-silica microstructured fiber. We demonstrate that the simultaneous excitation of the microstuctured fiber in its normal and anomalous dispersion regimes using the fundamental and second harmonic signals of a passively Q-switched microchip laser leads to a homogeneous supercontinuum in the visible range. This pumping scheme allows the suppression of the cascaded Raman effect predominance in favor of an efficient spectrum broadening induced by parametric phenomena. A flat supercontinuum extended from 400 to 700 nm is achieved.
Creating mosaics in Drosophila (1998)

The ability to create mosaic animals allows the phenotypic analysis of patches of groups of genetically different cells that develop in a wild type environment. In Drosophila, a variety of techniques have been developed over the years to generate mosaics, and in this chapter, I review the techniques that our laboratory has developed. These include the "Dominant Female Sterile" technique which allows the analysis of gene functions to oogenesis and embryogenesis; the "Gal4-UAS" technique which allows the control of where and when specific genes are expressed; and, the "Positive Marked Mutant Lineages" technique which allows clones of cells to express a specific reporter gene.
Tools for Visualizing Multidimensional Images from Living Specimens (2005)

Over the last 50 years modern cell biology has been driven by the development of powerful imaging techniques. In particular, new developments in light microscopy that provide the potential to image the dynamics of biological events have had significant impact. Optical sectioning techniques allow three-dimensional information to be obtained from living specimens noninvasively. When used with multimodal fluorescence microscopy, advanced optical sectioning techniques provide multidimensional image data that can reveal information not only about the changing cytoarchitecture of a cell but also about its physiology. These additional dimensions of information, although providing powerful tools, also pose significant visualization challenges to the investigator. Particularly in the current postgenomic era there is a greater need than ever for the development of effective tools for image visualization and management. In this review we discuss the visualization challenges presented by multidimensional imaging and describe three open-source software programs being developed to help address these challenges: ImageJ, the Open Microscopy Environment, and VisBio.
The Role of NiOx Overlayers on Spontaneous Growth of NiSix Nanowires from Ni Seed Layers (2008)

We report a controllably reproducible and spontaneous growth of single-crystalline NiSix nanowires using NiOx/Ni seed layers during SiH4 chemical vapor deposition (CVD). We provide evidence that upon the reactions of SiH4 (vapor)-Ni seed layers (solid), the presence of the NiOx overlayer on Ni seed layers plays the key role to promote the spontaneous one-dimensional growth of NiSix single crystals without employing catalytic nanocrystals. Specifically, the spontaneous nanowire formation on the NiOx overlayer is understood within the frame of the SiH4 vapor-phase reaction with out-diffused Ni from the Ni underlayers, where the Ni diffusion is controlled by the NiOx overlayers for the limited nucleation. We show that single-crystalline NiSix nanowires by this self-organized fashion in our synthesis display a narrow diameter distribution, and their average length is set by the thickness of the Ni seed layers. We argue that our simple CVD method employing the bilayers of transition metal and their oxides as the seed layers can provide implication as the general synthetic route for the spontaneous growth of metal-silicide nanowires in large scales.
Therapeutic effects of a fusogenic newcastle disease virus in treating head and neck cancer (2010)

We demonstrate that a fusogenic NDV exerts potent oncolytic effects against human head and neck cancer and support its continued investigation for clinical application.
HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function (2000)

The use of peptide-human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8(+) T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8(+) T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1beta, and perforin is analyzed by FACS((R)) within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8(+) T cells compared with cytomegalovirus (CMV)-specific CD8(+) T cells in HIV chronic infection. We show that the majority of circulating CD8(+) T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-gamma and MIP-1beta but not TNF-alpha. However, a striking finding is that HIV-specific CD8(+) T cells express significantly lower levels of perforin than CMV-specific CD8(+) T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8(+) T cells are impaired in cytolytic activity.
In situ investigation of the chemical composition of ceroid in human atherosclerosis by Raman spectroscopy (2002)

Abstract Fluorescent lipid peroxidation products (ceroid) form within the atheroma of an atherosclerotic lesion. At present, the initiation and propagation of such oxidative processes in situ are not well understood, in part because of the insolubility of the ceroid deposits. We investigated the chemical composition of ceroid in human atherosclerotic plaque by combining autofluorescence microscopy and Raman spectroscopy. In eight sectioned human atherosclerotic samples, we located granular and ring‐shaped ceroid deposits by autofluorescence microscopy. Subsequently, two‐dimensional Raman maps of the ceroid deposits and surrounding non‐fluorescent atheroma were acquired at 1 µm resolution. These Raman spectra were subjected to a K‐means clustering analysis. By assigning a different color to each cluster, pseudo‐color Raman images of the tissue sections were obtained. From these images the clusters belonging to ceroid and the non‐fluorescent surrounding tissue were selected. The averaged cluster spectra were analyzed by means of a least‐squares fit with the Raman spectra of pure chemical compounds. In addition, the Raman spectra were compared with the Raman spectra of normal and oxidized lipids. Marked differences between the Raman spectra of ceroid and surrounding, non‐fluorescent atheroma were observed, amidst large sample to sample variation in chemical composition. Compared with the non‐fluorescent tissue, the changes in the Raman spectra of the ceroid deposits could best be explained by larger signal contributions from hemoglobin and cholesteryl esters. We conclude that there is a large heterogeneity in the chemical composition of ceroid. Its composition is largely dependent on the chemical constituents of the surrounding atheroma. Heme or heme degradation products are consistently present in the ceroid deposits. Our results support the hypothesis that iron and heme can form complexes with the intravascular lipoproteins, thereby stimulating oxidation and initiating the formation of ceroid. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts (2016)

The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271(+) melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2(+)/VEGFR1(+)), and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271(+) melanoma cells represents a powerful therapeutic approach against metastatic melanoma.
Flavin model systems. 1. The electrochemistry of 1-hydroxyphenazine and pyocyanine in aprotic solvents (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFlavin model systems. 1. The electrochemistry of 1-hydroxyphenazine and pyocyanine in aprotic solventsMark M. Morrison, Eddie T. Seo, John K. Howie, and Donald T. SawyerCite this: J. Am. Chem. Soc. 1978, 100, 1, 207–211Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://pubs.acs.org/doi/10.1021/ja00469a035https://doi.org/10.1021/ja00469a035research-articleACS PublicationsRequest reuse permissionsArticle Views315Altmetric-Citations30LEARN 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
A comparison of three selection techniques for touchpads (1998)

Article A comparison of three selection techniques for touchpads Share on Authors: I. Scott MacKenzie Dept. of Computing & Information Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1 Dept. of Computing & Information Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1View Profile , Aleks Oniszczak Dept. of Computing & Information Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1 Dept. of Computing & Information Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1View Profile Authors Info & Claims CHI '98: Proceedings of the SIGCHI Conference on Human Factors in Computing SystemsJanuary 1998 Pages 336–343https://doi.org/10.1145/274644.274691Online:01 January 1998Publication History 55citation1,859DownloadsMetricsTotal Citations55Total Downloads1,859Last 12 Months197Last 6 weeks29 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
<title>Raman measurement of glucose in bioreactor materials</title> (1997)

The feasibility of using Raman spectroscopy to monitor the concentration of chemical species in a bioreactor has been examined. Successful operation of a bioreactor requires that nutrients and metabolic waste products be maintained within narrow ranges, and it is, therefore, important to provide accurate, reliable and timely measurement of the composition in the reactor. Raman spectroscopy offers the possibility of real time simultaneous monitoring of molecular components present in the millimolar and higher concentration range. Work reported here has focused on four analytes: glucose, glutamine, lactic acid and ammonia. Measurements have been made with a spectrograph providing a spectral window for simultaneous measurement of about 1800 cm<SUP>-1</SUP> on a multichannel CCD detector. Most measurements were made with an argon ion laser emitting at 514.5 nm. Some measurements are reported with a solid state diode laser operating at 785 nm. Locally constructed inexpensive silica fiber-optic probes delivered the laser light and collected the scattered radiation. Spectra of the four analytes n buffer and reactor media have been obtained. Analytical curves have been constructed and limits of detection measured. Limits of detection in buffer media are about 1 mM. Results are reported for off-line measurements on material drawn from a bioreactor.
Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency (1996)

In the present study, phagocytosis and the oxidative metabolism of neutrophil granulocytes from five clinically healthy persons with different degrees of myeloperoxidase deficiency were investigated and compared to those of normal persons. The identification of individuals with myeloperoxidase deficiency was performed with the Bayer/Technicon H3 blood cell counter, which differentiates the leukocytes by measuring the peroxidase activity. Neutrophils of three out of five investigated myeloperoxidase deficient persons showed extremely low peroxidase indices (-53 and lower), but only the neutrophils of one person totally lacked myeloperoxidase. This was demonstrated by comparing myeloperoxidase mass concentration measured with an enzyme immunoassay, lack of HOCl production, and was further confirmed by measuring luminol- and lucigenin-enhanced chemiluminescence. Characteristically, myeloperoxidase deficient granulocytes showed a strikingly decreased luminol-enhanced chemiluminescence while the lucigenin-enhanced chemiluminescence was significantly increased compared to normal granulocytes. Although there is a DNA sequence homology of about 70%, the activity of peroxidase in eosinophils was not affected in any myeloperoxidase deficient person investigated. Moreover, a person with a very rare defect of eosinophil peroxidase had completely normal myeloperoxidase activity. The lack of myeloperoxidase activity is compensated for by an increased phagocytic activity, an increased production of superoxide anion (lucigenin-chemiluminescence) and probably by an alternative metabolism of H2O2; since persons lacking myeloperoxidase activity do not normally suffer from severe infections, H2O2 is obviously metabolized to other reactive oxygen substrates than HOCl, e.g. to OH-radicals.