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Sample records for alpha selectively sensitizes

  1. Selective, sensitive and simple LC-APCI-MS method for the quantitation of Alpha-Tocopheryl Nicotinate in human plasma

    NASA Astrophysics Data System (ADS)

    Liang, Yan; Kang, An; Xie, Yuan; Liu, Xiao-Dong; Xie, Lin; Wang, Guang-Ji

    2008-06-01

    A sensitive and specific method using liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) has been developed and validated for the identification and quantification of Alpha-Tocopheryl Nicotinate in human plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts onto a C18 column with isocratic elution and detection using a single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The method was tested using six different plasma batches. Linearity was established for the concentration range 2-1500 ng/ml, with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision values were less than 15% and the deviations were within ± 5.0%. The lower limit of determination was reproducible at 0.5ng/ml with 0.5 ml plasma. The proposed method enables the unambiguous identification and quantification of Alpha-Tocopheryl Nicotinate for pre-clinical and clinical studies.

  2. DIFFERENCES IN SENSITIVITY BUT NOT SELECTIVITY OF XENOESTROGEN BINDING TO ALLIGATOR VERSUS HUMAN ESTROGEN RECEPTOR ALPHA

    PubMed Central

    Rider, Cynthia V.; Hartig, Phillip C.; Cardon, Mary C.; Lambright, Christy R.; Bobseine, Kathy L.; Guillette, Louis J.; Gray, L. Earl; Wilson, Vickie S.

    2010-01-01

    Reproductive abnormalities in alligators exposed to contaminants in Lake Apopka, Florida, USA represent a clear example of endocrine disruption in wildlife. Several of these contaminants that are not able to bind to mammalian estrogen receptors (such as atrazine and cyanazine) have previously been reported to bind to the alligator estrogen receptor from oviductal tissue. Binding of known Lake Apopka contaminants to full length estrogen receptors alpha from human (hERα) and alligator (aERα) was assessed in a side-by-side comparison within the same assay system. Baculovirus-expressed recombinant hERα and aERα were used in a competitive binding assay. Atrazine and cyanazine were not able to bind to either receptor. p,p′-Dicofol was able to bind to aERα with a concentration inhibiting 50% of binding (IC50) of 4 μM, while only partially displacing 17β-estradiol (E2) from hERα and yielding a projected IC50 of 45 μM. Chemicals that only partially displaced E2 from either receptor, including some dichlorodiphenyltrichloroethane (DDT) metabolites and trans-nonachlor, appeared to have higher affinity for aERα than hERα. p,p′-Dicofol-mediated transcriptional activation through aERα and hERα was assessed to further explore the preferential binding of p,p′-dicofol to aERα over hERα. p,p′-Dicofol was able to stimulate transcriptional activation in a similar manner with both receptors. However, the in vitro results obtained with p,p′-dicofol were not reflected in an in vivo mammalian model, where Kelthane™ (mixed o,p′-and p,p′-dicofol isomers) did not elicit estrogenic effects. In conclusion, although there was no evidence of exclusively species-specific estrogen receptor binders, some xenoestrogens, especially p,p′-dicofol, had a higher affinity for aERα than for hERα. PMID:20821664

  3. In Vitro Selection of Single-Stranded DNA Molecular Recognition Elements against S. aureus Alpha Toxin and Sensitive Detection in Human Serum

    PubMed Central

    Hong, Ka L.; Battistella, Luisa; Salva, Alysia D.; Williams, Ryan M.; Sooter, Letha J.

    2015-01-01

    Alpha toxin is one of the major virulence factors secreted by Staphylococcus aureus, a bacterium that is responsible for a wide variety of infections in both community and hospital settings. Due to the prevalence of S. aureus related infections and the emergence of methicillin-resistant S. aureus, rapid and accurate diagnosis of S. aureus infections is crucial in benefiting patient health outcomes. In this study, a rigorous Systematic Evolution of Ligands by Exponential Enrichment (SELEX) variant previously developed by our laboratory was utilized to select a single-stranded DNA molecular recognition element (MRE) targeting alpha toxin with high affinity and specificity. At the end of the 12-round selection, the selected MRE had an equilibrium dissociation constant (Kd) of 93.7 ± 7.0 nM. Additionally, a modified sandwich enzyme-linked immunosorbent assay (ELISA) was developed by using the selected ssDNA MRE as the toxin-capturing element and a sensitive detection of 200 nM alpha toxin in undiluted human serum samples was achieved. PMID:25633102

  4. Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy.

    PubMed

    Zouboulis, C C; Schröder, K; Garbe, C; Krasagakis, K; Krüger, S; Orfanos, C E

    1990-12-01

    Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10-10,000 U/ml rTNF-alpha applied for 72 h. The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments. The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE. Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha. In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment. On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant. The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment. Overall, rTNF-alpha enhanced the malignant immunophenotype of the cell lines tested. It increased the expression of the "late" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the "early" progression marker K.1.2. The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines. These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells. These effects may result in selection of rTNF-alpha-non-sensitive

  5. Alpha-particle sensitive test SRAMs

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Blaes, B. R.

    1990-01-01

    A bench-level test is being developed to evaluate memory-cell upsets in a test SRAM designed with a cell offset voltage. This offset voltage controls the critical charge needed to upset the cell. The effect is demonstrated using a specially designed 2-micron n-well CMOS 4-kb test SRAM and a Po-208 5.1-MeV 0.61-LET alpha-particle source. This test SRAM has been made sensitive to alpha particles through the use of a cell offset voltage, and this has allowed a bench-level characterization in a laboratory setting. The experimental data are linked to a alpha-particle interaction physics and to SPICE circuit simulations through the alpha-particle collection depth. The collection depth is determined by two methods and found to be about 7 micron. In addition, alpha particles that struck outside the bloated drain were able to flip the SRAM cells. This lateral charge collection was observed to be more than 6 micron.

  6. A position-sensitive alpha detector using a thin plastic scintillator combined with a position-sensitive photomultiplier tube

    NASA Astrophysics Data System (ADS)

    Yamamoto, Seiichi; Iida, Takao

    1998-12-01

    A position-sensitive alpha detector was developed and tested. The alpha detector consists of a thin plastic scintillator, a position-sensitive photomultiplier tube, a position calculation circuit and a personal computer based data acquisition system. Because the thin plastic scintillator has high-detection efficiency for alpha particles while it has low-sensitivity for beta particles or gamma ray, the detector can selectively detect alpha particles with low background counts. The spatial resolution of the detector was approximately 3 mm FWHM. An autoradiographic images of plutonium distribution in the lung of an animal as well as an image of an uranium particle were successively obtained. Spatial and energy distribution of radon daughters could also be measured. We conclude that the developed position-sensitive alpha detector is useful for some applications such as plutonium detection or alpha autoradiography as well as distribution analysis of radon daughters.

  7. Sensitive, Selective Test For Hydrazines

    NASA Technical Reports Server (NTRS)

    Roundbehler, David; Macdonald, Stephen

    1993-01-01

    Derivatives of hydrazines formed, then subjected to gas chromatography and detected via chemiluminescence. In method of detecting and quantifying hydrazine vapors, vapors reacted with dinitro compound to enhance sensitivity and selectivity. Hydrazine (HZ), monomethyl hydrazine, (MMH), and unsymmetrical dimethylhydrazine (UDMH) analyzed quantitatively and qualitatively, either alone or in mixtures. Vapors collected and reacted with 2,4-dinitrobenzaldehyde, (DNB), making it possible to concentrate hydrazine in derivative form, thereby increasing sensitivity to low initial concentrations. Increases selectivity because only those constituents of sample reacting with DNB concentrated for analysis.

  8. Selective and sensitized spectrophotometric determination of trace amounts of Ni(II) ion using alpha-benzyl dioxime in surfactant media.

    PubMed

    Ghaedi, Mehrorang

    2007-02-01

    Highly sensitive and interference-free sensitized spectrophotometric method for the determination of Ni(II) ions is described. The method is based on the reaction between Ni(II) ion and benzyl dioxime in micellar media in the presence of sodium dodecyl sulfate (SDS). The absorbance is linear from 0.1 up to 25.0 microg mL-1 in aqueous solution with repeatability (RSD) of 1.0% at a concentration of 1 microg mL-1 and a detection limit of 0.12 ng mL-1 and molar absorption coefficient of 68,600L mol-1 cm-1. The influence of reaction variables including type and amount of surfactant, pH, and amount of ligand and complexation time and the effect of interfering ions are investigated. The proposed procedure was applied to the determination of trace amounts of Ni(II) ion in tap water, river water, chocolate and vegetable without separation or organic solvent extraction. PMID:16843047

  9. Selective sorting of alpha-granule proteins

    PubMed Central

    Italiano, J.E.; Battinelli, E. M.

    2010-01-01

    Summary One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. The majority of this vast array of secreted proteins is stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets. PMID:19630794

  10. Crystallographic variant selection in {alpha}-{beta} brass

    SciTech Connect

    Stanford, N.; Bate, P.S. . E-mail: pete.bate@man.ac.uk

    2005-02-01

    The transformation texture of {alpha}/{beta} brass with a diffusional Widmanstaetten {alpha} growth morphology has been investigated. Electron micrographs and electron backscattered diffraction was used to determine that the orientation relationship between the {beta} phase and the {alpha} associated with nucleation at {beta} grain boundaries was 44.3 deg <1 1 6>. Crystallographic variant selection was observed across those prior {beta}/{beta} grain boundaries, but this has little effect on the transformation texture due to the crystal symmetry. The effect of the crystallographic variant selection on texture is further weakened by nucleation of diffusional transformed {alpha} in the grain interior.

  11. Entrainment of Human Alpha Oscillations Selectively Enhances Visual Conjunction Search

    PubMed Central

    Müller, Notger G.; Vellage, Anne-Katrin; Heinze, Hans-Jochen; Zaehle, Tino

    2015-01-01

    The functional role of the alpha-rhythm which dominates the human electroencephalogram (EEG) is unclear. It has been related to visual processing, attentional selection and object coherence, respectively. Here we tested the interaction of alpha oscillations of the human brain with visual search tasks that differed in their attentional demands (pre-attentive vs. attentive) and also in the necessity to establish object coherence (conjunction vs. single feature). Between pre- and post-assessment elderly subjects received 20 min/d of repetitive transcranial alternating current stimulation (tACS) over the occipital cortex adjusted to their individual alpha frequency over five consecutive days. Compared to sham the entrained alpha oscillations led to a selective, set size independent improvement in the conjunction search task performance but not in the easy or in the hard feature search task. These findings suggest that cortical alpha oscillations play a specific role in establishing object coherence through suppression of distracting objects. PMID:26606255

  12. Entrainment of Human Alpha Oscillations Selectively Enhances Visual Conjunction Search.

    PubMed

    Müller, Notger G; Vellage, Anne-Katrin; Heinze, Hans-Jochen; Zaehle, Tino

    2015-01-01

    The functional role of the alpha-rhythm which dominates the human electroencephalogram (EEG) is unclear. It has been related to visual processing, attentional selection and object coherence, respectively. Here we tested the interaction of alpha oscillations of the human brain with visual search tasks that differed in their attentional demands (pre-attentive vs. attentive) and also in the necessity to establish object coherence (conjunction vs. single feature). Between pre- and post-assessment elderly subjects received 20 min/d of repetitive transcranial alternating current stimulation (tACS) over the occipital cortex adjusted to their individual alpha frequency over five consecutive days. Compared to sham the entrained alpha oscillations led to a selective, set size independent improvement in the conjunction search task performance but not in the easy or in the hard feature search task. These findings suggest that cortical alpha oscillations play a specific role in establishing object coherence through suppression of distracting objects. PMID:26606255

  13. Object-based attentional selection modulates anticipatory alpha oscillations.

    PubMed

    Knakker, Balázs; Weiss, Béla; Vidnyánszky, Zoltán

    2014-01-01

    Visual cortical alpha oscillations are involved in attentional gating of incoming visual information. It has been shown that spatial and feature-based attentional selection result in increased alpha oscillations over the cortical regions representing sensory input originating from the unattended visual field and task-irrelevant visual features, respectively. However, whether attentional gating in the case of object based selection is also associated with alpha oscillations has not been investigated before. Here we measured anticipatory electroencephalography (EEG) alpha oscillations while participants were cued to attend to foveal face or word stimuli, the processing of which is known to have right and left hemispheric lateralization, respectively. The results revealed that in the case of simultaneously displayed, overlapping face and word stimuli, attending to the words led to increased power of parieto-occipital alpha oscillations over the right hemisphere as compared to when faces were attended. This object category-specific modulation of the hemispheric lateralization of anticipatory alpha oscillations was maintained during sustained attentional selection of sequentially presented face and word stimuli. These results imply that in the case of object-based attentional selection-similarly to spatial and feature-based attention-gating of visual information processing might involve visual cortical alpha oscillations. PMID:25628554

  14. [Alpha ERD and human visual selective attention].

    PubMed

    Ermachenko, N S; Ermachenko, A A; Latanov, A V

    2011-01-01

    We compared the alpha band EEG depression (event-related desynchnization, ERD) level in two tasks, involving activation of different attentional processes: visual search for a deviant relevant stimulus among many similar ones and visual oddball. Control data for the visual search task consisted of simple viewing of several stimuli being of the same shape as the relevant stimulus in the search trials. Gaze position was verified by eye tracking method. We interpreted alpha band ERD as a correlate of activation of attentional processes. Fixating the target in visual search task caused a significantly larger ERD than fixating the same stimuli in control trials over all leads. We suppose this to be related with task and visual environment complexities. The frontal ERD domination may indicate attentional control over voluntary movements execution (top-down attention). The caudal ERD may be related with updating of visual information as a result of search process (bottom-up attention). Both relevant and irrelevant stimuli in the oddball task also induced alpha band ERD, but it was larger in response to relevant one and reached maximum level over occipital leads. Domination of caudal ERD in oddball task is supposed to indicate bottom-up attention processes. PMID:22332425

  15. Michrochannel plate for position sensitive alpha particle detection

    SciTech Connect

    Paul Hurley and James Tinsley

    2007-08-31

    This paper will describe the use of a microchannel plate (MCP) as the associated particle detector on a sealed tube neutron generator. The generator produces neutrons and associated alpha particles for use as a probe to locate and identify hidden explosives in associated particle imaging (API). The MCP measures the position in two dimensions and precise timing of the incident alpha particle, information which is then used to calculate the emission time and direction of the corresponding neutron. The MCP replaces the position-sensitive photomultipler tube (PSPMT) which, until recently, had been the only detector available for measuring position and timing for alpha particles in neutron generator applications. Where the PSPMT uses charge division for generating position information, a process that requires a first order correction to each pulse, the MCP uses delay-line timing, which requires no correction. The result is a device with an order of magnitude improvement in both position resolution and timing compared to the PSPMT. Hardware and software development and the measurements made to characterize the MCP for API applications are described.

  16. Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells.

    PubMed

    Spada, Clayton S; Krauss, Achim H-P; Woodward, David F; Chen, June; Protzman, Charles E; Nieves, Amelia L; Wheeler, Larry A; Scott, David F; Sachs, George

    2005-01-01

    Bimatoprost is a synthetic analog of prostaglandin F(2 alpha) ethanolamide (prostamide F(2 alpha)), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F(2 alpha) carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F(2 alpha), fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists. Constant superfusion conditions obviated effective conversion of bimatoprost. Serial challenge with 100 nM bimatoprost and prostaglandin F(2 alpha) consistently evoked responses in different cells within the same tissue preparation, whereas prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) elicited signaling responses in the same cells. Bimatoprost-sensitive cells were consistently re-stimulated with bimatoprost only, and prostaglandin F(2 alpha) sensitive cells could only be re-stimulated with prostaglandin F(2 alpha). The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F(2 alpha), along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandin F(2 alpha) and bimatoprost. Further, prostaglandin F(2 alpha) but not bimatoprost potently stimulated calcium signaling in isolated human embryonic kidney cells stably transfected with the feline- and human-prostaglandin F(2 alpha) FP-receptor and in human dermal fibroblast cells, and only prostaglandin F(2 alpha) competed with radioligand binding in HEK-feFP cells. These studies provide further evidence for the existence of a bimatoprost-sensitive receptor that is distinct from

  17. Method for characterizing the upset response of CMOS circuits using alpha-particle sensitive test circuits

    NASA Technical Reports Server (NTRS)

    Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor); Nixon, Robert H. (Inventor); Soli, George A. (Inventor)

    1995-01-01

    A method for predicting the SEU susceptibility of a standard-cell D-latch using an alpha-particle sensitive SRAM, SPICE critical charge simulation results, and alpha-particle interaction physics. A technique utilizing test structures to quickly and inexpensively characterize the SEU sensitivity of standard cell latches intended for use in a space environment. This bench-level approach utilizes alpha particles to induce upsets in a low LET sensitive 4-k bit test SRAM. This SRAM consists of cells that employ an offset voltage to adjust their upset sensitivity and an enlarged sensitive drain junction to enhance the cell's upset rate.

  18. Sensitivity of alpha band ERD to individual differences in cognition.

    PubMed

    Neubauer, Aljoscha C; Fink, Andreas; Grabner, Roland H

    2006-01-01

    According to the neural efficiency hypothesis, brighter individuals might be characterized by lower and topographically more differentiated brain activation than less intelligent individuals, presumably reflecting a more specialized recruitment of task-related areas. The findings of several studies analyzing the event-related desynchronization (ERD) in the (upper) alpha frequency band have corroborated and elaborated the original neural efficiency hypothesis. In this chapter, we review classical and recent findings and argue in favor of a more differentiated picture of this phenomenon, emphasizing the role of participants' sex, task complexity, and material specificity, as well as the importance to select an adequate external criterion (intelligence measure). Also, recent ERD findings related to emotional intelligence and creativity as well as recent studies focusing on practice, learning ability, and expertise are presented, which point to the need of a broader neurophysiological ability concept. The reviewed findings point at the high suitability of the ERD method to uncover consistent and stable individual differences in people's brain activation patterns when engaged in performing cognitively demanding tasks. PMID:17071230

  19. The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist.

    PubMed Central

    Halliday, C. A.; Jones, B. J.; Skingle, M.; Walsh, D. M.; Wise, H.; Tyers, M. B.

    1991-01-01

    1. This paper describes the pharmacology of the novel alpha 2-adrenoceptor antagonist fluparoxan (GR 50360) which is currently being studied clinically as a potential anti-depressant. Idazoxan and yohimbine were included in many studies for comparison. 2. In the rat isolated, field-stimulated vas deferens and the guinea-pig isolated, field-stimulated ileum preparations, fluparoxan was a reversible competitive antagonist of the inhibitory responses to the alpha 2-adrenoceptor agonist UK-14304 with pKB values of 7.87 and 7.89 respectively. In the rat isolated anococcygeus muscle, fluparoxan was a much weaker competitive antagonist of the contractile response to the alpha 1-adrenoceptor agonist phenylephrine with a pKB of 4.45 giving an alpha 2: alpha 1-adrenoceptor selectivity ratio of greater than 2500. 3. In the conscious mouse, fluparoxan (0.2-3.0 mg kg-1) was effective by the oral route and of similar potency to idazoxan in preventing clonidine-induced hypothermia and antinociception. In the rat, UK-14304-induced hypothermia (ED50 = 1.4 mg kg-1, p.o. or 0.5 mg kg-1, i.v.) and rotarod impairment (ED50 = 1.1 mg kg-1 p.o. or 1.3 mg kg-1, i.v.) were antagonized by fluparoxan. Fluparoxan, 0.67-6 mg kg-1, p.o., also prevented UK-14304-induced sedation and bradycardia in the dog. 4. In specificity studies fluparoxan had low or no affinity for a wide range of neurotransmitter receptor sites at concentrations up to at least 1 x 10(-5) M. It displayed weak affinity for 5-HT1A (pIC50 = 5.9) and 5-HT1B (pKi = 5.5) binding sites in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1677298

  20. Reduced alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes as a modulator of fasting and postprandial triglyceride levels in men.

    PubMed

    Imbeault, P; Couillard, C; Tremblay, A; Després, J P; Mauriège, P

    2000-09-01

    This study examined the postprandial lipemia of two groups of men displaying similar age, body weight, and regional fat distribution, but characterized by either low (n = 11) or high (n = 15) alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes. In addition to fat cell lipolysis, adipose tissue lipoprotein lipase (AT-LPL) as well as postheparin plasma LPL activities were measured in the fasting state. Fasting AT-LPL and PH-LPL activities were similar in both groups. Maximal adipose cell lipolysis induced by isoproterenol (beta-adrenergic agonist) as well as the beta-adrenergic sensitivity did not differ between both groups of men. The selective alpha(2)-adrenergic agonist UK-14304 promoted a similar antilipolytic response in subcutaneous abdominal adipocytes from both groups. However, the alpha(2)-adrenergic sensitivity, defined as the dose of UK-14304 that produced half-maximal inhibition of lipolysis (IC(50)), was significantly different between groups (P < 0.0001). Men with low versus high subcutaneous abdominal fat cell alpha(2)-adrenergic sensitivity showed higher fasting TG levels. In the whole group, a positive relationship was observed between log-transformed IC(50) UK-14304 values of subcutaneous adipocytes and fasting TG levels (r = 0.39, P < 0.05), suggesting that a low abdominal adipose cell alpha(2)-adrenergic sensitivity is associated with high TG levels. After the consumption of a high-fat meal, subjects with low subcutaneous abdominal adipose cell alpha(2)-adrenergic sensitivity showed higher TG levels in total, medium, and small triglyceride-rich lipoprotein (TRL) fractions at 0- to 6-h time points than men with high adipocyte alpha(2)-adrenergic sensitivity (P values ranging from 0.01 to 0.05). Stepwise regression analysis showed that the fasting TG concentration was the only variable retained as a significant predictor of the area under the curve of TG levels in total TRL fractions (73% of variance) among independent variables

  1. Sensitive sandwich electrochemical immunosensor for alpha fetoprotein based on prussian blue modified hydroxyapatite.

    PubMed

    Dai, Yuxue; Cai, Yanyan; Zhao, Yanfang; Wu, Dan; Liu, Bao; Li, Ru; Yang, Minghui; Wei, Qin; Du, Bin; Li, He

    2011-10-15

    A sandwich electrochemical immunosensor for the sensitive determination of alpha fetoprotein (AFP) has been fabricated. Prussian blue modified hydroxyapatite (PB@HAP) was firstly prepared and used as electrochemical label due to the wonderful conductivity and good biocompatibility of HAP. The results proved that the immunosensor fabricated using the label based on PB@HAP loaded with horse radish peroxidase (HRP) and secondary anti-AFP antibody (Ab(2)) (PB@HAP-HRP-Ab(2)) had high sensitivity, and the sensitivity of the label PB@HAP-HRP-Ab(2) was much higher than labels of PB@HAP-Ab(2), PB-HRP-Ab(2) and HAP-HRP-Ab(2). The mixture of graphene sheet (GS) and thionine (TH) was not only used to immobilize anti-AFP antibody (Ab(1)) but also took part in the signal amplification. The amperometric signal increased linearly with AFP concentration in the range of 0.02-8 ng/mL with a low detection limit of 9 pg/mL. The immunosensor had the advantages of high sensitivity, good selectivity and good stability, and was applied to the analysis of AFP in serum sample with satisfactory results. Due to the low-cost and easy synthesis of PB@HAP, the screen-printed electrodes could be used instead of the bare glass carbon electrode in order to achieve mass production. In addition, it had potential application in the detection of other tumor markers. PMID:21802277

  2. Structural determinants of the alpha2 adrenoceptor subtype selectivity

    PubMed Central

    Ostopovici-Halip, Liliana; Curpăn, Ramona; Mracec, Maria; Bologa, Cristian G.

    2012-01-01

    Alpha2-adrenergic receptor (α2-AR) subtypes, acting mainly on the central nervous and cardiovascular systems, represent important targets for drug design, confirmed by the high number of studies published so far. Presently, only few α2-AR subtype selective compounds are known. Using homology modeling and ligand docking, the present study analyzes the similarities and differences between binding sites, and between extracellular loops of the three subtypes of α2-AR. Several α2-AR subtype selective ligands were docked in the active sites of the three α2-AR subtypes, key interactions between ligands and receptors were mapped, and the predicted results were compared to experimental results. Binding site analysis reveals a strong identity between important amino acid residues in each receptor, the very few differences being the key towards modulating selectivity of α2-AR ligands. The observed differences between binding site residues provide an excellent starting point for virtual screening of chemical databases in order to identify potentially selective ligands for α2-ARs. PMID:21602069

  3. Extended sensitivity for the calcium selective electrode.

    PubMed

    Morton, R W; Chung, J K; Miller, J L; Charlton, J P; Fager, R S

    1986-09-01

    Sensitivity of calcium-selective electrodes heretofore has been limited to calcium concentrations above 10(-8) M in the absence of competing ions. We describe the use of calcium buffers to stabilize the free calcium in the reference electrode. Electrode calibration is linear to 10(-8) M and is curvilinear to 10(-11) M in the presence of 0.1 M ionic strength. Selectivity with respect to competing cations, magnesium, potassium, sodium, and hydrogen is preserved. Electrode response time is less than 2 s for small changes in calcium activity. Response range is linear over 9 log units of calcium activity. Potential-time stability is less than 10 mV/h at saturation currents. Although the silver-silver chloride terminals are photosensitive throughout the visible and near-ultraviolet regions, housing the reference and indifferent in opaque barrels avoids false photovoltaic response. PMID:3777438

  4. Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy

    PubMed Central

    Hsieh, Yao-Te; Gang, Eun Ji; Geng, Huimin; Park, Eugene; Huantes, Sandra; Chudziak, Doreen; Dauber, Katrin; Schaefer, Paul; Scharman, Carlton; Shimada, Hiroyuki; Shojaee, Seyedmehdi; Klemm, Lars; Parameswaran, Reshmi; Loh, Mignon; Kang, Eun-Suk; Koo, Hong Hoe; Hofmann, Wolf-Karsten; Andrade, Jacob; Crooks, Gay M.; Willman, Cheryl L.; Müschen, Markus; Papayannopoulou, Thalia; Heisterkamp, Nora; Bönig, Halvard

    2013-01-01

    Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to gene expression analyses from 207 children with minimal residual disease, is highly associated with poorest outcome. We tested whether interference with alpha4-mediated stromal adhesion might be a new ALL treatment. Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210+] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL). Conditional deletion of alpha4 sensitized leukemia cell to nilotinib. Adhesion of primary pre-B ALL cells was alpha4-dependent; alpha4 blockade sensitized primary ALL cells toward chemotherapy. Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL. PMID:23319569

  5. Sensitivities of five alpha continuous air monitors for detection of airborne sup 239 Pu

    SciTech Connect

    McIsaac, C.V.; Amaro, C.R.

    1992-07-01

    Results of measurements of the sensitivities of five alpha continuous air monitors (CAMs) for detection of airborne {sup 239}Pu are presented. Four commercially available alpha CAMs (Kurz model 8311, Merlin Gerin Edgar, RADeCO model 452, and Victoreen model 758) and a prototype alpha CAM currently in use at Argonne National Laboratory- West (ANL-W) were tested sampling natural ambient air and laboratory-generated atmospheres laden with either blank dust or dust containing nCi/g concentrations of {sup 239}Pu. Cumulative alpha spectra were stored at 30 or 60 minute intervals during each sampling and were subsequently analyzed using three different commonly used alpha spectrum analysis algorithms. The effect of airborne dust concentration and sample filter porosity on detector resolution and sensitivity for airborne {sup 239}Pu are described.

  6. Sensitivities of five alpha continuous air monitors for detection of airborne {sup 239}Pu

    SciTech Connect

    McIsaac, C.V.; Amaro, C.R.

    1992-07-01

    Results of measurements of the sensitivities of five alpha continuous air monitors (CAMs) for detection of airborne {sup 239}Pu are presented. Four commercially available alpha CAMs (Kurz model 8311, Merlin Gerin Edgar, RADeCO model 452, and Victoreen model 758) and a prototype alpha CAM currently in use at Argonne National Laboratory- West (ANL-W) were tested sampling natural ambient air and laboratory-generated atmospheres laden with either blank dust or dust containing nCi/g concentrations of {sup 239}Pu. Cumulative alpha spectra were stored at 30 or 60 minute intervals during each sampling and were subsequently analyzed using three different commonly used alpha spectrum analysis algorithms. The effect of airborne dust concentration and sample filter porosity on detector resolution and sensitivity for airborne {sup 239}Pu are described.

  7. 5-Amino-pyrazoles as potent and selective p38[alpha] inhibitors

    SciTech Connect

    Das, Jagabandhu; Moquin, Robert V.; Dyckman, Alaric J.; Li, Tianle; Pitt, Sidney; Zhang, Rosemary; Shen, Ding Ren; McIntyre, Kim W.; Gillooly, Kathleen; Doweyko, Arthur M.; Newitt, John A.; Sack, John S.; Zhang, Hongjian; Kiefer, Susan E.; Kish, Kevin; McKinnon, Murray; Barrish, Joel C.; Dodd, John H.; Schieven, Gary L.; Leftheris, Katerina

    2012-02-07

    The synthesis and structure-activity relationships (SAR) of p38{alpha} MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38{alpha} MAP kinase with excellent cellular potency toward the inhibition of TNF{alpha} production. Compound 2j was highly efficacious in vivo in inhibiting TNF{alpha} production in an acute murine model of TNF{alpha} production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38{alpha} is also disclosed.

  8. Locus assignment of alpha-globin structural mutations by hybrid-selected translation.

    PubMed Central

    Liebhaber, S A; Cash, F E

    1985-01-01

    The two human alpha-globin genes, alpha 1 and alpha 2 located 3.4 kilobases apart on chromosome 16, encode identical alpha-globin proteins. A mutation in either gene could result in a structural hemoglobinopathy. It has only recently become possible to assign an alpha-chain mutant to one of these two loci by using recombinant DNA technology. While definitive, this approach has necessitated the cloning and sequencing of the specific gene in question. We present an alternative approach which results in rapid and definitive assignment of an alpha-globin mutation to its encoding genetic locus. This approach uses the technique of hybrid-selected translation. Reticulocyte RNA from individuals with alpha-globin mutations can be fractionated into beta-, alpha 9 (total)-, alpha 1-, and alpha 2-globin mRNA by selective hybridization of each mRNA species to its respective complementary DNA (cDNA) immobilized on nitrocellulose paper. Each mRNA purified in this way can be translated in vitro, and the mRNA species (and hence gene locus) encoding the globin mutant can then be directly identified by gel analysis of the radiolabeled translation products. This procedure can be used to identify globin mutants as alpha or beta and to localize alpha-globin mutants to the alpha 1 or alpha 2 gene. We have used this technique to localize the two alpha-globin mutants, alpha 125Pro (Hb Quong Sze) and alpha 47HIS (Hb Hasharon), to the alpha 2 locus. This approach could potentially be expanded to serve as an alternative to peptide analysis for the initial characterization of all globin structural mutants. Images PMID:2981252

  9. Exposure-sensitization relationship for alpha-amylase allergens in the baking industry.

    PubMed

    Houba, R; Heederik, D J; Doekes, G; van Run, P E

    1996-07-01

    Fungal alpha-amylase is an important occupational allergen in the bakery industry. Epidemiologic studies focusing on the relationship between alpha-amylase allergen exposure and work-related respiratory allergy, however, have not been reported yet. In this cross-sectional study, sensitization to occupational allergens and work-related symptoms were studied in 178 bakery workers and related to allergen exposure. Alpha-amylase allergen concentrations were measured in personal dust samples, using a sandwich enzyme immunoassay. All workers were categorized into groups on the basis of their job histories and the alpha-amylase exposure levels of their job titles. Of all workers 25% had one or more work-related symptoms. As much as 9% of the bakery workers showed a positive skin prick test reaction to fungal amylase, and in 8% amylase-specific IgE was demonstrated. Alpha-amylase exposure and atopy appeared to be the most important determinants of skin sensitization, with prevalence ratios for atopy of 20.8 (95% CI, 2.74 to 158) and for medium and high alpha-amylase exposure groups of 8.6 (95% CI, 1.01 to 74) and 15.9 (95% CI, 1.95 to 129), respectively. Furthermore, a positive association was found between positive skin prick tests to alpha-amylase and work-related respiratory symptoms. In conclusion, this study has shown that there is a strong and positive relationship between alpha-amylase allergen exposure levels in bakeries and specific sensitization in bakery workers. PMID:8680668

  10. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    PubMed

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  11. Subtype selective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia.

    PubMed

    Forray; Noble

    1999-12-01

    Benign prostatic hyperplasia (BPH) is highly prevalent in the male population beyond the age of 60. Impairment of urinary flow due to prostate enlargement gives rise to symptoms of 'prostatism' that have a detrimental impact on the quality of life. The current trend in the management of symptomatic BPH favours pharmacotherapy as a first line option, while the number of surgical procedures being performed has experienced a steady decline during the last ten years. Among the pharmacological treatments, the use of alpha1-adrenoceptor blockers has demonstrated to be an effective treatment option for BPH. These agents reduce the adrenergic tone to the prostate and increase urinary flow, with a concomitant reduction of lower urinary tract symptoms. The alpha1-blockers currently approved include compounds such as alfuzosin, terazosin and doxazosin, originally developed for the treatment of hypertension, and more recently tamsulosin, an alpha1-subtype selective drug. The blockade of alpha1-adrenoceptors present in vascular smooth muscle is largely responsible for the most prominent side effects of current drugs, which can be severe and require patients dose titration. The limitation imposed by side effects naturally raises the possibility that complete blockade of prostatic alpha1 receptors is not attained at the maximum tolerated dose. The extensive efforts by the pharmaceutical industry towards the development of uroselective alpha1-blockers, is the subject of this review. Advances in the molecular cloning of genes encoding three alpha1-adrenoceptors led to the identification of the alpha1A-subtype as the predominant receptor responsible for the contraction of prostate smooth muscle. In preclinical animal models, selective alpha1A-antagonists have consistently been found to have minimal cardiovascular effects, thus providing a pharmacological rationale for uroselectivity. It has also become apparent, however, that uroselectivity can emerge in a poorly understood manner

  12. [Alpha1-adrenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213)].

    PubMed

    Tatemichi, Satoshi; Kobayashi, Kumi; Maezawa, Ayaka; Kobayashi, Mamoru; Yamazaki, Yoshinobu; Shibata, Nobuo

    2006-03-01

    The selectivity of silodosin (KMD-3213), an antagonist of alpha(1)-adrenoceptor (AR), to the subtypes (alpha(1A)-, alpha(1B)- and alpha(1D)-ARs) was examined by a receptor-binding study and a functional pharmacological study, and we compared its subtype-selectivity with those of other alpha(1)-AR antagonists. In the receptor-binding study, a replacement experiment using [(3)H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human alpha(1)-AR subtypes was expressed. In the functional pharmacological study, the following isolated tissues were used as representative organs with high distribution densities of alpha(1)-AR subtypes (alpha(1A)-AR: rabbit prostate, urethra and bladder trigone; alpha(1B)-AR: rat spleen; alpha(1D)-AR: rat thoracic aorta). Using the Magnus method, we studied the inhibitory effect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. Silodosin showed higher selectivity for the alpha(1A)-AR subtype than tamsulosin hydrochloride, naftopidil or prazosin hydrochloride (affinity was highest for tamsulosin hydrochloride, followed by silodosin, prazosin hydrochloride and naftopidil in that order). Silodosin strongly antagonized noradrenaline-induced contractions in rabbit lower urinary tract tissues (including prostate, urethra and bladder trigone, with pA(2) or pKb values of 9.60, 8.71 and 9.35, respectively). On the other hand, the pA(2) values for antagonism of noradrenaline-induced contractions in rat isolated spleen and rat isolated thoracic aorta were 7.15 and 7.88, respectively. Selectivity for lower urinary tract was higher for silodosin than for the other alpha(1)-AR antagonists. Our data suggest that silodosin has a high selectivity for the alpha(1A)-AR subtype and for the lower urinary tract. PMID:16518085

  13. alpha 2-adrenoreceptors profile modulation. 2. Biphenyline analogues as tools for selective activation of the alpha 2C-subtype.

    PubMed

    Gentili, Francesco; Ghelfi, Francesca; Giannella, Mario; Piergentili, Alessandro; Pigini, Maria; Quaglia, Wilma; Vesprini, Cristian; Crassous, Pierre-Antoine; Paris, Hervé; Carrieri, Antonio

    2004-12-01

    A series of derivatives structurally related to biphenyline (3) was designed with the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results obtained demonstrated that the presence of a correctly oriented function with positive electronic effect (+sigma) in portion X of the ligands is an important factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and 19). Homology modeling and docking studies support experimental data and highlight the crucial role for the hydrogen bond between the pyridine nitrogen in position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in the alpha(2C)-subtype, only. PMID:15566287

  14. Selective flow path alpha particle detector and method of use

    DOEpatents

    Orr, Christopher Henry; Luff, Craig Janson; Dockray, Thomas; Macarthur, Duncan Whittemore

    2002-01-01

    A method and apparatus for monitoring alpha contamination are provided in which ions generated in the air surrounding the item, by the passage of alpha particles, are moved to a distant detector location. The parts of the item from which ions are withdrawn can be controlled by restricting the air flow over different portions of the apparatus. In this way, detection of internal and external surfaces separately, for instance, can be provided. The apparatus and method are particularly suited for use in undertaking alpha contamination measurements during the commissioning operations.

  15. Sensitive radioimmunoassay for detection of antibodies to recombinant human interferon-alpha A

    SciTech Connect

    Palleroni, A.V.; Trown, P.W.

    1986-12-01

    A radioimmunoassay (RIA) for the detection of antibodies to recombinant human leukocyte interferon A (rHuIFN-alpha A) in human serum has been developed and validated against the standard antiviral neutralization bioassay (ANB). The assay measures the binding of /sup 125/I-labeled rHuIFN-alpha A to immunoglobulins in serum. Aliquots of patients' sera are incubated with /sup 125/I-rHuIFN-alpha A and the complexes formed between antibodies in the sera and the /sup 125/I-rHuIFN-alpha A are precipitated with goat anti-human IgG serum. The radioactivity in the immune precipitate is a measure of the quantity of antibody (if present) in the serum. The sensitivity of this RIA is 5 ng of IgG/ml of serum.

  16. Selective depression of motion sensitivity during saccades.

    PubMed Central

    Burr, D C; Holt, J; Johnstone, J R; Ross, J

    1982-01-01

    1. Horizontal gratings flashed for 20 ms were used to compare visual contrast sensitivity during horizontal saccades with sensitivity during normal vision, at three luminance levels, 4 X 10(2), 4 X 10(-2), and 4 X 10(-4) cd/m2. 2. Greatest sensitivity loss during saccades was found at low spatial frequencies. There is little or no loss at high spatial frequencies. 3. As luminance level is decreased there is a decrease in the spatial frequency below which saccadic sensitivity loss occurs. This shift in spatial frequency with luminance level, considered in conjunction with measurements of stationary and drifting gratings, indicates the functional involvement of movement sensitive mechanisms in saccadic sensitivity loss. 4. At the two lower luminance levels (4 X 10(-2) and 4 X 10(-4) cd/m2) sensitivity during saccades is greater than normal at high spatial frequencies. This enhancement of sensitivity was confirmed by forced choice measurements. 5. It was also shown that sensitivity to abrupt changes in the trajectory of moving gratings is lowered during saccades. 6. It is concluded that mechanisms sensitive to movement and transients are damped during saccades, so preventing perception of image motion during saccades and thereby preserving visual stability. PMID:7182461

  17. Alpha(1) adrenoceptor subtype selectivity. 3D-QSAR models for a new class of alpha(1) adrenoceptor antagonists derived from the novel antipsychotic sertindole.

    PubMed

    Balle, Thomas; Andersen, Kim; Søby, Karina Krøjer; Liljefors, Tommy

    2003-06-01

    Receptor-binding affinities for the alpha(1) adrenoceptor subtypes alpha(1a), alpha(1b) and alpha(1d) for a series of 39 alpha(1) adrenoceptor antagonists derived from the antipsychotic sertindole are reported. The SAR of the compounds with respect to affinity for the alpha(1a), alpha(1b) and alpha(1d) adrenoceptor subtypes as well as affinity obtained by an alpha(1) assay (rat brain membranes) were investigated using a 3D-QSAR approach based on the GRID/GOLPE methodology. Good statistics (r(2)=0.91-0.96; q(2)=0.65-0.73) were obtained with the combination of the water (OH2) and methyl (C3) probes. The combination of steric repulsion and electrostatic attractions explain the affinities of the included molecules. The adrenergic alpha(1a) receptor seems to be more tolerant to large substituents in the area between the indole 5- and 6-positions compared to the adrenergic alpha(1b) and alpha(1d) receptor subtypes. There seems to be minor differences in the position of areas in the alpha(1b) receptor compared to alpha(1a) and alpha(1d) receptors where electrostatic interaction between the molecules and the receptor (OH2 probe) contribute to increased affinity. These observations may be used in the design of new subtype selective compounds. In addition, the model based on biological data from an alpha(1) assay (rat brain membranes) resembles the model for the alpha(1b) adrenoceptor subtype. PMID:12676239

  18. Cytochalasin B triggers a novel pertussis toxin sensitive pathway in TNF-alpha primed neutrophils

    PubMed Central

    Bylund, Johan; Pellmé, Sara; Fu, Huamei; Mellqvist, Ulf-Henrik; Hellstrand, Kristoffer; Karlsson, Anna; Dahlgren, Claes

    2004-01-01

    Background Cytochalasin B does not directly activate the oxygen-radical-producing NADPH oxidase activity of neutrophils but transfers desensitized G-protein coupled receptors (GPCR) into an active signaling state by uncoupling GCPR from the cytoskeleton. The receptor uncoupling results in respiratory burst activity when signals generated by reactivated formyl peptide receptors trigger the NADPH-oxidase to produce superoxide anions. Results Tumor necrosis factor alpha (TNF-alpha) primes neutrophils for subsequent activation by cytochalasin B. Pretreatment with TNF-alpha induced mobilization of receptor-storing neutrophil organelles, suggesting that receptor up-regulation significantly contributes to the response, but the receptor mobilization was not sufficient for induction of the cytochalasin B sensitive state. The TNF-alpha primed state resembled that of the desensitized non-signaling state of agonist-occupied neutrophil formyl peptide receptors. The fact that the TNF-alpha primed, cytochalasin B-triggered activation process was pertussis toxin sensitive suggests that the activation process involves a GPCR. Based on desensitization experiments the unidentified receptor was found to be distinct from the C5a receptor as well as the formyl peptide receptor family members FPR and FPRL1. Based on the fact the occupied and desensitized receptors for interleukin-8 and platelet activating factor could not be reactivated by cytochalasin B, also these could be excluded as receptor candidates involved in the TNF-alpha primed state. Conclusions The TNF-alpha-induced priming signals could possibly trigger a release of an endogenous GPCR-agonist, amplifying the response to the receptor-uncoupling effect of cytochalasin B. However, no such substance could be found, suggesting that TNF-alpha can transfer G-protein coupled receptors to a signaling state independently of agonist binding. PMID:15157285

  19. The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis

    SciTech Connect

    Wang, Yisong

    2005-10-01

    Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-{alpha} and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-{alpha}-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-{alpha}-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV related diseases with IFN.

  20. Molecularly imprinted solid phase extraction for the selective HPLC determination of alpha-tocopherol in bay leaves.

    PubMed

    Puoci, F; Cirillo, G; Curcio, M; Iemma, F; Spizzirri, U G; Picci, N

    2007-06-19

    A new sorbent for molecularly imprinted solid phase extraction (MISPE) was synthesized to extract and purify alpha-tocopherol (alpha-TP) from vegetable sources. Molecularly imprinted polymers (MIP) were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent using a photo-polymerization procedure. A thermo-polymerization was also performed but no imprinting effect in the resulting materials was raised. The proposed MISPE protocol could overcome the drawback of traditional detection methods, which require pre-treatments of the samples. The possibility to obtain the selective recognition of alpha-TP from natural samples in aqueous mixtures represents one of the main advantages of our materials. Our procedure involves the direct HPLC injection of eluate without any treatment and above all the use of no toxic and biocompatible organic solvents. After the evaluation of the selectivity of the alpha-TP imprinted polymers, the performance of these materials as solid phase extraction (SPE) sorbents was investigated. Our MISPE-HPLC procedure has a high sensitivity, LOD and LOQ were 3.49x10(-7) and 1.16x10(-6) mol L(-1), respectively, as well as good precision (intraday precision below 3.3% and interday precisions below 6.5%) and recovery (60%). Thus, it can be successfully used for the purification of alpha-TP from bay leaves. PMID:17543603

  1. Selective presynaptic insectotoxin (alpha-latroinsectotoxin) isolated from black widow spider venom.

    PubMed

    Magazanik, L G; Fedorova, I M; Kovalevskaya, G I; Pashkov, V N; Bulgakov, O V; Grishin, E V

    1992-01-01

    A homogenous protein of 120,000 mol. wt isolated from black widow spider (Lactrodectus mactans tredecimguttatus) venom and referred to as alpha-latroinsectotoxin was highly potent (4 nM) in the induction of an increase of the frequency of miniature excitatory postsynaptic potentials in blowfly (Calliphora vicina) larvae neuromuscular preparations. In the frog nerve ending, however, even 50 nM alpha-latroinsectotoxin failed to affect transmitter release. Pretreatment of insect preparations with alpha-latrotoxin or frog preparations with alpha-latroinsectotoxin did not prevent the specific effect of consequent applications of alpha-latroinsectotoxin (insect) and alpha-latrotoxin (frog), respectively. The binding of labelled [125I]alpha-latroinsectotoxin to insect and [125I]alpha-latrotoxin to bovine membrane preparations was saturable and highly specific. The presynaptic effect, but not the binding of alpha-latroinsectotoxin, was dependent on the presence of divalent cations in the external medium. Mg2+ could readily substitute for Ca2+ and increase of transmitter release induced by alpha-latroinsectotoxin also occurred in Ca(2+)-free solutions. Pretreatment of preparations with 300 micrograms/ml concanavalin A completely abolished both the presynaptic effect of alpha-latroinsectotoxin and its binding to insect membrane preparations. Thus, the phenomenology of alpha-latroinsectotoxin action on insects resembles in general that described for the action of alpha-latrotoxin on vertebrates. The selectivity of alpha-latrotoxin and alpha-latroinsectotoxin seems to be due to differences in the structure of neurotoxin receptors in nerve endings of vertebrates and insects, although the mode of presynaptic action has a great deal in common. PMID:1594101

  2. Desensitizing and non-desensitizing subtypes of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors in cockroach neurons.

    PubMed

    Salgado, Vincent L; Saar, Raimund

    2004-10-01

    Two alpha-bungarotoxin-sensitive nicotinic receptor subtypes in cockroach neurons are identified as desensitizing (nAChD), selectively inhibitable with 100 nM imidacloprid, and non-desensitizing (nAChN), selectively inhibitable with 100 pM methyllycaconitine. Although the desensitization rate of nAChD receptors is highly variable, pharmacology is largely independent of desensitization rate. Because desensitized states tightly bind agonists, nAChD receptors are potently inhibited by neonicotinoids and specifically measured in radiolabeled imidacloprid binding assays. However, they are not usually detected in binding assays with radiolabeled alpha-bungarotoxin, which has a Kd for the resting state of 21 nM, but binds poorly to desensitized states often present in binding assays. In contrast, nAChN receptors are specifically measured in binding assays with radiolabeled alpha-bungarotoxin, which binds them with a Kd of 1.3 nM. nAChN receptors are activated by neonicotinoids at micromolar concentrations, and allosterically by spinosyn A, with an EC50 of 27 nM. Spinosyn A weakly antagonizes nAChD receptors -23% at 10 microM. The roles of the two nAChR subtypes in insecticide poisoning are discussed. PMID:15518655

  3. Developmental changes in the role of a pertussis toxin sensitive guanine nucleotide binding protein in the rat cardiac alpha sub 1 -adrenergic system

    SciTech Connect

    Han, H.M.

    1989-01-01

    During development, the cardiac alpha{sub 1}-adrenergic chronotropic response changes from positive in the neonate to negative in the adult. This thesis examined the possibility of a developmental change in coupling of a PT-sensitive G-protein to the alpha{sub 1}-adrenergic receptor. Radioligand binding experiments performed with the iodinated alpha{sub 1}-selective radioligand ({sup 125}I)-I-2-({beta}-(4-hydroxphenyl)ethylaminomethyl)tetralone (({sup 125}I)-IBE 2254) demonstrated that the alpha{sub 1}-adrenergic receptor is coupled to a G-protein in both neonatal and adult rat hearts. However, in the neonate the alpha{sub 1}-adrenergic receptor is coupled to a PT-insensitive G-protein, whereas in the adult the alpha{sub 1}-adrenergic receptor is coupled to both a PT-insensitive and a PT-sensitive G-protein. Consistent with the results from binding experiments, PT did not have any effect on the alpha{sub 1}-mediated positive chronotropic response in the neonate, whereas in the adult the alpha{sub 1}-mediated negative chronotropic response was completely converted to a positive one after PT-treatment. This thesis also examined the possibility of an alteration in coupling of the alpha{sub 1}-adrenergic receptor to its effector under certain circumstances such as high potassium (K{sup +}) depolarization in nerve-muscle (NM) co-cultures, a system which has been previously shown to be a convenient in vitro model to study the mature inhibitory alpha{sub 1}-response.

  4. Monochromatic wavelength dispersive x-ray fluorescence providing sensitive and selective detection of uranium

    SciTech Connect

    Havrilla, George J; Collins, Michael L; Montoya, Velma M; Chen, Zewu; Wei, Fuzhong

    2010-01-01

    Monochromatic wavelength dispersive X-ray fluorescence (MWDXRF) is a sensitive and selective method for elemental compositional analyses. The basis for this instrumental advance is the doubly curved crystal (DCC) optic. Previous work has demonstrated the feasibility of sensitive trace element detection for yttrium as a surrogate for curium in aqueous solutions. Additional measurements have demonstrated similar sensitivity in several different matrix environments which attests to the selectivity of the DCC optic as well as the capabilities of the MWDXRF concept. The objective of this effort is to develop an improved Pu characterization method for nuclear fuel reprocessing plants. The MWDXRF prototype instrument is the second step in a multi-year effort to achieve an improved Pu assay. This work will describe a prototype MWDXRF instrument designed for uranium detection and characterization. The prototype consists of an X-ray tube with a rhodium anode and a DCC excitation optic incorporated into the source. The DCC optic passes the RhK{alpha} line at 20.214 keV for monochromatic excitation of the sample. The source is capable of 50 W power at 50 kV and 1.0 mA operation. The x-ray emission from the sample is collected by a DCC optic set at the UL{alpha} line of 13.613 keV. The collection optic transmits the UL{alpha} x-rays to the silicon drift detector. The x-ray source, sample, collection optic and detector are all mounted on motion controlled stages for the critical alignment of these components. The sensitivity and selectivity of the instrument is obtained through the monochromatic excitation and the monochromatic detection. The prototype instrument performance has a demonstrated for sensitivity for uranium detection of around 2 ppm at the current state of development. Further improvement in sensitivity is expected with more detailed alignment.

  5. Glycosylation sites selectively interfere with alpha-toxin binding to the nicotinic acetylcholine receptor.

    PubMed

    Kreienkamp, H J; Sine, S M; Maeda, R K; Taylor, P

    1994-03-18

    Sequence analysis reveals unique features in the alpha-subunit of nicotinic acetylcholine receptors from the alpha-toxin-resistant cobra and mongoose. Included are N-linked glycosylation signals just amino-terminal to the Tyr190, Cys192-Cys193 region of the ligand binding domain, substitution of Trp187 and Phe189 by non-aromatic residues and alteration of the proline sequence Pro194-X-X-Pro197. Glycosylation signals were inserted into the toxin-sensitive mouse alpha-subunit by the mutations F189N and W187N/F189T. The F189N alpha-subunit, when transfected with beta, gamma and delta, showed a 140-fold loss of alpha-bungarotoxin affinity, whereas the W187N/F189T double mutation exhibited a divergence in alpha-toxin affinities at the two sites, one class showing a 600-fold and the other showing an 11-fold reduction. The W187N mutant and the double mutant F189N/S191A lacking the requisite glycosylation signals exhibited little alteration in affinity, as did the P194L and P197H mutations. The glycosylation sites had little or no influence on binding of toxins of intermediate (alpha-conotoxin, 1500 Da) or small mass (lophotoxin, 500 Da) and of the agonist, carbamylcholine. The two sites for the binding of alpha-conotoxin M1 have widely divergent dissociation constants of 2.1 and 14,800 nM. Expression of alpha/gamma- and alpha/delta-subunit pairs indicated that the high and low affinity sites are formed by the alpha/delta and alpha/gamma contacts, respectively. PMID:7907588

  6. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl(alpha1-3)galactosylation.

    PubMed

    Takeuchi, Y; Liong, S H; Bieniasz, P D; Jäger, U; Porter, C D; Friedman, T; McClure, M O; Weiss, R A

    1997-08-01

    Vesicular stomatitis virus, human immunodeficiency virus type 2, and human foamy virus, which were produced by cell lines expressing galactosyl(alpha1-3)galactosyl (alphaGal) sugars, were found to be less stable in human serum than those from alphaGal-negative cells, indicating that galactosyl(alpha1-3)galactosylation sensitizes these viruses as well as mammalian type C oncoviruses (Rother et al., J. Exp. Med. 182:1345-1355, 1995; Takeuchi et al., Nature (London) 379:85-88, 1996) to complement killing via natural anti-alphaGal antibodies. Thus, virus killing mediated by anti-alphaGal antibodies may play a role as a barrier to animal-to-human infection of various enveloped viruses. Virus vectors for human in vivo gene therapy based on the viruses mentioned above should be produced from alphaGal-negative cells. PMID:9223512

  7. Expression of alpha subunit of alpha glucosidase II in adult mouse brain regions and selective organs

    PubMed Central

    Anji, Antje; Miller, Hayley; Raman, Chandrasekar; Phillips, Mathew; Ciment, Gary; Kumari, Meena

    2014-01-01

    Alpha glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in folding of nascent glycoproteins, is heterodimeric consisting of alpha (GIIα) and beta (GIIβ) subunits. The catalytic GIIα subunit with the help of mannose 6-phosphate receptor homology (MRH) domain of GIIβ sequentially hydrolyzes two α-1-3-linked glucose residues in the 2nd step of N-linked oligosaccharide-mediated protein folding. The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. N-glycosylation and correct protein folding is crucial for protein stability, trafficking, and cell surface expression of several proteins in the brain. Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies such as viral infection, cancer and diabetes. In spite of the widespread usage of GIIα inhibitory drugs and the role of GIIα in brain function little is known about its expression in brain and other tissues. Here, we report generation of a highly specific chicken antibody to GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. Using this antibody we show that the GIIα protein is highly expressed in testis, kidney, and lung, with the least amount in heart. GIIα polypeptide levels in whole brain were comparable to spleen. However, higher expression of GIIα protein was detected in cerebral cortex reflecting its continuous requirement in correct folding of cell surface proteins. PMID:25131991

  8. THE UV-CONTINUUM PROPERTIES OF Ly{alpha}-SELECTED GALAXIES AT z = 6.5

    SciTech Connect

    Cowie, Lennox L.; Hu, Esther M.; Songaila, Antoinette E-mail: acowie@ifa.hawaii.edu

    2011-07-10

    We report the first space-based very deep near-infrared continuum observations of a uniform sample of z = 6.5 galaxies with log(L(Ly{alpha})) = 42.5-43 erg s{sup -1} selected from narrowband line searches and with spectroscopically confirmed Ly{alpha} emission. The 1.4 {mu}m Hubble Space Telescope WFC3 observations are deep enough (AB(1{sigma}) = 28.75) to measure individual continuum magnitudes at this redshift for all of the objects. We compare the results with continuum-selected samples at the same redshift and find that Ly{alpha} emission is present in 24% of all galaxies with M{sub AB}(1350 A) < -20 at z = 6.5. The error in this quantity is dominated by systematic uncertainties, which could be as large as multiplicative factors of three. The Ly{alpha} galaxies are extended but small (size <1 kpc), and have star formation rates of approximately 10 M{sub sun} yr{sup -1}. We find a mean L(Ly{alpha})/{nu}L{sub {nu}} at 1400 A to be 0.08, with the seven objects showing a range from 0.026 to 0.26, implying that there is little sign of destruction of the Ly{alpha} line. All of the properties of the z = 6.5 sample appear to be very similar to those of Ly{alpha} emitters at lower redshifts.

  9. Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies.

    PubMed Central

    Kenny, B. A.; Miller, A. M.; Williamson, I. J.; O'Connell, J.; Chalmers, D. H.; Naylor, A. M.

    1996-01-01

    1. The profile of a range of alpha 1 adrenoceptor antagonists was determined in vitro against cloned human alpha 1A, alpha 1B and alpha 1D adrenoceptors and against noradrenaline-mediated contractions of rat aorta and human prostate. The in vivo profile of compounds was determined in an anaesthetized dog model which allowed the simultaneous assessment of antagonist potency against phenylephrine-mediated increases in blood pressure and prostatic pressure. 2. The quinazoline antagonists, prazosin, doxazosin and alfuzosin displayed high affinity but were non selective for the three cloned human alpha 1 adrenoceptors. Indoramin and SNAP 1069 showed selectivity for alpha 1A and alpha 1B adrenoceptors relative to the alpha 1D subtype. Rec 15/2739, WB 4101, SL 89,0591, (+)- and (-)- tamsulosin showed selectivity for alpha 1A and alpha 1D adrenoceptors relative to the alpha 1B subtype. RS 17053 showed high affinity and selectivity for alpha 1A adrenoceptors (pKi 8.6) relative to alpha 1B (pKi = 7.3) and alpha 1D (pKi = 7.1) subtypes. 3. (+)-Tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069 and RS 17053 appeared to act as competitive antagonists of noradrenaline-mediated contractions of rat aorta yielding pA2 affinity estimates which were similar to binding affinities at cloned human alpha 1D adrenoceptors. The following rank order was obtained: prazosin = (-)-tamsulosin > doxazosin > SL 89,0591 = (+)-tamsulosin > Rec 15/2739 > RS 17053 = SNAP 1069. 4. (-)-Tamsulosin was a very potent, insurmountable antagonist of noradrenaline-mediated contractions of human prostate, yielding an approximate pA2 estimate of 9.8 at 1 nM. The corresponding (+)-enantiomer was 30 fold weaker. SL 89,0591, SNAP 1069 and Rec 15/2739 yielded pA2 estimates which compared well with their alpha 1A binding affinities. The affinity estimate for prazosin on human prostate was lower than the corresponding binding affinity determined at alpha 1A adrenoceptors and RS 17053 was a very weak

  10. Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid.

    PubMed Central

    Widom, R L; Rhee, M; Karathanasis, S K

    1992-01-01

    has very little effect on the levels of expression regardless of the presence or absence of RA. However, while ARP-1 alone or ARP-1 and RXR alpha together dramatically repress expression in the absence of RA, the repression by ARP-1 and RXR alpha together, but not ARP-1 alone, is almost completely alleviated in the presence of RA. These results indicate that transcriptional repression by ARP-1 sensitizes apoAI gene responsiveness to RXR alpha and RA and suggest that the magnitude of this responsiveness is regulated by the intracellular ratio of ARP-1 to RXR alpha. These observations raise the possibility that transcriptional repression is a general mechanism for switching gene transcription between alternative transcription activation pathways. Images PMID:1321332

  11. Independent Causal Contributions of Alpha- and Beta-Band Oscillations during Movement Selection

    PubMed Central

    Stolk, Arjen; Marshall, Tom R.; Esterer, Sophie; Sharp, Poppy; Dijkerman, H. Chris; de Lange, Floris P.; Toni, Ivan

    2016-01-01

    To select a movement, specific neuronal populations controlling particular features of that movement need to be activated, whereas other populations are downregulated. The selective (dis)inhibition of cortical sensorimotor populations is governed by rhythmic neural activity in the alpha (8–12 Hz) and beta (15–25 Hz) frequency range. However, it is unclear whether and how these rhythms contribute independently to motor behavior. Building on a recent dissociation of the sensorimotor alpha- and beta-band rhythms, we test the hypothesis that the beta-band rhythm governs the disinhibition of task-relevant neuronal populations, whereas the alpha-band rhythm suppresses neurons that may interfere with task performance. Cortical alpha- and beta-band rhythms were manipulated with transcranial alternating current stimulation (tACS) while human participants selected how to grasp an object. Stimulation was applied at either 10 or 20 Hz and was imposed on the sensorimotor cortex contralaterally or ipsilaterally to the grasping hand. In line with task-induced changes in endogenous spectral power, the effect of the tACS intervention depended on the frequency and site of stimulation. Whereas tACS stimulation generally increased movement selection times, 10 Hz stimulation led to relatively faster selection times when applied to the hemisphere ipsilateral to the grasping hand, compared with other stimulation conditions. These effects occurred selectively when multiple movements were considered. These observations functionally differentiate the causal contribution of alpha- and beta-band oscillations to movement selection. The findings suggest that sensorimotor beta-band rhythms disinhibit task-relevant populations, whereas alpha-band rhythms inhibit neuronal populations that could interfere with movement selection. SIGNIFICANCE STATEMENT This study shows dissociable effects of 10 Hz and 20 Hz tACS on the duration of movement selection. These observations have two elements of

  12. Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors.

    PubMed

    Takei, R; Ikegaki, I; Shibata, K; Tsujimoto, G; Asano, T

    1999-04-01

    The pharmacological profiles of the alpha1-adrenoceptor antagonists naftopidil, tamsulosin and prazosin were studied in an anesthetized dog model that allowed the simultaneous assessment of their antagonist potency against phenylephrine-mediated increases in prostatic pressure and mean blood pressure. The intravenous administration of each of these compounds dose-dependently inhibited phenylephrine-induced increases in prostatic pressure and mean blood pressure. To further assess the ability of the three compounds to inhibit phenylephrine-induced responses, the doses required to produce a 50% inhibition of the phenylephrine-induced increases in prostatic and mean blood pressure and the selectivity index obtained from the ratio of those two doses were determined for each test compound. Forty minutes after the intravenous administration of naftopidil, the selectivity index was 3.76, and those of tamsulosin and prazosin were 1.23 and 0.61, respectively. These findings demonstrated that naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha1-adrenoceptor subtypes, naftopidil was selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes. PMID:10361884

  13. Isozyme hybrids within the protruding third loop domain of the barley alpha-amylase (beta/alpha)8-barrel. Implication for BASI sensitivity and substrate affinity.

    PubMed

    Juge, N; Rodenburg, K W; Guo, X J; Chaix, J C; Svensson, B

    1995-04-24

    Barley alpha-amylase isozymes AMY1 and AMY2 contain three structural domains: a catalytic (beta/alpha)8-barrel (domain A) with a protruding loop (domain B; residues 89-152) that binds Ca2+, and a small C-terminal domain. Different parts of domain B secure isozyme specific properties as identified for three AMY1-AMY2 hybrids, obtained by homeologous recombination in yeast, with crossing-over at residues 112, 116, and 144. The AMY1 regions Val90-Thr112 and Ala145-Leu161 thus confer high affinities for the substrates alpha-D-maltoheptaoside and amylose, respectively. Leu117-Phe144, and to a lesser degree Ala145-Leu161, are critical for the stability at low pH characteristic of AMY1 and for the sensitivity to barley alpha-amylase/subtilisin inhibitor specific to AMY2. PMID:7737421

  14. Binding of human interferon alpha to cells of different sensitivities: studies with internally radiolabeled interferon retaining full biological activity.

    PubMed Central

    Yonehara, S; Yonehara-Takahashi, M; Ishii, A

    1983-01-01

    The characteristics of interferon binding to various cells with different interferon sensitivity were studied by using [3H]leucine-labeled, pure human interferon alpha from Namalwa cells. Scatchard analysis of the binding data on cells sensitive to interferon alpha (human FL and fibroblasts and bovine MDBK) indicated the presence of two kinds of binding sites with high and low affinities. The binding constants of the high-affinity sites in these cells were similar (4 X 10(10) to 11 X 10(10) M-1). Cells insensitive to human interferon alpha (human HEC-1 and mouse L cells) were shown to have only low-affinity sites, suggesting that high-affinity binding sites are indispensable for interferon sensitivity and represent interferon receptors. However, the number of sites in three human diploid fibroblast strains and one strain trisomic for chromosome 21 were not proportionally correlated to the interferon sensitivity of the cells. The high-affinity binding to human cells was completely inhibited by both nonradioactive human interferons alpha and beta in a similar manner, but binding to bovine MDBK cells, on which human interferon beta is practically inactive, was inhibited effectively only by interferon alpha and not by beta. These results suggest that the receptor for human interferon alpha is common to human interferon beta in human cells, whereas the receptor on bovine cells binds only human interferon alpha. PMID:6300453

  15. Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

    SciTech Connect

    Summermatter, Serge; Santos, Gesa

    2011-04-29

    Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

  16. Variant Selection during Alpha Precipitation in Titanium Alloys: A Simulation Study

    NASA Astrophysics Data System (ADS)

    Shi, Rongpei

    Variant selection of alpha phase during its precipitation from beta matrix plays a key role in determining transformation texture and final mechanical properties of alpha/beta and beta titanium alloys. In this study we develop a three-dimensional quantitative phase field model (PFM) to predict variant selection and microstructure evolution during beta to alpha transformation in polycrystalline Ti-6Al-4V under the influence of different processing variables. The model links its inputs directly to thermodynamic and mobility databases, and incorporates crystallography of BCC to HCP transformation, elastic anisotropy, defects within semi-coherent alpha/beta interfaces and elastic inhomogeneities among different beta grains. In particular, microstructure and transformation texture evolution are treated simultaneously via orientation distribution function (ODF) modeling of alpha/beta two-phase microstructure in beta polycrystalline obtained by PFM. It is found that, for a given undercooling, the development of transformation texture of the alpha phase due to variant selection during precipitation depends on both externally applied stress or strain, initial texture state of parent beta sample and internal stress generated by the precipitation reaction itself. Moreover, the growth of pre-existing widmanstatten alpha precipitates is accompanied by selective nucleation and growth of secondary alpha plates of preferred variants. We further develop a crystallographic model based on the ideal Burgers orientation relationship (BOR) between GBalpha and one of the two adjacent beta grains to investigate how a prior beta grain boundary contributes to variant selection of grain boundary allotriomorph (GBalpha). The model is able to predict all possible special beta grain boundaries where GBalpha is able to maintain BOR with two neighboring grain. In particular, the model has been used to evaluate the validity of all current empirical variant selection rules to obtain more insight of

  17. A SUCCESSFUL BROADBAND SURVEY FOR GIANT Ly{alpha} NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

    SciTech Connect

    Prescott, Moire K. M.; Dey, Arjun; Jannuzi, Buell T.

    2012-04-01

    Giant Ly{alpha} nebulae (or Ly{alpha} 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Ly{alpha} nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Ly{alpha} nebulae at 2 {approx}< z {approx}< 3 within deep broadband imaging and have carried out a survey of the 9.4 deg{sup 2} NOAO Deep Wide-Field Survey Booetes field. With a total survey comoving volume of Almost-Equal-To 10{sup 8} h{sup -3}{sub 70} Mpc{sup 3}, this is the largest volume survey for Ly{alpha} nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Ly{alpha} nebula.

  18. In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

    PubMed

    Williams, T J; Blue, D R; Daniels, D V; Davis, B; Elworthy, T; Gever, J R; Kava, M S; Morgans, D; Padilla, F; Tassa, S; Vimont, R L; Chapple, C R; Chess-Williams, R; Eglen, R M; Clarke, D E; Ford, A P

    1999-05-01

    It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia. PMID:10369480

  19. Selective potentiation of alpha 1 glycine receptors by ginkgolic acid

    PubMed Central

    Maleeva, Galyna; Buldakova, Svetlana; Bregestovski, Piotr

    2015-01-01

    Glycine receptors (GlyRs) belong to the superfamily of pentameric cys-loop receptor-operated channels and are involved in numerous physiological functions, including movement, vision, and pain. In search for compounds performing subunit-specific modulation of GlyRs we studied action of ginkgolic acid, an abundant Ginkgo biloba product. Using patch-clamp recordings, we analyzed the effects of ginkgolic acid in concentrations from 30 nM to 25 μM on α1–α3 and α1/β, α2/β configurations of GlyR and on GABAARs expressed in cultured CHO-K1 cells and mouse neuroblastoma (N2a) cells. Ginkgolic acid caused an increase in the amplitude of currents mediated by homomeric α1 and heteromeric α1/β GlyRs and provoked a left-shift of the concentration-dependent curves for glycine. Even at high concentrations (10–25 μM) ginkgolic acid was not able to augment ionic currents mediated by α2, α2/β, and α3 GlyRs, or by GABAAR consisting of α1/β2/γ2 subunits. Mutation of three residues (T59A/A261G/A303S) in the α2 GlyR subunit to the corresponding ones from the α1 converted the action of ginkgolic acid to potentiation with a distinct decrease in EC50 for glycine, suggesting an important role for these residues in modulation by ginkgolic acid. Our results suggest that ginkgolic acid is a novel selective enhancer of α1 GlyRs. PMID:26578878

  20. Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor Alpha Selective

    SciTech Connect

    Li, J.; Kennedy, L; Shi, Y; Tao, S; Ye, X; Chen, S; Wang, Y; Hernandez, A; Wang, W; et al.

    2010-01-01

    An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and {approx}410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.

  1. Antidiabetic Property of Symplocos cochinchinensis Is Mediated by Inhibition of Alpha Glucosidase and Enhanced Insulin Sensitivity

    PubMed Central

    Antu, Kalathookunnel Antony; Riya, Mariam Philip; Mishra, Arvind; Anilkumar, Karunakaran S.; Chandrakanth, Chandrasekharan K.; Tamrakar, Akhilesh K.; Srivastava, Arvind K.; Raghu, K. Gopalan

    2014-01-01

    The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of ‘Nisakathakadi’ an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity. PMID:25184241

  2. Assessing the SEU resistance of CMOS latches using alpha-particle sensitive test circuits

    NASA Technical Reports Server (NTRS)

    Buehler, M.; Blaes, B.; Nixon, R.

    1990-01-01

    The importance of Cosmic Rays on the performance of integrated circuits (IC's) in a space environment is evident in the upset rate of the Tracking and Data Relay Satellite (TDRS) launched in Apr. 1983. This satellite experiences a single-event-upset (SEU) per day which must be corrected from the ground. Such experience caused a redesign of the Galileo spacecraft with SEU resistant IC's. The solution to the SEU problem continues to be important as the complexity of spacecraft grows, the feature size of IC's decreases, and as space systems are designed with circuits fabricated at non-radiation hardened foundries. This paper describes an approach for verifying the susceptibility of CMOS latches to heavy-ion induced state changes. The approach utilizes alpha particles to induce the upsets in test circuits. These test circuits are standard cells that have offset voltages which sensitize the circuits to upsets. These results are then used to calculate the upsetability at operating voltages. In this study results are presented for the alpha particle upset of a six-transistor static random access memory (SRAM) cell. Then a methodology is described for the analysis of a standard-cell inverter latch.

  3. Benzoporphyrins: Selective Co-sensitization in Dye-Sensitized Solar Cells.

    PubMed

    Lodermeyer, Fabian; Costa, Rubén D; Malig, Jenny; Jux, Norbert; Guldi, Dirk M

    2016-06-01

    A novel class of dyes, namely benzoporphyrins, was synthesized and implemented into dye-sensitized solar cells. They feature complementary absorptions compared to N719, which renders them promising candidates for co-sensitization in DSSCs. Notably, metallated benzoporphyrins reveal a TiO2 -nanoparticle attachment that is size and aggregation dependent. Therefore, unproductive energy-transfer events between the selectively attached dyes can be prevented. In light of the latter, an efficiency improvement of 39 % has been achieved upon selective adsorption of benzoporphyrins and N719 onto different layers of TiO2 photoelectrode. PMID:27105771

  4. Developmentally-regulated sodium channel subunits are differentially sensitive to {alpha}-cyano containing pyrethroids

    SciTech Connect

    Meacham, Connie A.; Brodfuehrer, Peter D.; Watkins, Jennifer A.; Shafer, Timothy J.

    2008-09-15

    Juvenile rats have been reported to be more sensitive to the acute neurotoxic effects of the pyrethroid deltamethrin than adults. While toxicokinetic differences between juveniles and adults are documented, toxicodynamic differences have not been examined. Voltage-gated sodium channels, the primary targets of pyrethroids, are comprised of {alpha} and {beta} subunits, each of which have multiple isoforms that are expressed in a developmentally-regulated manner. To begin to test whether toxicodynamic differences could contribute to age-dependent deltamethrin toxicity, deltamethrin effects were examined on sodium currents in Xenopus laevis oocytes injected with different combinations of rat {alpha} (Na{sub v}1.2 or Na{sub v}1.3) and {beta} ({beta}{sub 1} or {beta}{sub 3}) subunits. Deltamethrin induced tail currents in all isoform combinations and increased the percent of modified channels in a concentration-dependent manner. Effects of deltamethrin were dependent on subunit combination; Na{sub v}1.3-containing channels were modified to a greater extent than were Na{sub v}1.2-containing channels. In the presence of a {beta} subunit, deltamethrin effects were significantly greater, an effect most pronounced for Na{sub v}1.3 channels; Na{sub v}1.3/{beta}{sub 3} channels were more sensitive to deltamethrin than Na{sub v}1.2/{beta}{sub 1} channels. Na{sub v}1.3/{beta}{sub 3} channels are expressed embryonically, while the Na{sub v}1.2 and {beta}{sub 1} subunits predominate in adults, supporting the hypothesis for age-dependent toxicodynamic differences. Structure-activity relationships for sensitivity of these subunit combinations were examined for other pyrethroids. Permethrin and tetramethrin did not modify currents mediated by either subunit combination. Cypermethrin, {beta}-cyfluthrin, esfenvalerate and fenpropathrin all modified sodium channel function; effects were significantly greater on Na{sub v}1.3/{beta}{sub 3} than on Na{sub v}1.2/{beta}{sub 1} channels. These

  5. Selective Calcium Sensitivity in Immature Glioma Cancer Stem Cells

    PubMed Central

    Marinescu, Voichita Dana; Segerman, Anna; Schmidt, Linnéa; Hermansson, Annika; Dirks, Peter; Forsberg-Nilsson, Karin; Westermark, Bengt; Uhrbom, Lene; Linnarsson, Sten; Nelander, Sven; Andäng, Michael

    2014-01-01

    Tumor-initiating cells are a subpopulation in aggressive cancers that exhibit traits shared with stem cells, including the ability to self-renew and differentiate, commonly referred to as stemness. In addition, such cells are resistant to chemo- and radiation therapy posing a therapeutic challenge. To uncover stemness-associated functions in glioma-initiating cells (GICs), transcriptome profiles were compared to neural stem cells (NSCs) and gene ontology analysis identified an enrichment of Ca2+ signaling genes in NSCs and the more stem-like (NSC-proximal) GICs. Functional analysis in a set of different GIC lines regarding sensitivity to disturbed homeostasis using A23187 and Thapsigargin, revealed that NSC-proximal GICs were more sensitive, corroborating the transcriptome data. Furthermore, Ca2+ drug sensitivity was reduced in GICs after differentiation, with most potent effect in the NSC-proximal GIC, supporting a stemness-associated Ca2+ sensitivity. NSCs and the NSC-proximal GIC line expressed a larger number of ion channels permeable to potassium, sodium and Ca2+. Conversely, a higher number of and higher expression levels of Ca2+ binding genes that may buffer Ca2+, were expressed in NSC-distal GICs. In particular, expression of the AMPA glutamate receptor subunit GRIA1, was found to associate with Ca2+ sensitive NSC-proximal GICs, and decreased as GICs differentiated along with reduced Ca2+ drug sensitivity. The correlation between high expression of Ca2+ channels (such as GRIA1) and sensitivity to Ca2+ drugs was confirmed in an additional nine novel GIC lines. Calcium drug sensitivity also correlated with expression of the NSC markers nestin (NES) and FABP7 (BLBP, brain lipid-binding protein) in this extended analysis. In summary, NSC-associated NES+/FABP7+/GRIA1+ GICs were selectively sensitive to disturbances in Ca2+ homeostasis, providing a potential target mechanism for eradication of an immature population of malignant cells. PMID:25531110

  6. Imaging metals in biology: balancing sensitivity, selectivity and spatial resolution.

    PubMed

    Hare, Dominic J; New, Elizabeth J; de Jonge, Martin D; McColl, Gawain

    2015-10-01

    Metal biochemistry drives a diverse range of cellular processes associated with development, health and disease. Determining metal distribution, concentration and flux defines our understanding of these fundamental processes. A comprehensive analysis of biological systems requires a balance of analytical techniques that inform on metal quantity (sensitivity), chemical state (selectivity) and location (spatial resolution) with a high degree of certainty. A number of approaches are available for imaging metals from whole tissues down to subcellular organelles, as well as mapping metal turnover, protein association and redox state within these structures. Technological advances in micro- and nano-scale imaging are striving to achieve multi-dimensional and in vivo measures of metals while maintaining the native biochemical environment and physiological state. This Tutorial Review discusses state-of-the-art imaging technology as a guide to obtaining novel insight into the biology of metals, with sensitivity, selectivity and spatial resolution in focus. PMID:26505053

  7. The RNA polymerase II trigger loop functions in substrate selection and is directly targeted by alpha-amanitin.

    PubMed

    Kaplan, Craig D; Larsson, Karl-Magnus; Kornberg, Roger D

    2008-06-01

    Structural, biochemical, and genetic studies have led to proposals that a mobile element of multisubunit RNA polymerases, the Trigger Loop (TL), plays a critical role in catalysis and can be targeted by antibiotic inhibitors. Here we present evidence that the Saccharomyces cerevisiae RNA Polymerase II (Pol II) TL participates in substrate selection. Amino acid substitutions within the Pol II TL preferentially alter substrate usage and enzyme fidelity, as does inhibition of transcription by alpha-amanitin. Finally, substitution of His1085 in the TL specifically renders Pol II highly resistant to alpha-amanitin, indicating a functional interaction between His1085 and alpha-amanitin that is supported by rerefinement of an alpha-amanitin-Pol II crystal structure. We propose that alpha-amanitin-inhibited Pol II elongation, which is slow and exhibits reduced substrate selectivity, results from direct alpha-amanitin interference with the TL. PMID:18538653

  8. Modulation of ozone-sensitive genes in alpha-tocopherol transfer protein null mice

    PubMed Central

    Vasu, Vihas T.; Oommen, Saji; Lim, Yunsook; Valacchi, Giuseppe; Hobson, Brad; Eiserich, Jason P.; Leonard, Scott W.; Traber, Maret G.; Cross, Carroll E.; Gohil, Kishorchandra

    2009-01-01

    Alpha-tocopherol transfer protein (ATTP) null mice (ATTP−/−) have a systemic alpha-tocopherol (AT) deficiency, with their lung AT levels being < 10% of those in AT-replete ATTP+/+ mice when fed a standard rodent chow diet. ATTP+/+ and ATTP−/− mice (4 wk old male mice, n = 16 per group) were fed a standard diet (35 IU AT/kg diet) for 8–12 wk, exposed 6 h/day for 3 days to either to O3 (0.5 ppm) or filtered air, then sacrificed. No significant differences in plasma or lung AT concentrations were observed in response to this level of O3 exposure. Lung genomic responses of the lungs to O3 were determined using Affymetrix 430A 2.0 arrays containing over 22,600 probe sets representing 14,000 well-characterized mouse genes. As compared with filtered air exposure, O3 exposure resulted in 99 genes being differentially expressed in ATTP−/− mice, as compared to 52 differentially expressed genes in ATTP+/+ mice. The data revealed an O3-induced upregulation of genes related to cell proliferation/DNA repair and inflammatory-immune responses in both ATTP+/+ and ATTP−/− mice, with the expression of 22 genes being common to both, whereas 30 and 77 genes were unique to ATTP+/+ and ATTP−/− mice, respectively. The expressions of O3 sensitive genes—Timp1, Areg, Birc5 and Tnc—were seen to be further modulated by AT status. The present study reveals AT modulation of adaptive response of lung genome to O3 exposure. PMID:19555225

  9. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    SciTech Connect

    Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

    1989-05-01

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with (/sup 3/H)yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells.

  10. Selective production of interferon-alpha subtypes by cultured peripheral blood mononuclear cells and lymphoblastoid cell lines.

    PubMed Central

    Greenway, A L; Overall, M L; Sattayasai, N; Rowley, M J; Hertzog, P J; McMullen, G L; Cheetham, B F; Marzuki, S

    1992-01-01

    The biological significance of the existence of multiple interferon-alpha (IFN-alpha) subtypes is unknown but may represent a finely tuned mechanism whereby different subtypes are produced in response to different stimuli. To investigate the expression of individual IFN-alpha subtypes, polyclonal antipeptide antisera designed to react with all IFN-alpha subtypes, or with a particular subtype, IFN-alpha 2 or IFN-alpha 4, have been produced. In this study we demonstrate the utility of these antisera for the detection, using indirect immunofluorescence staining, of intracellular IFN-alpha produced by human peripheral blood mononuclear cells (PBMC) and lymphoblastoid cells. Secreted IFN-alpha was also investigated by bioassay and a sandwich radioimmunoassay (RIA), using two monoclonal antibodies (mAb) and specific for IFN-alpha 4. The PBMC were shown to produce IFN reactive with all three polyclonal antisera, after stimulation with Sendai virus. The lymphoblastoid cells also produced IFN, including IFN-alpha 2, but IFN-alpha 4 was not detected either intracellularly, by immunofluorescence, or in the medium, by sandwich RIA. The immunofluorescence studies also demonstrate that in the absence of viral stimulation IFN-alpha is found in the cytoplasm of PBMC and lymphoblastoid cells but not secreted in detectable levels. The finding that two lymphoblastoid cell lines do not produce the subtype IFN-alpha 4 raises important questions as to whether other cell lines and cell types produce IFN-alpha subtypes selectively, and whether individual IFN-alpha subtypes have different roles in human physiology and pathology. Images Figure 1 Figure 2 Figure 3 PMID:1537595

  11. Estimating the variation, autocorrelation, and environmental sensitivity of phenotypic selection.

    PubMed

    Chevin, Luis-Miguel; Visser, Marcel E; Tufto, Jarle

    2015-09-01

    Despite considerable interest in temporal and spatial variation of phenotypic selection, very few methods allow quantifying this variation while correctly accounting for the error variance of each individual estimate. Furthermore, the available methods do not estimate the autocorrelation of phenotypic selection, which is a major determinant of eco-evolutionary dynamics in changing environments. We introduce a new method for measuring variable phenotypic selection using random regression. We rely on model selection to assess the support for stabilizing selection, and for a moving optimum that may include a trend plus (possibly autocorrelated) fluctuations. The environmental sensitivity of selection also can be estimated by including an environmental covariate. After testing our method on extensive simulations, we apply it to breeding time in a great tit population in the Netherlands. Our analysis finds support for an optimum that is well predicted by spring temperature, and occurs about 33 days before a peak in food biomass, consistent with what is known from the biology of this species. We also detect autocorrelated fluctuations in the optimum, beyond those caused by temperature and the food peak. Because our approach directly estimates parameters that appear in theoretical models, it should be particularly useful for predicting eco-evolutionary responses to environmental change. PMID:26227394

  12. New alpha-selective thermal glycosylation of acetyl-protected 2-acetamido-2-deoxy-beta-D-glucopyranosyl diphenylphosphinate.

    PubMed

    Kadokawa, J; Nagaoka, T; Ebana, J; Tagaya, H; Chiba, K

    2000-07-24

    This paper describes new alpha-selective thermal glycosylation using acetyl-protected 2-acetamido-2-deoxy-beta-D-glucopyranosyl diphenylphosphinate (4) as a glycosyl donor. When the glycosylation of 4 with 1-hexanol was carried out under various conditions, the conditions using trimethylsilyl trifluoromethanesulfonate as a promoter in nitromethane at reflux temperature were most suitable for the formation of the alpha anomer. The glycosylation of 4 with the other common alcohols gave corresponding alpha-glycosides in relatively high yields under the conditions. When cholesterol, a very steric hindered alcohol, was used as a glycosyl acceptor, alpha-glycoside was also produced predominantly. PMID:10945682

  13. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis.

    PubMed

    Tanaka, Y; Engelender, S; Igarashi, S; Rao, R K; Wanner, T; Tanzi, R E; Sawa, A; L Dawson, V; Dawson, T M; Ross, C A

    2001-04-15

    Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic neural cell death occurs remains unknown. Proteins encoded by two other genes in which mutations cause familial PD, parkin and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway, suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in the mechanism by which these mutations cause PD. We established inducible PC12 cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by removing doxycycline. Differentiated PC12 cell lines expressing mutant alpha-synuclein showed decreased activity of proteasomes without direct toxicity. Cells expressing mutant alpha-synuclein showed increased sensitivity to apoptotic cell death when treated with sub-toxic concentrations of an exogenous proteasome inhibitor. Apoptosis was accompanied by mitochondrial depolarization and elevation of caspase-3 and -9, and was blocked by cyclosporin A. These data suggest that expression of mutant alpha-synuclein results in sensitivity to impairment of proteasome activity, leading to mitochondrial abnormalities and neuronal cell death. PMID:11309365

  14. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa

    PubMed Central

    Chan, Benjamin K.; Sistrom, Mark; Wertz, John E.; Kortright, Kaitlyn E.; Narayan, Deepak; Turner, Paul E.

    2016-01-01

    Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target bacterial pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example of such a management strategy, we isolated a lytic bacteriophage, OMKO1, (family Myoviridae) of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Although modern phage therapy is still in its infancy, we conclude that phages, such as OMKO1, represent a new approach to phage therapy where bacteriophages exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics. This approach, using phages as targeted antibacterials, could extend the lifetime of our current antibiotics and potentially reduce the incidence of antibiotic resistant infections. PMID:27225966

  15. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa.

    PubMed

    Chan, Benjamin K; Sistrom, Mark; Wertz, John E; Kortright, Kaitlyn E; Narayan, Deepak; Turner, Paul E

    2016-01-01

    Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target bacterial pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example of such a management strategy, we isolated a lytic bacteriophage, OMKO1, (family Myoviridae) of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Although modern phage therapy is still in its infancy, we conclude that phages, such as OMKO1, represent a new approach to phage therapy where bacteriophages exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics. This approach, using phages as targeted antibacterials, could extend the lifetime of our current antibiotics and potentially reduce the incidence of antibiotic resistant infections. PMID:27225966

  16. A highly sensitive biosensor for tumor maker alpha fetoprotein based on poly(ethylene glycol) doped conducting polymer PEDOT.

    PubMed

    Cui, Min; Song, Zhiling; Wu, Yumin; Guo, Bing; Fan, Xiaojian; Luo, Xiliang

    2016-05-15

    Biocompatible polymers, such as poly(ethylene glycol) (PEG), are of great significance in the development of bio-interfaces and biosensors, as they possess excellent biocompatibility and are easy for modification. A novel highly biocompatible polymer composite was synthesized herein through electrochemical polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and a PEG derivative, 4-arm PEG terminated with thiol groups. The electrodeposited conducting polymer composite of PEG doped PEDOT (PEDOT/PEG) exhibited flake-like nanostructure, large surface area and outstanding stability. In order to further immobilize antibodies, gold nanoparticles (AuNPs) were introduced to the PEDOT/PEG composite surface through their unique interaction with the thiol groups. AuNPs modified PEDOT/PEG provided a desirable support for the immobilization of various biomolecules such as antibodies for alpha fetoprotein (AFP), a vital tumor biomarker for liver cancer. The fabricated AFP biosensor demonstrated favorable selectivity, high sensitivity, and ultralow detection limit. Furthermore, owing to the presence of PEG polymers that are highly hydrophilic, such AuNPs/PEDOT/PEG based AFP biosensor also exhibited good anti-fouling ability, and it was capable of assaying target AFP in 10% (V/V) human serum samples, indicating highly feasible potential for clinical diagnosis. PMID:26774088

  17. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner.

    PubMed

    Neschen, Susanne; Morino, Katsutaro; Dong, Jianying; Wang-Fischer, Yanlin; Cline, Gary W; Romanelli, Anthony J; Rossbacher, Jörg C; Moore, Irene K; Regittnig, Werner; Munoz, David S; Kim, Jung H; Shulman, Gerald I

    2007-04-01

    Recent studies have suggested that n-3 fatty acids, abundant in fish oil, protect against high-fat diet-induced insulin resistance through peroxisome proliferator-activated receptor (PPAR)-alpha activation and a subsequent decrease in intracellular lipid abundance. To directly test this hypothesis, we fed PPAR-alpha null and wild-type mice for 2 weeks with isocaloric high-fat diets containing 27% fat from either safflower oil or safflower oil with an 8% fish oil replacement (fish oil diet). In both genotypes the safflower oil diet blunted insulin-mediated suppression of hepatic glucose production (P < 0.02 vs. genotype control) and PEPCK gene expression. Feeding wild-type mice a fish oil diet restored hepatic insulin sensitivity (hepatic glucose production [HGP], P < 0.002 vs. wild-type mice fed safflower oil), whereas in contrast, in PPAR-alpha null mice failed to counteract hepatic insulin resistance (HGP, P = NS vs. PPAR-alpha null safflower oil-fed mice). In PPAR-alpha null mice fed the fish oil diet, safflower oil plus fish oil, hepatic insulin resistance was dissociated from increases in hepatic triacylglycerol and acyl-CoA but accompanied by a more than threefold increase in hepatic diacylglycerol concentration (P < 0.0001 vs. genotype control). These data support the hypothesis that n-3 fatty acids protect from high-fat diet-induced hepatic insulin resistance in a PPAR-alpha-and diacylglycerol-dependent manner. PMID:17251275

  18. Selective sensitization of C-fiber nociceptors by hydrogen sulfide.

    PubMed

    Aoki, Yuka; Tsubota, Maho; Nishimoto, Yuta; Maeda, Yumi; Sekiguchi, Fumiko; Kawabata, Atsufumi

    2016-01-01

    We examined the effects of intraplantar (i.pl.) administration of NaHS, an H2S donor, known to cause T-type Ca(2+) channel (T-channel)-dependent mechanical hyperalgesia, on responsiveness to electric stimulation with 5, 250 and 2000 Hz sine waves (SW) that selectively excites C, Aδ and Aβ fibers, respectively. NaHS, given i.pl., caused behavioral hypersensitivity to SW stimulation at 5 Hz, but not 250 or 2000 Hz, in rats. NaHS also enhanced phosphorylation of spinal ERK following 5 Hz SW stimulation. Three distinct T-channel blockers abolished the NaHS-induced behavioral hypersensitivity to 5 Hz SW stimulation. Thus, H2S selectively sensitizes C-fiber nociceptors via T-channels. PMID:26826903

  19. Relative sensitivity of some selected aquatic organisms to phenol

    SciTech Connect

    Tisler, T.; Zagorc-Koncan, J.

    1995-05-01

    Although the possibility of adverse effects of materials on organisms was recognized earlier, not until the 1940s or 1950s short-term acute tests with fishes were being studied. The fishes have become the most popular test organism because the effects of toxic substances in streams have been most evident on the fishes. Many other organisms bearing the important role in the environment live in the waters and began to be used in the toxicological research. Nowadays such great variety of test methods and organisms make the selection of the suitable toxicity test difficult. One or two species of test organisms only are often applied in the determination of the toxic substances or wastewaters. The toxicity test with daphnids is widely used due to its sensitivity to the great part of toxic substances. The purpose of our research was to determine the toxicity of phenol to some aquatic organisms from the group of bacteria, algae, crustacea and fishes, and to determine the most sensitive kind. Test organisms have been selected from three basic groups in the food chain (bacteria - decomposers, algae - producers and crustacea, fish - consumers). Phenol, an organic degradable substance that is a frequent contaminant in wastewaters, has been chosen for the test substance. 29 refs., 3 tabs.

  20. ASH structure alignment package: Sensitivity and selectivity in domain classification

    PubMed Central

    Standley, Daron M; Toh, Hiroyuki; Nakamura, Haruki

    2007-01-01

    Background Structure alignment methods offer the possibility of measuring distant evolutionary relationships between proteins that are not visible by sequence-based analysis. However, the question of how structural differences and similarities ought to be quantified in this regard remains open. In this study we construct a training set of sequence-unique CATH and SCOP domains, from which we develop a scoring function that can reliably identify domains with the same CATH topology and SCOP fold classification. The score is implemented in the ASH structure alignment package, for which the source code and a web service are freely available from the PDBj website . Results The new ASH score shows increased selectivity and sensitivity compared with values reported for several popular programs using the same test set of 4,298,905 structure pairs, yielding an area of .96 under the receiver operating characteristic (ROC) curve. In addition, weak sequence homologies between similar domains are revealed that could not be detected by BLAST sequence alignment. Also, a subset of domain pairs is identified that exhibit high similarity, even though their CATH and SCOP classification differs. Finally, we show that the ranking of alignment programs based solely on geometric measures depends on the choice of the quality measure. Conclusion ASH shows high selectivity and sensitivity with regard to domain classification, an important step in defining distantly related protein sequence families. Moreover, the CPU cost per alignment is competitive with the fastest programs, making ASH a practical option for large-scale structure classification studies. PMID:17407606

  1. Dissociation of TNF-alpha cytotoxic and proinflammatory activities by p55 receptor- and p75 receptor-selective TNF-alpha mutants.

    PubMed Central

    Barbara, J A; Smith, W B; Gamble, J R; Van Ostade, X; Vandenabeele, P; Tavernier, J; Fiers, W; Vadas, M A; Lopez, A F

    1994-01-01

    Human tumour necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine capable of killing mammalian tumour cells in vitro and in vivo, and of enhancing the proinflammatory activity of leucocytes and endothelium, the latter effects limiting its usage as an antitumour agent in humans. Using TNF-alpha mutants with a selective capacity to bind to the TNF p55 receptor (TNFR55) or to the p75 receptor (TNFR75) we show here that these two major activities of TNF-alpha can be dissociated. The TNFR55-selective mutants (R32W, E146K and R32W-S86T) which bind poorly to TNFR75 displayed similar potency to wild-type TNF in causing cytotoxicity of a human laryngeal carcinoma-derived cell line (HEp-2) and cytostasis in a human leukaemic cell line (U937). However, these TNFR55-selective mutants exhibited lower proinflammatory activity than wild-type TNF. Specifically, TNF-alpha's priming of human neutrophils for superoxide production and antibody-dependent cell-mediated cytotoxicity, platelet-activating factor synthesis and adhesion to endothelium were reduced by up to 170-fold. Activation of human endothelial cell functions represented by human umbilical venular endothelial cell (HUVEC) adhesiveness for neutrophils, E-selectin expression, neutrophil transmigration and IL-8 secretion were also reduced by up to 280-fold. On the other hand, D143F, a TNFR75-selective mutant tested either alone or in combination with TNFR55-selective mutants, did not stimulate these activities despite being able to cause cytokine production in TNFR75-transfected PC60 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7509279

  2. Bench-level characterization of a CMOS standard-cell D-latch using alpha-particle sensitive test circuits

    SciTech Connect

    Blaes, B.R.; Soli, G.A.; Buehler, M.G. )

    1991-12-01

    This paper describes a methodology for predicting the SEU susceptibility of a standard-cell D-latch using an alpha-particle sensitive SRAM, SPICE critical charge simulation results, and alpha-particle interaction physics. Measurements were made on a 1.6-{mu}m n-well CMOS 4k-bit test SRAM irradiated with an Am-241 alpha-particle source. A collection depth of 6.09 {mu}m was determined using these results and TRIM computer code. Using this collection depth and SPICE derived critical charge results on the latch design, an LET threshold of 34 Mev cm{sup 2}/mg was predicted. Heavy ion tests were then performed on the latch and an LET threshold of 41 MeV cm{sup 2}/mg was determined.

  3. Bench-level characterization of a CMOS standard-cell D-latch using alpha-particle sensitive test circuits

    NASA Technical Reports Server (NTRS)

    Blaes, B. R.; Soli, G. A.; Buehler, M. G.

    1991-01-01

    A methodology is described for predicting the SEU susceptibility of a standard-cell D-latch using an alpha-particle sensitive SRAM, SPICE critical charge simulation results, and alpha-particle interaction physics. Measurements were made on a 1.6-micron n-well CMOS 4-kb test SRAM irradiated with an Am-241 alpha-particle source. A collection depth of 6.09 micron was determined using these results and TRIM computer code. Using this collection depth and SPICE derived critical charge results on the latch design, an LET threshold of 34 MeV sq cm/mg was predicted. Heavy ion tests were then performed on the latch and an LET threshold of 41 MeV sq cm/mg was determined.

  4. Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer

    PubMed Central

    Granata, A; Nicoletti, R; Tinaglia, V; De Cecco, L; Pisanu, M E; Ricci, A; Podo, F; Canevari, S; Iorio, E; Bagnoli, M; Mezzanzanica, D

    2014-01-01

    Background: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). Methods: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. Results: In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by 1H-magnetic spectroscopy analysis; (III) a 35–36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. Conclusion: We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with

  5. Increased dopaminergic neuron sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in transgenic mice expressing mutant A53T alpha-synuclein.

    PubMed

    Yu, Wai Haung; Matsuoka, Yasuji; Sziráki, István; Hashim, Audrey; Lafrancois, John; Sershen, Henry; Duff, Karen E

    2008-05-01

    Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the alpha-synuclein gene and mutant alpha-synuclein expression increases the vulnerability of neurons to exogenous insults. In this study, we analyzed the levels of dopamine and its metabolites in the olfactory bulb (OB), and nigrostriatal regions of transgenic mice expressing human, mutant A53T alpha-synuclein (alpha-syn tg) and their non-transgenic (ntg) littermates using a sub-toxic, moderate dose of MPTP to determine if mutant human alpha-synuclein sensitizes the central dopaminergic systems to oxidative stress. We observed that after a single, sub-lethal MPTP injection, dopamine levels were reduced in striatum and SN in both the alpha-syn tg and ntg mice. In the olfactory bulb, a region usually resistant to MPTP toxicity, levels were reduced only in the alpha-syn tg mice. In addition, we identified a significant increase in dopamine metabolism in the alpha-syn transgenic, but not ntg mice. Finally, MPTP treatment of alpha-syn tg mice was associated with a marked elevation in the oxidative product, 3-nitrotyrosine that co-migrated with alpha-synuclein. Cumulatively, the data support the hypothesis that mutant alpha-synuclein sensitizes dopaminergic neurons to neurotoxic insults and is associated with greater oxidative stress. The alpha-syn tg line is therefore useful to study the genetic and environmental inter-relationship in PD. PMID:17999181

  6. A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility "in vitro".

    PubMed

    Colciago, Alessandra; Mornati, Ornella; Ferri, Nicola; Castelnovo, Luca Franco; Fumagalli, Laura; Bolchi, Cristiano; Pallavicini, Marco; Valoti, Ermanno; Negri-Cesi, Paola

    2016-01-01

    The progression of prostate cancer (PC) to a metastatic hormone refractory disease is the major contributor to the overall cancer mortality in men, mainly because the conventional therapies are generally ineffective at this stage. Thus, other therapeutic options are needed as alternatives or in addition to the classic approaches to prevent or delay tumor progression. Catecholamines participate to the control of prostate cell functions by the activation of alpha1-adrenoreceptors (alpha1-AR) and increased sympathetic activity has been linked to PC development and evolution. Molecular and pharmacological studies identified three alpha1-AR subtypes (A, B and D), which differ in tissue distribution, cell signaling, pharmacology and physiological role. Within the prostate, alpha1A-ARs mainly control stromal cell functions, while alpha1B- and alpha1D- subtypes seem to modulate glandular epithelial cell growth. The possible direct contribution of alpha1D-ARs in tumor biology is supported by their overexpression in PC. The studies here presented investigate the "in vitro" antitumor action of A175, a selective alpha1D-AR antagonist we have recently obtained by modifying the potent, but not subtype-selective alpha1-AR antagonist (S)-WB4101, in the hormone-refractory PC3 and DU145 PC cell lines. The results indicate that A175 has an alpha1D-AR-mediated significant and dose-dependent antiproliferative action that possibly involves the induction of G0/G1 cell cycle arrest, but not apoptosis. In addition, A175 reduces cell migration and adhesiveness to culture plates. In conclusion, our work clarified some cellular aspects promoted by alpha1D-AR activity modulation and supports a further pharmacological approach in the cure of hormone-refractory PC, by targeting specifically this AR subtype. PMID:26621245

  7. Pupil Dilation and EEG Alpha Frequency Band Power Reveal Load on Executive Functions for Link-Selection Processes during Text Reading.

    PubMed

    Scharinger, Christian; Kammerer, Yvonne; Gerjets, Peter

    2015-01-01

    Executive working memory functions play a central role in reading comprehension. In the present research we were interested in additional load imposed on executive functions by link-selection processes during computer-based reading. For obtaining process measures, we used a methodology of concurrent electroencephalographic (EEG) and eye-tracking data recording that allowed us to compare epochs of pure text reading with epochs of hyperlink-like selection processes in an online reading situation. Furthermore, this methodology allowed us to directly compare the two physiological load-measures EEG alpha frequency band power and pupil dilation. We observed increased load on executive functions during hyperlink-like selection processes on both measures in terms of decreased alpha frequency band power and increased pupil dilation. Surprisingly however, the two measures did not correlate. Two additional experiments were conducted that excluded potential perceptual, motor, or structural confounds. In sum, EEG alpha frequency band power and pupil dilation both turned out to be sensitive measures for increased load during hyperlink-like selection processes in online text reading. PMID:26076026

  8. Pupil Dilation and EEG Alpha Frequency Band Power Reveal Load on Executive Functions for Link-Selection Processes during Text Reading

    PubMed Central

    Scharinger, Christian; Kammerer, Yvonne; Gerjets, Peter

    2015-01-01

    Executive working memory functions play a central role in reading comprehension. In the present research we were interested in additional load imposed on executive functions by link-selection processes during computer-based reading. For obtaining process measures, we used a methodology of concurrent electroencephalographic (EEG) and eye-tracking data recording that allowed us to compare epochs of pure text reading with epochs of hyperlink-like selection processes in an online reading situation. Furthermore, this methodology allowed us to directly compare the two physiological load-measures EEG alpha frequency band power and pupil dilation. We observed increased load on executive functions during hyperlink-like selection processes on both measures in terms of decreased alpha frequency band power and increased pupil dilation. Surprisingly however, the two measures did not correlate. Two additional experiments were conducted that excluded potential perceptual, motor, or structural confounds. In sum, EEG alpha frequency band power and pupil dilation both turned out to be sensitive measures for increased load during hyperlink-like selection processes in online text reading. PMID:26076026

  9. Selective solid-phase extraction of alpha-tocopherol by functionalized ionic liquid-modified mesoporous SBA-15 adsorbent.

    PubMed

    Li, Min; Pham, Patrisha J; Pittman, Charles U; Li, Tingyu

    2008-10-01

    Ordered mesoporous adsorbents were prepared by physically grafting functionalized ionic liquids onto SBA-15 (a mesoporous siliceous substrate) using incipient wetness immersion method. These adsorbents were successfully applied to the selective extraction and separation of alpha-tocopherol (an isomer of vitamin E) from a model mixture of soybean oil deodorizer distillate. Various parameters affecting adsorption process such as adsorption time, the structures and loadings of ionic liquids, the adsorption isotherm, and the reusability of adsorbent were investigated using liquid-solid extraction. As high as 211 mg/g adsorbent of the adsorption capacity for alpha-tocopherol was obtained through the adsorption isotherm tests using [emim][Gly]/SBA-15 (functionalized ionic liquid 1-ethyl-3-methylimidazolium glycine which was physically coated on SBA-15) as the adsorbent, in which the functionalized ionic liquids contained the amino acid glycine as the anion. The adsorbent [emim][Gly]/SBA-15 also exhibited a very high adsorption selectivity for alpha-tocopherol. The extraction selectivity or the ratio of distribution coefficients between alpha-tocopherol and the major interference component glyceryl triundecanoate (K(d(alpha-tocopherol))/K(d(triglyceride))) was 10.5. The concentration of alpha-tocopherol was significantly increased from 15.6% in original feedstock solution that contained fatty acid methyl ester, triglyceride and alpha-tocopherol to 73.0% after stripping by diethyl ether. Five adsorbent recycle tests showed good reusability of the functionalized ionic liquid-modified mesoporous adsorbent. PMID:18845881

  10. Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization

    PubMed Central

    Seshan, Surya V.; Kappel, Barry J.; Chattopadhyay, Debjit; May, Chad; McDevitt, Michael R.; Nolan, Daniel; Mittal, Vivek; Benezra, Robert; Scheinberg, David A.

    2007-01-01

    Background Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. Methodology and Principal Findings Actinium-225 (225Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, 225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in 225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following 225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following 225Ac-E4G10 therapy. Conclusions The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy. PMID:17342201

  11. Sodium selective erythrocyte glycocalyx and salt sensitivity in man.

    PubMed

    Oberleithner, Hans

    2015-06-01

    Negatively charged surfaces of erythrocytes (RBC) reflect properties of the endothelial glycocalyx. Plasma electrolytes counteract these charges and thus control the repulsive forces between RBC and endothelium. Although Na(+) is supposed to exert a rather high affinity to the RBC surface, a direct comparison between Na(+) and K(+) in counteracting the RBC surface has been never made. Therefore, we measured Na(+)/K(+) selectivity of the RBC surface in 20 healthy volunteers applying the previously published salt blood test (SBT). It turned out that the Na(+)/K(+) selectivity ratio of the RBC glycocalyx is on average 6.1 ± 0.39 (ranging from 3 to 9 in different individuals). Considering standard plasma Na(+) and K(+) concentrations, binding probability of Na(+)/K(+) at the RBC surface is about 180:1. The SBT reveals that plasma K(+) counteracts only about 7% of the negative charges in the RBC glycocalyx. As an in vivo proof of principle, a volunteer's blood was continuously tested over 6 months while applying a glycocalyx protective polyphenol-rich natural compound (hawthorn extract). It turned out that RBC Na(+) sensitivity (the inverse of Na(+) buffer capacity) decreased significantly by about 25% while Na(+)/K(+) selectivity of the RBC glycocalyx declined only slightly by about 8 %. Taken together, (i) plasma Na(+) selectively buffers the negative charges of the RBC glycocalyx, (ii) the contribution of K(+) in counteracting these negative surface charges is small, and (iii) natural polyphenols applied in vivo increase RBC surface negativity. In conclusion, low plasma Na(+) is supposed to favor frictionless RBC-slipping through blood vessels. PMID:25027385

  12. Bioinspired nanovalves with selective permeability and pH sensitivity

    NASA Astrophysics Data System (ADS)

    Zheng, Z.; Huang, X.; Schenderlein, M.; Moehwald, H.; Xu, G.-K.; Shchukin, D. G.

    2015-01-01

    Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications.Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications

  13. Chemically selective polymer substrate based direct isotope dilution alpha spectrometry of Pu.

    PubMed

    Paul, Sumana; Pandey, Ashok K; Shah, R V; Aggarwal, S K

    2015-06-01

    Quantification of actinides in the complex environmental, biological, process and waste streams samples requires multiple steps like selective preconcentration and matrix elimination, solid source preparations generally by evaporation or electrodeposition, and finally alpha spectrometry. To minimize the sample manipulation steps, a membrane based isotope dilution alpha spectrometry method was developed for the determination of plutonium concentrations in the complex aqueous solutions. The advantages of this method are that it is Pu(IV) selective at 3M HNO3, high preconcentration factor can be achieved, and obviates the need of solid source preparation. For this, a thin phosphate-sulfate bifunctional polymer layer was anchored on the surface of microporous poly(ethersulfone) membrane by UV induced surface grafting. The thickness of the bifunctional layer on one surface of the poly(ethersulfone) membrane was optimized. The thickness, physical and chemical structures of the bifunctional layer were studied by secondary ionization mass spectrometry (SIMS), scanning electron microscopy (SEM) and SEM-EDS (energy-dispersive spectroscopy). The optimized membrane was used for preconcentration of Pu(IV) from aqueous solutions having 3-4M HNO3, followed by direct quantification of the preconcentrated Pu(IV) by isotope dilution alpha spectrometry using (238)Pu spike. The chemical recovery efficiency of Pu(IV) was found to be 86±3% below Pu(IV) loading capacity (1.08 μg in 2×1 cm(2)) of the membrane sample. The experiments with single representative actinides indicated that Am(III) did not sorb to significant extent (7%) but U(VI) sorbed with 78±3% efficiency from the solutions having 3M HNO3 concentration. However, Pu(IV) chemical recovery in the membrane remained unaffected from the solution containing 1:1000 wt. proportion of Pu(IV) to U(VI). Pu concentrations in the (U, Pu)C samples and in the irradiated fuel dissolver solutions were determined. The results thus obtained

  14. Selective action of two aporphines at alpha 1-adrenoceptors and potential-operated Ca2+ channels.

    PubMed

    Ivorra, M D; Chuliá, S; Lugnier, C; D'Ocon, M P

    1993-02-01

    Contractions evoked by noradrenaline (1 microM) or a depolarizing solution of 60 mM KCl were concentration dependently depressed by the aporphine alkaloids (S)-boldine and (R)-apomorphine in rat aorta. Both drugs had a greater inhibitory potency on the contraction elicited by noradrenaline. Dose-response curves for noradrenaline were shifted to the right in presence of (S)-boldine. (R)-Apomorphine acted by a complex mechanism at alpha 1-adrenoceptors and its inhibitory effect was irreversible. The conformational features of these alkaloids may explain their different behaviour at alpha 1-adrenoceptors. In Ca(2+)-free solution, the alkaloids inhibited the contraction evoked by noradrenaline but did not modify (apomorphine) or increase (boldine) the contractile response induced by caffeine. Both alkaloids interacted with [3H]prazosin binding and with the benzothiazepine binding site of the Ca2+ entry receptor complex but had no effect at the dihydropyridine binding site in the rat cerebral cortex. Both drugs showed some selectivity as inhibitors of [3H]prazosin binding as opposed to [3H]d-cis diltiazem binding. (R)-Apomorphine slightly inhibited one of the two forms of the Ca(2+)-independent, low Km cyclic AMP-phosphodiesterase (type IV), whereas it did not have a significant effect on the other phosphodiesterase forms. (S)-Boldine had negligible inhibitory effects on all phosphodiesterase forms. The present study provides evidence that (S)-boldine and (R)-apomorphine have interesting properties as Ca2+ entry blockers (through the benzothiazepine receptor site in the Ca2+ channel) and at alpha 1-adrenoceptors. PMID:8384112

  15. Variant selection in transformation texture from the {beta} to {alpha} phase in Cu-40 mass% Zn alloy

    SciTech Connect

    Yasuda, H.Y.; Sakata, T.; Umakoshi, Y.

    1999-04-23

    The rolling texture and variant selection in texture during the phase transformation from {beta} to {alpha} in Cu-40 mass% Zn were investigated using X-ray back reflection and electron back-scatter diffraction pattern (EBSP) techniques. The rolling texture of the {beta} parent phase, before the phase transformation, was composed of {l_brace}111{r_brace}{l_angle}1{bar 1}0{r_angle}, {l_brace}001{r_brace}{l_angle}110{r_angle} and {l_brace}111{r_brace}{l_angle}{bar 1}{bar 1}2{r_angle}. Variant selection occurred during the {beta} to {alpha} phase transformation from the cold-rolled parent {beta} phase, even when the phase transformation following the Kurdjumov-Sachs relationship was controlled by a diffusion process. The variant selection was related to the Bain distortion for each {alpha} variant during the phase transformation from the {beta} to {alpha} phase. A limited set of {alpha} variants was chosen to minimize the residual stress induced in the deformed {beta} parent phase by the Bain distortion. The type of selected variants changed with the rolling texture of {beta} parent phase. The selectivity of specific variants increased and was stimulated by both annealing temperature and rolling reduction.

  16. The sensitivity of H alpha profiles to rapid electron beam fluctuations

    NASA Technical Reports Server (NTRS)

    Canfield, Richard C.; Gayley, Kenneth G.

    1986-01-01

    In order to understand the temporal relationship between H alpha and hard X-ray emission predicted by the nonthermal electron thick target model of impulsive-phase energy transport the time-dependent theoretical H alpha profiles were computed for the dynamic model atmospheres of Fisher, Canfield, and McClymont, which simulate the effects of an impulsively initiated power-law beam of electrons. On the basis of the physical analysis it was expected that a very rapid H alpha response to an instantaneous increase in the flux of a nonthermal deka-keV electron beam, as compared to the timescale associated with the propagation of these electrons over characteristic flare coronal loop spatial scales. It was concluded that observational efforts to test the thick target nonthermal electron model through detection of impulsive H alpha brightenings associated with impulsive hard X-ray or microwave bursts should initially focus attention on the H alpha line center. Additional simultaneous blue-wing measurements will have substantial diagnostic potential.

  17. Evaluation of passive alpha detectors for sensitive/inexpensive/fast characterization of radiological contamination on surfaces and in soils

    SciTech Connect

    Meyer, K.E.; Gammage, R.B.; Dudney, C.S.; Kotrappa, P.; Wheeler, R.; Salasky, M.

    1994-04-01

    Passive alpha-particle detectors, originally developed for indoor radon measurements, offer the potential for cost-effective and sensitive measurements of radiological contamination in soils and on surfaces for field screening and radiological survey applications. We have carried out field demonstrations of electret ionization chambers (EIC`s) and alpha track detectors (ATD`s). The EIC`s offer the advantages of immediate on-site readout, good sensitivity, ruggedness, and simplicity of operation. The use of parallel screened and unscreened EIC measurement allows the separation of alpha-particle response from radon/gamma/beta response. The advantages of the ATD`s include the potential for hot-particle counting, permanent records of contaminated and post-remediation activity levels, and inexpensive depth profiling of contamination in soil. At this time, the ATD`s are routinely shipped to the vendor after exposure in the field for processing and readout. It is feasible that the necessary processing and readout equipment could be deployed in a mobile laboratory for fast on-site analysis. We will present results from environmental measurements at the Nevada Test Site and indoor surface contamination measurements carried out at ORNL.

  18. Parallax-sensitive remapping of visual space in occipito-parietal alpha-band activity during whole-body motion.

    PubMed

    Gutteling, T P; Selen, L P J; Medendorp, W P

    2015-03-01

    Despite the constantly changing retinal image due to eye, head, and body movements, we are able to maintain a stable representation of the visual environment. Various studies on retinal image shifts caused by saccades have suggested that occipital and parietal areas correct for these perturbations by a gaze-centered remapping of the neural image. However, such a uniform, rotational, remapping mechanism cannot work during translations when objects shift on the retina in a more complex, depth-dependent fashion due to motion parallax. Here we tested whether the brain's activity patterns show parallax-sensitive remapping of remembered visual space during whole-body motion. Under continuous recording of electroencephalography (EEG), we passively translated human subjects while they had to remember the location of a world-fixed visual target, briefly presented in front of or behind the eyes' fixation point prior to the motion. Using a psychometric approach we assessed the quality of the memory update, which had to be made based on vestibular feedback and other extraretinal motion cues. All subjects showed a variable amount of parallax-sensitive updating errors, i.e., the direction of the errors depended on the depth of the target relative to fixation. The EEG recordings show a neural correlate of this parallax-sensitive remapping in the alpha-band power at occipito-parietal electrodes. At parietal electrodes, the strength of these alpha-band modulations correlated significantly with updating performance. These results suggest that alpha-band oscillatory activity reflects the time-varying updating of gaze-centered spatial information during parallax-sensitive remapping during whole-body motion. PMID:25505108

  19. Pharmacological analysis of the novel, selective alpha1-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand.

    PubMed

    Murata, S; Taniguchi, T; Muramatsu, I

    1999-05-01

    -AR selectivity and high affinity of KMD-3213, and indicate that [3H]-KMD can label selectively alpha1A-AR. PMID:10369451

  20. Immunodominant regions for T helper-cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis.

    PubMed Central

    Protti, M P; Manfredi, A A; Straub, C; Howard, J F; Conti-Tronconi, B M

    1990-01-01

    In myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor (AChR) occurs. The alpha subunit of the AChR contains both the epitope(s) that dominates the antibody response (main immunogenic region) and epitopes involved in T helper cell sensitization. In this study, overlapping synthetic peptides corresponding to the complete AChR alpha-subunit sequence were used to propagate polyclonal AChR-specific T helper cell lines from four myasthenic patients of different HLA types. Response of the T helper lines to the individual peptides was studied. Four immunodominant sequence segments were identified--i.e., residues 48-67, 101-120, 304-322, and 419-437. These regions did not include residues known to form the main immunogenic region or the cholinergic binding site, and they frequently contained sequence motifs that have been proposed to be related to T-epitope formation. Images PMID:2145582

  1. Identification of high-affinity anti-IL-1. alpha. autoantibodies in normal human serum as an interfering substance in a sensitive enzyme-linked immunosorbent assay for IL-1. alpha

    SciTech Connect

    Mae, N.; Liberato, D.J.; Chizzonite, R.; Satoh, H. )

    1991-04-01

    A highly reproducible, sensitive, and specific sandwich enzyme-linked immunosorbent assay (ELISA) for recombinant human IL-1 {alpha} (rhIL-1 alpha) has been developed. Results from this ELISA have demonstrated that the concentration of rhIL-1 {alpha} added to normal human serum (NHS) decreased by 16.3% after 3 h and 24.9% after 6 h at room temperature. Molecular exclusion column chromatography with Sephacryl S-300 HR revealed that 125I-labeled IL-1 {alpha} added to normal human serum rapidly formed higher molecular weight complexes without indication of proteolytic degradation. The observed reduction in immunoreactivity was correlated with this protein complex formation and accounted for the apparent instability of rhIL-1 {alpha} in NHS. Immunoblot analysis indicated that the molecular weight of the binding protein was 150-160K, and the IL-1 {alpha} binding activity was removed and recovered from NHS by Protein-G affinity chromatography; indicating that the binding protein was IL-1 {alpha}-specific IgG. The binding of 125I-labeled IL-1 {alpha} to the serum binding proteins could be inhibited by unlabeled IL-1 alpha (IC50 = 7.4 {times} 10(-11) M) but not by unlabeled IL-1 {beta}. Kinetic analysis with 125I-labeled IL-1 alpha revealed that the average binding affinity of these IL-1 {alpha}-specific IgGs was 4.7 {times} 10(10) M-1. These results suggest that these autoantibodies may interfere with the detection of IL-1 {alpha} in human serum by various assay systems and also could be a regulator of circulating IL-1 {alpha}.

  2. Ocular avirulence of a herpes simplex virus type 1 strain is associated with heightened sensitivity to alpha/beta interferon.

    PubMed Central

    Su, Y H; Oakes, J E; Lausch, R N

    1990-01-01

    BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determine the reason for the difference in virulence between the two HSV strains. Both HSV-1 strains replicated to similar titers in excised corneal "buttons." However, after in vivo infection of the cornea, the growth of strain 35 was evident only during the first 24 h postinfection, whereas the replication of strain RE persisted for at least 4 days. In vitro tests revealed that HSV-1(35) was greater than 10 times more sensitive to alpha/beta interferon (IFN-alpha/beta) than HSV-1(RE). Both strains induced comparable serum levels of IFN after intraperitoneal inoculation. The kinetics of HSV-1(35) clearance from the eye was markedly altered by treatment with rabbit anti-IFN-alpha/beta. Virus titers exceeding 10(4) PFU per eye could be demonstrated 4 to 5 days postinfection in mice given a single inoculation of antiserum 1 h after infection. Furthermore, anti-IFN treatment in 3-week-old mice infected with HSV-1(35) led to the development of clinically apparent corneal disease which subsequently progressed to stromal keratitis in the majority of recipients. These results indicate that the striking difference in the capacity of HSV-1(35) and HSV-1(RE) to induce corneal disease was related to the inherently greater sensitivity of strain 35 to IFN-alpha/beta produced by the host in response to infection. PMID:2157880

  3. A possible structural determinant of selectivity of boldine and derivatives for the alpha 1A-adrenoceptor subtype.

    PubMed Central

    Madrero, Y.; Elorriaga, M.; Martinez, S.; Noguera, M. A.; Cassels, B. K.; D'Ocon, P.; Ivorra, M. D.

    1996-01-01

    1. The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha 1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]-prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with high affinity from among the total [3H]-prazosin specific binding sites. 3. Boldine, predicentrine and glaucine also competed for [3H]-prazosin (0.2 nM) binding with shallow and biphasic curves recognizing 30-40% of the sites with high affinity. Drug affinities (pKi) at the high and low affinity sites were, 8.31 and 6.50, respectively, for boldine, 8.13 and 6.39 for predicentrine, and 7.12 and 5.92 for glaucine. The relative order of selectivity for alpha 1A-adrenoceptors was boldine (70 fold alpha 1A-selective) = predicentrine (60 fold, alpha 1A-selective) > glaucine (15 fold, alpha 1A-selective). 4. Pretreatment of rat cerebral cortex membranes with chloroethylclonidine (CEC, 10 microM) for 30 min at 37 degrees C followed by thorough washing out reduced specific [3H]-prazosin binding by approximately 70%. The CEC-insensitive [3H]-prazosin binding was inhibited by boldine monophasically (Hill slope = 0.93) with a single pKi value (7.76). 5. These results suggest that whereas the aporphine structure shared by these alkaloids is responsible for their selectively of action for the alpha 1A-adrenoceptor subtype in rat cerebral cortex, defined functional groups, namely the 2-hydroxy function, induces a significant increase in alpha 1A-subtype selectivity and affinity. PMID:8982502

  4. A possible structural determinant of selectivity of boldine and derivatives for the alpha 1A-adrenoceptor subtype.

    PubMed

    Madrero, Y; Elorriaga, M; Martinez, S; Noguera, M A; Cassels, B K; D'Ocon, P; Ivorra, M D

    1996-12-01

    1. The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha 1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]-prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with high affinity from among the total [3H]-prazosin specific binding sites. 3. Boldine, predicentrine and glaucine also competed for [3H]-prazosin (0.2 nM) binding with shallow and biphasic curves recognizing 30-40% of the sites with high affinity. Drug affinities (pKi) at the high and low affinity sites were, 8.31 and 6.50, respectively, for boldine, 8.13 and 6.39 for predicentrine, and 7.12 and 5.92 for glaucine. The relative order of selectivity for alpha 1A-adrenoceptors was boldine (70 fold alpha 1A-selective) = predicentrine (60 fold, alpha 1A-selective) > glaucine (15 fold, alpha 1A-selective). 4. Pretreatment of rat cerebral cortex membranes with chloroethylclonidine (CEC, 10 microM) for 30 min at 37 degrees C followed by thorough washing out reduced specific [3H]-prazosin binding by approximately 70%. The CEC-insensitive [3H]-prazosin binding was inhibited by boldine monophasically (Hill slope = 0.93) with a single pKi value (7.76). 5. These results suggest that whereas the aporphine structure shared by these alkaloids is responsible for their selectively of action for the alpha 1A-adrenoceptor subtype in rat cerebral cortex, defined functional groups, namely the 2-hydroxy function, induces a significant increase in alpha 1A-subtype selectivity and affinity. PMID:8982502

  5. Culture, Personality, Health, and Family Dynamics: Cultural Competence in the Selection of Culturally Sensitive Treatments

    ERIC Educational Resources Information Center

    Sperry, Len

    2010-01-01

    Cultural sensitivity and cultural competence in the selection of culturally sensitive treatments is a requisite for effective counseling practice in working with diverse clients and their families, particularly when clients present with health issues or medical problems. Described here is a strategy for selecting culturally sensitive treatments…

  6. SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation.

    PubMed

    Cohen, C; Bergis, O E; Galli, F; Lochead, A W; Jegham, S; Biton, B; Leonardon, J; Avenet, P; Sgard, F; Besnard, F; Graham, D; Coste, A; Oblin, A; Curet, O; Voltz, C; Gardes, A; Caille, D; Perrault, G; George, P; Soubrie, P; Scatton, B

    2003-07-01

    (5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2',3':5,6]pyrano[2,3-d]azepine (SSR591813) is a novel compound that binds with high affinity to the rat and human alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtypes (Ki = 107 and 36 nM, respectively) and displays selectivity for the alpha4beta2 nAChR (Ki, human alpha3beta4 > 1000, alpha3beta2 = 116; alpha1beta1deltagamma > 6000 nM and rat alpha7 > 6000 nM). Electrophysiological experiments indicate that SSR591813 is a partial agonist at the human alpha4beta2 nAChR subtype (EC50 = 1.3 micro M, IA =19% compared with the full agonist 1,1-dimethyl-4-phenyl-piperazinium). In vivo findings from microdialysis and drug discrimination studies confirm the partial intrinsic activity of SSR591813. The drug increases dopamine release in the nucleus accumbens shell (30 mg/kg i.p.) and generalizes to nicotine or amphetamine (10-20 mg/kg i.p.) in rats, with an efficacy approximately 2-fold lower than that of nicotine. Pretreatment with SSR591813 (10 mg/kg i.p.) reduces the dopamine-releasing and discriminative effects of nicotine. SSR591813 shows activity in animal models of nicotine dependence at doses devoid of unwanted side effects typically observed with nicotine (hypothermia and cardiovascular effects). The compound (10 mg/kg i.p.) also prevents withdrawal signs precipitated by mecamylamine in nicotine-dependent rats and partially blocks the discriminative cue of an acute precipitated withdrawal. SSR591813 (20 mg/kg i.p.) reduces i.v. nicotine self-administration and antagonizes nicotine-induced behavioral sensitization in rats. The present results confirm important role for alpha4beta2 nAChRs in mediating nicotine dependence and suggest that SSR591813, a partial agonist at this particular nAChR subtype, may have therapeutic potential in the clinical management of smoking cessation. PMID:12682217

  7. Temperature sensitivity of Cu K(alpha) imaging efficiency using a spherical Bragg reflecting crystal

    SciTech Connect

    Akli, K U; Key, M H; Chung, H K; Hansen, S B; Freeman, R R; Chen, M H; Gregori, G; Hatchett, S; Hey, D; Izumi, N; King, J A; Kuba, J; Norreys, P; Mackinnon, A J; Murphy, C D; Snavely, R; Stepehens, R; Stoeckel, C; Theobald, W; Zhang, B

    2006-08-07

    The Vulcan laser facility at the Rutherford Appleton Laboratory was used to study the interaction of a 75 J 10 ps, high intensity laser beam with low-mass solid, Cu targets. Two instruments were fielded as diagnostics of the Cu K-shell emission from the targets: A single photon counting CCD spectrometer provided the absolute K{sub {alpha}} yield and a spherically bent Bragg crystal recorded 2D monochromatic images with a spatial resolution of 10 {micro}m. Due to the shifting and broadening of the K{sub {alpha}} spectral lines with increasing temperature, there is a temperature dependence of the crystal collection efficiency. This provides a temperature diagnostic when cross calibrated against a single hit CCD spectrometer, and it affects measurements of the spatial pattern of electron transport. The experimental data showing changing collection efficiency are presented. The results are discussed in light of modeling of the temperature-dependent spectrum of Cu K-shell emission.

  8. Differential gene expression in the bovine corpus luteum during transition from early phase to midphase and its potential role in acquisition of luteolytic sensitivity to prostaglandin F2 alpha.

    PubMed

    Goravanahally, Madhusudan P; Salem, Mohamed; Yao, Jianbo; Inskeep, E Keith; Flores, Jorge A

    2009-05-01

    Prostaglandin F2 alpha (PGF(2alpha)) brings about regression of the bovine corpus luteum (CL). This luteolytic property of PGF(2alpha) is used in beef and dairy cattle to synchronize estrus. A limitation of this protocol is insensitivity of the early CL to luteolytic actions of PGF(2alpha). The mechanisms underlying this differential luteal sensitivity are poorly understood. The developing CL has a maximum number of PGF(2alpha) receptors; therefore, differences in signaling events may be responsible for luteal insensitivity. Hence, differential gene expression at two developmental stages of CL, Day 4 (D-4) and D-10 after estrus, might account for differences in signal transduction pathways associated with luteal sensitivity. This possibility was examined in these studies. Microarray analysis (n = 3 cows per stage) identified 167 genes that were differentially expressed (P < 0.05). These were categorized into genes involved in protein biosynthesis and modification (18.5%), transcription regulation and DNA biosynthesis (18.5%), miscellaneous (17.0%), cell signaling (12.0%), steroidogenesis and metabolism (10.2%), extracellular matrix and cytoskeletal proteins (9.5%), unknown functions (6.0%), protein degradation (5.3%), and antioxidant property (3.0%). Real-time PCR confirmed the differential expression of nine selected genes, including tyrosine 3-monooxygenase/tryptophan 5-monooxygense activation protein zeta polypeptide (YWHAZ) and regulator of G protein signaling 2 24-kDa (RGS2), observed in microarray. Furthermore, the in vivo effect of exogenous PGF(2alpha) (n = 3 cows per stage) on selected genes that were found to be differentially expressed during this developmental transition was examined. PGF(2alpha) increased the expression of a guanine nucleotide-binding protein (G protein) beta polypeptide 1 (GNB1) in D-4 CL and calcium/calmodulin-dependent kinase kinase 2 beta (CAMKK2) in D-10 CL. Therefore, GNB1, CAMKK2, YWHAZ, and RGS2 are candidate genes that may

  9. Acidity-controlled selective oxidation of alpha-pinene, isolated from Indonesian pine's turpentine oils (pinus merkusii)

    NASA Astrophysics Data System (ADS)

    Masruri; Farid Rahman, Mohamad; Nurkam Ramadhan, Bagus

    2016-02-01

    Alpha-pinene was isolated in high purity from turpentine oil harvested from Pinus merkusii plantation. The recent investigation on selective oxidation of alpha-pinene using potassium permanganate was undertaken under acidic conditions. The result taught the selective oxidation of alpha-pinene in acidic using potassium permanganate lead to the formation of 2-(3-acetyl-2,2-dimethylcyclobutyl)acetaldehyde or pinon aldehyde. The study method applied reaction in various different buffer conditions i.e. pH 3, 4, 5, and 6, respectively, and each reaction product was monitored using TLC every hour. Product determination was undertaken on spectrometry basis such as infrared, ultra violet-visible, gas chromatography- and liquid chromatography-mass spectrometry.

  10. In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107: preclinical considerations in Alzheimer's disease.

    PubMed

    Bitner, R Scott; Bunnelle, William H; Decker, Michael W; Drescher, Karla U; Kohlhaas, Kathy L; Markosyan, Stella; Marsh, Kennan C; Nikkel, Arthur L; Browman, Kaitlin; Radek, Rich; Anderson, David J; Buccafusco, Jerry; Gopalakrishnan, Murali

    2010-09-01

    We previously reported that alpha7 nicotinic acetylcholine receptor (nAChR) agonism produces efficacy in preclinical cognition models correlating with activation of cognitive and neuroprotective signaling pathways associated with Alzheimer's disease (AD) pathology. In the present studies, the selective and potent alpha7 nAChR agonist 5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole (ABT-107) was evaluated in behavioral assays representing distinct cognitive domains. Studies were also conducted to address potential issues that may be associated with the clinical development of an alpha7 nAChR agonist. Specifically, ABT-107 improved cognition in monkey delayed matching to sample, rat social recognition, and mouse two-trial inhibitory avoidance, and continued to improve cognitive performance at injection times when exposure levels continued to decline. Rats concurrently infused with ABT-107 and donepezil at steady-state levels consistent with clinical exposure showed improved short-term recognition memory. Compared with nicotine, ABT-107 did not produce behavioral sensitization in rats or exhibit psychomotor stimulant activity in mice. Repeated (3 days) daily dosing of ABT-107 increased extracellular cortical acetylcholine in rats, whereas acute administration increased cortical extracellular signal-regulated kinase and cAMP response element-binding protein phosphorylation in mice, neurochemical and biochemical events germane to cognitive function. ABT-107 increased cortical phosphorylation of the inhibitory residue (Ser9) of glycogen synthase kinase-3, a primary tau kinase associated with AD pathology. In addition, continuous infusion of ABT-107 in tau/amyloid precursor protein transgenic AD mice reduced spinal tau hyperphosphorylation. These findings show that targeting alpha7 nAChRs may have potential utility for symptomatic alleviation and slowing of disease progression in the treatment AD, and expand the understanding of the potential

  11. Sensitizing Students to the Selective Tradition in Children's Literature.

    ERIC Educational Resources Information Center

    Taxel, Joel

    In this paper, a professor discusses how he uses his college-level courses in children's literature as a vehicle through which the significance of selective tradition can be made apparent. Selected tradition is defined as an intentionally selected version of the past or present that is powerfully operative in the process of social and cultural…

  12. Selective LXR{alpha} inhibitory effects observed in plant extracts of MEH184 (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica)

    SciTech Connect

    Kim, Kang Ho; Choi, Seung Hyun; Lee, Thomas S.; Oh, Won Keun; Kim, Dong Sun; Kim, Jae Bum . E-mail: jaebkim@snu.ac.kr

    2006-10-20

    Liver X receptors (LXRs) are nuclear hormone receptors that behave as lipid sensors of cellular cholesterol and fatty acid. Although LXR activation can alleviate hypercholesterolemia by inducing cholesterol efflux, it also results in undesirable effects of fatty acid synthesis, resulting in hepatic steatosis and hyperlipidemia. Therefore, it is critical to identify LXR{alpha} inhibitory agents that would repress fatty acid synthesis and hepatic lipid accumulation. In current study, screening of plant extracts used for traditional oriental medicine resulted in the identification of two candidates demonstrating selective LXR{alpha} inhibitory activity. These were whole leaf methanol extracts of Parthenocissua tricuspidata (MEH184) and Euscaphis japonica (MEH185). Both MEH184 and MEH185 decreased transcriptional activity of LXR{alpha} and the expression of LXR{alpha} target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184 significantly reduced lipogenesis and adipocyte differentiation. Together, the data imply that MEH184 and MEH185 possess selective antagonistic properties on LXR{alpha} to downregulate lipogenesis.

  13. Temperature sensitivity of Cu K{sub {alpha}} imaging efficiency using a spherical Bragg reflecting crystal

    SciTech Connect

    Akli, K. U.; Key, M. H.; Chung, H. K.; Hansen, S. B.; Chen, M. H.; Hatchett, S.; Izumi, N.; Mackinnon, A. J.; Snavely, R.; Freeman, R. R.; Gregori, G.; Norreys, P.; Murphy, C. D.; Hey, D.; King, J.; Kuba, J.; Stephens, R. B.; Stoeckel, C.; Theobald, W.; Zhang, B.

    2007-02-15

    The interaction of a 75 J 10 ps, high intensity laser beam with low-mass, solid Cu targets is investigated. Two instruments were fielded as diagnostics of Cu K-shell emission from the targets: a single photon counting spectrometer provided the absolute K{sub {alpha}} yield [C. Stoeckl et al., Rev. Sci. Instrum. 75, 3705 (2004)] and a spherically bent Bragg crystal recorded 2D monochromatic images with a spatial resolution of 10 {mu}m [J. A. Koch et al., Rev. Sci. Instrum. 74, 2130 (2003)]. Due to the shifting and broadening of the K{sub {alpha}} spectral lines with increasing temperature, there is a temperature dependence of the crystal collection efficiency. This affects measurements of the spatial pattern of electron transport, and it provides a temperature diagnostic when cross calibrated against the single photon counting spectrometer. The experimental data showing changing collection efficiency are presented. The results are discussed in light of modeling of the temperature-dependent spectrum of Cu K-shell emission.

  14. Selecting step sizes in sensitivity analysis by finite differences

    NASA Technical Reports Server (NTRS)

    Iott, J.; Haftka, R. T.; Adelman, H. M.

    1985-01-01

    This paper deals with methods for obtaining near-optimum step sizes for finite difference approximations to first derivatives with particular application to sensitivity analysis. A technique denoted the finite difference (FD) algorithm, previously described in the literature and applicable to one derivative at a time, is extended to the calculation of several simultaneously. Both the original and extended FD algorithms are applied to sensitivity analysis for a data-fitting problem in which derivatives of the coefficients of an interpolation polynomial are calculated with respect to uncertainties in the data. The methods are also applied to sensitivity analysis of the structural response of a finite-element-modeled swept wing. In a previous study, this sensitivity analysis of the swept wing required a time-consuming trial-and-error effort to obtain a suitable step size, but it proved to be a routine application for the extended FD algorithm herein.

  15. Delving Deeper into the Solar Dynamo Mechanism: Alpha Effect, Parity Selection and Large Scale Flows.

    NASA Astrophysics Data System (ADS)

    Nandy, D.

    2003-05-01

    Visible manifestations of the 22 year solar magnetic cycle have been the subject of study spanning centuries starting with the telescopic observations of sunspots by Johann Fabricius, Christoph Scheiner and Galileo Galilei in the early 1600s. Coupled with these observations of magnetic features on the solar surface, the advent of the field of helioseismology in recent years has made it possible to map large scale flows in the solar interior - believed to play a crucial role in sustaining the solar cycle. However, a complete understanding of the hydromagnetic dynamo mechanism that powers this solar cycle remains elusive. Here we report studies of the solar dynamo addressing some of the important unresolved questions regarding the nature and location of the alpha effect, solar magnetic parity selection and the role of large scale flows and their variation, with a goal to understand the exact means by which the Sun generates its magnetic cycle. This study was supported by NASA through SR&T grant NAG5-6110.

  16. Branching enzyme assay: selective quantitation of the alpha 1,6-linked glucosyl residues involved in the branching points.

    PubMed

    Krisman, C R; Tolmasky, D S; Raffo, S

    1985-06-01

    Methods previously described for glycogen or amylopectin branching enzymatic activity are insufficiently sensitive and not quantitative. A new, more sensitive, specific, and quantitative one was developed. It is based upon the quantitation of the glucose residues joined by alpha 1,6 bonds introduced by varying amounts of branching enzyme. The procedure involved the synthesis of a polysaccharide from Glc-1-P and phosphorylase in the presence of the sample to be tested. The branched polysaccharide was then purified and the glucoses involved in the branching points were quantitated after degradation with phosphorylase and debranching enzymes. This method appeared to be useful, not only in enzymatic activity determinations but also in the study of the structure of alpha-D-glucans when combined with those of total polysaccharide quantitation, such as iodine and phenol-sulfuric acid. PMID:3160257

  17. Alpha 1-proteinase inhibitor is more sensitive to inactivation by cigarette smoke than is leukocyte elastase

    SciTech Connect

    Janoff, A.; Dearing, R.

    1982-10-01

    Aqueous solutions of gas phase cigarette smoke were incubated with pure human leukocyte elastase or with crude human leukocyte granule extract, and the effects on enzyme activity were determined using a synthetic amide substrate. Simultaneously, the same smoke solutions were incubated with 10% human serum under identical conditions, and the effects on serum inhibition of purified or crude leukocyte elastase were similarly measured. In addition, aqueous solutions of unfractionated cigarette smoke were incubated with leukocyte elastase or serum, and the abilities of the smoke-treated enzyme to digest elastin and of the smoke-treated serum to inhibit elastin digestion were determined. Both experimental protocols showed that serum elastase-inhibiting capacity (primarily caused by alpha 1-proteinase inhibitor) is more susceptible to inactivation by aqueous solutions of cigarette smoke than is leukocyte elastase, suggesting that elastase inhibition (rather than elastase activity) may be predominantly suppressed by cigarette smoke inhalation in vivo.

  18. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    SciTech Connect

    Weiland, N.G.; Wise, P.M.

    1987-11-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

  19. Interactions of Plakoglobin and [beta]-Catenin with Desmosomal Cadherins BASIS OF SELECTIVE EXCLUSION OF [alpha]- AND [beta]-CATENIN FROM DESMOSOMES

    SciTech Connect

    Choi, Hee-Jung; Gross, Julia C.; Pokutta, Sabine; Weis, William I.; Stanford-MED

    2009-11-18

    Plakoglobin and {beta}-catenin are homologous armadillo repeat proteins found in adherens junctions, where they interact with the cytoplasmic domain of classical cadherins and with {alpha}-catenin. Plakoglobin, but normally not {beta}-catenin, is also a structural constituent of desmosomes, where it binds to the cytoplasmic domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of {beta}-catenin and {alpha}-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between {beta}-catenin and E-cadherin. Trypsin sensitivity experiments indicate that the plakoglobin arm domain by itself is more flexible than that of {beta}-catenin. Binding of plakoglobin and {beta}-catenin to the intracellular regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal titration calorimetry. Plakoglobin and {beta}-catenin bind strongly and with similar thermodynamic parameters to E-cadherin. In contrast, {beta}-catenin binds to desmoglein-1 more weakly than does plakoglobin. {beta}-Catenin and plakoglobin bind with similar weak affinities to desmocollin-1. Full affinity binding of desmoglein-1 requires sequences C-terminal to the region homologous to the catenin-binding domain of classical cadherins. Although pulldown assays suggest that the presence of N- and C-terminal {beta}-catenin 'tails' that flank the armadillo repeat region reduces the affinity for desmosomal cadherins, calorimetric measurements show no significant effects of the tails on binding to the cadherins. Using purified proteins, we show that desmosomal cadherins and {alpha}-catenin compete directly for binding to plakoglobin, consistent with the absence of {alpha}-catenin in desmosomes.

  20. High-sensitivity fluorescence anisotropy detection of protein-folding events: application to alpha-lactalbumin.

    PubMed

    Canet, D; Doering, K; Dobson, C M; Dupont, Y

    2001-04-01

    An experimental procedure has been devised to record simultaneously fluorescence intensity and fluorescence anisotropy. A photoelastic modulator on the excitation beam enables the anisotropy signal to be recorded in one pass using a single photomultiplier tube and eliminates the need for a polarizer on the emission path. In conjunction with a stopped-flow mixer, providing a time-resolved capability, this procedure was used to study the refolding of apo alpha-lactalbumin following dilution from guanidinium chloride. Although the fluorescence intensity does not change detectably, the fluorescence anisotropy was found to resolve the conformational changes occurring between the initial unfolded state and the molten globule state formed either kinetically during refolding at pH 7.0 or at equilibrium at pH 2.0 (A-state). This result provides further evidence that fluorescence anisotropy is a valuable probe of protein structural transitions and that the information it provides concerning the rotational mobility of a fluorophore can be complementary to the information about the local environment provided by fluorescence intensity. PMID:11259312

  1. Transforming growth factor-alpha promotes mammary tumorigenesis through selective survival and growth of secretory epithelial cells.

    PubMed Central

    Smith, G. H.; Sharp, R.; Kordon, E. C.; Jhappan, C.; Merlino, G.

    1995-01-01

    Transforming growth factor (TGF)-alpha stimulates the growth and development of mammary epithelial cells and is implicated in the pathogenesis of human breast cancer. In this report we evaluate the consequences of overexpressing TGF-alpha in the mammary gland of transgenic mice and examine associated cellular mechanisms. When operating on a FVB/N genetic background (line MT100), TGF-alpha induced the stochastic development of mammary adenomas and adenocarcinomas f secretory epithelial origin in 64% of multiparous females. In contrast, tumors were exceedingly rare in virgin MT100 females, MT100 males, and multiparous FVB/N females. In MT100 females multiple foci of hyperplastic secretory lesions preceded the development of frank tumors; these initial lesions appeared during the involution period after the first lactation. Serial transplantation of these hyperplasias indicated an absence of proliferative immortality. Nevertheless, they gave rise to tumors at a low frequency and after a prolonged latency in virgin hosts; in multiparous hosts, tumors developed earlier and at a high incidence. The TGF-alpha transgene was highly expressed in hyperplasias and tumors but not in virgin and nonlesion-bearing tissue, suggesting that TGF-alpha overexpression provides a selective growth advantage. TGF-alpha also induced at lactation a 6.4-fold increase in DNA synthesis in MT100 epithelial cells, many of which were binucleated. MT100 mammary tissue experienced an obvious delay in involution, resulting in the postlactational survival of a significant population of unregressed secretory epithelial cells. In contrast, another line of transgenic mice on a CD-1 genetic background (MT42), in which TGF-alpha overexpression induced liver but not mammary tumors, failed to demonstrate postlactational epithelial cell survival. These data show that TGF-alpha promotes mammary tumorigenesis in multiparous MT100 mice by stimulating secretory epithelial cell proliferation during lactation and

  2. Selective Vaporization of Superheated Nanodroplets for Rapid, Sensitive, Acoustic Biosensing.

    PubMed

    Chattaraj, Rajarshi; Mohan, Praveena; Besmer, Jeremy D; Goodwin, Andrew P

    2015-08-26

    Superheated perfluorocarbon nano-droplets exhibit promise as sensitive acoustic biosensors. Aggregation of biotin-decorated lipid-shelled droplets by streptavidin greatly increases the yield of bubbles formed by ultrasound-induced vaporization. Streptavidin is sensed down to 1 × 10(-13) m, with differentiable signal appearing in as little as two minutes, using a scalable assay without washing, processing, or development steps. PMID:26084414

  3. Selective detector of cosmic particles based on diamond sensitive elements

    NASA Astrophysics Data System (ADS)

    Altukhov, A. A.; Zaharchenko, K. V.; Kolyubin, V. A.; Lvov, S. A.; Nedosekin, P. G.; Tyurin, E. M.; Ibragimov, R. F.; Kadilin, V. V.; Nikolaev, I. V.

    2016-02-01

    The article describes the device for selective registration of electrons, protons and heavy ions fluxes from the solar and galactic cosmic rays in the twelve energy ranges, built on a base of diamond detector. The use of the diamond detectors allowed for the creation a device for registration of cosmic particles fluxes at the external spacecraft surface with the resource not less than 20 years. Selective detector is aimed for continuous monitoring of radiation situation on board the spacecrafts, in order to predict the residual life of their work and prompt measures to actively protect the spacecraft when the flow of cosmic particles is sharply increased.

  4. Synapsin Is Selectively Required for Anesthesia-Sensitive Memory

    ERIC Educational Resources Information Center

    Knapek, Stephan; Gerber, Bertram; Tanimoto, Hiromu

    2010-01-01

    Odor-shock memory in "Drosophila melanogaster" consists of heterogeneous components each with different dynamics. We report that a null mutant for the evolutionarily conserved synaptic protein Synapsin entails a memory deficit selectively in early memory, leaving later memory as well as sensory motor function unaffected. Notably, a consolidated…

  5. Sensitive And Selective Chemical Sensor With Nanostructured Surfaces.

    DOEpatents

    Pipino, Andrew C. R.

    2003-02-04

    A chemical sensor is provided which includes an optical resonator including a nanostructured surface comprising a plurality of nanoparticles bound to one or more surfaces of the resonator. The nanoparticles provide optical absorption and the sensor further comprises a detector for detecting the optical absorption of the nanoparticles or their environment. In particular, a selective chemical interaction is provided which modifies the optical absorption of the nanoparticles or their environment, and an analyte is detected based on the modified optical absorption. A light pulse is generated which enters the resonator to interrogate the modified optical absorption and the exiting light pulse is detected by the detector.

  6. Alpha-synuclein aggregation involves a bafilomycin A1-sensitive autophagy pathway

    PubMed Central

    Klucken, Jochen; Poehler, Anne-Maria; Ebrahimi-Fakhari, Darius; Schneider, Jacqueline; Nuber, Silke; Rockenstein, Edward; Schlötzer-Schrehardt, Ursula; Hyman, Bradley T.; McLean, Pamela J.; Masliah, Eliezer; Winkler, Juergen

    2012-01-01

    Synucleinopathies like Parkinson disease and dementia with Lewy bodies (DLB) are characterized by α-synuclein aggregates within neurons (Lewy bodies) and their processes (Lewy neurites). Whereas α-synuclein has been genetically linked to the disease process, the pathological relevance of α-synuclein aggregates is still debated. Impaired degradation is considered to result in aggregation of α-synuclein. In addition to the ubiquitin-proteasome degradation, the autophagy-lysosomal pathway (ALP) is involved in intracellular degradation processes for α-synuclein. Here, we asked if modulation of ALP affects α-synuclein aggregation and toxicity. We have identified an induction of the ALP markers LAMP-2A and LC3-II in human brain tissue from DLB patients, in a transgenic mouse model of synucleinopathy, and in a cell culture model for α-synuclein aggregation. ALP inhibition using bafilomycin A1 (BafA1) significantly potentiates toxicity of aggregated α-synuclein species in transgenic mice and in cell culture. Surprisingly, increased toxicity is paralleled by reduced aggregation in both in vivo and in vitro models. The dichotomy of effects on aggregating and nonaggregating species of α-synuclein was specifically sensitive to BafA1 and could not be reproduced by other ALP inhibitors. The present study expands on the accumulating evidence regarding the function of ALP for α-synuclein degradation by isolating an aggregation specific, BafA1-sensitive, ALP-related pathway. Our data also suggest that protein aggregation may represent a detoxifying event rather than being causal for cellular toxicity. PMID:22647715

  7. Alpha-synuclein aggregation involves a bafilomycin A 1-sensitive autophagy pathway.

    PubMed

    Klucken, Jochen; Poehler, Anne-Maria; Ebrahimi-Fakhari, Darius; Schneider, Jacqueline; Nuber, Silke; Rockenstein, Edward; Schlötzer-Schrehardt, Ursula; Hyman, Bradley T; McLean, Pamela J; Masliah, Eliezer; Winkler, Juergen

    2012-05-01

    Synucleinopathies like Parkinson disease and dementia with Lewy bodies (DLB) are characterized by α-synuclein aggregates within neurons (Lewy bodies) and their processes (Lewy neurites). Whereas α-synuclein has been genetically linked to the disease process, the pathological relevance of α-synuclein aggregates is still debated. Impaired degradation is considered to result in aggregation of α-synuclein. In addition to the ubiquitin-proteasome degradation, the autophagy-lysosomal pathway (ALP) is involved in intracellular degradation processes for α-synuclein. Here, we asked if modulation of ALP affects α-synuclein aggregation and toxicity. We have identified an induction of the ALP markers LAMP-2A and LC3-II in human brain tissue from DLB patients, in a transgenic mouse model of synucleinopathy, and in a cell culture model for α-synuclein aggregation. ALP inhibition using bafilomycin A 1 (BafA1) significantly potentiates toxicity of aggregated α-synuclein species in transgenic mice and in cell culture. Surprisingly, increased toxicity is paralleled by reduced aggregation in both in vivo and in vitro models. The dichotomy of effects on aggregating and nonaggregating species of α-synuclein was specifically sensitive to BafA1 and could not be reproduced by other ALP inhibitors. The present study expands on the accumulating evidence regarding the function of ALP for α-synuclein degradation by isolating an aggregation specific, BafA1-sensitive, ALP-related pathway. Our data also suggest that protein aggregation may represent a detoxifying event rather than being causal for cellular toxicity. PMID:22647715

  8. Differentiation of alpha-amylase from various sources: an approach using selective inhibitors.

    PubMed

    Quarino, L; Hess, J; Shenouda, M; Ristenbatt, R R; Gold, J; Shaler, R C

    1993-01-01

    A radial diffusion assay in an agarose/starch gel utilizing crude kidney bean extract and a commercially prepared alpha-amylase inhibitor isolated from wheat seeds was developed and assessed to determine its ability to differentiate alpha-amylase from various sources. Kidney bean extract was found to have a greater inhibitory effect on AMY2, while the wheat lectin inhibitor was found to have a greater inhibitory effect on AMY1. Neither inhibitor was found to have any effect on commercially prepared bacterial alpha-amylase extract in both liquid preparations and dried stains. Mixtures of varying concentrations of pancreatic and salivary extracts also gave interpretable results. Additionally, dried stains prepared from human body fluids having high levels of AMY2 were differentiated from dried stains prepared from human body fluids containing high levels of AMY1. PMID:8360608

  9. Selective and controlled synthesis of alpha- and beta-cobalt hydroxides in highly developed hexagonal platelets.

    PubMed

    Liu, Zhaoping; Ma, Renzhi; Osada, Minoru; Takada, Kazunori; Sasaki, Takayoshi

    2005-10-12

    We report on the controlled synthesis of single-crystal platelets of alpha- and beta-Co(OH)2 via homogeneous precipitation using hexamethylenetetramine as a hydrolysis agent. The alpha- and beta-Co(OH)2 hexagonal platelets of several micrometers in width and about 15 nm in thickness were reproducibly yielded in rather dilute CoCl2 solutions in the presence and absence of NaCl at 90 degrees C, respectively. The phase and size control of the products were achieved by varying both CoCl2 and NaCl concentrations. Polarized optical microscope observations revealed clear liquid crystallinity of colloidal suspensions of these high aspect-ratio platelets. The as-prepared alpha-Co(OH)2 containing interlayer chloride ions was intercalated with various inorganic or organic anions, keeping its high crystallinity and hexagonal platelike morphology. PMID:16201808

  10. Toward selective CK2alpha and CK2alpha' inhibitors: Development of a novel whole-cell kinase assay by Autodisplay of catalytic CK2alpha'.

    PubMed

    Bollacke, Andre; Nienberg, Christian; Le Borgne, Marc; Jose, Joachim

    2016-03-20

    Human protein kinase CK2 is an emerging target for the development of novel anti-cancer therapeutics. CK2 is a tetramer composed of two catalytically active α- and/or α'-subunits, bound to a dimer of the regulatory β-subunit. Inhibitors targeting one of the two isoforms of the catalytically active CK2-subunit (α- and α') are important to study the distinct functions of these isoforms toward different CK2 associated pathologies. The present study for the first time describes the successful Autodisplay of the CK2α'-subunit, the paralogous isoform of CK2α. Expression on the cell surface of E. coli of CK2α' alone and in combination with the regulatory CK2β-subunit was confirmed by outer membrane isolation and protease accessibility test. Kinase activity of surface displayed CK2 could be detected with a CE-based assay and was found to be 3.06×10(-6) μmol/min for CK2α' alone and 1.02×10(-5) μmol/min when expressed in combination with CK2β. The comparison of the influence of NaCl on activity of the α'-subunit alone and in combination with the non-catalytically active β-subunit indicated interaction of both subunits on the cell surface. TMCB (4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)acetic acid), a known CK2 inhibitor described with distinct Ki values of 83 nM and 21 nM for the two different catalytic CK2 subunits α and α' was used for testing. First, inhibition of TMCB toward the purified CK2 holoenzyme CK2α2β2 was determined and resulted in a Ki value of 10.1 nM. Second, Ki values were determined with the surface displayed isoform CK2 holoenzymes and turned out to be of 31.1 nM for CK2α2β2 and 19.6 nM for CK2α'2β2. The inhibition data as obtained represented the distinct affinities of TMCB toward the two isoform holoenzymes. This indicated, that the surface display of CKα and CK2α', in the context of the corresponding holoenzymes, can be used to identify selective compounds. A set of twelve ATP competitive CK2 inhibitors

  11. A Selective Na(+) Aptamer Dissected by Sensitized Tb(3+) Luminescence.

    PubMed

    Zhou, Wenhu; Ding, Jinsong; Liu, Juewen

    2016-08-17

    A previous study of two RNA-cleaving DNAzymes, NaA43 and Ce13d, revealed the possibility of a common Na(+) aptamer motif. Because Na(+) binding to DNA is a fundamental biochemical problem, the interaction between Ce13d and Na(+) was studied in detail by using sensitized Tb(3+) luminescence spectroscopy. Na(+) displaces Tb(3+) from the DNAzyme, and thus quenches the emission from Tb(3+) . The overall requirement for Na(+) binding includes the hairpin and the highly conserved 16-nucleotide loop in the enzyme strand, along with a few unpaired nucleotides in the substrate. Mutation studies indicate good correlation between Na(+) binding and cleavage activity, thus suggesting a critical role of Na(+) binding for the enzyme activity. Ce13d displayed a Kd of ∼20 mm with Na(+) (other monovalent cations: 40-60 mm). The Kd values for other metal ions are mainly due to non-specific competition. With a single nucleotide mutation, the specific Na(+) binding was lost. Another mutant improved Kd to 8 mm with Na(+) . This study has demonstrated a Na(+) aptamer with important biological implications and analytical applications. It has also defined the structural requirements for Na(+) binding and produced an improved mutant. PMID:27238890

  12. Sensitivity of Alpha and Beta Oscillations to Sensorimotor Characteristics of Action: An EEG Study of Action Production and Gesture Observation

    PubMed Central

    Quandt, Lorna C.; Marshall, Peter J.; Shipley, Thomas F.; Beilock, Sian L.; Goldin-Meadow, Susan

    2012-01-01

    The sensorimotor experiences we gain when performing an action have been found to influence how our own motor systems are activated when we observe others performing that same action. Here we asked whether this phenomenon applies to the observation of gesture. Would the sensorimotor experiences we gain when performing an action on an object influence activation in our own motor systems when we observe others performing a gesture for that object? Participants were given sensorimotor experience with objects that varied in weight, and then observed video clips of an actor producing gestures for those objects. Electroencephalography (EEG) was recorded while participants first observed either an iconic gesture (pantomiming lifting an object) or a deictic gesture (pointing to an object) for an object, and then grasped and lifted the object indicated by the gesture. We analyzed EEG during gesture observation to determine whether oscillatory activity was affected by the observer’s sensorimotor experiences with the object represented in the gesture. Seeing a gesture for an object previously experienced as light was associated with a suppression of power in alpha and beta frequency bands, particularly at posterior electrodes. A similar pattern was found when participants lifted the light object, but over more diffuse electrodes. Moreover, alpha and beta bands at right parieto-occipital electrodes were sensitive to the type of gesture observed (iconic vs. deictic). These results demonstrate that sensorimotor experience with an object affects how a gesture for that object is processed, as measured by the gesture-observer’s EEG, and suggest that different types of gestures recruit the observer’s own motor system in different ways. PMID:22910276

  13. IL-1 alpha, but not IL-1 beta, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity.

    PubMed

    Nakae, S; Naruse-Nakajima, C; Sudo, K; Horai, R; Asano, M; Iwakura, Y

    2001-12-01

    Contact hypersensitivity (CHS) is a T cell-mediated cellular immune response caused by epicutaneous exposure to contact allergens. In this reaction, after the first epicutaneous allergen sensitization, Langerhans cells (LC) catch allergens and migrate from the skin to draining lymph nodes (LN) and activate naive T cells. Although IL-1 is suggested to be involved in these processes, the mechanisms have not been elucidated completely. In this report, to elucidate roles of IL-1alpha and IL-1beta in CHS, we analyzed ear swelling in 2,4,6-trinitrochlorobenzene (TNCB)-induced CHS using gene-targeted mice. We found that ear swelling was suppressed in IL-1alpha-deficient (IL-1alpha(-/-)) mice but not in IL-1beta(-/-) mice. LC migration from the skin into LN was delayed in both IL-1alpha(-/-) and IL-1beta(-/-) mice, suggesting that this defect was not the direct cause for the reduced CHS in these mice. However, we found that the proliferative response of trinitrophenyl (TNP)-specific T cells after sensitization with TNCB was specifically reduced in IL-1alpha(-/-) mice. Furthermore, adoptive transfer of TNP-conjugated IL-1-deficient epidermal cells (EC) into wild-type mice indicated that only IL-1alpha, but not IL-1beta, produced by antigen-presenting cells in EC could prime allergen-specific T cells. These observations indicate that IL-1alpha, but not IL-1beta, plays a crucial role in TNCB-induced CHS by sensitizing TNP-specific T cells. PMID:11717188

  14. Di-tert-butylsilylene-directed alpha-selective synthesis of 4-methylumbelliferyl T-antigen.

    PubMed

    Imamura, Akihiro; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto

    2005-09-29

    [reaction: see text] We have succeeded in the facile synthesis of 4-methylumbelliferyl T-antigen as a substrate for endo-alpha-N-acetylgalactosaminidase by exploiting the combination of the di-tert-butylsilylene effect and the Mitsunobu reaction. PMID:16178547

  15. Selective deficit in no-go performance induced by blockade of prefrontal cortical alpha 2-adrenoceptors in monkeys.

    PubMed

    Ma, Chao-Lin; Qi, Xue-Lian; Peng, Ji-Yun; Li, Bao-Ming

    2003-05-23

    Two monkeys (Macaca mulatta) were trained to make a go response (go to touch a computer screen) when a red signal (go signal) was presented or a no-go response (inhibit the screen-touching action) when a green signal (no-go signal) was given. The alpha2-adrenergic antagonist yohimbine was infused locally, bilaterally and continuously for 8 days into the prefrontal cortex (PFC) by using mini-osmotic pump. The no-go but not go performance was selectively impaired during the 8-day administration of yohimbine: the monkeys showed an inability to inhibit the touching response to the no-go signal, indicating that there was a deficit in the inhibitory ability of the animals. Similar infusion of saline into the same cortical area was without effect. The present study provides behavioral pharmacological evidence that alpha2-adrenoceptors in the PFC are involved in the neural mechanisms underlying response inhibition. PMID:12802193

  16. Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha-2-delta-1 subunit protein

    PubMed Central

    Zhou, Chunyi; Luo, Z. David

    2013-01-01

    Background Voltage-gated calcium channel α2δ1 subunit is the binding site for gabapentin, an effective drug in controlling neuropathic pain states including thermal hyperalgesia. Hyperalgesia to noxious thermal stimuli in both spinal-nerve-ligated (SNL) and voltage-gated calcium channel α2δ1 over-expressing transgenic (Tg) mice correlates with higher α2δ1 levels in dorsal root ganglia and dorsal spinal cord. In this study, we investigated whether abnormal synaptic transmission is responsible for thermal hyperalgesia induced by elevated α2δ1 expression in these models. Methods Behavioral sensitivities to thermal stimuli were test in L4 SNL and sham mice, as well as in α2δ1 Tg and wild-type mice. Miniature excitatory (mEPSC) and inhibitory (mIPSC) postsynaptic currents were recorded in superficial dorsal spinal cord neurons from these models using whole-cell patch clamp slice recording techniques. Results The frequency, but not amplitude, of mEPSC in superficial dorsal horn neurons was increased in SNL and α2δ1 Tg mice, which could be attenuated by gabapentin dose dependently. Intrathecal α2δ1 antisense oligodeoxynucleotide treatment diminished increased mEPSC frequency and gabapentin's inhibitory effects in elevated mEPSC frequency in the SNL mice. In contrast, neither the frequency, nor the amplitude, of mIPSC was altered in superficial dorsal horn neurons from the SNL and α2δ1 Tg mice. Conclusions Our findings support a role of peripheral nerve injury-induced α2δ1 in enhancing presynaptic excitatory input onto superficial dorsal spinal cord neurons that contributes to nociception development. PMID:24151064

  17. Correction: A Co(2+)-selective and chirality-sensitive supermolecular metallohydrogel with a nanofiber network skeleton.

    PubMed

    Wang, Xiaojuan; He, Ting; Yang, Lan; Wu, Huiqiong; Zhang, Rui; Zhang, Zhenzhu; Shen, Rujuan; Xiang, Juan; Zhang, Yi; Wei, Chuanwan

    2016-04-21

    Correction for 'A Co(2+)-selective and chirality-sensitive supermolecular metallohydrogel with a nanofiber network skeleton' by Xiaojuan Wang et al., Nanoscale, 2016, DOI: 10.1039/c6nr00822d. PMID:27021200

  18. Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

    SciTech Connect

    James, W.M.; Emerick, M.C.; Agnew, W.S. )

    1989-07-11

    The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated binding and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.

  19. Correlation of the ionisation response at selected points of IC sensitive regions with SEE sensitivity parameters under pulsed laser irradiation

    SciTech Connect

    Gordienko, A V; Mavritskii, O B; Egorov, A N; Pechenkin, A A; Savchenkov, D V

    2014-12-31

    The statistics of the ionisation response amplitude measured at selected points and their surroundings within sensitive regions of integrated circuits (ICs) under focused femtosecond laser irradiation is obtained for samples chosen from large batches of two types of ICs. A correlation between these data and the results of full-chip scanning is found for each type. The criteria for express validation of IC single-event effect (SEE) hardness based on ionisation response measurements at selected points are discussed. (laser applications and other topics in quantum electronics)

  20. Thrombin inhibition by the highly selective 'reversible suicide substrate' N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester.

    PubMed

    Ascenzi, Paolo; Gallina, Carlo; Bolognesi, Martino

    2005-07-01

    Thrombin is the last enzyme in the blood coagulation cascade. All pharmacological aspects support the use of thrombin inhibitors as antithrombotic agents. Here, we review the unusual inhibition behavior of the highly selective 'reversible suicide substrate' N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) targeted to the active center of human alpha-thrombin. Eoc-D-Phe-Pro-azaLys-ONp is an acylating agent, but its hydrolysis product 1(N-ethoxycarbonyl-D-phenylalanyl-L-prolyl)-2(4-aminobutyl) hydrazine behaves as a highly selective human alpha-thrombin competitive inhibitor. PMID:16029155

  1. A sensitive fluorescent sensor for quantification of alpha-fetoprotein based on immunosorbent assay and click chemistry.

    PubMed

    Xie, Qunfang; Weng, Xiuhua; Lu, Lijun; Lin, Zhenyu; Xu, Xiongwei; Fu, Caili

    2016-03-15

    A novel fluoresencent immunosensor for determination of cancer biomarkers such as alpha-fetoprotein (AFP) was designed by utilizing both the high specificity of antigen-antibody sandwich structure and the high sensitivity of the click chemistry based fluorescence detection. Instead of an enzyme or fluorophore, the CuO nanoparticles are labeled on the detection antibody, which was not susceptible to the change of the external environments. The CuO nanoparticles which were modified on the sandwich structure can be dissolved to produce Cu(2+) ions with the help of HCl and then the Cu(2+) ions were reduced by sodium ascorbate to produce Cu(+) ions which triggered the Cu(+) catalyzed alkyne-azide cycloaddition (CuAAC) reaction between the weak fluorescent compound (3-azido-7-hydroxycoumarin) and propargyl alcohol to form a strong fluorescent compound. A good linear relationship was observed between the fluorescence increase factor of the system and the concentration of AFP in the range of 0.025-5.0 ng/mL with a detection limit of 12 pg/mL (S/N=3). The proposed fluorescent sensor had been applied to detect AFP in the human serum samples and gave satisfactory results. PMID:26386330

  2. Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist.

    PubMed

    Crassous, Pierre-Antoine; Cardinaletti, Claudia; Carrieri, Antonio; Bruni, Bruno; Di Vaira, Massimo; Gentili, Francesco; Ghelfi, Francesca; Giannella, Mario; Paris, Hervé; Piergentili, Alessandro; Quaglia, Wilma; Schaak, Stéphane; Vesprini, Cristian; Pigini, Maria

    2007-08-01

    To assess the stereochemical requirements for efficient alpha2C-adrenoreceptor activation, the enantiomeric forms of m-nitrobiphenyline [(+/-)-5] were prepared and tested on cells expressing the human alpha2-adrenoreceptor subtypes. The importance of chirality was confirmed, since the enantiomer (R)-(+)-5 was much more efficient than (S)-(-)-5 in producing alpha2C-activation. Surprising reversal of enantioselectivity was observed with respect to structurally similar biphenyline [(+/-)-1] whose (S)-(-)-form proved the preferred alpha2C-configuration. PMID:17630725

  3. Estrogen Receptors Alpha (ERα) and Beta (ERβ): Subtype-Selective Ligands and Clinical Potential

    PubMed Central

    Paterni, Ilaria; Granchi, Carlotta; Katzenellenbogen, John A.; Minutolo, Filippo

    2014-01-01

    Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications. PMID:24971815

  4. Synthesis and biological evaluation of fluorine-18 labeled RS-15385-197 analogs: Potent and selective alpha-2 adrenergic receptor radioligands for PET

    SciTech Connect

    Enas, J.D.; VanBrocklin, H.F.; Budinger, T.F.; Clark, R.D.

    1997-12-31

    Aberrations in the {alpha}{sub 2}-adrenergic receptor system have been implicated in a number of disease states including hypertension, drug abuse, depression, and neurodegenerative disorders such as Alzheimer`s Disease. RS-15385-FP (1) and RS-15385-FPh (2) are analogs of the {alpha}{sub 2}-adrenergic receptor antagonist RS- 15385-197 which display a high receptor binding affinity (K{sub i} = 0.2 and 0.5 nM, respectively) as well as a high degree of {alpha}{sub 2}/{alpha}{sub 1} selectivity (7000:1 and 2000:1, respectively). We synthesized [F-18]-2 was synthesized by fluoro-for-nitro exchange on the corresponding nitrophenyl derivative which was produced in two steps from the hydroxypropyl sulfonamide. In vivo distribution studies in rats and PET studies in monkeys demonstrate uptake in {alpha}{sub 2}-adrenergic receptor rich regions of the brain, particularly the locus coeruleus.

  5. Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein.

    PubMed Central

    Murphy, J R; Bishai, W; Borowski, M; Miyanohara, A; Boyd, J; Nagle, S

    1986-01-01

    The structural gene for diphtheria toxin, tox, has been modified at its Sph I site by the introduction of an oligonucleotide linker encoding a unique Pst I restriction endonuclease site and a synthetic oligonucleotide encoding alpha-melanocyte-stimulating hormone (alpha-MSH). The resulting fusion gene directs the expression of a diphtheria toxin-related alpha-MSH hybrid protein in which the diphtheria toxin receptor-binding domain has been replaced with alpha-MSH sequences. The chimeric toxin has been partially purified from periplasmic extracts of recombinant Escherichia coli K-12 and has been found to be selectively toxic for alpha-MSH receptor-positive human malignant melanoma NEL-M1 cells in vitro. Images PMID:3095831

  6. Na(+)-, ouabain-, Ca(2+)-, and thapsigargin-sensitive ATPase activity expressed in chimeras between the calcium and the sodium pump alpha subunits.

    PubMed Central

    Ishii, T; Lemas, M V; Takeyasu, K

    1994-01-01

    Using the chicken sarcoplasmic/endoplasmic reticulum Ca2+ (SERCA)-ATPase as a parental molecule and replacing various portions with the corresponding portions of the chicken Na+,K(+)-ATPase alpha 1 subunit, Ca2+/thapsigargin- and Na+/ouabain-sensitive domains critical for these P-type ATPase activities were identified. In the chimera, [n/c]CC, the amino-terminal amino acids Met-1 to Asp-162 of the SERCA (isoform 1) (SERCA1) ATPase were replaced with the corresponding portion (Met-1-Asp-200) of the Na+,K(+)-ATPase alpha 1 subunit. In the chimera CC[c/n], the carboxyl-terminal amino acids (Ser-830 to COOH) of the SERCA1 ATPase were replaced with the corresponding segment (Leu-861 to COOH) of the Na+,K(+)-ATPase alpha 1 subunit, and in the chimera CNC, the middle part (Gly-354-Lys-712) of the SERCA1 ATPase was exchanged with the Na+,K(+)-ATPase alpha 1 subunit (Gly-378-Lys-724). None of the chimeric molecules exhibited any detectable ouabain-sensitive Na+,K(+)-ATPase activity, but they did exhibit thapsigargin-sensitive Ca(2+)-ATPase activity. Therefore, the segments Ile-163-Gly-354 and Lys-712-Ser-830 of the SERCA1 ATPase are sufficient for Ca2+ and thapsigargin sensitivity. The SERCA1-ATPase activity of [n/c]CC, but not of CCC, CNC, or CC[c/n], was further stimulated by addition of Na+ in the assay medium containing Ca2+. This additional stimulation of SERCA1-ATPase activity by Na+ was abolished when the amino-terminal region (Met-1-Leu-69) of [n/c]CC was deleted ([delta n/c]CC). In the absence of Na+, the SERCA1-ATPase activity of [n/c]CC was inhibited by ouabain, and, in the presence of Na+, its activity was stimulated by this drug. On the other hand, the ATPase activity of [delta n/c]CC was not affected by ouabain, although [delta n/c]CC can still bind [3H]ouabain. These results suggest that a distinct Na(+)-sensitive domain (Na+ sensor) located within the restricted amino-terminal region (Met-1-Leu-69) of the Na+,K(+)-ATPase alpha 1 subunit regulates ATPase

  7. A qualitative model structure sensitivity analysis method to support model selection

    NASA Astrophysics Data System (ADS)

    Van Hoey, S.; Seuntjens, P.; van der Kwast, J.; Nopens, I.

    2014-11-01

    The selection and identification of a suitable hydrological model structure is a more challenging task than fitting parameters of a fixed model structure to reproduce a measured hydrograph. The suitable model structure is highly dependent on various criteria, i.e. the modeling objective, the characteristics and the scale of the system under investigation and the available data. Flexible environments for model building are available, but need to be assisted by proper diagnostic tools for model structure selection. This paper introduces a qualitative method for model component sensitivity analysis. Traditionally, model sensitivity is evaluated for model parameters. In this paper, the concept is translated into an evaluation of model structure sensitivity. Similarly to the one-factor-at-a-time (OAT) methods for parameter sensitivity, this method varies the model structure components one at a time and evaluates the change in sensitivity towards the output variables. As such, the effect of model component variations can be evaluated towards different objective functions or output variables. The methodology is presented for a simple lumped hydrological model environment, introducing different possible model building variations. By comparing the effect of changes in model structure for different model objectives, model selection can be better evaluated. Based on the presented component sensitivity analysis of a case study, some suggestions with regard to model selection are formulated for the system under study: (1) a non-linear storage component is recommended, since it ensures more sensitive (identifiable) parameters for this component and less parameter interaction; (2) interflow is mainly important for the low flow criteria; (3) excess infiltration process is most influencing when focussing on the lower flows; (4) a more simple routing component is advisable; and (5) baseflow parameters have in general low sensitivity values, except for the low flow criteria.

  8. (3H)bunazosin, a novel selective radioligand of alpha 1 adrenoceptors in human prostates

    SciTech Connect

    Yamada, S.; Suzuki, M.; Matsuoka, Y.; Kato, Y.; Kimura, R.; Maruyama, M.; Kawabe, K. )

    1991-09-01

    The binding properties of a new radioligand, (3H)bunazosin, were studied in membranes of human prostates with benign prostatic hypertrophy (BPH). Specific binding of (3H)bunazosin was saturable, reversible, and of high affinity (Kd = 0.55 {plus minus} 0.04 nM). The density of (3H)bunazosin binding sites (Bmax) was 676 {plus minus} 33 fmol/mg. protein. (3H)Bunazosin rapidly associated with its binding sites in membranes of human prostates and reached steady state by 20 min. at 25C. The rate constants for association and dissociation of (3H)bunazosin binding were calculated to be 0.11 {plus minus} 0.01/nM/min. and 0.05 {plus minus} 0.02/min. (n = 4), respectively. Seven alpha 1 adrenoceptor antagonists competed with (3H)bunazosin for the binding sites in the rank order: R-(-)-YM-12617 greater than prazosin greater than SGB-1534 greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil. In parallel studies with (3H)bunazosin, the Kd and Bmax values for (3H)prazosin binding in human prostates were slightly lower. There was a similarity in the potency and rank order of seven alpha 1, adrenoceptor antagonists for the inhibition of (3H) bunazosin and (3H)prazosin binding in human prostates. The new (3H)bunazosin binding assay in human prostates is remarkable for its low degree of nonspecific binding as compared to (3H)prazosin, especially at high ligand concentrations. Thus, (3H)bunazosin may become a useful radioligand for the further analysis of the alph 1 adrenoceptor binding sites in human prostates.

  9. Comparative cleavage sites within the reactive-site loop of native and oxidized alpha1-proteinase inhibitor by selected bacterial proteinases.

    PubMed

    Rapala-Kozik, M; Potempa, J; Nelson, D; Kozik, A; Travis, J

    1999-10-01

    Human alpha1-proteinase inhibitor (alpha1-PI) is responsible for the tight control of neutrophil elastase activity which, if down regulated, may cause local excessive tissue degradation. Many bacterial proteinases can inactivate alpha1-PI by hydrolytic cleavage within its reactive site, resulting in the down regulation of elastase, and this mechanism is likely to contribute to the connective tissue damage often associated with bacterial infections. Another pathway of the inactivation of alpha1-PI is reversible and involves oxidation of a critical active-site methionine residue that may influence inhibitor susceptibility to proteolytic inactivation. Hence, the aim of this work was to determine whether this oxidation event might affectthe rate and pattern of the cleavage of the alpha1-PI reactive-site loop by selected bacterial proteinases, including thermolysin, aureolysin, serralysin, pseudolysin, Staphylococcus aureus serine proteinase, streptopain, and periodontain. A shift of cleavage specificity was observed after alpha1-PI oxidation, with a preference for the Glu354-Ala355 bond by most of the proteinases tested. Only aureolysin and serralysin cleave the oxidized form of alpha1-PI faster than the native inhibitor, suggesting that bacteria which secrete these metalloproteinases may specifically take advantage of the host defense oxidative mechanism to accelerate elimination of alpha1-PI and, consequently, tissue degradation by neutrophil elastase. PMID:10595584

  10. Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

    PubMed

    de Fiebre, C M; Romm, E; Collins, J T; Draski, L J; Deitrich, R A; Collins, A C

    1991-03-01

    Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans. PMID:2058804

  11. Selecting a sensitive battery of bioassays to detect toxic effects of metals in effluents.

    PubMed

    de Paiva Magalhães, Danielly; da Costa Marques, Mônica Regina; Fernandes Baptista, Darcilio; Forsin Buss, Daniel

    2014-09-01

    The use of bioassay batteries is necessary to evaluate toxic effects at various biological levels. The selection of bioassays without prior testing and determination of the most sensitive/suitable groups for each impact may allow the discharge of effluents that pose a threat to the environment. The present study tested and selected a battery of sensitive ecotoxicological bioassays for detecting toxic effects of metals. The sensitivities of six organisms were evaluated (algae Pseudokirchneriella subcapitata and Chlorella vulgaris, Cladocera Daphnia similis and Ceriodaphnia dubia, and fish Poecilia reticulata and Danio rerio) after exposure to 10 individual metal species deemed toxic to the aquatic environment (Ag(+), Cd(2+), Cu(+), Cu(2+), Cr(3+), Cr(6+), Pb(2+), Ni(2+), Zn(2+), and Hg(2+)) and to real (steel-mill) and laboratory simulated effluents. In the bioassays, fish were the least sensitive; D. rerio showed no sensitivity to any of the effluents tested. P. subcapitata was a good bioindicator of Cr(3+) toxicity, and D. similis was the most sensitive organism to Hg(2+); but the toxic effect of effluents with higher levels of Hg(2+) was better detected by C. dubia. The most sensitive battery of bioassays to detect low concentrations of dissolved metals in effluents was the 72-h chronic test with C. vulgaris and the 48-h acute test with C. dubia. PMID:25199585

  12. Recent progress in research on peroxisome proliferator-activated receptor alpha-selective ligands.

    PubMed

    Miyachi, Hiroyuki

    2004-08-01

    The understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor a (PPARalpha) as a regulator of lipid and lipoprotein homeostasis, and the rapid development of parallel high-throughput screening assays to evaluate the activity toward other PPAR subtypes (PPARdelta and PPARgamma), have provided an opportunity to develop novel PPARalpha-selective, PPARalpha/gamma dual and PPAR pan agonists for the treatment of various metabolic diseases. This review focuses on the molecular pharmacology of PPARalpha, and summarizes recent literature and patent applications disclosing medicinal chemistry strategies to identify new PPARalpha-selective agonists. The species selectivity of some classes of PPARalpha-selective agonists in response to in vitro PPARalpha transactivation activity is also reported. PMID:15334308

  13. Adaptation of quantal content to decreased postsynaptic sensitivity at single endplates in alpha-bungarotoxin-treated rats.

    PubMed Central

    Plomp, J J; van Kempen, G T; Molenaar, P C

    1992-01-01

    1. Rats were injected once every 48 h with alpha-bungarotoxin (alpha BTX) for periods up to 6 weeks. Injections caused weakness of facial muscles which lasted about 8 h. Hemidiaphragms were dissected for biochemical and electrophysiological measurements. 2. In muscles from animals treated for 2-3 weeks with toxin, the binding of 125I-alpha BTX was reduced to 58%, and the ACh content to 81% of control values. Choline acetyltransferase activity was unchanged. ACh release evoked by 3 Hz nerve stimulation was increased to 175% of control values. 3. The use of mu-conotoxin, which specifically blocks muscle action potentials, enabled the recording of full-sized endplate potentials (EPPs) and miniature endplate potentials (MEPPs) at normal muscle membrane potentials (-70 to -80 mV). The amplitude of MEPPs was decreased to 57% in muscles from animals treated for 3 weeks with alpha BTX. The mean of the quantal contents, calculated from the ratio of the corrected EPPs and the MEPPs, was increased to 154%. 4. Within individual muscles of both alpha BTX-treated and control rats, there was an inverse relationship between the quantal content of an endplate and its MEPP amplitude. 5. The MEPP frequency of endplates from control muscles was positively correlated with the quantal content. However, this correlation was not found in alpha BTX-affected muscles. 6. Three hours after a single injection of alpha BTX the amplitude of the MEPPs was reduced to about 60% of control values but no increase of the quantal content was found. During the first few days of alpha BTX treatment the quantal content gradually increased; it reached a plateau between 20 and 30 days. 7. The results suggest the existence of an adaptive mechanism, operating at individual endplates, in which retrograde signals at the motor nerve terminals modulate ACh release when neuromuscular transmission is endangered by block of acetylcholine receptors. PMID:1302275

  14. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

    NASA Technical Reports Server (NTRS)

    Oliver, A. E.; Deamer, D. W.

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

  15. A highly sensitive and selective immunoassay for the detection of tetrabromobisphenol A in soil and sediment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant. A sensitive and selective enzyme-linked immunosorbent assay (ELISA) for the detection of TBBPA was developed. Six haptens (T1-T6) mimicking different structural elements of TBBPA were synthesized and coupled to keyhole...

  16. Highly Sensitive and Selective Ethanol Sensor Fabricated with In-Doped 3DOM ZnO.

    PubMed

    Wang, Zhihua; Tian, Ziwei; Han, Dongmei; Gu, Fubo

    2016-03-01

    ZnO is an important n-type semiconductor sensing material. Currently, much attention has been attracted to finding an effective method to prepare ZnO nanomaterials with high sensing sensitivity and excellent selectivity. A three-dimensionally ordered macroporous (3DOM) ZnO nanostructure with a large surface area is beneficial to gas and electron transfer, which can enhance the gas sensitivity of ZnO. Indium (In) doping is an effective way to improve the sensing properties of ZnO. In this paper, In-doped 3DOM ZnO with enhanced sensitivity and selectivity has been synthesized by using a colloidal crystal templating method. The 3DOM ZnO with 5 at. % of In-doping exhibits the highest sensitivity (∼88) to 100 ppm ethanol at 250 °C, which is approximately 3 times higher than that of pure 3DOM ZnO. The huge improvement to the sensitivity to ethanol was attributed to the increase in the surface area and the electron carrier concentration. The doping by In introduces more electrons into the matrix, which is helpful for increasing the amount of adsorbed oxygen, leading to high sensitivity. The In-doped 3DOM ZnO is a promising material for a new type of ethanol sensor. PMID:26844815

  17. Sensitivity analysis of standardization procedures in drought indices to varied input data selections

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Ren, Liliang; Hong, Yang; Zhu, Ye; Yang, Xiaoli; Yuan, Fei; Jiang, Shanhu

    2016-07-01

    Reasonable input data selection is of great significance for accurate computation of drought indices. In this study, a comprehensive comparison is conducted on the sensitivity of two commonly used standardization procedures (SP) in drought indices to datasets, namely the probability distribution based SP and the self-calibrating Palmer SP. The standardized Palmer drought index (SPDI) and the self-calibrating Palmer drought severity index (SC-PDSI) are selected as representatives of the two SPs, respectively. Using meteorological observations (1961-2012) in the Yellow River basin, 23 sub-datasets with a length of 30 years are firstly generated with the moving window method. Then we use the whole time series and 23 sub-datasets to compute two indices separately, and compare their spatiotemporal differences, as well as performances in capturing drought areas. Finally, a systematic investigation in term of changing climatic conditions and varied parameters in each SP is conducted. Results show that SPDI is less sensitive to data selection than SC-PDSI. SPDI series derived from different datasets are highly correlated, and consistent in drought area characterization. Sensitivity analysis shows that among the three parameters in the generalized extreme value (GEV) distribution, SPDI is most sensitive to changes in the scale parameter, followed by location and shape parameters. For SC-PDSI, its inconsistent behaviors among different datasets are primarily induced by the self-calibrated duration factors (p and q). In addition, it is found that the introduction of the self-calibrating procedure for duration factors further aggravates the dependence of drought index on input datasets compared with original empirical algorithm that Palmer uses, making SC-PDSI more sensitive to variations in data sample. This study clearly demonstrate the impacts of dataset selection on sensitivity of drought index computation, which has significant implications for proper usage of drought

  18. Effect of the Administration of Alpha-Lipoic Acid on Contrast Sensitivity in Patients with Type 1 and Type 2 Diabetes

    PubMed Central

    Gębka, Anna; Raczyńska, Dorota

    2014-01-01

    The aim of this study was to estimate the effects of oral supplementation of alpha-lipoic acid (ALA) on contrast sensitivity (CS) in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The study included 12 patients with T1DM aged 43±12 years, 48 patients with T2DM aged 59±10 years, and 20 control subjects aged 33±8 years. Patients from each studied group, including the control group, were randomly assigned to receive 300 mg of ALA orally once daily for 3 months. CS was evaluated with the Functional Acuity Contrast Test (FACT, Stereo Optical). In the group of patients with T1DM receiving ALA for 3 months CS remained stable and improved in those with T2DM. Reduction of CS in both T1DM and T2DM patients without alpha-lipoic acid supplementation was observed. In the control group on alpha-lipoic acid supplementation, CS improvement was noticed at one spatial frequency. Changes in the CS were observed, despite stable visual acuity and eye fundus image in all studied subjects. Our study demonstrated that oral administration of alpha-lipoic acid had influence on CS in both T1DM and T2DM patients. PMID:24665163

  19. Reaction rate sensitivity of 44Ti production in massive stars and implications of a thick target yield measurement of 40Ca(alpha,gamma)44Ti

    SciTech Connect

    Hoffman, R D; Sheets, S A; Burke, J T; Scielzo, N D; Rauscher, T; Norman, E B; Tumey, S; Brown, T A; Grant, P G; Hurst, A M; Phair, L; Stoyer, M A; Wooddy, T; Fisker, J L; Bleuel, D

    2010-02-16

    We evaluate two dominant nuclear reaction rates and their uncertainties that affect {sup 44}Ti production in explosive nucleosynthesis. Experimentally we develop thick-target yields for the {sup 40}Ca({alpha},{gamma}){sup 44}Ti reaction at E{sub {alpha}} = 4.13, 4.54, and 5.36 MeV using {gamma}-ray spectroscopy. At the highest beam energy, we also performed an activation measurement which agrees with the thick target result. From the measured yields a stellar reaction rate was developed that is smaller than current statistical-model calculations and recent experimental results, which would suggest lower {sup 44}Ti production in scenarios for the {alpha}-rich freeze out. Special attention has been paid to assessing realistic uncertainties of stellar reaction rates produced from a combination of experimental and theoretical cross sections. With such methods, we also develop a re-evaluation of the {sup 44}Ti({alpha},p){sup 47}V reaction rate. Using these two rates we carry out a sensitivity survey of {sup 44}Ti synthesis in eight expansions representing peak temperature and density conditions drawn from a suite of recent supernova explosion models. Our results suggest that the current uncertainty in these two reaction rates could lead to as large an uncertainty in {sup 44}Ti synthesis as that produced by different treatments of stellar physics.

  20. Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion

    PubMed Central

    Whitt, Jason D.; Keeton, Adam B.; Gary, Bernard D.; Sklar, Larry A.; Sodani, Kamlesh; Chen, Zhe-Sheng; Piazza, Gary A.

    2016-01-01

    Abstract ATP-binding cassette (ABC) transpo rters ABCC1 (MRP1), ABCB1 (P-gp), and ABCG2 (BCRP) contribute to chemotherapy failure. The primary goals of this study were to characterize the efficacy and mechanism of the non­steroidal anti-inflammatory drug (NSAID), sulindac sulfide, to reverse ABCC1 mediated resistance to chemother­apeutic drugs and to determine if sulindac sulfide can influence sensitivity to chemotherapeutic drugs independently of drug efflux. Cytotoxicity assays were performed to measure resistance of ABC-expressing cell lines to doxoru­bicin and other chemotherapeutic drugs. NSAIDs were tested for the ability to restore sensitivity to resistance selected tumor cell lines, as well as a large panel of standard tumor cell lines. Other experiments characterized the mechanism by which sulindac sulfide inhibits ABCC1 substrate and co-substrate (GSH) transport in isolated membrane vesicles and intact cells. Selective reversal of multi-drug resistance (MDR), decreased efflux of doxor­ubicin, and fluorescent substrates were demonstrated by sulindac sulfide and a related NSAID, indomethacin, in resistance selected and engineered cell lines expressing ABCC1, but not ABCB1 or ABCG2. Sulindac sulfide also inhibited transport of leukotriene C4 into membrane vesicles. Sulindac sulfide enhanced the sensitivity to doxoru­bicin in 24 of 47 tumor cell lines, including all melanoma lines tested (7-7). Sulindac sulfide also decreased intra­cellular GSH in ABCC1 expressing cells, while the glutathione synthesis inhibitor, BSO, selectively increased sensitivity to sulindac sulfide induced cytotoxicity. Sulindac sulfide potently and selectively reverses ABCC1-mediated MDR at clinically achievable concentrations. ABCC1 expressing tumors may be highly sensitive to the direct cytotoxicity of sulindac sulfide, and in combination with chemotherapeutic drugs that induce oxidative stress.

  1. Brief Report: Sensitivity of Children with Autism Spectrum Disorders to Face Appearance in Selective Trust.

    PubMed

    Li, Pengli; Zhang, Chunhua; Yi, Li

    2016-07-01

    The current study examined how children with Autism Spectrum Disorders (ASD) could selectively trust others based on three facial cues: the face race, attractiveness, and trustworthiness. In a computer-based hide-and-seek game, two face images, which differed significantly in one of the three facial cues, were presented as two cues for selective trust. Children had to selectively trust the own-race, attractive and trustworthy faces to get the prize. Our findings demonstrate an intact ability of selective trust based on face appearance in ASD compared to typical children: they could selectively trust the informant based on face race and attractiveness. Our results imply that despite their face recognition deficits, children with ASD are still sensitive to some aspects of face appearance. PMID:26936158

  2. The amino-terminal 200 amino acids of the plasma membrane Na+,K+-ATPase alpha subunit confer ouabain sensitivity on the sarcoplasmic reticulum Ca(2+)-ATPase.

    PubMed Central

    Ishii, T; Takeyasu, K

    1993-01-01

    Cardiac glycosides such as G-strophanthin (ouabain) bind to and inhibit the plasma membrane Na+,K(+)-ATPase but not the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, whereas thapsigargin specifically blocks the SR Ca(2+)-ATPase. The chimera [n/c]CC, in which the amino-terminal amino acids Met1 to Asp162 of the SR Ca(2+)-ATPase (SERCA1) were replaced with the corresponding portion of the Na+,K(+)-ATPase alpha 1 subunit (Met1 to Asp200), retained thapsigargin- and Ca(2+)-sensitive ATPase activity, although the activity was lower than that of the wild-type SR Ca(2+)-ATPase. Moreover, this Ca(2+)-sensitive ATPase activity was inhibited by ouabain. The chimera NCC, in which Met1-Gly354 of the SR Ca(2+)-ATPase were replaced with the corresponding portion of the Na+,K(+)-ATPase, lost the thapsigargin-sensitive Ca(2+)-ATPase activity seen in CCC and [n/c]CC. [3H]Ouabain binding to [n/c]CC and NCC demonstrated that the affinity for this inhibitor seen in the wild-type chicken Na+,K(+)-ATPase was restored in these chimeric molecules. Thus, the ouabain-binding domains are distinct from the thapsigargin sites; ouabain binds to the amino-terminal portion (Met1 to Asp200) of the Na+,K(+)-ATPase alpha 1 subunit, whereas thapsigargin interacts with the regions after Asp162 of the Ca(2+)-ATPase. Moreover, the amino-terminal 200 amino acids of the Na+,K(+)-ATPase alpha 1 subunit are sufficient to exert ouabain-dependent inhibition even after incorporation into the corresponding portion of the Ca(2+)-ATPase, and the segment Ile163 to Gly354 of the SR Ca(2+)-ATPase is critical for thapsigargin- and Ca(2+)-sensitive ATPase activity. Images Fig. 5 PMID:8415625

  3. Positive selection of invariant V alpha 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells.

    PubMed Central

    Adachi, Y; Koseki, H; Zijlstra, M; Taniguchi, M

    1995-01-01

    V alpha 14+ T cells are a unique subset expressing an invariant T-cell antigen receptor alpha chain encoded by V alpha 14 and J alpha 281 gene fragments with a 1-nt N region. Most invariant V alpha 14+ T cells develop in extrathymic organs, independent of thymus, and expand at a high frequency in various mouse strains regardless of major histocompatibility complex (MHC) haplotype. In this paper, we show that the positive selection of invariant V alpha 14+ T cells requires a beta 2-microglobulin-associated MHC class I-like molecule not linked to the MHC on chromosome 17. This was determined by linkage analysis on DNA from recombinant mice generated by crossing a C57BL/6 mouse with a wild mouse, Mus musculus molossinus, that is negative for invariant V alpha 14 TCR expression. However, the peptide transporter TAP1 is not necessary for positive selection of invariant V alpha 14+ T cells, indicating the direct recognition of the MHC class I-like molecule without peptide by the invariant V alpha 14 TCR. Further, experiments with bone marrow-chimeric mice show that invariant V alpha 14+ T cells in the periphery are selected by bone marrow cells, suggesting a unique lineage of V alpha 14+ T cells differentiated through a selection process distinct from that of conventional alpha beta TCR+ T cells. Images Fig. 1 Fig. 2 Fig. 3 PMID:7862661

  4. Sensitivity analysis for volcanic source modeling quality assessment and model selection

    NASA Astrophysics Data System (ADS)

    Cannavó, Flavio

    2012-07-01

    The increasing knowledge and understanding of volcanic sources has led to the development and implementation of sophisticated and complex mathematical models with the main goal of describing field and experimental data. Quantification of the model's ability in describing the data becomes fundamental for a realistic estimate of the model parameters. The analysis of sensitivity can help us in identifying the parameters that significantly affect the model's output and in assessing its quality factor. In this paper, we describe the Global Sensitivity Analysis (GSA) methods based both on Fourier Amplitude Sensitivity Test and on the Sobol' approach and discuss their implementation in a Matlab software tool (GSAT). We also introduce a new criterion for model selection based on sensitivity analysis. The proposed approach is tested and applied to quantify the fitting ability of an analytic volcanic source model on a synthetic deformation data. Results show the validity of the method, against the traditional approaches, in supporting the volcanic model selection and the flexibility of the GSAT software tool in analyzing the model sensitivity.

  5. Pyrazolo-Pyrimidines: A Novel Heterocyclic Scaffold for Potent and Selective p38alpha Inhibitors

    SciTech Connect

    Das,J.; Moquin, R.; Pitt, S.; Zhang, R.; Shen, D.; McIntyre, K.; Gillooly, K.; Doweyko, A.; Sack, J.; et al

    2008-01-01

    The synthesis and structure-activity relationships (SAR) of p38a MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38a MAP kinase with excellent cellular potency toward the inhibition of TNFa production. Compound 2x was highly efficacious in vivo in inhibiting TNFa production in an acute murine model of TNFa production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38a is also disclosed.

  6. Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

    SciTech Connect

    Pratt, B.L.; Takahashi, J.S.

    1988-07-01

    The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxin partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.

  7. The effects of (RS)-alpha-cyclopropyl-4-phosphonophenylglycine ((RS)-CPPG), a potent and selective metabotropic glutamate receptor antagonist.

    PubMed Central

    Toms, N. J.; Jane, D. E.; Kemp, M. C.; Bedingfield, J. S.; Roberts, P. J.

    1996-01-01

    1. In this study we describe the potent antagonist activity of a novel metabotropic glutamate (mGlu) receptor antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine ((RS)-CPPG) which exhibits selectivity for mGlu receptors (group II and III) negatively coupled to adenylyl cyclase in the adult rat cortex. 2. Both the L-2-amino-4-phosphonobutyrate (L-AP4) and (2S, 1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1) inhibition of forskolin-stimulated cyclic AMP accumulation were potently reversed by (RS)-CPPG (IC50 values: 2.2 +/- 0.6 nM and 46.2 +/- 18.2 nM, respectively). 3. In contrast, (RS)-CPPG acted as a weak antagonist against group I mGlu receptors. In neonatal rat cortical slices, (RS)-CPPG antagonized (KB = 0.65 +/- 0.07 mM) (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD)-stimulated phosphoinositide hydrolysis. (RS)-CPPG (100 microM) failed to influence L-quisqualate-stimulated phosphoinositide hydrolysis in cultured cerebellar granule cells. 4. In the rat cerebral cortex, (RS)-CPPG is the most potent antagonist of group II/III mGlu receptors yet described (with 20 fold selectivity for group III mGlu receptors), having negligible activity at group I mGlu receptors. PMID:8922731

  8. Perceptual load manipulation reveals sensitivity of the face-selective N170 to attention.

    PubMed

    Mohamed, Tarik N; Neumann, Markus F; Schweinberger, Stefan R

    2009-05-27

    It has been controversial whether the face-sensitive N170 is affected by selective attention. We manipulated attention sensu Lavie's perceptual load theory to short (200 ms) presentations of task-irrelevant unfamiliar faces or houses, while participants identified superimposed target letters 'X' versus 'N'. These targets were strings of either six identical (low load) or six different letters (high load). Under low load, we found a prominent face-selective N170 response. Under high load, however, we not only observed a dramatic reduction of the face N170 but also an unexpected enhancement of the house N170, such that face selectivity was almost completely lost. We conclude that the early stages of face processing indexed by the N170 strongly depend on selective attention. PMID:19369907

  9. New highly sensitive and selective catalytic DNA biosensors for metal ions.

    PubMed

    Lu, Yi; Liu, Juewen; Li, Jing; Bruesehoff, Peter J; Pavot, Caroline M-B; Brown, Andrea K

    2003-05-01

    While remarkable progress has been made in developing sensors for metal ions such as Ca(II) and Zn(II), designing and synthesizing sensitive and selective metal ion sensors remains a significant challenge. Perhaps the biggest challenge is the design and synthesis of a sensor capable of specific and strong metal binding. Since our knowledge about the construction of metal-binding sites in general is limited, searching for sensors in a combinatorial way is of significant value. Therefore, we have been able to use a combinatorial method called in vitro selection to obtain catalytic DNA that can bind a metal ion of choice strongly and specifically. The metal ion selectivity of the catalytic DNA was further improved using a 'negative selection' strategy where catalytic DNA that are selective for competing metal ions are discarded in the in vitro selection processes. By labeling the resulting catalytic DNA with a fluorophore/quencher pair, we have made a new class of metal ion fluorescent sensors that are the first examples of catalytic DNA biosensors for metal ions. The sensors combine the high selectivity of catalytic DNA with the high sensitivity of fluorescent detection, and can be applied to the quantitative detection of metal ions over a wide concentration range and with high selectivity. The use of DNA sensors in detection and quantification of lead ions in environmental samples such as water from Lake Michigan has been demonstrated. DNA is stable, cost-effective, environmentally benign, and easily adaptable to optical fiber and microarray technology for device manufacture. Thus, the DNA sensors explained here hold great promise for on-site and real-time monitoring of metal ions in the fields of environmental monitoring, developmental biology, clinical toxicology, wastewater treatment, and industrial process monitoring. PMID:12706559

  10. STACKED REST-FRAME ULTRAVIOLET SPECTRA OF Ly{alpha}-EMITTING AND CONTINUUM-SELECTED GALAXIES AT 2 < z < 3.5

    SciTech Connect

    Berry, Michael; Gawiser, Eric; Guaita, Lucia; Padilla, Nelson; Francke, Harold; Treister, Ezequiel; Blanc, Guillermo A.; Ciardullo, Robin; Gronwall, Caryl

    2012-04-10

    We present properties of individual and composite rest-UV spectra of continuum- and narrowband-selected star-forming galaxies (SFGs) at a redshift of 2 < z < 3.5 discovered by the MUSYC collaboration in the Extended Chandra Deep Field-South. Among our sample of 81 UV-bright SFGs, 59 have R < 25.5, of which 32 have rest-frame equivalent widths of W{sub Ly{alpha}} > 20 A, the canonical limit to be classified as an Ly{alpha}-emitting galaxy. We divide our data set into subsamples based on properties that we are able to measure for each individual galaxy: Ly{alpha} equivalent width, rest-frame UV colors, and redshift. Among our subsample of galaxies with R < 25.5, those with rest frame W{sub Ly{alpha}} > 20 A have bluer UV continua, weaker low-ionization interstellar absorption lines, weaker C IV absorption, and stronger Si II* nebular emission than those with W{sub Ly{alpha}} < 20 A. We measure a velocity offset of {Delta}v {approx} 600 km s{sup -1} between Ly{alpha} emission and low-ionization absorption, which does not vary substantially among any of our subsamples. We find that the interstellar component, as opposed to the stellar component, dominates the high-ionization absorption line profiles. We find that the low- and high-ionization Si ionization states have similar kinematic properties, yet the low-ionization absorption is correlated with Ly{alpha} emission and the high-ionization absorption is not. These trends are consistent with outflowing neutral gas being in the form of neutral clouds embedded in ionized gas as previously suggested by Steidel et al. Moreover, our galaxies with bluer UV colors have stronger Ly{alpha} emission, weaker low-ionization absorption, and more prominent nebular emission line profiles. From a redshift of 2.7 < z < 3.5 to 2.0 < z < 2.7, our subsample of galaxies with W{sub Ly{alpha}} < 20 Angstrom-Sign shows no significant evolution in their physical properties or the nature of their outflows. Among our data set, UV-bright galaxies

  11. Antireflection treatment of thickness sensitive spectrally selective (TSSS) paints for thermal solar absorbers

    SciTech Connect

    Lundh, M.; Waeckelgaard, E.; Blom, T.

    2010-01-15

    There are several methods to produce solar absorbers, and one cheap alternative is painted absorbers, preferably painted with a spectrally selective paint. The optical properties of Thickness Sensitive Spectrally Selective (TSSS) paints are, however, limited by the thickness of the paint layer. In this study it is shown that the solar absorptance of two commercial TSSS paints can be increased between 0.01 and 0.02 units with an antireflection treatment using a silicon dioxide layer deposited from silica-gel. It was found that the thermal emittance (100 C) did not change significantly after the treatment. (author)

  12. Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity.

    PubMed

    Martini, P G; Delage-Mourroux, R; Kraichely, D M; Katzenellenbogen, B S

    2000-09-01

    We find that prothymosin alpha (PTalpha) selectively enhances transcriptional activation by the estrogen receptor (ER) but not transcriptional activity of other nuclear hormone receptors. This selectivity for ER is explained by PTalpha interaction not with ER, but with a 37-kDa protein denoted REA, for repressor of estrogen receptor activity, a protein that we have previously shown binds to ER, blocking coactivator binding to ER. We isolated PTalpha, known to be a chromatin-remodeling protein associated with cell proliferation, using REA as bait in a yeast two-hybrid screen with a cDNA library from MCF-7 human breast cancer cells. PTalpha increases the magnitude of ERalpha transcriptional activity three- to fourfold. It shows lesser enhancement of ERbeta transcriptional activity and has no influence on the transcriptional activity of other nuclear hormone receptors (progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, or retinoic acid receptor) or on the basal activity of ERs. In contrast, the steroid receptor coactivator SRC-1 increases transcriptional activity of all of these receptors. Cotransfection of PTalpha or SRC-1 with increasing amounts of REA, as well as competitive glutathione S-transferase pulldown and mammalian two-hybrid studies, show that REA competes with PTalpha (or SRC-1) for regulation of ER transcriptional activity and suppresses the ER stimulation by PTalpha or SRC-1, indicating that REA can function as an anticoactivator in cells. Our data support a model in which PTalpha, which does not interact with ER, selectively enhances the transcriptional activity of the ER but not that of other nuclear receptors by recruiting the repressive REA protein away from ER, thereby allowing effective coactivation of ER with SRC-1 or other coregulators. The ability of PTalpha to directly interact in vitro and in vivo with REA, a selective coregulator of the ER, thereby enabling the interaction of ER with coactivators, appears to explain

  13. Reactive chromophores for sensitive and selective detection of chemical warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Frye-Mason, Greg; Leuschen, Martin; Wald, Lara; Paul, Kateri; Hancock, Lawrence F.

    2005-05-01

    A reactive chromophore developed at MIT exhibits sensitive and selective detection of surrogates for G-class nerve agents. This reporter acts by reacting with the agent to form an intermediate that goes through an internal cyclization reaction. The reaction locks the molecule into a form that provides a strong fluorescent signal. Using a fluorescent sensor platform, Nomadics has demonstrated rapid and sensitive detection of reactive simulants such as diethyl chloro-phosphate (simulant for sarin, soman, and related agents) and diethyl cyanophosphate (simulant for tabun). Since the unreacted chromophore does not fluoresce at the excitation wavelength used for the cyclized reporter, the onset of fluo-rescence can be easily detected. This fluorescence-based detection method provides very high sensitivity and could enable rapid detection at permissible exposure levels. Tests with potential interferents show that the reporter is very selective, with responses from only a few highly toxic, electrophilic chemicals such as phosgene, thionyl chloride, and strong acids such as HF, HCl, and nitric acid. Dimethyl methyl phosphonate (DMMP), a common and inactive simu-lant for other CW detectors, is not reactive enough to generate a signal. The unique selectivity to chemical reactivity means that a highly toxic and hazardous chemical is present when the reporter responds and illustrates that this sensor can provide very low false alarm rates. Current efforts focus on demonstrating the sensitivity and range of agents and toxic industrial chemicals detected with this reporter as well as developing additional fluorescent reporters for a range of chemical reactivity classes. The goal is to produce a hand-held sensor that can sensitively detect a broad range of chemical warfare agent and toxic industrial chemical threats.

  14. Selectivity and sensitivity of some thin-layer chromatographic detection systems.

    PubMed

    Fodor-Csorba, K; Dutka, F

    1986-09-19

    The selectivity and sensitivity of some thin-layer chromatographic detection systems widely used internationally and developed in our laboratory were studied. Halogenated organophosphorus pesticides were found to interfere with the detection of organochlorine pesticides when using silver nitrate-2-phenoxyethanol. The stability of colours formed by the 4-(4'-nitrobenzyl)pyridine-tetraethylenepentamine system was enhanced by spraying with acetic acid and allowed densitometric evaluation. The most sensitive detection method for thiocarbamates is the reaction with 2,6-dichlorobenzoquinone-N-chloroimine or its dibromo analogue (50 ng). Application of this method for sulphur-containing organophosphorus insecticides results in the same or better sensitivity. Quantitation of these compounds was carried out by densitometry. PMID:3771705

  15. An aqueous fluorescent probe for Hg(2+) detection with high selectivity and sensitivity.

    PubMed

    Fang, Qian; Liu, Qian; Song, Xiangzhi; Kang, Jian

    2015-12-01

    An aqueous fluorescent probe, 1, was developed for the rapid detection of Hg(2+) with high sensitivity and excellent selectivity. Upon the addition of Hg(2+) in pure aqueous media, the Hg(2+)-mediated hydrolysis of vinyl ether and subsequent cyclization reactions converted probe 1 into the corresponding iminocoumarin dye, which is strongly fluorescent when excited. The application of this probe for the detection of intracellular Hg(2+) was successfully demonstrated in living cells. PMID:25761896

  16. Metal selectivity of Sargassum spp. and their alginates in relation to their alpha-L-guluronic acid content and conformation.

    PubMed

    Davis, Thomas A; Llanes, Francisco; Volesky, Bohumil; Mucci, Alfonso

    2003-01-15

    The discovery of a consistent and unusual enrichment in homopolymeric alpha-L-guluronic acid G-blocks in alginates extracted from a suite of Sargassum brown algae is described in this study. 1H NMR spectroscopy was used to characterize these alginates which display homopolymeric guluronic acid block (G-block) frequency values (F(GG)) between 0.37 and 0.81. The presence of these G-blocks results in an enhanced selectivity for cadmium or calcium relative to monovalent ions such as sodium and the proton as well as smaller divalent ions such as magnesium. Results of competitive exchange experiments for the Cd-Ca-alginate system yield selectivity coefficient, K*(Cd)Ca, values between 0.43 +/- 0.10 and 1.32 +/- 0.02 for a range in F(GG) of 0.23 to 0.81. In contrast to the Cd-Ca-alginate system, the Mg-Ca-alginate and Mg-Cd-alginate systems yielded maximum values of K*(Mg)Ca (18.0 +/- 1.4) and K*(Mg)Cd (16.0 +/- 0.9) for the alginates extracted from Sargassum fluitans (F(GG) = 0.81; Cuba) and Sargassum thunbergii (F(GG) = 0.75; Korea), respectively. Selectivity studies with mixed-metal pair alginate systems highlight the importance of the specific macromolecular conformation of the alginate polymer in determining metal binding behavior in multiple-metal systems. Furthermore, they demonstrate the importance of the conformation of the alginate as it occurs within the tissue of Sargassum in determining the metal binding behavior of this algal biosorbent. The unique composition of the alginates present in species of Sargassum may represent a distinct advantage over other brown algal species when considering their implementation for the strategic removal of toxic heavy metals from contaminated and industrial wastewaters. PMID:12564896

  17. Perceived egocentric distance sensitivity and invariance across scene-selective cortex.

    PubMed

    Persichetti, Andrew S; Dilks, Daniel D

    2016-04-01

    Behavioral studies in many species and studies in robotics have demonstrated two sources of information critical for visually-guided navigation: sense (left-right) information and egocentric distance (proximal-distal) information. A recent fMRI study found sensitivity to sense information in two scene-selective cortical regions, the retrosplenial complex (RSC) and the occipital place area (OPA), consistent with hypotheses that these regions play a role in human navigation. Surprisingly, however, another scene-selective region, the parahippocampal place area (PPA), was not sensitive to sense information, challenging hypotheses that this region is directly involved in navigation. Here we examined how these regions encode egocentric distance information (e.g., a house seen from close up versus far away), another type of information crucial for navigation. Using fMRI adaptation and a regions-of-interest analysis approach in human adults, we found sensitivity to egocentric distance information in RSC and OPA, while PPA was not sensitive to such information. These findings further support that RSC and OPA are directly involved in navigation, while PPA is not, consistent with the hypothesis that scenes may be processed by distinct systems guiding navigation and recognition. PMID:26963085

  18. Nonmaternal Care's Association With Mother's Parenting Sensitivity: A Case of Self-Selection Bias?

    PubMed

    Nomaguchi, Kei M; Demaris, Alfred

    2013-06-01

    Although attachment theory posits that the use of nonmaternal care undermines quality of mothers' parenting, empirical evidence for this link is inconclusive. Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,233), the authors examined the associations between nonmaternal care characteristics and maternal sensitivity during the first 3 years of children's lives, with special attention to selection effects and moderation by resource levels. Findings from fixed-effects regression models suggested that, on average, there is little relationship between nonmaternal care characteristics and maternal sensitivity, once selection factors are held constant. Some evidence of moderation effects was found, however. Excellent-quality care is related to more sensitivity for mothers with lower family income. Poor-quality care is related to lower sensitivity for single mothers, but not partnered mothers. In sum, nonmaternal care characteristics do not seem to have as much influence on mothers' parenting as attachment theory claims. PMID:23772093

  19. [Alpha1-adrenoceptor subtypes and alpha1-adrenoceptor antagonists].

    PubMed

    Muramatsu, Ikunobu; Suzuki, Fumiko; Tanaka, Takashi; Yamamoto, Hatsumi; Morishima, Shigeru

    2006-03-01

    Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) have been cloned and show different pharmacologic profiles. In addition, a putative alpha(1)-adrenoceptor (alpha(1L) subtype) has also been proposed. Recently, three drugs (tamsulosin, naftopidil, and silodosin) have been developed in Japan for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. In this review, we describe recent alpha(1)-adrenoceptor subclassifications and the pharmacologic characteristics (subtype selectivity and clinical relevance) of alpha(1)-adrenoceptor antagonists. PMID:16518082

  20. Highly sensitive and doubly orientated selective molecularly imprinted electrochemical sensor for Cu(2.).

    PubMed

    Li, Jianping; Zhang, Lianming; Wei, Ge; Zhang, Yun; Zeng, Ying

    2015-07-15

    Studies on molecularly imprinted electrochemical sensors for metal ions determination have been widely reported. However, the sensitivity and selectivity of the sensors needs to be improved urgently. In the current work, a novel molecularly imprinted electrochemical sensor was originally developed for selective determination of ultratrace Cu(2+) by combining the metal-ligand chelate orientated recognition with enzyme amplification effect. The detection relied on a competition reaction between Cu(2+)-glycine (Cu-Gly) and horse radish peroxidase (HRP)-labeled Cu-Gly on the imprinted polymer membrane modified electrode. The sensitivity of this sensor was promoted by enzyme amplification. Selectivity was improved by the double-specificity derived from ligand-to-metal ion and metal-ligand chelate orientated recognition of 3D imprinted cavities. This technique was quantitatively sensitive to Cu(2+) concentrations ranging from 0.5nmol/L to 30nmol/L, with a detection limit of 42.4pmol/L. which was lower than those in most of the reported methods. The allowable amounts of interference ions were higher when it compared to other common molecularly imprinted sensors. Moreover, the results of assaying several real samples have proven its feasibility for practical applications. PMID:25771304

  1. The sexually differentiated metabolism of [6,7-3H]17 beta-oestradiol in rats: male-specific 15 alpha- and male-selective 16 alpha-hydroxylation and female-selective catechol formation.

    PubMed

    Maggs, J L; Morgan, P; Park, B K

    1992-03-01

    The oxygenated-metabolite profiles of exogenous 17 beta-oestradiol (E2) in adult male and female Wistar rats have been characterized and major sex-dependent biotransformations observed which correlate with the regioselectivities of known sexually differentiated hepatic P450. [6,7-3H]E2 (27 micrograms/kg) was given i.v. The metabolites of E2 were rapidly and extensively excreted in bile (46 and 78% of the dose over 1 and 6 h, respectively). Female rats metabolized E2 by one major pathway: oxidation to oestrone (E1) followed by C-2 hydroxylation and O-methylation; the principal aglycones (0-1 h bile collections) were E1 (14%), 2-hydroxyE1 (2-OHE1) (42%) and 2-methoxyE1 (24%). Male rats metabolized E2 principally by two parallel composite pathways of E1 hydroxylation which yielded a complex mixture of mono- and di-oxygenated compounds: 15 alpha-OHE1 (33%), 2,15 alpha-diOHE1 (7%), and 2-methoxy-15 alpha OHE1 (14%); 16 alpha-OHE1 (13%), 2,16 alpha-diOHE1 (4%) and 2-methoxy-16 alpha-OHE1 (2%). 15 alpha-Hydroxylation was unique to males. The balance of aromatic and alkyl hydroxylation in males was dose-dependent: at 3 mg/kg, 15 alpha-hydroxylation was decreased approx. 50% in favour of 2-hydroxylation whilst 16 alpha-hydroxylation was largely unaffected. The male-specific 15 alpha-hydroxylation and male-predominant 16 alpha-hydroxylation of E1 derived from E2 in vivo may be ascribable to the male-specific isoforms P450IIC13 and P450IIC11, respectively. PMID:1313694

  2. Synthesis and computational investigation of molecularly imprinted nanospheres for selective recognition of alpha-tocopherol succinate

    PubMed Central

    Piacham, Theeraphon; Nantasenamat, Chanin; Isarankura-Na-Ayudhya, Chartchalerm; Prachayasittikul, Virapong

    2013-01-01

    Molecularly imprinted polymers (MIPs) are macromolecular matrices that can mimic the functional properties of antibodies, receptors and enzymes while possessing higher durability. As such, these polymers are interesting materials for applications in biomimetic sensor, drug synthesis, drug delivery and separation. In this study, we prepared MIPs and molecularly imprinted nanospheres (MINs) as receptors with specific recognition properties toward tocopherol succinate (TPS) in comparison to tocopherol (TP) and tocopherol nicotinate (TPN). MIPs were synthesized using methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as crosslinking agent and dichloromethane or acetronitrile as porogenic solvent under thermal-induced polymerization condition. Results indicated that imprinted polymers of TPS-MIP, TP-MIP and TPN-MIP all bound specifically to their template molecules at 2 folds greater than the non-imprinted polymers. The calculated binding capacity of all MIP was approximately 2 mg per gram of polymer when using the optimal rebinding solvent EtOH:H2O (3:2, v/v). Furthermore, the MINs toward TPS and TP were prepared by precipitation polymerization that yielded particles that are 200-400 nm in size. The binding capacities of MINs to their templates were greater than that of the non-imprinted nanospheres when using the optimal rebinding solvent EtOH:H2O (4:1, v/v). Computer simulation was performed to provide mechanistic insights on the binding modalities of template-monomer complexes. In conclusion, we had successful prepared MIPs and MINs for binding specifically to TP and TPS. Such MIPs and MINs have great potential for industrial and medical applications, particularly for the selective separation of TP and TPS. PMID:26622214

  3. Mechanical stimulation of skeletal muscle increases prostaglandin F2(alpha) synthesis and cyclooxygenase activity by a pertussis toxin sensitive mechanism

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Shansky, Janet; Solerssi, Rosa; Chromiak, Joseph

    1992-01-01

    Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increases the production of prostaglandin F(sub 2(alpha)), an anabolic stimulator of myofiber growth. Within 4 h of initiating mechanical activity, the activity of cyclooxygenase, a regulatory enzyme in prostaglandin synthesis, was increased 82% (P is less than .005), and this increase was maintained for at least 24 h. Kinetic analysis of the stretch-activated cyclooxygenase indicated a two to three-fold decrease in the enzyme's K(sub m) with no change in V(sub max). The stretch-induced increase in enzymatic activity was not inhibited by cycloheximide, was independent of cellular electrical activity (tetrodotoxin-insensitive), but was prevented by the G protein inhibitor pertussis toxin. Pertussis toxin also inhibited the stretch-induced increases in PGF(sub 2(alpha)) production, and cell growth. It is concluded that stretch of skeletal muscle increases the synthesis of the anabolic modulator PGF(sub 2(alpha)) by a G protein-dependent process which involves activation of cyclooxygenase by a posttranslational mechanism.

  4. Alpha-emitting radioisotopes for switchable neutron generators

    NASA Astrophysics Data System (ADS)

    Hertz, K. L.; Hilton, N. R.; Lund, J. C.; Van Scyoc, J. M.

    2003-06-01

    Traditionally, radioisotopic neutron generators mix an alpha-emitting radioisotope with beryllium. The disadvantage of such an alpha-Be source is that they emit neutrons at a steady rate even when stored. These conventional generators are extremely awkward to use in many applications because of the neutron shielding required to prevent exposure to personnel and sensitive electronics. Recently, at our laboratory and others, the possibility of using switchable radioactive neutron sources has been investigated. These sources rely on a mechanical operation to separate the alpha-emitting radioisotope from the Be target, thus allowing the source to be switched on and off. The utility of these new switchable sources is critically dependent on the selection of the alpha-emitting radioisotope. In this paper we discuss issues that determine the desirability of an alpha-emitting source for a switchable neutron generator, and select alpha emitters that are best suited for use in this application.

  5. The C-terminal 165 amino acids of the plasma membrane Ca(2+)-ATPase confer Ca2+/calmodulin sensitivity on the Na+,K(+)-ATPase alpha-subunit.

    PubMed Central

    Ishii, T; Takeyasu, K

    1995-01-01

    The C-terminal 165 amino acids of the rat brain plasma membrane (PM) Ca(2+)-ATPase II containing the calmodulin binding auto-inhibitory domain was connected to the C-terminus of the ouabain sensitive chicken Na+,K(+)-ATPase alpha 1 subunit. Expression of this chimeric molecule in ouabain resistant mouse L cells was assured by the high-affinity binding of [3H]ouabain. In the presence of Ca2+/calmodulin, this chimeric molecule exhibited ouabain inhibitable Na+,K(+)-ATPase activity; the putative chimeric ATPase activity was absent in the absence of Ca2+/calmodulin and activated by Ca2+/calmodulin in a dose-dependent manner. Furthermore, this chimeric molecule could bind monoclonal IgG 5 specific to the chicken Na+,K(+)-ATPase alpha 1 subunit only in the presence of Ca2+/calmodulin, suggesting that the epitope for IgG 5 in this chimera is masked in the absence of Ca2+/calmodulin and uncovered in their presence. These results propose a direct interaction between the calmodulin binding auto-inhibitory domain of the PM Ca(2+)-ATPase and the specific regions of the Na+,K(+)-ATPase alpha 1 subunit that are structurally homologous to the PM Ca(2+)-ATPase. A comparison of the deduced amino acid sequences revealed several possible regions within the Na+,K(+)-ATPase that might interact with the auto-inhibitory domain of the PM Ca(2+)-ATPase. Images PMID:7828596

  6. Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

    SciTech Connect

    Li, Yong; Kovach, Amanda; Suino-Powell, Kelly; Martynowski, Dariusz; Xu, H. Eric

    2008-07-23

    The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1{alpha} indicate that the first PGC-1{alpha} motif is necessary and sufficient for PGC-1{alpha} to coactivate PPAR{gamma} in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPAR{gamma} and PGC-1{alpha} in glucose homeostasis and adipocyte differentiation.

  7. Effect of electrode material and design on sensitivity and selectivity for high temperature impedancemetric NOx sensors

    SciTech Connect

    Woo, L Y; Glass, R S; Novak, R F; Visser, J H

    2009-09-23

    Solid-state electrochemical sensors using two different sensing electrode compositions, gold and strontium-doped lanthanum manganite (LSM), were evaluated for gas phase sensing of NO{sub x} (NO and NO{sub 2}) using an impedance-metric technique. An asymmetric cell design utilizing porous YSZ electrolyte exposed both electrodes to the test gas (i.e., no reference gas). Sensitivity to less than 5 ppm NO and response/recovery times (10-90%) less than 10 s were demonstrated. Using an LSM sensing electrode, virtual identical sensitivity towards NO and NO{sub 2} was obtained, indicating that the equilibrium gas concentration was measured by the sensing electrode. In contrast, for cells employing a gold sensing electrode the NO{sub x} sensitivity varied depending on the cell design: increasing the amount of porous YSZ electrolyte on the sensor surface produced higher NO{sub 2} sensitivity compared to NO. In order to achieve comparable sensitivity for both NO and NO{sub 2}, the cell with the LSM sensing electrode required operation at a lower temperature (575 C) than the cell with the gold sensing electrode (650 C). The role of surface reactions are proposed to explain the differences in NO and NO{sub 2} selectivity using the two different electrode materials.

  8. A simple and rapid chemiluminescence aptasensor for acetamiprid in contaminated samples: Sensitivity, selectivity and mechanism.

    PubMed

    Qi, Yingying; Xiu, Fu-Rong; Zheng, Minfeng; Li, Baoxin

    2016-09-15

    Ultralow concentration and selective detection of pesticide residue is important to evaluate the environmental and biological pollution and the threat to human health which single component pesticide can bring. Herein, we report an amplified chemiluminescence (CL) sensing platform for ultrasensitive and selective acetamiprid (widely used pesticide) detection. It is based on aptamer's high binding affinity to target and the relevance between AuNPs' morphology and its catalytic effect to stimulate the generation of CL in the presence of H2O2 and luminol. Moreover, AuNPs morphological slight change induced by aptamers' conformation during targets binding could lead to the significant change of catalytic properties. Therefore, the proposed sensing platform for pesticide residue exhibited a high sensitivity toward acetamiprid with a detection limit of 62pM, which was about 100-fold lower than that of other aptamer-based sensor for acetamiprid detection. Because of the intrinsic specificity of aptamer's recognization, this sensing platform has high selectivity. So, this sensing platform provides a label-free and cost-effective approach for sensitive and selective detection of single component pesticide residue. More importantly, this CL method was successfully used to determine acetamiprid in real contaminated samples. PMID:27131997

  9. THE FIRST SYSTEMATIC SURVEY FOR Ly{alpha} EMITTERS AT z = 7.3 WITH RED-SENSITIVE SUBARU/SUPRIME-CAM

    SciTech Connect

    Shibuya, Takatoshi; Kashikawa, Nobunari; Iye, Masanori; Ota, Kazuaki; Ouchi, Masami; Furusawa, Hisanori; Shimasaku, Kazuhiro; Hattori, Takashi

    2012-06-20

    We have performed deep imaging surveys for Ly{alpha} emitters (LAEs) at redshift {approx}7.3 in two blank fields, the Subaru Deep Field (SDF) and the Subaru/XMM-Newton Deep survey Field (SXDF), using the Subaru/Suprime-Cam equipped with new red-sensitive CCDs and a new narrowband filter, NB1006 ({lambda}{sub c} = 10052 Angstrom-Sign , FWHM {Delta}{lambda} = 214 A). We identified four objects as LAE candidates that exhibit luminosity excess in NB1006. By carrying out deep follow-up spectroscopy for three of them using Subaru/FOCAS and Keck/DEIMOS, a definitively asymmetric emission line is detected for one of them, SXDF-NB1006-2. Assuming this line is Ly{alpha}, this object is an LAE at z = 7.215 which has a luminosity of 1.2{sup +1.5}{sub -0.6} Multiplication-Sign 10{sup 43} erg s{sup -1} and a weighted skewness S{sub {omega}} = 4.90 {+-} 0.86. Another object, SDF-NB1006-2, shows variable photometry and is thus probably a quasar (QSO) or an active galactic nucleus. It shows an asymmetric emission line at 10076 A which may be due to either Ly{alpha} at z = 7.288 or [O II] at z = 1.703. The third object, SDF-NB1006-1, is likely a galaxy with temporal luminosity enhancement associated with a supernova explosion, as the brightness of this object varies between the observed epochs. Its spectrum does not show any emission lines. The inferred decrease in the number density of LAEs toward higher redshift is n{sup z={sup {sup 7.3}{sub Ly{alpha}}}}/n{sub Ly{alpha}}{sup z={sup {sup 5.7}}} = 0.05{sup +0.11}{sub -0.05} from z = 5.7 to 7.3 down to L{sup Ly{alpha}} = 1.0 Multiplication-Sign 10{sup 43} erg s{sup -1}. The present result is consistent with the interpretation in previous studies that the neutral hydrogen fraction is rapidly increasing from z = 5.7 to 7.3.

  10. A nonionic surfactant-decorated liquid crystal sensor for sensitive and selective detection of proteins.

    PubMed

    Wang, Yi; Hu, Qiongzheng; Tian, Tongtong; Gao, Yan'an; Yu, Li

    2016-09-21

    Proteins are responsible for most biochemical events in human body. It is essential to develop sensitive and selective methods for the detection of proteins. In this study, liquid crystal (LC)-based sensor for highly selective and sensitive detection of lysozyme, concanavalin A (Con A), and bovine serum albumin (BSA) was constructed by utilizing the LC interface decorated with a nonionic surfactant, dodecyl β-d-glucopyranoside. A change of the LC optical images from bright to dark appearance was observed after transferring dodecyl β-d-glucopyranoside onto the aqueous/LC interface due to the formation of stable self-assembled surfactant monolayer, regardless of pH and ion concentrations studied in a wide range. The optical images turned back from dark to bright appearance after addition of lysozyme, Con A and BSA, respectively. Noteworthy is that these proteins can be further distinguished by adding enzyme inhibitors and controlling incubation temperature of the protein solutions based on three different interaction mechanisms between proteins and dodecyl β-d-glucopyranoside, viz. enzymatic hydrolysis, specific saccharide binding, and physical absorption. The LC-based sensor decorated with dodecyl β-d-glucopyranoside shows high sensitivity for protein detection. The limit of detection (LOD) for lysozyme, Con A and BSA reaches around 0.1 μg/mL, 0.01 μg/mL and 0.001 μg/mL, respectively. These results might provide new insights into increasing selectivity and sensitivity of LC-based sensors for the detection of proteins. PMID:27590553

  11. Sensitive and selective tumor imaging with novel and highly activatable fluorescence strategies

    NASA Astrophysics Data System (ADS)

    Urano, Yasuteru

    2008-02-01

    Nowadays, several tumor imaging modalities such as MRI, PET and fluorescence imaging techniques have been extensively investigated. One of the central problems associated with these conventional tumor-targeted imaging methods, however, is the fact that the signal contrast between tumor and surrounding tissues relies on the efficient targeting to the tumor and the rapid sequestration or excretion of unbound agent. Among these modalities, only fluorescence imaging technique has a significant feature, in that great signal activation could be achieved which potentially leads to the selective imaging of cancer with higher tumor-to-background ratio. In this symposium, I will present some examples of fluorescence cancer imaging based on highly activatable strategies with using precisely designed novel fluorescence probes. Recently, we developed highly sensitive fluorescence probes for β-galactosidase which is applicable for living cell system. By utilizing these probes, we could establish a novel and highly activatable strategy for sensitive and selective optical imaging of imbedded tumor in the peritoneum. We took a two step procedure in that a lectin is used to localize β-galactosidase to cancer cells as an activating enzyme, and subsequent administration of a highly-sensitive fluorescence probe for the enzyme have afforded remarkable fluorescence activation selectively in tumor mass. Since the tumor-targeted enzyme can catalyze numerous substrate turnovers, a great number of fluorescent molecules could be produced and hence the rapid and sensitive detection of tumor in vivo with high tumor-to-background ratio could be achieved. Moreover, the consequent close-up investigation using fluorescence microscopy revealed that cancer microfoci as small as 200 μm could be successfully visualized.

  12. Selection tool alpha-fetoprotein for patients waiting for liver transplantation: How to easily manage a fractal algorithm

    PubMed Central

    Lai, Quirino; Levi Sandri, Giovanni Battista; Lerut, Jan

    2015-01-01

    Alpha-fetoprotein (AFP) behavior in patients with hepatocellular carcinoma (HCC) waiting for liver transplant (LT) represents a perfect biological example of a fractal model in which its progressive modification and possible future prediction of its values are very hard to capture. As a consequence, AFP represents a useful but poorly manageable tool to increase the ability to better select HCC patients waiting for LT. Trying to find a “fil-rouge” in the recent literature, no definitive answers can be done to several open questions: (1) the best AFP value to adopt; (2) the best cut-off measurement; and (3) the best way to comfortably capture the effective, time-related, fluctuations of this biological marker. More, structured and prospective, studies using serial determination of AFP values within and without the context of locoregional therapies are needed in order to find the “ideal” (static and dynamic) cut-off values allowing to respond to all the still open questions in this field of transplant oncology. PMID:26244064

  13. Amino acid replacements can selectively affect the interaction energy of autonomous folding units in the alpha subunit of tryptophan synthase.

    PubMed

    Chen, X; Rambo, R; Matthews, C R

    1992-03-01

    Amino acid replacements were made at the interface between two autonomous folding units in the alpha subunit of tryptophan synthase from Salmonella typhimurium to test their mutual interaction energy. The results of equilibrium studies of the urea-induced unfolding reaction of the wild-type and mutant proteins in which phenylalanine 22 is replaced by leucine, isoleucine, and valine can be understood in terms of a selective decrease in the interaction energy between the two folding units; the intrinsic stability of each folding unit is not significantly altered. Kinetic studies of the rate-limiting step in unfolding show that the interaction energy appears in the transition state preceding the native conformation. Comparisons of the individual effects of these nonpolar side chains show that both hydrophobic and steric effects play important roles in the interaction energy between the folding units. The implication of these results is that the high cooperativity observed in the folding of many globular proteins may be reduced by appropriate amino acid replacements. PMID:1540577

  14. Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

    SciTech Connect

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    1986-03-01

    Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.

  15. Crystal Structures of Trypanosoma brucei Sterol 14[alpha]-Demethylase and Implications for Selective Treatment of Human Infections

    SciTech Connect

    Lepesheva, Galina I.; Park, Hee-Won; Hargrove, Tatiana Y.; Vanhollebeke, Benoit; Wawrzak, Zdzislaw; Harp, Joel M.; Sundaramoorthy, Munirathinam; Nes, W. David; Pays, Etienne; Chaudhuri, Minu; Villalta, Fernando; Waterman, Michael R.

    2010-01-25

    Sterol 14{alpha}-demethylase (14DM, the CYP51 family of cytochrome P450) is an essential enzyme in sterol biosynthesis in eukaryotes. It serves as a major drug target for fungal diseases and can potentially become a target for treatment of human infections with protozoa. Here we present 1.9 {angstrom} resolution crystal structures of 14DM from the protozoan pathogen Trypanosoma brucei, ligand-free and complexed with a strong chemically selected inhibitor N-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(5-phenyl-1,3,4-oxadi-azol-2-yl)benzamide that we previously found to produce potent antiparasitic effects in Trypanosomatidae. This is the first structure of a eukaryotic microsomal 14DM that acts on sterol biosynthesis, and it differs profoundly from that of the water-soluble CYP51 family member from Mycobacterium tuberculosis, both in organization of the active site cavity and in the substrate access channel location. Inhibitor binding does not cause large scale conformational rearrangements, yet induces unanticipated local alterations in the active site, including formation of a hydrogen bond network that connects, via the inhibitor amide group fragment, two remote functionally essential protein segments and alters the heme environment. The inhibitor binding mode provides a possible explanation for both its functionally irreversible effect on the enzyme activity and its selectivity toward the 14DM from human pathogens versus the human 14DM ortholog. The structures shed new light on 14DM functional conservation and open an excellent opportunity for directed design of novel antiparasitic drugs.

  16. Depolarization Controls TRAIL-Sensitization and Tumor-Selective Killing of Cancer Cells: Crosstalk with ROS

    PubMed Central

    Suzuki-Karasaki, Yoshihiro; Suzuki-Karasaki, Miki; Uchida, Mayumi; Ochiai, Toyoko

    2014-01-01

    Conventional genotoxic anti-cancer drugs target the proliferative advantage of tumor cells over normal cells. This kind of approach lacks the selectivity of treatment to cancer cells, because most of the targeted pathways are essential for the survival of normal cells. As a result, traditional cancer treatments are often limited by undesirable damage to normal cells (side-effects). Ideal anti-cancer drugs are expected to be highly effective against malignant tumor cells with minimal cytotoxicity toward normal cells. Such selective killing can be achieved by targeting pathways essential for the survival of cancer cells, but not normal cells. As cancer cells are characterized by their resistance to apoptosis, selective apoptosis induction is a promising approach for selective killing of cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising tumor-selective anti-cancer drug. However, the congenital and acquired resistance of some cancer cell types, including malignant melanoma cells, currently impedes effective TRAIL therapy, and an innovative approach that can override TRAIL resistance is urgently required. Apoptosis is characterized by cell shrinkage caused by disruption of the maintenance of the normal physiological concentrations of K+ and Na+ and intracellular ion homeostasis. The disrupted ion homeostasis leads to depolarization and apoptosis. Recent evidence suggests that depolarization is an early and prerequisite event during TRAIL-induced apoptosis. Moreover, diverse natural products and synthetic chemicals capable of depolarizing the cell membrane exhibit tumor-selective killing and TRAIL-sensitizing effects. Here, we discuss the role of depolarization in selective killing of cancer cells in connection with the emerging concept that oxidative stress is a critical mediator of mitochondrial and endoplasmic reticulum dysfunctions and serves as a tumor-selective target in cancer treatment. PMID:24910845

  17. Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

    SciTech Connect

    Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Weijun; Smith, Richard D.

    2012-04-01

    Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.

  18. Molecular imprinting ratiometric fluorescence sensor for highly selective and sensitive detection of phycocyanin.

    PubMed

    Wang, Xiaoyan; Yu, Jialuo; Kang, Qi; Shen, Dazhong; Li, Jinhua; Chen, Lingxin

    2016-03-15

    A facile strategy was developed to prepare molecular imprinting ratiometric fluorescence sensor for highly selective and sensitive detection of phycocyanin (PC) based on fluorescence resonance energy transfer (FRET), via a sol-gel polymerization process using nitrobenzoxadiazole (NBD) as fluorescent signal source. The ratio of two fluorescence peak emission intensities of NBD and PC was utilized to determine the concentration of PC, which could effectively reduce the background interference and fluctuation of diverse conditions. As a result, this sensor obtained high sensitivity with a low detection limit of 0.14 nM within 6 min, and excellent recognition specificity for PC over its analogues with a high imprinting factor of 9.1. Furthermore, the sensor attained high recoveries in the range of 93.8-110.2% at three spiking levels of PC, with precisions below 4.7% in seawater and lake water samples. The developed sensor strategy demonstrated simplicity, reliability, rapidity, high selectivity and high sensitivity, proving to be a feasible way to develop high efficient fluorescence sensors and thus potentially applicable for ultratrace analysis of complicated matrices. PMID:26485176

  19. Sensitive and selective real-time electrochemical monitoring of DNA repair (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Slinker, Jason D.; McWilliams, Marc; Anka, Fadwa; Balkus, Kenneth

    2015-10-01

    Unrepaired DNA damage can lead to mutation, cancer, and death of cells or organisms. However, due to the subtlety of DNA damage, it is difficult to sense the repair of damage products with high selectivity and sensitivity. Here, we show sensitive and selective electrochemical sensing of the repair activity of 8-oxoguanine and uracil glycosylases within DNA monolayers on gold by multiplexed analysis with silicon chips and low-cost electrospun nanofibers. Our approach involves comparing the electrochemical signal of redox probe modified monolayers containing the defect versus the rational control of defect-free monolayers. We find sequence-specific sensitivity thresholds on the order of femtomoles of proteins and dynamic ranges of over two orders of magnitude for each target. For 8-oxoguanine repair, temperature-dependent kinetics are extracted, showing exponential signal loss with time constants of seconds. Electrospun fibers are shown to behave similarly to conventional gold-on-silicon devices, showing the potential of these low-cost devices for sensing applications.

  20. Highly sensitive and selective sugar detection by terahertz nano-antennas

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Kyu; Kang, Ji-Hun; Lee, Jun-Seok; Kim, Hyo-Seok; Kim, Chulki; Hun Kim, Jae; Lee, Taikjin; Son, Joo-Hiuk; Park, Q.-Han; Seo, Minah

    2015-10-01

    Molecular recognition and discrimination of carbohydrates are important because carbohydrates perform essential roles in most living organisms for energy metabolism and cell-to-cell communication. Nevertheless, it is difficult to identify or distinguish various carbohydrate molecules owing to the lack of a significant distinction in the physical or chemical characteristics. Although there has been considerable effort to develop a sensing platform for individual carbohydrates selectively using chemical receptors or an ensemble array, their detection and discrimination limits have been as high in the millimolar concentration range. Here we show a highly sensitive and selective detection method for the discrimination of carbohydrate molecules using nano-slot-antenna array-based sensing chips which operate in the terahertz (THz) frequency range (0.5-2.5 THz). This THz metamaterial sensing tool recognizes various types of carbohydrate molecules over a wide range of molecular concentrations. Strongly localized and enhanced terahertz transmission by nano-antennas can effectively increase the molecular absorption cross sections, thereby enabling the detection of these molecules even at low concentrations. We verified the performance of nano-antenna sensing chip by both THz spectra and images of transmittance. Screening and identification of various carbohydrates can be applied to test even real market beverages with a high sensitivity and selectivity.

  1. Highly sensitive and selective sugar detection by terahertz nano-antennas.

    PubMed

    Lee, Dong-Kyu; Kang, Ji-Hun; Lee, Jun-Seok; Kim, Hyo-Seok; Kim, Chulki; Kim, Jae Hun; Lee, Taikjin; Son, Joo-Hiuk; Park, Q-Han; Seo, Minah

    2015-01-01

    Molecular recognition and discrimination of carbohydrates are important because carbohydrates perform essential roles in most living organisms for energy metabolism and cell-to-cell communication. Nevertheless, it is difficult to identify or distinguish various carbohydrate molecules owing to the lack of a significant distinction in the physical or chemical characteristics. Although there has been considerable effort to develop a sensing platform for individual carbohydrates selectively using chemical receptors or an ensemble array, their detection and discrimination limits have been as high in the millimolar concentration range. Here we show a highly sensitive and selective detection method for the discrimination of carbohydrate molecules using nano-slot-antenna array-based sensing chips which operate in the terahertz (THz) frequency range (0.5-2.5 THz). This THz metamaterial sensing tool recognizes various types of carbohydrate molecules over a wide range of molecular concentrations. Strongly localized and enhanced terahertz transmission by nano-antennas can effectively increase the molecular absorption cross sections, thereby enabling the detection of these molecules even at low concentrations. We verified the performance of nano-antenna sensing chip by both THz spectra and images of transmittance. Screening and identification of various carbohydrates can be applied to test even real market beverages with a high sensitivity and selectivity. PMID:26494203

  2. Selective and Sensitive Sensing of Flame Retardant Chemicals Through Phage Display Discovered Recognition Peptide.

    PubMed

    Jin, Hyo-Eon; Zueger, Chris; Chung, Woo-Jae; Wong, Winnie; Lee, Byung Yang; Lee, Seung-Wuk

    2015-11-11

    We report a highly selective and sensitive biosensor for the detection of an environmentally toxic molecule, decabrominated diphenyl ether (DBDE), one of the most common congeners of the polybrominated frame retardants (polybrominated diphenyl ether (PBDE)), using newly discovered DBDE peptide receptors integrated with carbon nanotube field-effect transistors (CNT-FET). The specific DBDE peptide receptor was identified using a high-throughput screening process of phage library display. The resulting binding peptide carries an interesting consensus binding pocket with two Trp-His/Asn-Trp repeats, which binds to the DBDE in a multivalent manner. We integrated the novel DBDE binding peptide onto the CNT-FET using polydiacetylene coating materials linked through cysteine-maleimide click chemistry. The resulting biosensor could detect the desired DBDE selectively with a 1 fM detection limit. Our combined approaches of selective receptor discovery, material nanocoating through click chemistry, and integration onto a sensitive CNT-FET electronic sensor for desired target chemicals will pave the way toward the rapid development of portable and easy-to-use biosensors for desired chemicals to protect our health and environment. PMID:26455834

  3. A highly selective electrochemical impedance spectroscopy-based aptasensor for sensitive detection of acetamiprid.

    PubMed

    Fan, Lifang; Zhao, Guohua; Shi, Huijie; Liu, Meichuan; Li, Zhengxin

    2013-05-15

    A simple aptasensor for sensitive and selective detection of acetamiprid has been developed based on electrochemical impedance spectroscopy (EIS). To improve sensitivity of the aptasensor, gold nanoparticles (AuNPs) were electrodeposited on the bare gold electrode surface by cycle voltammetry (CV), which was employed as a platform for aptamer immobilization. With the addition of acetamiprid, the formation of acetamiprid-aptamer complex on the AuNPs-deposited electrode surface resulted in an increase of electron transfer resistance (Ret). The change of Ret strongly depends on acetamiprid concentration, which is applied for acetamiprid quantification. A wide linear range was obtained from 5 to 600nM with a low detection limit of 1nM. The control experiments performed by employing the pesticides that may coexist or have similar structure with acetamiprid demonstrate that the aptasensor has only specific recognition to acetamiprid, resulting in high selectivity of the aptasensor. The dissociation constant, Kd of 23.41nM for acetamiprid-aptamer complex has been determined from the differential capacitance (Cd) by assuming a Langmuir isotherm, which indicates strong interaction between acetamiprid and aptamer, further proving high selectivity of the aptasensor. Besides, the applicability of the developed aptasensor has been successfully evaluated by determining acetamiprid in the real samples, wastewater and tomatoes. PMID:23274191

  4. Highly sensitive and selective sugar detection by terahertz nano-antennas

    PubMed Central

    Lee, Dong-Kyu; Kang, Ji-Hun; Lee, Jun-Seok; Kim, Hyo-Seok; Kim, Chulki; Hun Kim, Jae; Lee, Taikjin; Son, Joo-Hiuk; Park, Q-Han; Seo, Minah

    2015-01-01

    Molecular recognition and discrimination of carbohydrates are important because carbohydrates perform essential roles in most living organisms for energy metabolism and cell-to-cell communication. Nevertheless, it is difficult to identify or distinguish various carbohydrate molecules owing to the lack of a significant distinction in the physical or chemical characteristics. Although there has been considerable effort to develop a sensing platform for individual carbohydrates selectively using chemical receptors or an ensemble array, their detection and discrimination limits have been as high in the millimolar concentration range. Here we show a highly sensitive and selective detection method for the discrimination of carbohydrate molecules using nano-slot-antenna array-based sensing chips which operate in the terahertz (THz) frequency range (0.5–2.5 THz). This THz metamaterial sensing tool recognizes various types of carbohydrate molecules over a wide range of molecular concentrations. Strongly localized and enhanced terahertz transmission by nano-antennas can effectively increase the molecular absorption cross sections, thereby enabling the detection of these molecules even at low concentrations. We verified the performance of nano-antenna sensing chip by both THz spectra and images of transmittance. Screening and identification of various carbohydrates can be applied to test even real market beverages with a high sensitivity and selectivity. PMID:26494203

  5. A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity.

    PubMed

    Liu, Juewen; Brown, Andrea K; Meng, Xiangli; Cropek, Donald M; Istok, Jonathan D; Watson, David B; Lu, Yi

    2007-02-13

    Here, we report a catalytic beacon sensor for uranyl (UO2(2+)) based on an in vitro-selected UO2(2+)-specific DNAzyme. The sensor consists of a DNA enzyme strand with a 3' quencher and a DNA substrate with a ribonucleotide adenosine (rA) in the middle and a fluorophore and a quencher at the 5' and 3' ends, respectively. The presence of UO2(2+) causes catalytic cleavage of the DNA substrate strand at the rA position and release of the fluorophore and thus dramatic increase of fluorescence intensity. The sensor has a detection limit of 11 parts per trillion (45 pM), a dynamic range up to 400 nM, and selectivity of >1-million-fold over other metal ions. The most interfering metal ion, Th(IV), interacts with the fluorescein fluorophore, causing slightly enhanced fluorescence intensity, with an apparent dissociation constant of approximately 230 microM. This sensor rivals the most sensitive analytical instruments for uranium detection, and its application in detecting uranium in contaminated soil samples is also demonstrated. This work shows that simple, cost-effective, and portable metal sensors can be obtained with similar sensitivity and selectivity as much more expensive and sophisticated analytical instruments. Such a sensor will play an important role in environmental remediation of radionuclides such as uranium. PMID:17284609

  6. A Catalytic Beacon Sensor for Uranium with Parts-per-Trillion Sensitivity and Millionfold Selectivity

    SciTech Connect

    Liu, Juewen; Brown, Andrea K.; Meng, Xiangli; Cropek, Donald M.; IstokD., Jonathan; Watson, David B; Liu, Yi

    2007-01-01

    Here, we report a catalytic beacon sensor for uranyl (UO{sub 2}{sup 2+}) based on an in vitro-selected UO{sub 2}{sup 2+}-specific DNAzyme. The sensor consists of a DNA enzyme strand with a 3' quencher and a DNA substrate with a ribonucleotide adenosine (rA) in the middle and a fluorophore and a quencher at the 5' and 3' ends, respectively. The presence of UO{sub 2}{sup 2+} causes catalytic cleavage of the DNA substrate strand at the rA position and release of the fluorophore and thus dramatic increase of fluorescence intensity. The sensor has a detection limit of 11 parts per trillion (45 pM), a dynamic range up to 400 nM, and selectivity of >1-million-fold over other metal ions. The most interfering metal ion, Th(IV), interacts with the fluorescein fluorophore, causing slightly enhanced fluorescence intensity, with an apparent dissociation constant of {approx}230 {micro}M. This sensor rivals the most sensitive analytical instruments for uranium detection, and its application in detecting uranium in contaminated soil samples is also demonstrated. This work shows that simple, cost-effective, and portable metal sensors can be obtained with similar sensitivity and selectivity as much more expensive and sophisticated analytical instruments. Such a sensor will play an important role in environmental remediation of radionuclides such as uranium.

  7. Leveraging zinc interstitials and oxygen vacancies for sensitive biomolecule detection through selective surface functionalization

    NASA Astrophysics Data System (ADS)

    Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Chaudhry, Shajee; Prasad, Shalini

    2015-03-01

    In this study, functionally engineered EIS technique was implemented to investigate the influence of surface functionalization on sensitivity of biomolecule detection using nanostructured ZnO platform. Organic molecules with thiol and carboxylic functional groups were chosen to control biomolecule immobilization on zinc and oxygen-terminated 2D planar and 1D nanostructured ZnO surfaces. The amount of functionalization and its influence on charge perturbations at the ZnO-electrolyte interface were studied using fluorescence and EIS measurements. We observed the dependence of charge transfer on both the polarity of platform and concentration of cross-linker molecules. Such selectively modified surfaces were used for detection of cortisol, a major stress indicator. Results demonstrated preferential binding of thiol groups to Zn terminations and thus leveraging ZnO interstitials increases the sensitivity of detection over larger dynamic range with detection limit at 10fg/mL.

  8. Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements.

    PubMed

    Morley, Thomas S; Xia, Jonathan Y; Scherer, Philipp E

    2015-01-01

    Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure. Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels. These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity. Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis. PMID:26243466

  9. Sensitive and selective detection of copper ions with highly stable polyethyleneimine-protected silver nanoclusters.

    PubMed

    Yuan, Zhiqin; Cai, Na; Du, Yi; He, Yan; Yeung, Edward S

    2014-01-01

    Copper is a highly toxic environmental pollutant with bioaccumulative properties. Therefore, sensitive Cu(2+) detection is very important to prevent over-ingestion, and visual detection using unaugmented vision is preferred for practical applications. In this study, hyperbranched polyethyleneimine-protected silver nanoclusters (hPEI-AgNCs) were successfully synthesized using a facile, one-pot reaction under mild conditions. The hPEI-AgNCs were very stable against extreme pH, ionic strength, temperature, and photoillumination and could act as sensitive and selective Cu(2+) sensing nanoprobes in aqueous solutions with a 10 nM limit of detection. In addition, hPEI-AgNCs-doped agarose hydrogels were developed as an instrument-free and regenerable platform for visual Cu(2+) and water quality monitoring. PMID:24274096

  10. Sensitive hydrogen sensor based on selectively infiltrated photonic crystal fiber with Pt-loaded WO₃ coating.

    PubMed

    Wang, Ying; Wang, D N; Yang, Fan; Li, Zhi; Yang, Minghong

    2014-07-01

    A sensitive hydrogen sensing device based on a selectively infiltrated photonic crystal fiber (PCF) coated with Pt-loaded WO₃ is demonstrated. With Pt-loaded WO₃ coating acting as the catalytic layer, hydrogen undergoes an exothermic reaction with oxygen and releases heat when the device is exposed to gas mixtures of air and hydrogen, which induces local temperature change in the PCF and hence leads to the resonant wavelength shift of the proposed device. The maximum wavelength shift of 98.5 nm is obtained with a 10-mm-long infiltrated PCF for 4% (v/v) H₂ concentration, and a hydrogen sensitivity of 32.3 nm/% (v/v) H₂ is achieved within the range of 1%-4% (v/v) H₂ in air. PMID:24978759

  11. Highly Sensitive and Selective Gas Sensor Using Hydrophilic and Hydrophobic Graphenes

    PubMed Central

    Some, Surajit; Xu, Yang; Kim, Youngmin; Yoon, Yeoheung; Qin, Hongyi; Kulkarni, Atul; Kim, Taesung; Lee, Hyoyoung

    2013-01-01

    New hydrophilic 2D graphene oxide (GO) nanosheets with various oxygen functional groups were employed to maintain high sensitivity in highly unfavorable environments (extremely high humidity, strong acidic or basic). Novel one-headed polymer optical fiber sensor arrays using hydrophilic GO and hydrophobic reduced graphene oxide (rGO) were carefully designed, leading to the selective sensing of volatile organic gases for the first time. The two physically different surfaces of GO and rGO could provide the sensing ability to distinguish between tetrahydrofuran (THF) and dichloromethane (MC), respectively, which is the most challenging issue in the area of gas sensors. The eco-friendly physical properties of GO allowed for faster sensing and higher sensitivity when compared to previous results for rGO even under extreme environments of over 90% humidity, making it the best choice for an environmentally friendly gas sensor. PMID:23736838

  12. Highly sensitive and selective odorant sensor using living cells expressing insect olfactory receptors

    PubMed Central

    Misawa, Nobuo; Mitsuno, Hidefumi; Kanzaki, Ryohei; Takeuchi, Shoji

    2010-01-01

    This paper describes a highly sensitive and selective chemical sensor using living cells (Xenopus laevis oocytes) within a portable fluidic device. We constructed an odorant sensor whose sensitivity is a few parts per billion in solution and can simultaneously distinguish different types of chemicals that have only a slight difference in double bond isomerism or functional group such as ─OH, ─CHO and ─C(═O)─. We developed a semiautomatic method to install cells to the fluidic device and achieved stable and reproducible odorant sensing. In addition, we found that the sensor worked for multiple-target chemicals and can be integrated with a robotic system without any noise reduction systems. Our developed sensor is compact and easy to replace in the system. We believe that the sensor can potentially be incorporated into a portable system for monitoring environmental and physical conditions. PMID:20798064

  13. Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery.

    PubMed

    Satoh, M; Enomoto, K; Koike, K

    2001-01-01

    The antagonistic effects of MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine at rat thoracic aorta and rabbit iliac artery alpha1-adrenoceptors were investigated in this study. Selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin dose-dependently shifted the concentration-response curves for noradrenaline to the right. Schild plots of the results obtained from the inhibition by MDL73005EF (pA2 8.30 +/- 0.04) and tamsulosin (pA2 10.51 +/- 0.06) of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta. The slopes of Schild plots obtained from the inhibition by MDL73005EF and tamsulosin of noradrenaline were significantly different from unity in rabbit iliac artery. Schild plots of the results obtained from the inhibition by clonidine and tizanidine of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta (pA2 7.08 +/- 0.04 and 7.32 +/- 0.04, respectively). These results suggest that alpha1D-adrenoceptors play a significant role in the alpha1-adrenoceptor-agonist-induced contraction of rat thoracic aorta and rabbit iliac artery, and that clonidine and tizanidine interact with the alpha1D-adrenoceptor subtype as competitive antagonists in rat thoracic aorta. PMID:11206183

  14. Intrinsic Selectivity and Structure Sensitivity of Rhodium Catalysts for C(2+) Oxygenate Production.

    PubMed

    Yang, Nuoya; Medford, Andrew J; Liu, Xinyan; Studt, Felix; Bligaard, Thomas; Bent, Stacey F; Nørskov, Jens K

    2016-03-23

    Synthesis gas (CO + H2) conversion is a promising route to converting coal, natural gas, or biomass into synthetic liquid fuels. Rhodium has long been studied as it is the only elemental catalyst that has demonstrated selectivity to ethanol and other C2+ oxygenates. However, the fundamentals of syngas conversion over rhodium are still debated. In this work a microkinetic model is developed for conversion of CO and H2 into methane, ethanol, and acetaldehyde on the Rh (211) and (111) surfaces, chosen to describe steps and close-packed facets on catalyst particles. The model is based on DFT calculations using the BEEF-vdW functional. The mean-field kinetic model includes lateral adsorbate-adsorbate interactions, and the BEEF-vdW error estimation ensemble is used to propagate error from the DFT calculations to the predicted rates. The model shows the Rh(211) surface to be ∼6 orders of magnitude more active than the Rh(111) surface, but highly selective toward methane, while the Rh(111) surface is intrinsically selective toward acetaldehyde. A variety of Rh/SiO2 catalysts are synthesized, tested for catalytic oxygenate production, and characterized using TEM. The experimental results indicate that the Rh(111) surface is intrinsically selective toward acetaldehyde, and a strong inverse correlation between catalytic activity and oxygenate selectivity is observed. Furthermore, iron impurities are shown to play a key role in modulating the selectivity of Rh/SiO2 catalysts toward ethanol. The experimental observations are consistent with the structure-sensitivity predicted from theory. This work provides an improved atomic-scale understanding and new insight into the mechanism, active site, and intrinsic selectivity of syngas conversion over rhodium catalysts and may also guide rational design of alloy catalysts made from more abundant elements. PMID:26958997

  15. TU-C-BRE-08: IMRT QA: Selecting Meaningful Gamma Criteria Based On Error Detection Sensitivity

    SciTech Connect

    Steers, J; Fraass, B

    2014-06-15

    Purpose: To develop a strategy for defining meaningful tolerance limits and studying the sensitivity of IMRT QA gamma criteria by inducing known errors in QA plans. Methods: IMRT QA measurements (ArcCHECK, Sun Nuclear) were compared to QA plan calculations with induced errors. Many (>24) gamma comparisons between data and calculations were performed for each of several kinds of cases and classes of induced error types with varying magnitudes (e.g. MU errors ranging from -10% to +10%), resulting in over 3,000 comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using various gamma criteria. Results: This study demonstrates that random, case-specific, and systematic errors can be detected by the error curve analysis. Depending on location of the peak of the error curve (e.g., not centered about zero), 3%/3mm threshold=10% criteria may miss MU errors of up to 10% and random MLC errors of up to 5 mm. Additionally, using larger dose thresholds for specific devices may increase error sensitivity (for the same X%/Ymm criteria) by up to a factor of two. This analysis will allow clinics to select more meaningful gamma criteria based on QA device, treatment techniques, and acceptable error tolerances. Conclusion: We propose a strategy for selecting gamma parameters based on the sensitivity of gamma criteria and individual QA devices to induced calculation errors in QA plans. Our data suggest large errors may be missed using conventional gamma criteria and that using stricter criteria with an increased dose threshold may reduce the range of missed errors. This approach allows quantification of gamma criteria sensitivity and is straightforward to apply to other combinations of devices and treatment techniques.

  16. Selective and sensitive detection of chromium(VI) in waters using electrospray ionization mass spectrometry.

    PubMed

    Weldy, Effie; Wolff, Chloe; Miao, Zhixin; Chen, Hao

    2013-09-01

    From 2000 through 2011, there were 14 criminal cases of violations of the Clean Water Act involving the discharge of chromium, a toxic heavy metal, into drinking and surface water sources. As chromium(VI), a potential carcinogen present in the environment, represents a significant safety concern, it is currently the subject of an EPA health risk assessment. Therefore, sensitive and selective detection of this species is highly desired. This study reports the analysis of chromium(VI) in water samples by electrospray ionization mass spectrometry (ESI-MS) following its reduction and complexation with ammonium pyrrolidinedithiocarbamate (APDC). The reduction and subsequent complexation produce a characteristic [Cr(III)O]-PDC complex which can be detected as a protonated ion of m/z 507 in the positive ion mode. The detection is selective to chromium(VI) under acidic pH, even in the presence of chromium(III) and other metal ions, providing high specificity. Different water samples were examined, including deionized, tap, and river waters, and sensitive detection was achieved. In the case of deionized water, quantification over the concentration range of 3.7 to 148ppb gave an excellent correlation coefficient of 0.9904 using the enhanced MS mode scan. Using the single-reaction monitoring (SRM) mode (monitoring the characteristic fragmentation of m/z 507 to m/z 360), the limit of detection (LOD) was found to be 0.25ppb. The LOD of chromium(VI) for both tap and river water samples was determined to be 2.0ppb. A preconcentration strategy using simple vacuum evaporation of the aqueous sample was shown to further improve the ESI signal by 15 fold. This method, with high sensitivity and selectivity, should provide a timely solution for the real-world analysis of toxic chromium(VI). PMID:23937937

  17. Cheat sensitive quantum bit commitment via pre- and post-selected quantum states

    NASA Astrophysics Data System (ADS)

    Li, Yan-Bing; Wen, Qiao-Yan; Li, Zi-Chen; Qin, Su-Juan; Yang, Ya-Tao

    2014-01-01

    Cheat sensitive quantum bit commitment is a most important and realizable quantum bit commitment (QBC) protocol. By taking advantage of quantum mechanism, it can achieve higher security than classical bit commitment. In this paper, we propose a QBC schemes based on pre- and post-selected quantum states. The analysis indicates that both of the two participants' cheat strategies will be detected with non-zero probability. And the protocol can be implemented with today's technology as a long-term quantum memory is not needed.

  18. A Sensitive Ratiometric Fluorescent Sensor for Zinc(II) with High Selectivity

    PubMed Central

    Lv, Yuanyuan; Cao, Mingda; Li, Jiakai; Wang, Junbo

    2013-01-01

    A new fluorescent Zn2+ chemosensor (P1) based on a functionalized porphyrin was synthesized and characterized. P1 displayed dramatic ratiometric variations in absorption and fluorescent emission spectra upon exposure to Zn2+ due to the formation of a 1:1 Zn2+/P1 complex. The sensor also exhibited high selectivity and sensitivity toward Zn2+ over other common metal ions in the physiological pH range with a detection limit of 1.8 μM. The sensor showed fast response times and excellent reproducibility, thus confirming its potential applicability as a fluorescent sensor for Zn2+ sensing. PMID:23467028

  19. Sensitization of vascular smooth muscle cell to TNF-{alpha}-mediated death in the presence of palmitate

    SciTech Connect

    Rho, Mun-Chual; Ah Lee, Kyeong; Mi Kim, Sun; Sik Lee, Chang; Jeong Jang, Min; Kook Kim, Young; Sun Lee, Hyun; Hyun Choi, Yung; Yong Rhim, Byung; Kim, Koanhoi . E-mail: koanhoi@pusan.ac.kr

    2007-05-01

    Saturated free fatty acids (FFAs), including palmitate, can activate the intrinsic death pathway in cells. However, the relationship between FFAs and receptor-mediated death pathway is still unknown. In this study, we have investigated whether FFAs are able to trigger receptor-mediated death. In addition, to clarify the mechanisms responsible for the activation, we examined the biochemical changes in dying vascular smooth muscle cell (VSMC) and the effects of various molecules to the receptor-mediated VSMC death. Tumor necrosis factor (TNF)-{alpha}-mediated VSMC death occurred in the presence of sub-cytotoxic concentration of palmitate as determined by assessing viability and DNA degradation, while the cytokine did not influence VSMC viability in the presence of oleate. The VSMC death was inhibited by the gene transfer of a dominant-negative Fas-associated death domain-containing protein and the baculovirus p35, but not by the bcl-xL or the c-Jun N-terminal kinase (JNK) binding domain of JNK-interacting protein-1, in tests utilizing recombinant adenoviruses. The VSMC death was also inhibited by a neutralizing anti-TNF receptor 1 antibody, the caspase inhibitor z-VAD, and the cathepsin B inhibitor CA074, a finding indicative of the role of both caspases and cathepsin B in this process. Consistent with this finding, caspase-3 activation and an increase in cytosolic cathepsin B activity were detected in the dying VSMC. Palmitate inhibited an increase of TNF-{alpha}-mediated nuclear factor kappa B (NF-{kappa}B) activity, the survival pathway activated by the cytokine, by hindering the translocation of the NF-{kappa}B subunit of p65 from the cytosol into the nucleus. The gene transfer of inhibitor of NF-{kappa}B predisposed VSMC to palmitate-induced cell death. To the best of our knowledge, this study is the first report to demonstrate the activation of TNF-{alpha}-mediated cell death in the presence of palmitate. The current study proposes that FFAs would take part in

  20. A highly sensitive and selective fluorescent probe for fluoride anions based on intramolecular charge transfer.

    PubMed

    Liu, Jingkai; Xu, Zhenghe; Liu, Caiyun; Xu, Lirong; Wang, Zhongpeng; Zhu, Baocun

    2016-08-01

    Currently, there is a great need to develop methods for the selective detection of fluoride anions (F(-) ) owing to their toxicity in the environment and biological function in living systems. In this study, we developed a new fluorescent probe (probe 1) employing a Si-O bond as a highly selective recognition receptor for detecting F(-) via intramolecular charge transfer. Probe 1 could detect F(-) quantitatively using the turn-on fluorescence spectroscopy method with excellent sensitivity in the range of 4-38 μM and a detection limit of 0.26 μM; the detection time was < 17 min. We anticipate that probe 1 would be used widely to monitor F(-) in the environment. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26467672

  1. Highly selective and sensitive fluorescent paper sensor for nitroaromatic explosive detection.

    PubMed

    Ma, Yingxin; Li, Hao; Peng, Shan; Wang, Leyu

    2012-10-01

    Rapid, sensitive, and selective detection of explosives such as 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenol (TNP), especially using a facile paper sensor, is in high demand for homeland security and public safety. Although many strategies have been successfully developed for the detection of TNT, it is not easy to differentiate the influence from TNP. Also, few methods were demonstrated for the selective detection of TNP. In this work, via a facile and versatile method, 8-hydroxyquinoline aluminum (Alq(3))-based bluish green fluorescent composite nanospheres were successfully synthesized through self-assembly under vigorous stirring and ultrasonic treatment. These polymer-coated nanocomposites are not only water-stable but also highly luminescent. Based on the dramatic and selective fluorescence quenching of the nanocomposites via adding TNP into the aqueous solution, a sensitive and robust platform was developed for visual detection of TNP in the mixture of nitroaromatics including TNT, 2,4-dinitrotoluene (DNT), and nitrobenzene (NB). Meanwhile, the fluorescence intensity is proportional to the concentration of TNP in the range of 0.05-7.0 μg/mL with the 3σ limit of detection of 32.3 ng/mL. By handwriting or finger printing with TNP solution as ink on the filter paper soaked with the fluorescent nanocomposites, the bluish green fluorescence was instantly and dramatically quenched and the dark patterns were left on the paper. Therefore, a convenient and rapid paper sensor for TNP-selective detection was fabricated. PMID:22946839

  2. Computational structural investigation of select II-VI compounds and radtkeite (alpha-mercury(3) sulfur(2) chlorine iodine)

    NASA Astrophysics Data System (ADS)

    Sellepack, Steven Matthew

    2000-12-01

    Computational modeling of novel materials is an increasingly powerful tool being used in the development of advanced materials and their device applications. This course of study has been undertaken to discern: (1) the present state of computational simulation of materials; (2) the present ability of computational hardware and software to model new materials; and (3) the ability to apply computational modeling to a relatively poorly studied solid state system, namely mercury(II) chalcogenide halides. Initial interest in this system was fostered by the reported tubular growth of radtkeite (alpha-Hg3S2ClI), which can display a tubular crystal habit tens of micrometers long and micrometers in diameter. To validate that the structures and energies of mercury(II) chalcogenides could be accurately modeled the pressure induced phase transitions in the HgS system were studied using ab initio DF (density functional) calculations. Select MS (M = Ca, Ba, Zn, Cd, Hg, S) compounds were modeled in the cinnabar and zinc-blende structures to discern that they could be accurately modeled. A qualitative description of the MS compounds in the cinnabar structure is provided along with reasoning concerning their relative stability. Three possible radtkeite structures were identified using a brute force methodology of powder x-ray diffraction pattern simulation and then modeled using A initio DF calculations. The cell based upon the gamma-Hg3S 2Cl2 structure was deemed as the best match. This study has validated that computational methods can be used for structural prediction of mercury(II) chalcogenides and chalcogenide halides, however certain methods produced unacceptable results. Materials application statement. This study seeks to discern halogen interactions within II--VI semiconducting materials, namely the mercury(II) chalcogenides. The strategy and methodology of the research will be to invoke computer simulations. The ultimate goal being the correlation of atomic to bulk scale

  3. Selective polyamine-binding proteins. Spermine binding by an androgen-sensitive phosphoprotein.

    PubMed

    Liang, T; Mezzetti, G; Chen, C; Liao, S

    1978-09-01

    Rat ventral prostate contains an acidic protein which can bind spermine selectively. The relative binding affinities of various aliphatic amines for the protein are, in decreasing order, spermine greater than thermine greater than greater than putrecine greater than 1,10-diaminodecane, cadaverine and 1,12-diaminododecane. The binding protein has an isoelectric point at pH 4.3 and a sedimentation coefficient of 3 S. Its molecular weight is approx. 30 000. Histones and nuclear chromatin preparations of the prostate can interact with the binding protein. The spermine-binding activity of the purified prostate protein can be inactivated by treatment with intestinal alkaline phosphatases. The phosphatase treated preparation can then be reactivated by beef heart protein kinase in the presence of cyclic AMP and ATP. The spermine-binding activity of the prostate cytosol protein fraction decreases after castration, but increases very rapidly after the castrated rats are injected with 5alpha-dihydrotestosterone. This finding raises the possibility that, in the postate, certain androgen actions may be dependent on the androgen-induced increase in the acidic protein binding of polyamines and their translocation to a functional cellular site such as nuclear chromatin. In the prostate cytosol, spermine also binds to 4-S tRNAs and to a unique RNA which has a sedimentation coefficient of 1.5 S. PMID:28786

  4. Synthesis of Au/Graphene Oxide Composites for Selective and Sensitive Electrochemical Detection of Ascorbic Acid

    NASA Astrophysics Data System (ADS)

    Song, Jian; Xu, Lin; Xing, Ruiqing; Li, Qingling; Zhou, Chunyang; Liu, Dali; Song, Hongwei

    2014-12-01

    In this work, we present a novel ascorbic acid (AA) sensor applied to the detection of AA in human sera and pharmaceuticals. A series of Au nanoparticles (NPs) and graphene oxide sheets (Au NP/GO) composites were successfully synthesized by reduction of gold (III) using sodium citrate. Then the Au NP/GO composites were used to construct nonenzymatic electrodes in practical AA measurement. The electrode that has the best performance presents attractive analytical features, such as a low working potential of +0.15 V, a high sensitivity of 101.86 μA mM-1 cm-2 to AA, a low detection limit of 100 nM, good reproducibility and excellent selectivity. And more,it was also employed to accurately and practically detect AA in human serum and clinical vitamin C tablet with the existence of some food additive. The enhanced AA electrochemical properties of the Au NP/GO modified electrode in our work can be attributed to the improvement of electroactive surface area of Au NPs and the synergistic effect from the combination of Au NPs and GO sheets. This work shows that the Au NP/GO/GCEs hold the prospect for sensitive and selective determination of AA in practical clinical application.

  5. Ultra-sensitive and selective Hg{sup 2+} detection based on fluorescent carbon dots

    SciTech Connect

    Liu, Ruihua; Li, Haitao; Kong, Weiqian; Liu, Juan; Liu, Yang; Tong, Cuiyan; Zhang, Xing; Kang, Zhenhui

    2013-07-15

    Graphical abstract: Fluorescent carbon dots were efficiently synthesized by one-step sodium hydroxide-assisted reflux method from PEG and demonstrated to show high selectivity toward Hg2+ ions detection. - Highlights: • FCDs were synthesized by one-step sodium hydroxide-assisted reflux method from PEG. • The FCDs emit blue photoluminescence and have upconversion fluorescent property. • The FCDs show ultra-sensitive detective ability for Hg{sup 2+} ions. - Abstract: Fluorescent carbon dots (FCDs) were efficiently synthesized by one-step sodium hydroxide-assisted reflux method from poly(ethylene glycol) (PEG). The obtained FCDs exhibit excellent water-solubility and high stability. Under the UV irradiation, the FCDs could emit bright blue photoluminescence, and also they were found to show excellent up-conversion fluorescence. It was further demonstrated that such FCDs can serve as effective fluorescent sensing platform for Hg{sup 2+} ions detection with ultra-sensitivity and selectivity. The sensing system achieved a limit of detection as low as 1 fM, which is much lower than all the previous reported sensing systems for Hg{sup 2+} ions detection. This FCDs sensing system has been successfully applied for the analysis of Hg{sup 2+} ions in water samples from river, lake, and tap water, showing good practical feasibility.

  6. Synthesis of Au/Graphene Oxide Composites for Selective and Sensitive Electrochemical Detection of Ascorbic Acid

    PubMed Central

    Song, Jian; Xu, Lin; Xing, Ruiqing; Li, Qingling; Zhou, Chunyang; Liu, Dali; Song, Hongwei

    2014-01-01

    In this work, we present a novel ascorbic acid (AA) sensor applied to the detection of AA in human sera and pharmaceuticals. A series of Au nanoparticles (NPs) and graphene oxide sheets (Au NP/GO) composites were successfully synthesized by reduction of gold (III) using sodium citrate. Then the Au NP/GO composites were used to construct nonenzymatic electrodes in practical AA measurement. The electrode that has the best performance presents attractive analytical features, such as a low working potential of +0.15 V, a high sensitivity of 101.86 μA mM−1 cm−2 to AA, a low detection limit of 100 nM, good reproducibility and excellent selectivity. And more,it was also employed to accurately and practically detect AA in human serum and clinical vitamin C tablet with the existence of some food additive. The enhanced AA electrochemical properties of the Au NP/GO modified electrode in our work can be attributed to the improvement of electroactive surface area of Au NPs and the synergistic effect from the combination of Au NPs and GO sheets. This work shows that the Au NP/GO/GCEs hold the prospect for sensitive and selective determination of AA in practical clinical application. PMID:25515430

  7. Discovery of a sensitive, selective, and tight binding fluorogenic substrate of bovine plasma amine oxidase

    PubMed Central

    Ling, Ke-Qing; Sayre, Lawrence M.

    2008-01-01

    We report a novel fluorogenic substrate of bovine plasma amine oxidase (BPAO), namely (2-(6-(aminomethyl)naphthalen-2-yloxy)ethyl)trimethylammonium (ANETA), which displays extremely tight binding to BPAO (Km 183±14 nM), and yet is metabolized fairly quickly (kcat 0.690±0.010 s−1), with the aldehyde turnover product (2-(6-formylnaphthalen-2-yloxy)ethyl)trimethylammonium serving as a real time reporting fluorophore of the enzyme activity. This allowed for the development of a fluorometric non-coupled assay that is two orders of magnitude more sensitive than the spectrophotometric benzylamine assay. The discovery of ANETA involved elaboration of the lead compound 6-methoxy-2-naphthalenemethaneamine by structure-based design, which recognized the ancillary cation binding site of BPAO as the most significant structural features controlling binding affinity. Structure-based design further ensured a high level of selectivity: ANETA is a good substrate of BPAO, but is not a substrate of either porcine kidney diamine oxidase (pkDAO) or rat liver monoamine oxidase (MAO-B). ANETA represents the first highly sensitive, selective, and tight binding fluorogenic substrate of a copper amine oxidase that is able to respond directly to the enzyme activity in real time. PMID:19053593

  8. Aptamer-based colorimetric sensing of acetamiprid in soil samples: sensitivity, selectivity and mechanism.

    PubMed

    Shi, Huijie; Zhao, Guohua; Liu, Meichuan; Fan, Lifang; Cao, Tongcheng

    2013-09-15

    A simple and selective aptamer-based colorimetric method was developed for highly sensitive detection of acetamiprid, taking advantages of the sensitive target-induced colour changes that arisen from the interparticle plasmon coupling during the aggregation of Au nanoparticles (NPs). The results showed that the established method could be applied to detect acetamiprid in the linear range between 75 nM to 7.5 μM, with a low detection limit of 5 nM. Meanwhile, by employing an "artificial antibody" acetamiprid-binding aptamer (ABA) as recognition element, highly selective and specific colorimetric visualization of acetamiprid was obtained. It indicated that pesticides which may coexist with acetamiprid could not interfere with the detection of acetamiprid even that had similar structure with acetamiprid, such as imidacloprid and chlorpyrifos. Mechanism study suggested that it could be attributed to the specific supramolecular interaction between ABA and acetamiprid, as well as the resulted target-binding event induced conformation changes of ABA from random coil to hairpin structure. The practical application of the colorimetric method was realized for detecting acetamiprid in real soil samples and monitoring its natural degradation process. PMID:23846126

  9. Highly selective and sensitive nanoprobes for cyanide based on gold nanoclusters with red fluorescence emission

    NASA Astrophysics Data System (ADS)

    Zhang, Guomei; Qiao, Yunyun; Xu, Ting; Zhang, Caihong; Zhang, Yan; Shi, Lihong; Shuang, Shaomin; Dong, Chuan

    2015-07-01

    We report a novel and environmentally friendly fluorescent probe for detecting the cyanide ion (CN-) using l-amino acid oxidase (LAAOx)-protected Au nanoclusters (LAAOx@AuNCs) with red emission. The fluorescence-based sensing behaviour of LAAOx@AuNCs towards anions was investigated in buffered aqueous media. Among the anions studied, CN- was found to effectively quench the fluorescence emission of AuNCs based on CN- induced Au core decomposition. Excellent sensitivity and selectivity toward the detection of CN- in aqueous solution were observed. The CN- detection limit was determined to be approximately 180 nM, which is 15 times lower than the maximum level (2700 nM) of CN- in drinking water permitted by the World Health Organization (WHO). A linear relationship between the fluorescence intensity and CN- concentration was observed in two ranges of CN- concentration, including 3.2 × 10-6 to 3.4 × 10-5 mol L-1 and 3.81 × 10-5 to 1.04 × 10-4 mol L-1. The high sensitivity and selectivity to CN- among the 17 types of anions make the AuNCs good candidates for use in fluorescent nanoprobes of CN-.

  10. Highly sensitive and selective nonenzymatic detection of glucose using three-dimensional porous nickel nanostructures.

    PubMed

    Niu, Xiangheng; Lan, Minbo; Zhao, Hongli; Chen, Chen

    2013-04-01

    Highly sensitive and selective nonenzymatic detection of glucose has been achieved using a novel disposable electrochemical sensor based on three-dimensional (3D) porous nickel nanostructures. The enzyme-free sensor was fabricated through in situ growing porous nickel networks on a homemade screen-printed carbon electrode substrate via electrochemically reducing the Ni(2+) precursor, along with continuously liberating hydrogen bubbles. The resulting nickel-modified electrode was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectrometry (EDX), powder X-ray diffractometry (XRD), and electrochemical techniques. Cyclic voltammetric, alternating-current impedance, and amperometric methods were used to investigate the catalytic properties of the assembled sensor for glucose electro-oxidation in alkaline media. Under optimized conditions, the enzymeless sensor exhibited excellent performance for glucose analysis selectively, offering a much wider linear range (from 0.5 μM to 4 mM), an extremely low detection limit (0.07 μM, signal-to-noise ratio (S/N) of 3), and an ultrahigh sensitivity of 2.9 mA/(cm(2) mM). Importantly, favorable reproducibility and long-term performance stability were obtained thanks to the robust frameworks. Application of the proposed sensor in monitoring blood glucose was also demonstrated. PMID:23458297

  11. A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy

    PubMed Central

    Liu, Wenpeng; Zhou, Mian; Li, Zhengke; Li, Hongzhi; Polaczek, Piotr; Dai, Huifang; Wu, Qiong; Liu, Changwei; Karanja, Kenneth K.; Popuri, Vencat; Shan, Shu-ou; Schlacher, Katharina; Zheng, Li; Campbell, Judith L.; Shen, Binghui

    2016-01-01

    Cancer cells frequently up-regulate DNA replication and repair proteins such as the multifunctional DNA2 nuclease/helicase, counteracting DNA damage due to replication stress and promoting survival. Therefore, we hypothesized that blocking both DNA replication and repair by inhibiting the bifunctional DNA2 could be a potent strategy to sensitize cancer cells to stresses from radiation or chemotherapeutic agents. We show that homozygous deletion of DNA2 sensitizes cells to ionizing radiation and camptothecin (CPT). Using a virtual high throughput screen, we identify 4-hydroxy-8-nitroquinoline-3-carboxylic acid (C5) as an effective and selective inhibitor of DNA2. Mutagenesis and biochemical analysis define the C5 binding pocket at a DNA-binding motif that is shared by the nuclease and helicase activities, consistent with structural studies that suggest that DNA binding to the helicase domain is necessary for nuclease activity. C5 targets the known functions of DNA2 in vivo: C5 inhibits resection at stalled forks as well as reducing recombination. C5 is an even more potent inhibitor of restart of stalled DNA replication forks and over-resection of nascent DNA in cells defective in replication fork protection, including BRCA2 and BOD1L. C5 sensitizes cells to CPT and synergizes with PARP inhibitors. PMID:27211550

  12. Ultrathin pH-sensitive nanoporous membranes for superfast size-selective separation.

    PubMed

    Zhang, Qiu Gen; Deng, Chao; Liu, Rong Rong; Lin, Zhen; Li, Hong Mei; Zhu, Ai Mei; Liu, Qing Lin

    2015-05-01

    Stimuli-responsive nanoporous membranes have attracted increasing interest in various fields due to their abrupt changes of permeation/separation in response to the external environment. Here we report ultrathin pH-sensitive nanoporous membranes that are easily fabricated by the self-assembly of poly(acrylic acid) (PAA) in a metal hydroxide nanostrand solution. PAA-adsorbed nanostrands (2.5-5.0 nm) and PAA-Cu(II) nanogels (2.0-2.5 nm) grow competitively during self-assembly. The PAA-adsorbed nanostrands are deposited on a porous support to fabricate ultrathin PAA membranes. The membranes display ultrafast water permeation and good rejection as well as significant pH-sensitivity. The 28 nm-thick membrane has a water flux decrease from 3740 to 1350 L m(-1)  h(-1)  bar(-1) (pH 2.0 to 7.0) with a sharp decrease at pH 5.0. This newly developed pH-sensitive nanoporous membranes may find a wide range of applications such as controlled release and size- and charge-selective separation. PMID:25736206

  13. A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy.

    PubMed

    Liu, Wenpeng; Zhou, Mian; Li, Zhengke; Li, Hongzhi; Polaczek, Piotr; Dai, Huifang; Wu, Qiong; Liu, Changwei; Karanja, Kenneth K; Popuri, Vencat; Shan, Shu-Ou; Schlacher, Katharina; Zheng, Li; Campbell, Judith L; Shen, Binghui

    2016-04-01

    Cancer cells frequently up-regulate DNA replication and repair proteins such as the multifunctional DNA2 nuclease/helicase, counteracting DNA damage due to replication stress and promoting survival. Therefore, we hypothesized that blocking both DNA replication and repair by inhibiting the bifunctional DNA2 could be a potent strategy to sensitize cancer cells to stresses from radiation or chemotherapeutic agents. We show that homozygous deletion of DNA2 sensitizes cells to ionizing radiation and camptothecin (CPT). Using a virtual high throughput screen, we identify 4-hydroxy-8-nitroquinoline-3-carboxylic acid (C5) as an effective and selective inhibitor of DNA2. Mutagenesis and biochemical analysis define the C5 binding pocket at a DNA-binding motif that is shared by the nuclease and helicase activities, consistent with structural studies that suggest that DNA binding to the helicase domain is necessary for nuclease activity. C5 targets the known functions of DNA2 in vivo: C5 inhibits resection at stalled forks as well as reducing recombination. C5 is an even more potent inhibitor of restart of stalled DNA replication forks and over-resection of nascent DNA in cells defective in replication fork protection, including BRCA2 and BOD1L. C5 sensitizes cells to CPT and synergizes with PARP inhibitors. PMID:27211550

  14. Selective induction of apoptosis in the hamster flank sebaceous gland organ by a topical liposome 5-alpha-reductase inhibitor: a treatment strategy for acne.

    PubMed

    Li, Lingna; Tang, Li; Baranov, Eugene; Yang, Meng; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-02-01

    Acne is a very widespread cosmesis problem. Isotretinoin, a synthetic oral retinoid is used to treat acne, which is androgen dependent. Numerous side-effects occur from this treatment. 5-alpha-Reductase plays a critical role in normal and pathological androgen-dependent processes. We have taken the approach to develop a selective, effective, topically-applied 5-alpha-reductase inhibitor to modify unwanted or pathological processes in the pilosebaceous unit such as acne. Toward this goal, we have previously developed a selective liposome hair follicle targeting system. We demonstrate in this report that the 5-alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide (4-MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland. We have compared topical application of liposome 4-MA and solvent-formulated 4-MA and observed selective efficacy of topical application of liposome 4-MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4-MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (transferase deoxytidyl uridine end labeling) and by observation of condensed and fragmented nuclei. When 4-MA was topically applied formulated in ethanol and glycerol without liposomes, the selective efficacy was lost. Liposome 4-MA did not significantly affect prostate weight, testosterone/DHT ratios or bodyweight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA for pathological processes such as acne. PMID:20175850

  15. In Vitro Selection of a Single-Stranded DNA Molecular Recognition Element against Clostridium difficile Toxin B and Sensitive Detection in Human Fecal Matter

    PubMed Central

    Maher, Eamonn; Williams, Ryan M.; Sooter, Letha J.

    2015-01-01

    Toxin B is one of the major virulence factors of Clostridium difficile, a bacterium that is responsible for a significant number of diarrhea cases in acute care settings. Due to the prevalence of C. difficile induced diarrhea, rapid and correct diagnosis is crucial in the disease management. In this study, we have employed a stringent in vitro selection method to identify single-stranded DNA molecular recognition elements (MRE) specific for toxin B. At the end of the 12-round selection, one MRE with high affinity (Kd = 47.3 nM) for toxin B was identified. The selected MRE demonstrated low cross binding activities on negative targets: bovine serum albumin, Staphylococcus aureus alpha toxin, Pseudomonas aeruginosa exotoxin A, and cholera toxin of Vibrio cholera. A modified sandwich ELISA assay was developed utilizing the selected ssDNA MRE as the antigen capturing element and achieved a sensitive detection of 50 nM of toxin B in human fecal preparations. PMID:25734010

  16. Investigation of the sensitivity, selectivity, and reversibility of the chemically-sensitive field-effect transistor (CHEMFET) to detect nitrogen dioxide, dimethyl methylphosphonate, and boron trifluoride. Master's thesis

    SciTech Connect

    Hauschild, N.T.

    1993-09-01

    This study investigated the sensitivity, selectivity, and reversibility of a chemically-sensitive field-effect transistor (CHEMFET) gas microsensor. Various physical operating parameters were tested to determine which produced the most significant sensitivity, selectivity, and reversibility which were computed from response changes generated from electrical conductivity modulations when exposed to challenge gases. The variable operating parameters included: thinfilm material, film thickness, challenge gas specie, challenge gas concentration, and operating temperature. Copper phthalocyanine and lead phthalocyanine were used as thin films to detect the following challenge gases: nitrogen dioxide, dimethyl methylphosphonate, boron trifluoride, methanol, carbon monoxide, vinyl chloride, and trichloroethylene. Tests revealed that copper phthalocyanine was the most sensitive to dimethyl methylphosphonate and boron trifluoride, whereas lead phthalocyanine was the most sensitive to the remaining challenge gases. The CHEMFET was selective to the binary challenge gas combinations. The films were most selective for nitrogen dioxide. The CHEMFET was fully reversibly, and the time duration for full reversibility increased with increasing challenge gas concentrations and increasing time of exposure.

  17. A peptide derived from alpha-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen.

    PubMed

    Bennett, James A; Mesfin, Fassil B; Andersen, Thomas T; Gierthy, John F; Jacobson, Herbert I

    2002-02-19

    An 8-mer peptide (EMTOVNOG) derived from alpha-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen-receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF-7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was found to be resistant to tamoxifen in vivo. Peptide completely prevented the xenograft growth of this tamoxifen-resistant subline of MCF-7. Neither peptide nor tamoxifen was effective in slowing the xenograft growth of the estrogen-receptor-negative MDA-MB-231 human breast cancer. A worrisome side effect of tamoxifen is its hypertrophic effect on the uterus. In this study, tamoxifen was shown to stimulate the growth of the immature mouse uterus in vivo, and the peptide significantly inhibited tamoxifen's uterotrophic effect. The mechanism of action of peptide is different from that of tamoxifen in that the peptide does not interfere with the binding of [(3)H]estradiol to the estrogen receptor. In conclusion, alpha-fetoprotein-derived peptide appears to be a novel agent that interferes with the growth of tamoxifen-sensitive as well as tamoxifen-resistant estrogen-receptor-positive human breast cancers; it inhibits the uterotrophic side effect of tamoxifen and, thus, it may be useful in combination with or in place of tamoxifen for treatment of estrogen-receptor-positive human breast cancers. PMID:11830647

  18. Y-box proteins interact with the S1 nuclease-sensitive site in the chicken alpha 2(I) collagen gene promoter.

    PubMed Central

    Bayarsaihan, D; Enkhmandakh, B; Lukens, L N

    1996-01-01

    The sequence of the chicken alpha 2(I) collagen promoter from -712 to -85, relative to exon 1, has been shown to be important for transcriptional activity. Within this region a pyrimidine/purine asymmetrical element at -200 bp forms an in vitro S1 nuclease-sensitive site. The pyrimidine-rich strand of this element interacts specifically with single-stranded DNA-binding proteins present in fibroblast nuclear extracts [Bayarsaihan and Lukens (1996) Biochem. J. 314, 293-296]. To identify these proteins we performed expression screening of a chick embryo fibroblast cDNA library using a single-stranded polypyrimidine sequence derived from this element. One of the isolated clones was found to encode a member of the cold-shock gene family, either chicken YB-1 or a highly homologous protein. This protein and a known chicken Y-box protein were both found to bind sequence-specifically to the pyrimidine-rich strand of the pyrimidine/purine asymmetrical element in the chicken alpha 2(I) collagen promoter. The binding mechanism of these proteins could be based on the formation of a non-canonical triplex DNA structure (H-DNA). Although members of this widespread and conserved protein family have been reported to modulate the expression of a number of genes, the findings reported here provide the first evidence for a possible role of cold-shock proteins in the regulation of type I collagen genes. PMID:8870670

  19. High sensitivity boron quantification in bulk silicon using the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be nuclear reaction

    SciTech Connect

    Moro, Marcos V.; Silva, Tiago F. da; Added, Nemitala; Rizutto, Marcia A.; Tabacniks, Manfredo H.; Neira, John B.; Neto, Joao B. F.

    2013-05-06

    There is a great need to quantify sub-ppm levels of boron in bulk silicon. There are several methods to analyze B in Si: Nuclear Reaction Analysis using the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be reaction exhibits a quantification limit of some hundreds ppm of B in Si. Heavy Ion Elastic Recoil Detection Analysis offers a detection limit of 5 to 10 at. ppm. Secondary Ion Mass Spectrometry is the method of choice of the semiconductor industry for the analysis of B in Si. This work verifies the use of NRA to quantify B in Si, and the corresponding detection limits. Proton beam with 1.6 up to 2.6 MeV was used to obtain the cross-section of the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be nuclear reaction at 170 Degree-Sign scattering angle. The results show good agreementwith literature indicating that the quantification of boron in silicon can be achieved at 100 ppm level (high sensitivity) at LAMFI-IFUSP with about 16% uncertainty. Increasing the detection solid angle and the collected beam charge, can reduce the detection limit to less than 100 ppm meeting present technological needs.

  20. N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p-nitrophenyl ester: a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin.

    PubMed

    Balliano, G; Milla, P; Giordano, C; Gallina, C; Coletta, M; Menegatti, E; Rizzi, M; Bolognesi, M; Ascenzi, P

    1996-08-14

    The serine proteinase catalyzed hydrolysis of N-ethoxycarbonyl-D-phenylalanyl-L-prolyl-alpha-azalysine p- nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) was investigated at pH 6.2 and 21.0 degrees C. The results are consistent with the minimum three-step catalytic mechanism. The acylation step is rate limiting for human (Lys 77 species) and porcine plasmin, and for bovine beta-trypsin, the deacylation rate being limiting, on the other hand, for human and bovine alpha-, beta- and gamma-thrombin. Moreover the M(r) 33,000 species of human urokinase and the neuraminidase-treated porcine pancreatic beta-kallikrein-B do not catalyze the hydrolysis of the tripeptide. According to the specificity properties of the serine proteinases considered. Eoc-D-Phe- Pro-azaLys-ONp shows the characteristics of a novel, high selective and optimal chromogenic active site titrant for human and bovine alpha-, beta- and gamma-thrombin. PMID:8753800

  1. Highly sensitive and selective fluorescence assays for rapid screening of endothelin-converting enzyme inhibitors.

    PubMed Central

    Luciani, N; de Rocquigny, H; Turcaud, S; Romieu, A; Roques, B P

    2001-01-01

    The highly potent vasoconstrictor peptide endothelin (ET) is generated from an inactive precursor, big endothelin (bET), by endothelin-converting enzyme (ECE). ECE is a phosphoramidon-sensitive zinc metallopeptidase, which is closely related to neprilysin (neutral endopeptidase). It is possible that compounds which inhibit the formation of ET may be used as new drugs for the treatment of cardiovascular diseases. Such an approach requires a fast, simple and selective assay to measure ECE activity, allowing rapid screening of inhibitors. We describe here two new ECE substrates based on the concept of 'intramolecularly quenched fluorescence' which may fulfill this aim. One, S(1) [Pya(21)-Nop(22)-bET-1(19--35)], is the (19--35) fragment of the natural peptide big-ET-1(1--38), which is modified by introducing the fluorescent amino acid, pyrenylalanine (Pya), in position 21 and a quencher, p-nitrophenylalanine (Nop), in position 22. The second substrate (S(2)) is a small peptide, Ac-Ser-Gly-Pya-Lys-Ala-Phe-Ala-Nop-Gly-Lys-NH(2), from a biased substrate peptide library. The recombinant, hECE-1c, cleaved both Pya(21)-Nop(22)-bET-1(19--35) and the natural substrate selectively between residues 21 and 22, whereas cleavage occurred between alanine and phenylalanine in the small peptide. In both cases, this generated intense fluorescence emission. The synthesis and kinetic parameters of these substrates are described. These assays, which can be used directly on tissue homogenates, are the most sensitive and selective described to date for ECE, and are easily automated for a high-throughput screening of inhibitors. PMID:11389689

  2. TC-5619: An alpha7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia

    PubMed Central

    Hauser, T.A.; Kucinski, A.; Jordan, K.G.; Gatto, G.J.; Wersinger, S.R.; Hesse, R.A.; Stachowiak, E.K.; Stachowiak, M.K.; Papke, R.L.; Lippiello, P.M.; Bencherif, M.

    2010-01-01

    A growing body of evidence suggests that the alpha7 neuronal nicotinic receptor (NNR) subtype is an important target for the development of novel therapies to treat schizophrenia, offering the possibility to address not only the positive but also the cognitive and negative symptoms associated with the disease. In order to probe the relationship of alpha7 function to relevant behavioral correlates we employed TC-5619, a novel selective agonist for the alpha7 NNR subtype. TC-5619 binds with very high affinity to the alpha7 subtype and is a potent full agonist. TC-5619 has little or no activity at other nicotinic receptors, including the α4β2, ganglionic (α3β4) and muscle subtypes. The transgenic th(tk−)/th(tk−) mouse model that reflects many of the developmental, anatomical, and multi-transmitter biochemical aspects of schizophrenia was used to assess the antipsychotic effects of TC-5619. In these mice TC-5619 acted both alone and synergistically with the antipsychotic clozapine to correct impaired pre-pulse inhibition (PPI) and social behavior which model positive and negative symptoms, respectively. Antipsychotic and cognitive effects of TC-5619 were also assessed in rats. Similar to the results in the transgenic mice, TC-5619 significantly reversed apomorphine-induced PPI deficits. In a novel object recognition paradigm in rats TC-5619 demonstrated long-lasting enhancement of memory over a wide dose range. These results suggest that alpha7-selective agonists such as TC-5619, either alone or in combination with antipsychotics, could offer a new approach to treating the constellation of symptoms associated with schizophrenia, including cognitive dysfunction. PMID:19482012

  3. FIRST SPECTROSCOPIC MEASUREMENTS OF [O III] EMISSION FROM Ly{alpha} SELECTED FIELD GALAXIES AT z {approx} 3.1

    SciTech Connect

    McLinden, Emily M.; Rhoads, James E.; Malhotra, Sangeeta; Hibon, Pascale; Richardson, Mark L. A.; Finkelstein, Steven L.; Cresci, Giovanni; Quirrenbach, Andreas; Pasquali, Anna; Bian Fuyan; Fan Xiaohui; Woodward, Charles E.

    2011-04-01

    We present the first spectroscopic measurements of the [O III] 5007 A line in two z {approx} 3.1 Ly{alpha} emitting galaxies (LAEs) using the new near-infrared instrument LUCIFER1 on the 8.4 m Large Binocular Telescope. We also describe the optical imaging and spectroscopic observations used to identify these LAEs. Using the [O III] line we have measured accurate systemic redshifts for these two galaxies, and discovered a velocity offset between the [O III] and Ly{alpha} lines in both, with the Ly{alpha} line peaking 342 and 125 km s{sup -1} redward of the systemic velocity. These velocity offsets imply that there are powerful outflows in high-redshift LAEs. They also ease the transmission of Ly{alpha} photons through the interstellar medium and intergalactic medium around the galaxies. By measuring these offsets directly, we can refine both Ly{alpha}-based tests for reionization, and Ly{alpha} luminosity function measurements where the Ly{alpha} forest affects the blue wing of the line. Our work also provides the first direct constraints on the strength of the [O III] line in high-redshift LAEs. We find [O III] fluxes of 7 and 36 x10{sup -17} erg s{sup -1} cm{sup -2} in two z {approx} 3.1 LAEs. These lines are strong enough to dominate broadband flux measurements that include the line (in this case, K{sub s} -band photometry). Spectral energy distribution fits that do not account for the lines would therefore overestimate the 4000 A (and/or Balmer) break strength in such galaxies, and hence also the ages and stellar masses of such high-z galaxies.

  4. Three mutations identified in the voltage-sensitive sodium channel alpha-subunit gene of permethrin-resistant human head lice reduce the permethrin sensitivity of house fly Vssc1 sodium channels expressed in Xenopus oocytes.

    PubMed

    SupYoon, Kyong; Symington, Steven B; Hyeock Lee, Si; Soderlund, David M; Marshall Clark, J

    2008-03-01

    Point mutations in the para-orthologous sodium channel alpha-subunit of the head louse (M815I, T917I, and L920F) are associated with permethrin resistance and DDT resistance. These mutations were inserted in all combinations using site-directed mutagenesis at the corresponding amino acid sequence positions (M827I, T929I, and L932F) of the house fly para-orthologous voltage-sensitive sodium channel alpha-subunit (Vssc1(WT)) gene and heterologously co-expressed with the sodium channel auxiliary subunit of house fly (Vsscbeta) in Xenopus oocytes. The double mutant possessing M827I and T929I (Vssc1(MITI)/Vsscbeta) caused a approximately 4.0mV hyperpolarizing shift and the triple mutant, Vssc1(MITILF)/Vsscbeta, caused a approximately 3.2mV depolarizing shift in the voltage dependence of activation curves. Vssc1(MITI)/Vsscbeta, Vssc1(TILF)/Vsscbeta, and Vssc1(MITILF)/Vsscbeta caused depolarizing shifts ( approximately 6.6, approximately 7.6, and approximately 8.8mV, respectively) in the voltage dependence of steady-state inactivation curves. The M827I and L932F mutations reduced permethrin sensitivity when expressed alone but the T929I mutation, either alone or in combination, virtually abolished permethrin sensitivity. Thus, the T929I mutation is the principal cause of permethrin resistance in head lice. Comparison of the expression rates of channels containing single, double and triple mutations with that of Vssc1(WT)/Vsscbeta channels indicates that the M827I mutation may play a role in rescuing the decreased expression of channels containing T929I. PMID:18252244

  5. PKC regulates alpha(1)-adrenoceptor-mediated contractions and baseline Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia.

    PubMed

    Xiao, Daliao; Huang, Xiaohui; Longo, Lawrence D; Zhang, Lubo

    2010-01-01

    Chronic hypoxia has a profound effect on uterine artery adaptation to pregnancy. The present studies tested the hypothesis that pregnant kinase C (PKC) differentially regulates alpha(1)-adrenoceptor-mediated contractions and Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia. Uterine arteries were isolated from nonpregnant (NPUA) and near-term pregnant (PUA) ewes maintained at high altitude (3801 m, Pao(2) approximately 60 torr) for 110 days. Phorbol 12,13-dibutyrate (PDBu) decreased phenylephrine-induced contractions in PUA but not in NPUA, which was partly inhibited by the PKC inhibitor GF109203X. Additionally, GF109203X shifted the concentration-response curve of phenylephrine-induced contractions to the right in PUA. In beta-escin-permeabilized arteries, Ca(2+)-induced increases in 20-kDa myosin light chain phosphorylation (MLC(20)-P) were similar in NPUA and PUA. However, Ca(2+) produced a concentration-dependent increase in the ratio of tension to MLC(20)-P in PUA, as compared with NPUA. PKC inhibition decreased Ca(2+)-induced contractions in both NPUA and PUA. PDBu induced contractions of PUA in the absence of changes in MLC(20)-P, which was not affected by PD098059. There was a significant increase in the basal activity of PKCvarepsilon in PUA, but not in NPUA, in hypoxic sheep, as compared with normoxic animals. The results demonstrate that the inhibitory effect of PKC on alpha(1)-adrenoceptor-mediated contractions of uterine arteries is preserved in pregnant sheep at high altitude. However, the PKC-mediated thin-filament regulatory pathway is upregulated, resulting in increased baseline Ca(2+) sensitivity in the uterine artery during pregnancy at high altitude. PMID:20586600

  6. Imaging alpha particle detector

    DOEpatents

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  7. Imaging alpha particle detector

    DOEpatents

    Anderson, David F.

    1985-01-01

    A method and apparatus for detecting and imaging alpha particles sources is described. A conducting coated high voltage electrode (1) and a tungsten wire grid (2) constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source (3) to be quantitatively or qualitatively analyzed. A thin polyester film window (4) allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  8. Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase.

    PubMed Central

    Pauwels, R; Andries, K; Debyser, Z; Van Daele, P; Schols, D; Stoffels, P; De Vreese, K; Woestenborghs, R; Vandamme, A M; Janssen, C G

    1993-01-01

    In vitro evaluation of a large chemical library of pharmacologically acceptable prototype compounds in a high-capacity, cellular-based screening system has led to the discovery of another family of human immunodeficiency virus type 1 (HIV-1) inhibitors. Through optimization of a lead compound, several alpha-anilinophenylacetamide (alpha-APA) derivatives have been identified that inhibit the replication of several HIV-1 strains (IIIB/LAI, RF, NDK, MN, HE) in a variety of host cell types at concentrations that are 10,000- to 100,000-fold lower than their cytotoxic concentrations. The IC50 of the alpha-APA derivative R 89439 for HIV-1 cytopathicity in MT-4 cells was 13 nM. The median 90% inhibitory concentration (IC90) in a variety of host cells was 50-100 nM. Although these alpha-APA derivatives are active against a tetrahydroimidazo [4,5,1-jk][1,4]benzodiazepin-2(1H)-thione-(TIBO)-resistant HIV-1 strain, they do not inhibit replication of HIV-2 (strains ROD and EHO) or simian immunodeficiency virus (strains Mac251, mndGB1, and agm3). An HIV-1 strain containing the Tyr181-->Cys mutation in the reverse transcriptase region displayed reduced sensitivity. alpha-APA derivative R 89439 inhibited virion and recombinant reverse transcriptase of HIV-1 but did not inhibit that of HIV-2. Reverse transcriptase inhibition depended upon the template/primer used. The relatively uncomplicated synthesis of R 89439, its potent anti-HIV-1 activity, and its favorable pharmacokinetic profile make R 89439 a good candidate for clinical studies. PMID:7680476

  9. Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks.

    PubMed

    Lukawski, Krzysztof; Kamiński, Rafał M; Czuczwar, Stanisław J

    2008-01-28

    The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system. The mice were treated with either 2-PMPA (50, 100 and 150 mg/kg i.p.) or N-methyl-d-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) at doses of: 0.05, 0.1, 0.15 and 0.2 mg/kg i.p., as a comparator. In the passive avoidance task, the drugs were administered once before or immediately after training, and before retention test. 2-PMPA at the doses used did not affect retention of passive avoidance; however, it increased the latency to enter the dark box during the training day. In the Y-maze task, 2-PMPA (150 mg/kg i.p.) impaired spontaneous alternation and reduced locomotion while the lower dose of 100 mg/kg was ineffective. In the locomotor activity test, 2-PMPA (100 and 150 mg/kg i.p.) did not significantly affect horizontal activity. MK-801 (0.2 mg/kg i.p.) injected before training reduced retention in the passive avoidance task. In the Y-maze task, MK-801 (0.1 mg/kg i.p.) impaired alternation behavior and considerably increased locomotion in the Y-maze and locomotor activity test. These results indicate that NAALADase inhibition may impair alternation behavior. PMID:18031726

  10. Sensitive and selective SERS probe for trivalent chromium detection using citrate attached gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Ye, Yingjie; Liu, Honglin; Yang, Liangbao; Liu, Jinhuai

    2012-09-01

    In this article, we have demonstrated a sensitive and selective surface enhanced Raman spectroscopy (SERS) probe, based on citrate-capped gold nanoparticles (AuNPs), for trivalent chromium (Cr3+) detection. After introducing Tween 20 to a solution of citrate-capped AuNPs, the as-prepared Tween 20/citrate-AuNP probe could recognize Cr3+ at a 50 × 10-9 M level in an aqueous medium at a pH of 6.0. Tween 20 can stabilize the citrate-capped AuNPs against conditions of high ionic strength. Due to the chelation between Cr3+ and citrate ions, AuNPs undergo aggregation. As a result, it formed several hot spots and provided a significant enhancement of the Raman signal intensity through electromagnetic (EM) field enhancements. A detailed mechanism for tremendous SERS intensity change had been discussed. The selectivity of this system toward Cr3+ was 400-fold, remarkably greater than other metal ions.In this article, we have demonstrated a sensitive and selective surface enhanced Raman spectroscopy (SERS) probe, based on citrate-capped gold nanoparticles (AuNPs), for trivalent chromium (Cr3+) detection. After introducing Tween 20 to a solution of citrate-capped AuNPs, the as-prepared Tween 20/citrate-AuNP probe could recognize Cr3+ at a 50 × 10-9 M level in an aqueous medium at a pH of 6.0. Tween 20 can stabilize the citrate-capped AuNPs against conditions of high ionic strength. Due to the chelation between Cr3+ and citrate ions, AuNPs undergo aggregation. As a result, it formed several hot spots and provided a significant enhancement of the Raman signal intensity through electromagnetic (EM) field enhancements. A detailed mechanism for tremendous SERS intensity change had been discussed. The selectivity of this system toward Cr3+ was 400-fold, remarkably greater than other metal ions. Electronic supplementary information (ESI) available: Fig. S1-S5. See DOI: 10.1039/c2nr31985c

  11. Tumor Necrosis Factor Alpha Inhibits L-Type Ca2+ Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway

    PubMed Central

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca2+ channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  12. Mutational analysis of essential IncP alpha plasmid transfer genes traF and traG and involvement of traF in phage sensitivity.

    PubMed Central

    Waters, V L; Strack, B; Pansegrau, W; Lanka, E; Guiney, D G

    1992-01-01

    Although the broad-host-range IncP plasmids can vegetatively replicate in diverse gram-negative bacteria, the development of shuttle vector systems has established that the host range for IncP plasmid conjugative transfer is greater than the range of bacteria that sustain IncP replicons. Towards understanding IncP plasmid conjugation and the connection between IncP conjugation and Agrobacterium tumefaciens T-DNA transfer to plants, two sets of mutants were generated in the larger transfer region (Tra1) of the IncP alpha plasmid RK2. Mutagenesis strategies were chosen to minimize transcriptional polar effects. Mutant Tra1 clones were mapped, sequenced, and processed to reconstruct 49.5-kb Tra2-containing plasmid derivatives in order to assay for transfer activity and IncP plasmid-specific phage sensitivity. Focusing on the activities of the gene products of traF and traG in Escherichia coli, we found that mutations in traF abolished transfer activity and rendered the host cells phage resistant and mutations in traG abolished transfer activity but had no effect on phage sensitivity. Complementation of these mutant derivatives with corresponding trans-acting clones carrying traF or traG restored transfer activity and, in the case of the traF mutant, the phage sensitivity of the host cell. We conclude that in E. coli, both TraF and TraG are essential for IncP plasmid transfer and that TraF is necessary (but not sufficient) for donor-specific phage sensitivity, and sequencing data suggest that both TraF and TraG are membrane spanning. Images PMID:1400217

  13. Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    PubMed

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María; Montaño, Luis M

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  14. Sensitive and Selective Detection of HIV-1 RRE RNA Using Vertical Silicon Nanowire Electrode Array.

    PubMed

    Lee, Jaehyung; Hong, Min-Ho; Han, Sanghun; Na, Jukwan; Kim, Ilsoo; Kwon, Yong-Joon; Lim, Yong-Beom; Choi, Heon-Jin

    2016-12-01

    In this study, HIV-1 Rev response element (RRE) RNA was detected via an Au-coated vertical silicon nanowire electrode array (VSNEA). The VSNEA was fabricated by combining bottom-up and top-down approaches and then immobilized by artificial peptides for the recognition of HIV-1 RRE. Differential pulse voltammetry (DPV) analysis was used to measure the electrochemical response of the peptide-immobilized VSNEA to the concentration and types of HIV-1 RRE RNA. DPV peaks showed linearity to the concentration of RNA with a detection limit down to 1.513 fM. It also showed the clear different peaks to the mutated HIV-1 RRE RNA. The high sensitivity and selectivity of VSNEA for the detection of HIV-1 RRE RNA may be attributed to the high surface-to-volume ratio and total overlap diffusion mode of ions of the one-dimensional nanowire electrodes. PMID:27448026

  15. Highly selective, sensitive and fast-responsive fluorescent sensor for Hg2 +

    NASA Astrophysics Data System (ADS)

    Niu, Qingfen; Wu, Xingxing; Li, Tianduo; Cui, Yuezhi; Zhang, Shanshan; Li, Xiaoyan

    2016-06-01

    A phenylamine-oligothiophene-based fluorescent sensor 2TBEA was reported. This sensor exhibited highly selective, sensitive and rapid detection of Hg2 + ion in THF/H2O (7/3, v/v) solution through fluorescence quenching. The detection was unaffected by the coexistence of other competitive metal cations including Na+, K+, Ag+, Ca2 +, Fe3 +, Al3 +, Co2 +, Cu2 +, Ni2 +, Zn2 +, Pb2 +, Cd2 +, Fe2 + and Cr3 +. A1:1 binding ratio for 2TBEA - Hg2 + was demonstrated by Job's plot and mole-ratio curves. The coordination process was chemically reversible with EDTA. The detection limit was evaluated to be as low as 6.164 × 10- 8 M.

  16. A new hydroxynaphthyl benzothiazole derived fluorescent probe for highly selective and sensitive Cu(2+) detection.

    PubMed

    Tang, Lijun; He, Ping; Zhong, Keli; Hou, Shuhua; Bian, Yanjiang

    2016-12-01

    A new reactive probe, 1-(benzo[d]thiazol-2-yl)naphthalen-2-yl-picolinate (BTNP), was designed and synthesized. BTNP acts as a highly selective probe to Cu(2+) in DMSO/H2O (7/3, v/v, Tris-HCl 10mM, pH=7.4) solution based on Cu(2+) catalyzed hydrolysis of the picolinate ester moiety in BTNP, which leads to the formation of an ESIPT active product with dual wavelength emission enhancement. The probe also possesses the advantages of simple synthesis, rapid response and high sensitivity. The pseudo-first-order reaction rate constant was calculated to be 0.205min(-1). Moreover, application of BTNP to Cu(2+) detection in living cells and real water samples was also explored. PMID:27391231

  17. Sensitive and Selective Detection of HIV-1 RRE RNA Using Vertical Silicon Nanowire Electrode Array

    NASA Astrophysics Data System (ADS)

    Lee, Jaehyung; Hong, Min-Ho; Han, Sanghun; Na, Jukwan; Kim, Ilsoo; Kwon, Yong-Joon; Lim, Yong-beom; Choi, Heon-Jin

    2016-07-01

    In this study, HIV-1 Rev response element (RRE) RNA was detected via an Au-coated vertical silicon nanowire electrode array (VSNEA). The VSNEA was fabricated by combining bottom-up and top-down approaches and then immobilized by artificial peptides for the recognition of HIV-1 RRE. Differential pulse voltammetry (DPV) analysis was used to measure the electrochemical response of the peptide-immobilized VSNEA to the concentration and types of HIV-1 RRE RNA. DPV peaks showed linearity to the concentration of RNA with a detection limit down to 1.513 fM. It also showed the clear different peaks to the mutated HIV-1 RRE RNA. The high sensitivity and selectivity of VSNEA for the detection of HIV-1 RRE RNA may be attributed to the high surface-to-volume ratio and total overlap diffusion mode of ions of the one-dimensional nanowire electrodes.

  18. Selective and sensitive determination of dopamine by composites of polypyrrole and graphene modified electrodes.

    PubMed

    Si, Peng; Chen, Hailan; Kannan, Palanisamy; Kim, Dong-Hwan

    2011-12-21

    A novel method is developed to fabricate the polypyrrole (PPy) and graphene thin films on electrodes by electrochemical polymerization of pyrrole with graphene oxide (GO) as a dopant, followed by electrochemical reduction of GO in the composite film. The composite of PPy and electrochemically reduced graphene oxide (eRGO)-modified electrode is highly sensitive and selective toward the detection of dopamine (DA) in the presence of high concentrations of ascorbic acid (AA) and uric acid (UA). The sensing performance of the PPy/eRGO-modified electrode is investigated by differential pulse voltammetry (DPV), revealing a linear range of 0.1-150 μM with a detection limit of 23 nM (S/N = 3). The practical application of the PPy/eRGO-modified electrode is successfully demonstrated for DA determination in human blood serum. PMID:22010122

  19. Highly selective, sensitive and fast-responsive fluorescent sensor for Hg(2.).

    PubMed

    Niu, Qingfen; Wu, Xingxing; Li, Tianduo; Cui, Yuezhi; Zhang, Shanshan; Li, Xiaoyan

    2016-06-15

    A phenylamine-oligothiophene-based fluorescent sensor 2TBEA was reported. This sensor exhibited highly selective, sensitive and rapid detection of Hg(2+) ion in THF/H2O (7/3, v/v) solution through fluorescence quenching. The detection was unaffected by the coexistence of other competitive metal cations including Na(+), K(+), Ag(+), Ca(2+), Fe(3+), Al(3+), Co(2+), Cu(2+), Ni(2+), Zn(2+), Pb(2+), Cd(2+), Fe(2+) and Cr(3+). A1:1 binding ratio for 2TBEA - Hg(2+) was demonstrated by Job's plot and mole-ratio curves. The coordination process was chemically reversible with EDTA. The detection limit was evaluated to be as low as 6.164×10(-8)M. PMID:27049866

  20. A new diketopyrrolopyrrole-based probe for sensitive and selective detection of sulfite in aqueous solution

    NASA Astrophysics Data System (ADS)

    Yang, Xiaofeng; Cui, Yu; Li, Yexin; Zheng, Luyi; Xie, Lijun; Ning, Rui; Liu, Zheng; Lu, Junling; Zhang, Gege; Liu, Chunxiang; Zhang, Guangyou

    2015-02-01

    A new probe was synthesized by incorporating an α,β -unsaturated ketone to a diketopyrrolopyrrole fluorophore. The probe had exhibited a selective and sensitive response to the sulfite against other thirteen anions and biothiols (Cys, Hcy and GSH), through the nucleophilic addition of sulfite to the alkene of probe with the detection limit of 0.1 μM in HEPES (10 mM, pH 7.4) THF/H2O (1:1, v/v). Meanwhile, it could be easily observed that the probe for sulfite changed from pink to colorless by the naked eye, and from pink to blue under UV lamp after the sulfite was added for 20 min. The NMR and Mass spectral analysis demonstrated the expected addition of sulfite to the Cdbnd C bonds.

  1. A new hydroxynaphthyl benzothiazole derived fluorescent probe for highly selective and sensitive Cu2 + detection

    NASA Astrophysics Data System (ADS)

    Tang, Lijun; He, Ping; Zhong, Keli; Hou, Shuhua; Bian, Yanjiang

    2016-12-01

    A new reactive probe, 1-(benzo[d]thiazol-2-yl)naphthalen-2-yl-picolinate (BTNP), was designed and synthesized. BTNP acts as a highly selective probe to Cu2 + in DMSO/H2O (7/3, v/v, Tris-HCl 10 mM, pH = 7.4) solution based on Cu2 + catalyzed hydrolysis of the picolinate ester moiety in BTNP, which leads to the formation of an ESIPT active product with dual wavelength emission enhancement. The probe also possesses the advantages of simple synthesis, rapid response and high sensitivity. The pseudo-first-order reaction rate constant was calculated to be 0.205 min- 1. Moreover, application of BTNP to Cu2 + detection in living cells and real water samples was also explored.

  2. Sensitive and selective detection of thrombin by using a cyclic peptide as affinity ligand.

    PubMed

    Zhao, Qiang; Gao, Jie

    2015-01-15

    Here we describe a sensitive assay for thrombin by using a high binding-affinity cyclic peptide against thrombin as affinity ligand. The cyclic peptide is immobilized on the magnetic beads or microplates to selectively capture thrombin. The enriched thrombin then catalyzes the cleavage of a substrate of thrombin to a detectable product. The detection of thrombin is finally achieved by measuring the generated product. This assay enables the detection of thrombin at tens fM in 100 µL of sample solution when fluorogenic substrate was applied, while detection limits reached pM level when chromogenic substrate was used. Thrombin in plasma sample can be detected with this assay. This cyclic peptide affinity ligand shows potentials for thrombin analysis in other detection formats. PMID:25048449

  3. Surface-selective laser sintering of thermolabile polymer particles using water as heating sensitizer

    NASA Astrophysics Data System (ADS)

    Antonov, E. N.; Krotova, L. I.; Minaev, N. V.; Minaeva, S. A.; Mironov, A. V.; Popov, V. K.; Bagratashvili, V. N.

    2015-11-01

    We report the implementation of a novel scheme for surface-selective laser sintering (SSLS) of polymer particles, based on using water as a sensitizer of laser heating and sintering of particles as well as laser radiation at a wavelength of 1.94 μm, corresponding to the strong absorption band of water. A method of sintering powders of poly(lactide-co-glycolide), a hydrophobic bioresorbable polymer, after modifying its surface with an aqueous solution of hyaluronic acid is developed. The sintering thresholds for wetted polymer are by 3 - 4 times lower than those for sintering in air. The presence of water restricts the temperature of the heated polymer, preventing its thermal destruction. Polymer matrices with a developed porous structure are obtained. The proposed SSLS method can be applied to produce bioresorbable polymer matrices for tissue engineering.

  4. Highly sensitive and selective electrochemical dopamine sensing properties of multilayer graphene nanobelts

    NASA Astrophysics Data System (ADS)

    Karthick Kannan, Padmanathan; Moshkalev, Stanislav A.; Sekhar Rout, Chandra

    2016-02-01

    In the present study, we report the electrochemical sensing property of multi-layer graphene nanobelts (GNBs) towards dopamine (DA). GNBs are synthesized from natural graphite and characterized by using techniques like field-emission scanning electron microscopy, atomic force microscopy and Raman spectroscopy. An electrochemical sensor based on GNBs is developed for the detection of DA. From the cyclic voltammetry and amperometry studies, it is found that GNBs possess excellent electrocatalytic activity towards DA molecules. The developed DA sensor showed a sensitivity value of 0.95 μA μM-1 cm-2 with a linear range of 2 μM to 0.2 mM. The interference data exhibited that GNB is highly selective to DA even in the presence of common interfering species like ascorbic acid, uric acid, glucose and lactic acid.

  5. Conducting Polymer-Based Nanohybrid Transducers: A Potential Route to High Sensitivity and Selectivity Sensors

    PubMed Central

    Park, Seon Joo; Kwon, Oh Seok; Lee, Ji Eun; Jang, Jyongsik; Yoon, Hyeonseok

    2014-01-01

    The development of novel sensing materials provides good opportunities to realize previously unachievable sensor performance. In this review, conducting polymer-based nanohybrids are highlighted as innovative transducers for high-performance chemical and biological sensing devices. Synthetic strategies of the nanohybrids are categorized into four groups: (1) impregnation, followed by reduction; (2) concurrent redox reactions; (3) electrochemical deposition; (4) seeding approach. Nanocale hybridization of conducting polymers with inorganic components can lead to improved sorption, catalytic reaction and/or transport behavior of the material systems. The nanohybrids have thus been used to detect nerve agents, toxic gases, volatile organic compounds, glucose, dopamine, and DNA. Given further advances in nanohybrids synthesis, it is expected that sensor technology will also evolve, especially in terms of sensitivity and selectivity. PMID:24561406

  6. Highly sensitive and selective spectrophotometric and spectrofluorimetric methods for the determination of ropinirole hydrochloride in tablets

    NASA Astrophysics Data System (ADS)

    Aydoğmuş, Zeynep

    2008-06-01

    Three sensitive, selective, accurate spectrophotometric and spectrofluorimetric methods have been developed for the determination of ropinirole hydrochloride in tablets. The first method was based on measuring the absorbance of drug solution in methanol at 250 nm. The Beer's law was obeyed in the concentration range 2.5-24 μg ml -1. The second method was based on the charge transfer reaction of drug, as n-electron donor with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as π-acceptor in acetonitrile to give radical anions that are measured at 842 nm. The Beer's law was obeyed in the concentration range 0.6-8 μg ml -1. The third method was based on derivatization reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 followed by measuring the fluorescence intensity at 525 nm with excitation at 464 nm in chloroform. Beer's law was obeyed in the concentration range 0.01-1.3 μg ml -1. The derivatization reaction product of drug with NBD-Cl was characterized by IR, 1H NMR and mass spectroscopy. The developed methods were validated. The following analytical parameters were investigated: the molar absorptivity ( ɛ), limit of detection (LOD, μg ml -1) and limit of quantitation (LOQ, μg ml -1), precision, accuracy, recovery, and Sandell's sensitivity. Selectivity was validated by subjecting stock solution of ropinirole to acidic, basic, oxidative, and thermal degradation. No interference was observed from common excipients present in formulations. The proposed methods were successfully applied for determination of drug in tablets. The results of these proposed methods were compared with each other statistically.

  7. Highly sensitive and selective spectrophotometric and spectrofluorimetric methods for the determination of ropinirole hydrochloride in tablets.

    PubMed

    Aydoğmuş, Zeynep

    2008-06-01

    Three sensitive, selective, accurate spectrophotometric and spectrofluorimetric methods have been developed for the determination of ropinirole hydrochloride in tablets. The first method was based on measuring the absorbance of drug solution in methanol at 250 nm. The Beer's law was obeyed in the concentration range 2.5-24 microg ml(-1). The second method was based on the charge transfer reaction of drug, as n-electron donor with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as pi-acceptor in acetonitrile to give radical anions that are measured at 842 nm. The Beer's law was obeyed in the concentration range 0.6-8 microg ml(-1). The third method was based on derivatization reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 followed by measuring the fluorescence intensity at 525 nm with excitation at 464 nm in chloroform. Beer's law was obeyed in the concentration range 0.01-1.3 microg ml(-1). The derivatization reaction product of drug with NBD-Cl was characterized by IR, 1H NMR and mass spectroscopy. The developed methods were validated. The following analytical parameters were investigated: the molar absorptivity (epsilon), limit of detection (LOD, microg ml(-1)) and limit of quantitation (LOQ, microg ml(-1)), precision, accuracy, recovery, and Sandell's sensitivity. Selectivity was validated by subjecting stock solution of ropinirole to acidic, basic, oxidative, and thermal degradation. No interference was observed from common excipients present in formulations. The proposed methods were successfully applied for determination of drug in tablets. The results of these proposed methods were compared with each other statistically. PMID:17719838

  8. Multi-ion and pH sensitivity of AgGeSe ion selective electrodes

    NASA Astrophysics Data System (ADS)

    Conde Garrido, J. M.; Silveyra, J. M.; Ureña, M. A.

    2016-02-01

    Many chalcogenide glasses have been found to combine benefits such as good chemical durability, selectivity, and reproducibility for applications as solid-state sensitive membranes of ion selective electrodes (ISEs). In previous works, we have shown that ISEs with ionic conductive AgGeSe membranes have good sensitivity to Ag+ ions. In the present work, we explore the Agx(Ge0.25Se0.75)100-x, 10≤x≤30 (at%) system as candidate for ISEs applications detecting several other ions (K+, Mg2+, Cr3+, Fe3+, Ni2+, Cd2+, Hg2+, and Pb2+). We evaluated ISEs fabricated with bulk as well as with thin film membranes. We found no dependence of the sensing properties on the Ag content of the ionic conductive membranes. Thin films exhibited the same properties than bulk membranes, indicating that these chalcogenide glasses have great potential for miniaturization. The ISEs showed a high response (Nernstian or super-Nernstian) to the presence of Hg2+, Pb2+, and Fe3+, a low response (sub-Nernstian) to the presence of Cr3+, and a total lack of response to the presence of Cd2+, Ni2+, Mg2+, and K+. We also tested how the pH of the solution affected the response of the ISEs. The potentials of the ISEs were practically constant in neutral or acidic solutions, while decreased drastically in basic solutions when the primary ion was not present. The latter phenomenon was caused by the slow dissolution of the membrane into the solution, meaning that long-term basic environments should be avoided for these ISEs. We concluded that ISEs with ionic conductive AgGeSe membranes are good candidates to integrate multi-electrode systems.

  9. The alpha 1 Na(+)-K+ pump of the Dahl salt-sensitive rat exhibits altered Na+ modulation of K+ transport in red blood cells.

    PubMed

    Canessa, M; Romero, J R; Ruiz-Opazo, N; Herrera, V L

    1993-06-01

    The properties of the alpha 1 Na(+)-K+ pump were compared in Dahl salt-sensitive (DS) and salt-resistant (DR) strains by measuring ouabain-sensitive fluxes (mmol/liter cell x hr = FU, Mean +/- SE) in red blood cells (RBCs) and varying internal (i) and external (o) Na+ and K+ concentrations. Kinetic parameters of several modes of operation, i.e., Na+/K+, K+/K+, Na+/Na+ exchanges, were characterized and analyzed for curve-fitting using the Enzfitter computer program. In unidirectional flux studies (n = 12 rats of each strain) into fresh cells incubated in 140 mM Na(+) + 5 mM K+, ouabain-sensitive K+ influx was substantially lower in the DS than in DR RBCs, while ouabain-sensitive Na+ efflux and Nai were similar in both strains. Thus, the coupling ratio between unidirectional Na+:K+ fluxes was significantly higher in DS than in DR cells at similar RBC Na+ content. In the presence of 140 mM Nao, activation of ouabain-sensitive K+ influx by Ko had a lower Km and Vmax in DS as estimated by the Garay equation (N = 2.70 +/- 0.33, Km 0.74 +/- 0.09 mM; Vmax 2.87 +/- 0.09 FU) than in DR rats (N = 1.23 +/- 0.36, Km 2.31 +/- 0.16 mM; Vmax 5.70 +/- 0.52 FU). However, the two kinetic parameters were similar following Nao removal. The activation of ouabain-sensitive K+ influx by Nai had significantly lower Vmax in DS (9.3 +/- 0.4 FU) than in DR (14.5 +/- 0.6 FU) RBCs but similar Km. These data suggest that the low K+ influx in DS cells is caused by a defect in modulation by Nao and Nai. Na+ efflux showed no differences in Nai activation or trans effects by Nao and Ko, thus accounting for the different Na+:K+ coupling ratio in the Dahl strains. Further evidence for the differences in the coupling of ouabain-sensitive fluxes was found in studies of net Na+ and K+ fluxes, where the net ouabain-sensitive Na+ losses showed similar magnitudes in the two Dahl strains while the net ouabain-sensitive K+ gains were significantly greater in the DR than the DS RBCs. Ouabain-sensitive Na

  10. Novel fluorescent silver nanoparticles: sensitive and selective turn off sensor for cadmium ions

    NASA Astrophysics Data System (ADS)

    Makwana, Bharat A.; Vyas, Disha J.; Bhatt, Keyur D.; Darji, Savan; Jain, Vinod K.

    2016-04-01

    The synthesis of metal nanoparticles by eco-friendly and reliable processes is an important aspect in many fields. In this study, octamethoxy resorcin [4] arene tetrahydrazide (OMRTH)-reduced and stabilized silver nanoparticles were synthesized via a simple one-pot method. Synthesized silver nanoparticles were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM) and particle size analyzer (PSA). Furthermore, the application of OMRTH-AgNps as a simple, cost-effective and sensitive fluorescent sensor for rapid detection of cadmium was explored. Under optimum conditions, the fluorescence intensity of OMRTH-AgNps was inversely proportional to the cadmium concentration. Using OMRTH-AgNps as a selective and sensitive fluorescent probe, cadmium can be detected at a minimum concentration level of 10-8 M in a facile way of fluorescence quenching, i.e., by a "turn off" mechanism. The method has been successfully applied for determination of Cd[II] ions in groundwater and industrial effluent wastewater samples.

  11. A highly sensitive and selective impedimetric aptasensor for interleukin-17 receptor A.

    PubMed

    Jo, Hunho; Kim, Seong-Kyeong; Youn, Hyungjun; Lee, Heehyun; Lee, Kwanghyun; Jeong, Jian; Mok, Jihyun; Kim, Seung-Hyun; Park, Hae-Sim; Ban, Changill

    2016-07-15

    Interleukin-17 receptor A (IL-17RA) has been recognized as a valuable biomarker for diverse diseases, including autoimmune diseases. In this work, an electrochemical biosensor with great sensitivity and selectivity toward IL-17RA was fabricated using an IL-17RA aptamer (Kd=14.00nM) for the first time. The aptasensor was manufactured using electrodeposition of gold nanoparticles, and then quantitative detection of IL-17RA was performed based on impedimetry. The developed sensor exhibited a superior analytical performance for IL-17RA with a wide dynamic range of 10-10,000pg/mL in buffer and a detection limit of 2.13pg/mL, which is lower than that of commercially available ELISA kits. In addition, we validated the high specificity of the designed aptasensor to only IL-17RA, which showed good sensitivity even in human serum solution. Furthermore, the detection of the differentiated HL-60 cells expressing IL-17RA was successfully performed. Clinical applicability of the sensor was also demonstrated utilizing neutrophils separated from asthma patients. It is expected that the fabricated aptasensor will become an excellent diagnostic platform for IL-17RA-mediated diseases. PMID:26921556

  12. Phosphinic acid functionalized carbon nanotubes for sensitive and selective sensing of chromium(VI).

    PubMed

    Deep, Akash; Sharma, Amit L; Tuteja, Satish K; Paul, A K

    2014-08-15

    Single-walled carbon nanotubes (SWCNTs) have been functionalized with a phosphinic acid derivative 'bis(2,4,4-trimethylpentyl) phosphinic acid' (PA/d). It has been achieved by treating the chlorinated SWCNTs with PA/d at 80°C. Successful functionalization and different nanomaterial properties have been investigated by UV-vis-NIR, FTIR, Raman spectroscopy, AFM and FE-SEM. PA/d conjugated SWCNTs (CNT-PA) are dispersible in some common organic solvents, e.g. CH2Cl2, DMF, CHCl3, and THF. The 'CNT-PA' complex was spin-casted on boron doped silicon wafer. Thus fabricated sensing electrode is demonstrated for sensitive and selective electrochemical sensing of chromium(VI) ions. A linear response is obtained over a wide range of Cr(VI) concentration (0.01-10 ppb). The sensor's sensitivity and the limit of detection are observed to be 35 ± 4 nA/ppb and 0.01 ppb, respectively. The practical utility of the proposed sensor is demonstrated by determining the Cr(VI) concentration in an industrial effluent sample and an underground water sample. PMID:25016454

  13. Long-Term Memories Bias Sensitivity and Target Selection in Complex Scenes

    PubMed Central

    Patai, Eva Zita; Doallo, Sonia; Nobre, Anna Christina

    2014-01-01

    In everyday situations we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention, and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location (Summerfield, Lepsien, Gitelman, Mesulam, & Nobre, 2006; Summerfield, Rao, Garside, & Nobre, 2011). The present study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc event-related potential to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top-down sources of information. PMID:23016670

  14. A novel NiO-Au hybrid nanobelts based sensor for sensitive and selective glucose detection.

    PubMed

    Ding, Yu; Liu, Yixin; Parisi, Joseph; Zhang, Lichun; Lei, Yu

    2011-10-15

    A novel amperometric nonenzymatic glucose sensor based on Au-doped NiO nanobelts has been successfully fabricated and applied to nonenzymatic glucose detection. Its electrochemical behavior towards the oxidation of glucose was compared with NiO nanofibers and Au microparticles prepared with a similar procedure. The NiO-Au hybrid nanobelts modified electrode displays greatly enhanced electrocatalytic activity towards glucose oxidation, revealing a synergistic effect between the matrix NiO and the doped Au. The as-prepared NiO-Au nanobelts based glucose sensor displays significantly lower onset potential, lower detection limit, higher sensitivity, and wider linear range than that of pristine NiO nanofibers modified electrode. Moreover, Au nanoparticles distributed in NiO nanofibers enabled amperometric glucose detection with insignificant interference from ascorbic acid and uric acid. These results indicate that the NiO-Au hybrid nanobelt is a promising candidate in the development of highly sensitive and selective nonenzymatic glucose sensors. PMID:21852103

  15. Reactive chromophores for sensitive and selective detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Frye-Mason, Greg; Leuschen, Martin; la Grone, Marcus; Wald, Lara; Aker, Craig; Dock, Matt; Hancock, Lawrence F.; Fagan, Steve; Paul, Kateri

    2004-08-01

    A new sensor for highly toxic species including chemical warfare (CW) agents has been developed. This sensor is based on a unique CW indicating chromophore (CWIC) developed by Professor Tim Swager at MIT. The CWIC was designed to be sensitive to the reactivity that makes these chemicals so toxic. Since it requires the reactivity of the agent to be detected, the CWIC technology has shown remarkable selectivity for nerve agent surrogates and some other highly toxic species, thereby demonstrating the potential to provide low false alarm rate detection. Since the chromophore has mini-mal fluorescence prior to reaction with an electrophilic and toxic chemical, the sensor acts in a dark field fluorescence mode. This provides the sensor with exceptional sensitivity and a potential to detect priority analytes well below levels detected by current hand held sensors. Finally, it is based on a simple optical detection scheme that enables small and rugged sensors to be developed and produced at a low enough cost so they can be widely utilized.

  16. Microarray study of temperature-dependent sensitivity and selectivity of metal/oxide sensing interfaces

    NASA Astrophysics Data System (ADS)

    Tiffany, Jason; Cavicchi, Richard E.; Semancik, Stephen

    2001-02-01

    Conductometric gas microsensors offer the benefits of ppm-level sensitivity, real-time data, simple interfacing to electronics hardware, and low power consumption. The type of device we have been exploring consists of a sensor film deposited on a "microhotplate"- a 100 micron platform with built-in heating (to activate reactions on the sensing surface) and thermometry. We have been using combinatorial studies of 36-element arrays to characterize the relationship between sensor film composition, operating temperature, and response, as measured by the device's sensitivity and selectivity. Gases that have been tested on these arrays include methanol, ethanol, dichloromethane, propane, methane, acetone, benzene, hydrogen, and carbon monoxide, and are of interest in the management of environmental waste sites. These experiments compare tin oxide films modified by catalyst overlayers, and ultrathin metal seed layers. The seed layers are used as part of a chemical vapor deposition process that uses each array element's microheater to activate the deposition of SnO2, and control its microstructure. Low coverage (20 Ê) catalytic metals (Pd, Cu, Cr, In, Au) are deposited on the oxides by masked evaporation or sputtering. This presentation demonstrates the value of an array-based approach for developing film processing methods, measuring performance characteristics, and establishing reproducibility. It also illustrates how temperature-dependent response data for varied metal/oxide compositions can be used to tailor a microsensor array for a given application.

  17. Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.

    PubMed

    Baru, Abdul Mannan; Hartl, Andrea; Lahl, Katharina; Krishnaswamy, Jayendra Kumar; Fehrenbach, Heinz; Yildirim, Ali O; Garn, Holger; Renz, Harald; Behrens, Georg M N; Sparwasser, Tim

    2010-08-01

    Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance. PMID:20544727

  18. Force-sensitive detents improve user performance for linear selection tasks.

    PubMed

    Berdahl, E; Smith, J O; Weinzierl, S; Niemeyer, G

    2013-01-01

    Haptic technology, providing force cues and creating a programmable interface, can assist users in more accurately using an interface. This paper investigates haptic assistance in combination with auditory feedback instead of visual feedback. A user test is carried out in which participants select fundamental frequencies from a continuous range to play brief musical melodies. Two control conditions are compared with two detent-based haptic assistance conditions. The detents gently guide the users toward locations of equal tempered fundamental frequencies. Results from the user test confirm improved accuracy brought about by the detents. It is further helpful to provide regulation of the strength of haptic assistance in real time, allowing the user to remain always in control. This concept motivated the force-sensitive detent condition, which enables the user to adjust the strength of the haptic assistance in real time by changing the downward force applied to the haptic device. The work implies that users of graphical user interfaces could similarly benefit from force-sensitive detents and more generally real-time regulation of the strength of haptic assistance. PMID:24808304

  19. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance.

    PubMed

    Schneider, E; Horton, J K; Yang, C H; Nakagawa, M; Cowan, K H

    1994-01-01

    A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4'-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered topoisomerase II, no mutations were detected in either the ATP-binding nor the putative breakage/resealing regions of either DNA topoisomerase II alpha or II beta. In addition, the steady-state intracellular VP-16 concentration was reduced by 2-fold in the resistant cells, in the absence of detectable mdr1/P-gp expression and without any change in drug efflux. In contrast, expression of the gene encoding the MRP was increased at least 10-fold in resistant MCF7/VP cells as compared to sensitive MCF7/WT cells. These results suggest that resistance to epipodophyllotoxins in MCF7/VP cells is multifactorial, involving a reduction in intracellular drug concentration, possibly as a consequence of MRP overexpression, and an altered DNA topoisomerase II drug sensitivity. PMID:7903202

  20. Elucidating band-selective sensitization in iron(II) polypyridine-TiO2 assemblies.

    PubMed

    Bowman, David N; Blew, James H; Tsuchiya, Takashi; Jakubikova, Elena

    2013-08-01

    Iron(II) polypyridines represent a cheaper and nontoxic alternative to analogous Ru(II) polypyridine dyes successfully used as photosensitizers in dye-sensitized solar cells (DSSCs). We employ density functional theory (DFT) and time-dependent DFT (TD-DFT) to study ground and excited state properties of [Fe(bpy)(CN)4](2-), [Fe(bpy-dca)(CN)4](2-), and [Fe(bpy-dca)2(CN)2] complexes, where bpy = 2,2'-bipyridine and dca = 4,4'-dicarboxylic acid. Quantum dynamics simulations are further used to investigate the interfacial electron transfer (IET) between the excited Fe(II) dyes and a TiO2 nanoparticle. All three dyes investigated display two bands in the visible region of the absorption spectrum, with the major transitions corresponding to the metal-to-ligand charge transfer states. The calculated IET rates from the particle states created by the excitation of the lower-energy absorption band are comparable to or slower than the rate of the excited state decay into the nonemissive, metal-centered states of the Fe(II) dyes (∼100 fs), indicating that the IET upon the excitation of this band is unlikely. Several particle states in the higher-energy absorption band display IET rates at or below 100 fs, suggesting the possibility of the IET between the Fe(II)-sensitizer and TiO2 nanoparticle upon excitation with visible light. Our results are consistent with the previous experimental work on Fe(II) sensitizers (Ferrere, S. Chem. Mater. 2000, 12, 1083) and elucidate the band-selective nature of the IET in these compounds. PMID:23837840

  1. Strategies for improving sensitivity and selectivity for the quantitation of biotherapeutics in biological matrix using LC-MS/MS.

    PubMed

    Shen, Jim X; Liu, Guowen; Zhao, Yue

    2015-04-01

    In recent years, the applicability of using LC-MS/MS as a complementary technique to traditional ligand binding assays in the absolute quantitation of therapeutic proteins in biologic matrix has been demonstrated. Protein quantitation workflow via LC-MS/MS is primarily based on a enzymatic digestion model and recent works seek to improve selectivity and sensitivity. This review focuses on recent innovations in this field and discusses the following in detail: the applicability of two-dimensional liquid chromatography and its use to improve sensitivity and alleviate matrix ion suppression; the use of derivatization agents after digestion to improve extraction and MS ionization efficiency; techniques to reduce excess protein background and their positive effects on sensitivity, selectivity, and extraction consistency; the application of immunoaffinity extraction of proteins to enrich the analyte(s) of interest while improving selectivity and sensitivity. PMID:25776016

  2. Highly Sensitive and Selective Detection of Nanomolar Ferric Ions Using Dopamine Functionalized Graphene Quantum Dots.

    PubMed

    Dutta Chowdhury, Ankan; Doong, Ruey-An

    2016-08-17

    The good stability, low cytotoxicity, and excellent photoluminescence property of graphene quantum dots (GQDs) make them an emerging class of promising materials in various application fields ranging from sensor to drug delivery. In the present work, the dopamine-functionalized GQDs (DA-GQDs) with stably bright blue fluorescence were successfully synthesized for low level Fe(3+) ions detection. The as-synthesized GQDs are uniform in size with narrow-distributed particle size of 4.5 ± 0.6 nm and high quantum yield of 10.2%. The amide linkage of GQDs with dopamine, confirmed by using XPS and FTIR spectra, results in the specific interaction between Fe(3+) and catechol moiety of dopamine at the interfaces for highly sensitive and selective detection of Fe(3+). A linear range of 20 nM to 2 μM with a detection limit of 7.6 nM is obtained for Fe(3+) detection by DA-GQDs. The selectivity of DA-GQDs sensing probe is significantly excellent in the presence of other interfering metal ions. In addition, the reaction mechanism for Fe(3+) detection based on the complexation and oxidation of dopamine has been proposed and validated. Results obtained in this study clearly demonstrate the superiority of surface functionalized GQDs to Fe(3+) detection, which can pave an avenue for the development of high performance and robust sensing probes for detection of metal ions and other organic metabolites in environmental and biomedical applications. PMID:27472083

  3. Selective and sensitive liquid chromatographic determination method of 5-hydroxyindoles with fluorous and fluorogenic derivatization.

    PubMed

    Sakaguchi, Yohei; Ikenaga, Jun; Yoshida, Hideyuki; Hayama, Tadashi; Itoyama, Miki; Todoroki, Kenichiro; Imakyure, Osamu; Yamaguchi, Masatoshi; Nohta, Hitoshi

    2015-10-10

    A liquid chromatographic (LC) method with improved selectivity for the simultaneous determination of 5-hydroxyindoles (5-HIs; 5-hydroxytryptophan, 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, 5-hydroxyindole-3-acetic acid, and 5-hydroxytryptophol) is described. This method involves precolumn derivatization with 4-(3',3',4',4',5',5',6',6',7',7',8',8',9',9',10',10',10'-heptadecafluorodecyl)benzylamine (HFBA) and separation of the derivatives using a fluorous LC column. In this study, stable benzoxazole derivatives of 5-HIs with HFBA have been obtained by a simple derivatization procedure; their fluorescent properties enabled highly sensitive detection. In addition, only the HFBA derivatives of 5-HIs has been selectively retained on the fluorous LC column via fluorous interaction whereby perfluoroalkyl compounds show affinities with each other, while the non-fluorous compounds did not. The HFBA derivatives were separated within 30 min and the detection limits for 5-HIs in a 20-μL injection volume were 1.2-14 fmol (S/N=3). Furthermore, this method was applied to the analysis of 5-HIs in the human plasma from healthy subjects. PMID:26112924

  4. A Sensitive Secondary Users Selection Algorithm for Cognitive Radio Ad Hoc Networks

    PubMed Central

    Li, Aohan; Han, Guangjie; Wan, Liangtian; Shu, Lei

    2016-01-01

    Secondary Users (SUs) are allowed to use the temporarily unused licensed spectrum without disturbing Primary Users (PUs) in Cognitive Radio Ad Hoc Networks (CRAHNs). Existing architectures for CRAHNs impose energy-consuming Cognitive Radios (CRs) on SUs. However, the advanced CRs will increase energy cost for their cognitive functionalities, which is undesirable for the battery powered devices. A new architecture referred to as spectral Requirement-based CRAHN (RCRAHN) is proposed to enhance energy efficiency for CRAHNs in this paper. In RCRAHNs, only parts of SUs are equipped with CRs. SUs equipped with CRs are referred to as Cognitive Radio Users (CRUs). To further enhance energy efficiency of CRAHNs, we aim to select minimum CRUs to sense available spectrum. A non-linear programming problem is mathematically formulated under the constraints of energy efficiency and real-time. Considering the NP-hardness of the problem, a framework of a heuristic algorithm referred to as Sensitive Secondary Users Selection (SSUS) was designed to compute the near-optimal solutions. The simulation results demonstrate that SSUS not only improves the energy efficiency, but also achieves satisfied performances in end-to-end delay and communication reliability. PMID:27023562

  5. A Sensitive Secondary Users Selection Algorithm for Cognitive Radio Ad Hoc Networks.

    PubMed

    Li, Aohan; Han, Guangjie; Wan, Liangtian; Shu, Lei

    2016-01-01

    Secondary Users (SUs) are allowed to use the temporarily unused licensed spectrum without disturbing Primary Users (PUs) in Cognitive Radio Ad Hoc Networks (CRAHNs). Existing architectures for CRAHNs impose energy-consuming Cognitive Radios (CRs) on SUs. However, the advanced CRs will increase energy cost for their cognitive functionalities, which is undesirable for the battery powered devices. A new architecture referred to as spectral Requirement-based CRAHN (RCRAHN) is proposed to enhance energy efficiency for CRAHNs in this paper. In RCRAHNs, only parts of SUs are equipped with CRs. SUs equipped with CRs are referred to as Cognitive Radio Users (CRUs). To further enhance energy efficiency of CRAHNs, we aim to select minimum CRUs to sense available spectrum. A non-linear programming problem is mathematically formulated under the constraints of energy efficiency and real-time. Considering the NP-hardness of the problem, a framework of a heuristic algorithm referred to as Sensitive Secondary Users Selection (SSUS) was designed to compute the near-optimal solutions. The simulation results demonstrate that SSUS not only improves the energy efficiency, but also achieves satisfied performances in end-to-end delay and communication reliability. PMID:27023562

  6. Sensitive and selective magnetoimmunosensing platform for determination of the food allergen Ara h 1.

    PubMed

    Ruiz-Valdepeñas Montiel, V; Campuzano, S; Pellicanò, A; Torrente-Rodríguez, R M; Reviejo, A J; Cosio, M S; Pingarrón, J M

    2015-06-23

    A highly sensitive disposable amperometric immunosensor based on the use of magnetic beads (MBs) is described for determination of Ara h 1, the major peanut allergen, in only 2h. The approach uses a sandwich configuration involving selective capture and biotinylated detector antibodies and carboxylic acid-modified MBs (HOOC-MBs). The MBs bearing the immunoconjugates are captured by a magnet placed under the surface of a disposable screen-printed carbon electrode (SPCE) and the affinity reactions are monitored amperometrically at -0.20 V (vs a Ag pseudo-reference electrode) in the presence of hydroquinone (HQ) as electron transfer mediator and upon addition of H2O2 as the enzyme substrate. The developed immunosensor exhibits a wide range of linearity between 20.8 and 1000.0 ng mL(-1) Ara h 1, a detection limit of 6.3 ng mL(-1), a great selectivity, a good reproducibility with a RSD of 6.3% for six different immunosensors and a useful lifetime of 25 days. The usefulness of the immunosensor was demonstrated by determining Ara h 1 in different matrices (food extracts and saliva). The results correlated properly with those provided by a commercial ELISA method offering a reliable and promising analytical screening tool in the development of user-friendly devices for on-site determination of Ara h 1. PMID:26092337

  7. FTIR gas analysis with improved sensitivity and selectivity for CWA and TIC detection

    NASA Astrophysics Data System (ADS)

    Phillips, Charles M.; Tan, Huwei

    2010-04-01

    This presentation describes the use of an FTIR (Fourier Transform Infrared)-based spectrometer designed to continuously monitor ambient air for the presence of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). The necessity of a reliable system capable of quickly and accurately detecting very low levels of CWAs and TICs while simultaneously retaining a negligible false alarm rate will be explored. Technological advancements in FTIR sensing have reduced noise while increasing selectivity and speed of detection. These novel analyzer design characteristics are discussed in detail and descriptions are provided which show how optical throughput, gas cell form factor, and detector response are optimized. The hardware and algorithms described here will explain why this FTIR system is very effective for the simultaneous detection and speciation of a wide variety of toxic compounds at ppb concentrations. Analytical test data will be reviewed demonstrating the system's sensitivity to and selectivity for specific CWAs and TICs; this will include recent data acquired as part of the DHS ARFCAM (Autonomous Rapid Facility Chemical Agent Monitor) project. These results include analyses of the data from live agent testing for the determination of CWA detection limits, immunity to interferences, detection times, residual noise analysis and false alarm rates. Sensing systems such as this are critical for effective chemical hazard identification which is directly relevant to the CBRNE community.

  8. Method for Sorting and Pairwise Selection of Nanobodies for the Development of Highly Sensitive Sandwich Immunoassays.

    PubMed

    Rossotti, Martín A; Pirez, Macarena; Gonzalez-Techera, Andres; Cui, Yongliang; Bever, Candace S; Lee, Kin S S; Morisseau, Christophe; Leizagoyen, Carmen; Gee, Shirley; Hammock, Bruce D; González-Sapienza, Gualberto

    2015-12-01

    Single domain heavychain binders (nanobodies) obtained from camelid antibody libraries hold a great promise for immunoassay development. However, there is no simple method to select the most valuable nanobodies from the crowd of positive clones obtained after the initial screening. In this paper, we describe a novel nanobody-based platform that allows comparison of the reactivity of hundreds of clones with the labeled antigen, and identifies the best nanobody pairs for two-site immunoassay development. The output clones are biotinylated in vivo in 96-well culture blocks and then used to saturate the biotin binding capacity of avidin coated wells. This standardizes the amount of captured antibody allowing their sorting by ranking their reactivity with the labeled antigen. Using human soluble epoxide hydrolase (sEH) as a model antigen, we were able to classify 96 clones in four families and confirm this classification by sequencing. This provided a criterion to select a restricted panel of five capturing antibodies and to test each of them against the rest of the 96 clones. The method constitutes a powerful tool for epitope binning, and in our case allowed development of a sandwich ELISA for sEH with a detection limit of 63 pg/mL and four log dynamic range, which performed with excellent recovery in different tissue extracts. This strategy provides a systematic way to test nanobody pairwise combinations and would have a broad utility for the development of highly sensitive sandwich immunoassays. PMID:26544909

  9. An enhanced and sensitive autocrine stimulation by transforming growth factor-alpha is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line.

    PubMed

    Fang, K

    1996-12-01

    Transforming growth factor-alpha (TGF-alpha)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGF-alpha-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-alpha inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 125I-labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-alpha is lower in the conditioned medium of H226Br than in that of NCI-H226. demonstrating down-regulation of TGF-alpha transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-alpha and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line. PMID:8956792

  10. RNA Interference in Schistosoma mansoni Schistosomula: Selectivity, Sensitivity and Operation for Larger-Scale Screening

    PubMed Central

    Horn, Martin; Braschi, Simon; Sojka, Daniel; Ruelas, Debbie S.; Suzuki, Brian; Lim, Kee-Chong; Hopkins, Stephanie D.; McKerrow, James H.; Caffrey, Conor R.

    2010-01-01

    Background The possible emergence of resistance to the only available drug for schistosomiasis spurs drug discovery that has been recently incentivized by the availability of improved transcriptome and genome sequence information. Transient RNAi has emerged as a straightforward and important technique to interrogate that information through decreased or loss of gene function and identify potential drug targets. To date, RNAi studies in schistosome stages infecting humans have focused on single (or up to 3) genes of interest. Therefore, in the context of standardizing larger RNAi screens, data are limited on the extent of possible off-targeting effects, gene-to-gene variability in RNAi efficiency and the operational capabilities and limits of RNAi. Methodology/Principal Findings We investigated in vitro the sensitivity and selectivity of RNAi using double-stranded (ds)RNA (approximately 500 bp) designed to target 11 Schistosoma mansoni genes that are expressed in different tissues; the gut, tegument and otherwise. Among the genes investigated were 5 that had been previously predicted to be essential for parasite survival. We employed mechanically transformed schistosomula that are relevant to parasitism in humans, amenable to screen automation and easier to obtain in greater numbers than adult parasites. The operational parameters investigated included defined culture media for optimal parasite maintenance, transfection strategy, time- and dose- dependency of RNAi, and dosing limits. Of 7 defined culture media tested, Basch Medium 169 was optimal for parasite maintenance. RNAi was best achieved by co-incubating parasites and dsRNA (standardized to 30 µg/ml for 6 days); electroporation provided no added benefit. RNAi, including interference of more than one transcript, was selective to the gene target(s) within the pools of transcripts representative of each tissue. Concentrations of dsRNA above 90 µg/ml were directly toxic. RNAi efficiency was transcript

  11. Fatty acid specificity of hormone-sensitive lipase. Implication in the selective hydrolysis of triacylglycerols.

    PubMed

    Raclot, T; Holm, C; Langin, D

    2001-12-01

    The selective mobilization of fatty acids from white fat cells depends on their molecular structure, in particular the degree of unsaturation. The present study was designed to examine if the release of fatty acids by hormone-sensitive lipase (HSL) in vitro i) is influenced by the amount of unsaturation, ii) depends on the temperature, and iii) could explain the selective pattern of fatty acid mobilization and notably the preferential mobilization of certain highly unsaturated fatty acids. Recombinant rat and human HSL were incubated with a lipid emulsion. The hydrolysis of 35 individual fatty acids, ranging in chain length from 12 to 24 carbon atoms and in unsaturation from 0 to 6 double bonds was measured. Fatty acid composition of in vitro released NEFA was compared with that of fat cell triacylglycerols (TAG), the ratio % NEFA/% TAG being defined as the relative hydrolysis. The relative hydrolysis of individual fatty acids differed widely, ranging from 0.44 (24:1n-9) to 1.49 (18:1n-7) with rat HSL, and from 0.38 (24:1n-9) to 1.67 (18:1n-7) with human HSL. No major difference was observed between rat and human HSL. The relative release was dependent on the number of double bonds according to chain length. The amount of fatty acid released by recombinant rat HSL was decreased but remained robust at 4 degrees C compared with 37 degrees C, and the relative hydrolysis of some individual fatty acids was affected. The relative hydrolysis of fatty acids moderately, weakly, and highly mobilized by adipose tissue in vivo was similar and close to unity in vitro. We conclude that i) the release of fatty acids by HSL is only slightly affected by their degree of unsaturation, ii) the ability of HSL to efficiently and selectively release fatty acids at low temperature could reflect a cold adaptability for poikilotherms or hibernators when endogenous lipids are needed, and iii) the selectivity of fatty acid hydrolysis by HSL does not fully account for the selective pattern of

  12. Human alpha-thrombin inhibition by the highly selective compounds N-ethoxycarbonyl-D-Phe-Pro-alpha-azaLys p-nitrophenyl ester and N-carbobenzoxy-Pro-alpha-azaLys p-nitrophenyl ester: a kinetic, thermodynamic and X-ray crystallographic study.

    PubMed

    De Simone, G; Balliano, G; Milla, P; Gallina, C; Giordano, C; Tarricone, C; Rizzi, M; Bolognesi, M; Ascenzi, P

    1997-06-20

    Kinetics, thermodynamics and structural aspects of human alpha-thrombin (thrombin) inhibition by newly synthesized low molecular weight derivatives of alpha-azalysine have been investigated. The thrombin catalyzed hydrolysis of N-ethoxycarbonyl-D-Phe-Pro-alpha-azaLys p-nitrophenyl ester (Eoc-D-Phe-Pro-azaLys-ONp) and N-carbobenzoxy-Pro-alpha-azaLys p-nitrophenyl ester (Cbz-Pro-azaLys-ONp) was investigated at pH 6.2 and 21.0 degrees C, and analyzed in parallel with that of N-alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp). Decarboxylation following the enzymatic hydrolysis of these p-nitrophenyl esters gave the corresponding 1-peptidyl-2(4-aminobutyl) hydrazines (peptidyl-Abh) showing properties of thrombin competitive inhibitors. Therefore, thermodynamics for the reversible binding of D-Phe-Pro-Abh, Cbz-Pro-Abh and Dmc-Abh to thrombin was examined. These results are consistent with the minimum four-step catalytic mechanism for product inhibition of serine proteinases. Eoc-D-Phe-Pro-azaLys-ONp and Eoc-D-Phe-Pro-Abh display a sub-micromolar affinity for thrombin together with a high selectivity versus homologous plasmatic and pancreatic serine proteinases acting on cationic substrates. The three-dimensional structures of the reversible non-covalent thrombin:Eoc-D-Phe-Pro-Abh and thrombin:Cbz-Pro-Abh complexes have been determined by X-ray crystallography at 2.0 A resolution (R-factor = 0.169 and 0.179, respectively), and analyzed in parallel with that of the thrombin:Dmc-azaLys acyl-enzyme adduct. Both Eoc-D-Phe-Pro-Abh and Cbz-Pro-Abh competitive inhibitors are accommodated in the thrombin active center, spanning the region between the aryl binding site and the S1 primary specificity subsite. PMID:9217260

  13. Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes

    PubMed Central

    de Paola, Matilde; Bello, Oscar Daniel; Michaut, Marcela Alejandra

    2015-01-01

    Cortical granule exocytosis (CGE), also known as cortical reaction, is a calcium- regulated secretion that represents a membrane fusion process during meiotic cell division of oocytes. The molecular mechanism of membrane fusion during CGE is still poorly understood and is thought to be mediated by the SNARE pathway; nevertheless, it is unkown if SNAP (acronym for soluble NSF attachment protein) and NSF (acronym for N-ethilmaleimide sensitive factor), two key proteins in the SNARE pathway, mediate CGE in any oocyte model. In this paper, we documented the gene expression of α-SNAP, γ-SNAP and NSF in mouse oocytes. Western blot analysis showed that the expression of these proteins maintains a similar level during oocyte maturation and early activation. Their localization was mainly observed at the cortical region of metaphase II oocytes, which is enriched in cortical granules. To evaluate the function of these proteins in CGE we set up a functional assay based on the quantification of cortical granules metaphase II oocytes activated parthenogenetically with strontium. Endogenous α-SNAP and NSF proteins were perturbed by microinjection of recombinant proteins or antibodies prior to CGE activation. The microinjection of wild type α-SNAP and the negative mutant of α-SNAP L294A in metaphase II oocytes inhibited CGE stimulated by strontium. NEM, an irreversibly inhibitor of NSF, and the microinjection of the negative mutant NSF D1EQ inhibited cortical reaction. The microinjection of anti-α-SNAP and anti-NSF antibodies was able to abolish CGE in activated metaphase II oocytes. The microinjection of anti-γ SNAP antibody had no effect on CGE. Our findings indicate, for the first time in any oocyte model, that α-SNAP, γ-SNAP, and NSF are expressed in mouse oocytes. We demonstrate that α-SNAP and NSF have an active role in CGE and propose a working model. PMID:26267363

  14. Cortical Granule Exocytosis Is Mediated by Alpha-SNAP and N-Ethilmaleimide Sensitive Factor in Mouse Oocytes.

    PubMed

    de Paola, Matilde; Bello, Oscar Daniel; Michaut, Marcela Alejandra

    2015-01-01

    Cortical granule exocytosis (CGE), also known as cortical reaction, is a calcium- regulated secretion that represents a membrane fusion process during meiotic cell division of oocytes. The molecular mechanism of membrane fusion during CGE is still poorly understood and is thought to be mediated by the SNARE pathway; nevertheless, it is unkown if SNAP (acronym for soluble NSF attachment protein) and NSF (acronym for N-ethilmaleimide sensitive factor), two key proteins in the SNARE pathway, mediate CGE in any oocyte model. In this paper, we documented the gene expression of α-SNAP, γ-SNAP and NSF in mouse oocytes. Western blot analysis showed that the expression of these proteins maintains a similar level during oocyte maturation and early activation. Their localization was mainly observed at the cortical region of metaphase II oocytes, which is enriched in cortical granules. To evaluate the function of these proteins in CGE we set up a functional assay based on the quantification of cortical granules metaphase II oocytes activated parthenogenetically with strontium. Endogenous α-SNAP and NSF proteins were perturbed by microinjection of recombinant proteins or antibodies prior to CGE activation. The microinjection of wild type α-SNAP and the negative mutant of α-SNAP L294A in metaphase II oocytes inhibited CGE stimulated by strontium. NEM, an irreversibly inhibitor of NSF, and the microinjection of the negative mutant NSF D1EQ inhibited cortical reaction. The microinjection of anti-α-SNAP and anti-NSF antibodies was able to abolish CGE in activated metaphase II oocytes. The microinjection of anti-γ SNAP antibody had no effect on CGE. Our findings indicate, for the first time in any oocyte model, that α-SNAP, γ-SNAP, and NSF are expressed in mouse oocytes. We demonstrate that α-SNAP and NSF have an active role in CGE and propose a working model. PMID:26267363

  15. SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets.

    PubMed

    Guo, Jing; Liu, Hui; Zheng, Jie

    2016-01-01

    Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would

  16. Laser selective microablation of sensitized intracellular components within auditory receptor cells

    NASA Astrophysics Data System (ADS)

    Harris, David M.; Evans, Burt N.; Santos-Sacchi, Joseph

    1995-05-01

    A laser system can be coupled to a light microscope for laser microbeam ablation and trapping of single cells in vitro. We have extended this technology by sensitization of target structures with vital dyes to provide selective ablation of specific subcellular components. Isolated auditory receptor cells (outer hair cells, OHCs) are known to elongate and contract in response to electrical, chemical and mechanical stimulation. Various intracellular structures are candidate components mediating motility of OHCs, but the exact mechanism(s) is currently unknown. In ongoing studies of OHC motility, we have used the microbeam for selective ablation of lateral wall components and of an axial cytoskeletal core that extends from the nucleus to the cell apex. Both the area beneath the subsurface cistemae of the lateral wall and the core are rich in mitochondria. OHCs isolated from guinea pig cochlea are suspended in L- 15 medium containing 2.0 (mu) M Rhodamine 123, a porphyrin with an affinity for mitochondria. A spark-pumped nitrogen laser pumping a dye cell (Coumarin 500) was aligned on the optical axis of a Nikon Optiphot-2 to produce a 3 ns, 0.5 - 10 micrometers spot (diameter above ablation threshold w/50X water immersion, N.A. 0.8), and energy at the target approximately equals 10 (mu) J/pulse. At short incubation times in Rh123 irradiation caused local blebbing or bulging of cytoplastic membrane and thus loss of the OHC's cylindrical shape. At longer Rh123 incubation times when the central axis of the cell was targeted we observed cytoplasmic clearing, immediate cell elongation (approximately equals 5%) and clumping of core material at nuclear and apical attachments. Experiments are underway to examine the significance of these preliminary observations.

  17. Synthesis of Water-Dispersible Molecularly Imprinted Electroactive Nanoparticles for the Sensitive and Selective Paracetamol Detection.

    PubMed

    Luo, Jing; Ma, Qiang; Wei, Wei; Zhu, Ye; Liu, Ren; Liu, Xiaoya

    2016-08-17

    A novel kind of water-dispersible molecularly imprinted electroactive nanoparticles was prepared combining macromolecular self-assembly with molecularly imprinting technique employing paracetamol (PCM) as template molecule. An amphiphilic electroactive copolymer (P(NVC-EHA-AA), PNEA) containing carbazole group was first synthesized through a one-pot free radical copolymerization. The coassembly of the electroactive copolymers with the template molecules (PCM) in aqueous solution generated nanoparticles embedded with PCM, leading to the formation of molecularly imprinted electroactive nanoparticles (MIENPs). A robust MIP film was formed on the surface of electrode by electrodeposition of MIENPs and subsequent electropolymerization of the carbazole units in MIENPs. After the extraction of PCM molecules, a MIP sensor was successfully constructed. It should be noted that electropolymerization of the electroactive units in MIENPs creates cross-conjugated polymer network, which not only locks the recognition sites but also significantly accelerates the electron transfer and thus enhances the response signal of the MIP sensor. These advantages endowed the MIP sensor with good selectivity and high sensitivity for PCM detection. The MIP sensor could recognize PCM from its possible interfering substances with good selectivity. Under the optimal conditions, two linear ranges from 1 μM to 0.1 mM and 0.1 to 10 mM with a detection limit of 0.3 μM were obtained for PCM detection. The MIP sensor also showed good stability and repeatability, which has been successfully used to analyze PCM in tablets and human urine samples with satisfactory results. PMID:27463123

  18. A Sensitive Ratiometric Long-Wavelength Fluorescent Probe for Selective Determination of Cysteine/Homocysteine.

    PubMed

    Manibalan, Kesavan; Chen, Sin-Ming; Mani, Veerappan; Huang, Tsung-Tao; Huang, Sheng-Tung

    2016-07-01

    The development of sensitive fluorescence probes to detect biothiols such as cysteine and homocysteine has attracted great attention in recent times. Herein, we described the design and synthesis of coumarin based long-wavelength fluorescence probe, Bromo-2-benzothiazolyl-3-cyano-7-hydroxy coumarin (BBCH, 2) for selective detections of cysteine and homocysteine. The probe is rationally designed in such a way that both sulfhydryl and adjacent amino groups of thiols are involved in sensing process. Only cysteine/homocysteine able to react with BBCH to release fluorescence reporter (BCH, 1); while, glutathione and other amino acids unable to react with BBCH due to the absence of adjacent amino groups. In presence of cysteine, the color of BBCH is turns from colorless to red and thus BBCH is a naked eye fluorescence indicator for cysteine. Besides, BBCH can discriminate cysteine and homocysteine based on color changes and different reaction rates. The described sensing platform showed good sensing performances to detect cysteine and homocysteine with detection limits of 0.87 and 0.19 μM, respectively. Practical applicability was verified in biological and pharmaceutical samples. PMID:27290640

  19. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

    PubMed Central

    Yang, Hua; Qiao, Jingjuan; Pu, Fan; Jiang, Jie; Hubbard, Kendra; Hekmatyar, Khan; Langley, Jason; Salarian, Mani; Long, Robert C.; Bryant, Robert G.; Hu, Xiaoping Philip; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2015-01-01

    With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery. PMID:25971726

  20. Determination of the biotin content of select foods using accurate and sensitive HPLC/avidin binding

    PubMed Central

    Staggs, C.G.; Sealey, W.M.; McCabe, B.J.; Teague, A.M.; Mock, D.M.

    2006-01-01

    Assessing dietary biotin content, biotin bioavailability, and resulting biotin status are crucial in determining whether biotin deficiency is teratogenic in humans. Accuracy in estimating dietary biotin is limited both by data gaps in food composition tables and by inaccuracies in published data. The present study applied sensitive and specific analytical techniques to determine values for biotin content in a select group of foods. Total biotin content of 87 foods was determined using acid hydrolysis and the HPLC/avidin-binding assay. These values are consistent with published values in that meat, fish, poultry, egg, dairy, and some vegetables are relatively rich sources of biotin. However, these biotin values disagreed substantially with published values for many foods. Assay values varied between 247 times greater than published values for a given food to as much as 36% less than the published biotin value. Among 51 foods assayed for which published values were available, only seven agreed within analytical variability (720%). We conclude that published values for biotin content of foods are likely to be inaccurate. PMID:16648879

  1. Highly sensitive and selective fluorescent assay for guanine based on the Cu2 +/eosin Y system

    NASA Astrophysics Data System (ADS)

    Shi, Huimin; Cui, Yi; Gong, Yijun; Feng, Suling

    2016-05-01

    A fluorescent probe has been developed for the determination of guanine based on the quenched fluorescence signal of Cu2 +/eosin Y. Cu2 + interacted with eosin Y, resulting in fluorescence quenching. Subsequently, with the addition of guanine to the Cu2 +/eosin Y system, guanine reacted with Cu2 + to form 1:1 chelate cation, which further combined with eosin Y to form a 1:1 ternary ion-association complex by electrostatic attraction and hydrophobic interaction, resulting in significant decrease of the fluorescence. Hence, a fluorescent system was constructed for rapid, sensitive and selective detection of guanine with a detection limit as low as 1.5 nmol L- 1 and a linear range of 3.3-116 nmol L- 1. The method has been applied satisfactorily to the determination of guanine in DNA and urine samples with the recoveries from 98.7% to 105%. This study significantly expands the realm of application of ternary ion-association complex in fluorescence probe.

  2. Golgi Phosphoprotein 4 (GPP130) is a Sensitive and Selective Cellular Target of Manganese Exposure

    PubMed Central

    Masuda, Melisa; Braun-sommargren, Michelle; Crooks, Dan; Smith, Donald R.

    2014-01-01

    Chronic elevated exposure to manganese (Mn) is associated with neurocognitive and fine motor deficits in children. However, relatively little is understood about cellular responses to Mn spanning the transition between physiologic to toxic levels of exposure. Here, we investigated the specificity, sensitivity, and time course of the Golgi Phosphoprotein 4 (GPP130) response to Mn exposure in AF5 GABAergic neuronal cells, and we determined the extent to which GPP130 degradation occurs in brain cells in vivo in rats subchronically exposed to Mn. Our results show that GPP130 degradation in AF5 cells was specific to Mn, and did not occur following exposure to cobalt, copper, iron, nickel, or zinc. GPP130 degradation occurred without measurable increases in intracellular Mn levels and at Mn exposures as low as 0.54 µM. GPP130 protein was detectable by immunofluorescence in only ~15–30% of cells in striatal and cortical rat brain slices, and Mn-exposed animals exhibited a significant reduction in both the number of GPP130-positive cells, and the overall levels of GPP130 protein, demonstrating the in vivo relevance of this Mn-specific response within the primary target organ of Mn toxicity. These results provide insight into specific mechanism(s) of cellular Mn regulation and toxicity within the brain, including the selective susceptibility of cells to Mn cytotoxicity. PMID:23280773

  3. Contaminant tailing in highly heterogeneous porous formations: Sensitivity on model selection and material properties

    NASA Astrophysics Data System (ADS)

    Maghrebi, Mahdi; Jankovic, Igor; Weissmann, Gary S.; Matott, L. Shawn; Allen-King, Richelle M.; Rabideau, Alan J.

    2015-12-01

    Coupled impacts of slow advection, diffusion and sorption were investigated using two heterogeneity models that differ in structure and in the mathematical framework that was used to simulate flow and transport and to quantify contaminant tailing. Both models were built using data from a highly heterogeneous exposure of the Borden Aquifer at a site located 2 km north-west of the Stanford-Waterloo experimental site at Canadian Forces Base Borden, Ontario, Canada. The inclusions-based model used a simplified representation of the different materials found at the site, while the second model was based on transitional probability geostatistics of the formation. These two models were used to investigate sensitivity of contaminant tailing on model selection and on geometric and material properties. While simulations were based on data collected at Borden, models were exercised beyond the geometric and material properties that characterize the site. Various realizations have identified very low conductive silty clay, found at volume fraction of 23.4%, as the material with dominant influence on tailing, and vertical diffusion in and out of low conductive units, affected by sorption, as the dominant transport mechanism causing tailing. The two models yielded almost identical transport results when vertical correlation lengths of silty clay were matched. Several practical implications relevant for characterization of low conductive units were identified and briefly discussed.

  4. Sensitive and Selective Determination of Orotic Acid in Biological Specimens Using a Novel Fluorogenic Reaction.

    PubMed

    Yin, Sheng; Dragusha, Shpend; Ejupi, Valon; Shibata, Takayuki; Kabashima, Tsutomu; Kai, Masaaki

    2015-07-01

    Orotic acid is an intermediate in the synthesis pathway of uridine-5'-monophosphate, and increases in body fluids of patients suffering from hereditary disorders such as orotic aciduria and hyperammonemia. In this study, we developed a spectrofluorometric method with or without high-performance liquid chromatography for the selective and sensitive quantification of orotic acid in human biological specimens, using 4-trifluoromethylbenzamidoxime (4-TFMBAO) as a fluorogenic reagent. This reagent provided intensive fluorescence for only orotic acid amongst 62 compounds including structurally related bio-substances such as nucleic acid bases, nucleosides, nucleotides, amino acids, vitamins, bilirubin, uric acid, urea, creatine, creatinine and sugars. Under optimized reaction conditions, orotic acid was reacted with 4-TFMBAO, K3[Fe(CN)6] and K2CO3 in an aqueous solution. The fluorescence produced from the orotic acid derivative was measured at an excitation of 340 nm and an emission of 460 nm. A concentration of 1.2 μM orotic acid per 1.0 mM creatinine in normal urine and 0.64 nmol orotic acid per 5.0 × 10(5) HeLa cells were determined by this method. The present method permitted the facile quantification of orotic acid in healthy human urine and cultured HeLa cells by spectrofluorometry and/or high-performance liquid chromatography. PMID:26026930

  5. A highly sensitive and selective fluorescent Cu2+ sensor synthesized with silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Zheng, Jiannan; Xiao, Chuan; Fei, Qiang; Li, Ming; Wang, Baojun; Feng, Guodong; Yu, Hongmei; Huan, Yanfu; Song, Zhiguang

    2010-01-01

    A novel fluorescent nanosensor for the determination of Cu2+ was synthesized with N-(quinoline-8-yl)-2-(3-triethoxysilyl-propylamino)-acetamide (QlOEt) grafted onto the surface of silica nanoparticles (SiNPs) using the reverse microemulsion method. Spherical SiNPs were used as substrate and QlOEt was used simultaneously as the binding and readout system for Cu2+. This sensor has been realized as a highly sensitive and selective technique for the detection and quantification of trace amounts of Cu2+. The probe exhibits a dynamic response range for Cu2+ from 2.0 × 10-6 to 2.0 × 10-5 M, with a detection limit of 3.8 × 10-7 M. Other alkali, alkaline earth, and transitional metal ions including Li+, K+, Mg2+, Ca2+, Sr2+, Mn2+, Zn2+, Mo6+, Pb2+, Ag+ had no significant interference on Cu2+ determination. Poisonous and flammable reagents are avoided during the synthesis of this nanosensor. Therefore the strategy explored in this work can be extended to the synthesis of other chemo- and biosensors for direct detection of specific targets in an intracellular environment.

  6. Highly selective and sensitized spectrophotometric determination of iron (III) following potentiometric study.

    PubMed

    Shokrollahi, Ardeshir; Ghaedi, Mehrorang; Rajabi, Hamid Reza

    2007-09-01

    A simple, selective and sensitized spectrophotometric method for determination of trace amounts of Fe3+ ion in tap and waste water solutions has been described. The spectrophotometric determination of Fe3+ ion using Ferron in the presence of N,N-Dodecytrimethylammonium bromide (DTAB) has been carried out. The Beer's law is obeyed over the concentration range of 0.05-2.6 microg mL(-1) of Fe3+ ion with the relative standard deviation (RSD %) <0.2% and the molar absorptivity of complexes in pH 3.5 is 3.8 x 10(3) L mol(-1) cm(-1). Potentiometric pH titration has been used for prediction of protonation constants of ferron, and evaluating its stoichiometry and respective stability constant with Fe3+ ion. As it is obvious the most likely species of ferron alone and its complexes are LH (log = 7.64), LH2 (logK = 10.52), LH3 (logK = 11.74) and ML2 (logbeta = 23.68), ML3 (logbeta = 23.68), ML3H (logbeta = 23.68), ML3H2 (logbta = 23.68) and ML(OH)2 (logbeta = 23.68) respectively. PMID:17970298

  7. Simple, Selective and Sensitive Determination of CH₃Hg⁺ Using Gold Nanocluster.

    PubMed

    Chen, Xiaoxia; Zhao, Jiating; Cong, Wenshu; Li, Xixuan; Fan, Hongyi; Sun, Jinzhe; Lin, Jing; Li, Bai; Gao, Yuxi; Qin, Chuan; Li, Yu-Feng

    2016-01-01

    Mercury is a potent neurotoxin, which causes serious and permanent damage to biota including human beings. Nanomaterials like gold have been used to detect mercury, especially the mercuric ions in recent years, but few have been done on the determination of methylmercury (CH₃Hg⁺). In this study, we present a simple, selective and sensitive method for the determination of CH₃Hg⁺ co-existing with Hg²⁺ based on the fluorescence quenching of bovine serum albumin (BSA) stabilized gold nanoclusters (BSA-Au NCs). It was found that the fluorescence quenching of BSA-Au NCs by Hg²⁺ is stronger than CH₃Hg⁺ at the same concentration. Hg²⁺ can be masked by EDTA while CH₃Hg⁺ is less affected. Therefore, the determination of CH₃Hg⁺ was achieved through EDTA masking. The detection limit for CH₃Hg⁺ is 35 nmol/L after masking Hg²⁺ with EDTA. This method has been successfully applied to quantify CH₃Hg⁺ in rice paddy water from Qingzhen, Guizhou and tap water from Beijing. PMID:27398521

  8. Enhanced sensitivity and selectivity in a dual cell ion mobility spectrometer

    NASA Astrophysics Data System (ADS)

    Griffin, Matthew T.; Fulton, Jack E., Jr.; McAtee, Robert F.; Gao, Rong; Tsoukalas, Lefteri H.

    2003-08-01

    While ion mobility spectrometry (IMS) has been used as a portable trace vapor detector, these handheld systems suffer from poor selectivity. Their low resolution makes confident identification of chemical species difficult. One major application for these IMS systems is in Homeland Defense. IMS systems are fielded for the detection of chemical warfare agents, explosives, narcotics, and other hazardous chemicals. Recently, a novel signal processing methodology using wavelet filtering, statistical evaluators, and genetic algorithms was demonstrated to improve sensitivity and specificity of an ion mobility spectrometer. Previous work involved a single (single polarity) IMS cell. Since both positive and negative ions are created in the same environment and a common sample interface is used for the dual IMS system, there is cross talk between the positive and negative cell. Typically, this cross talk provides little information on the identity of the chemical species present. However, using this new methodology, valuable sample information is obtained. Moreover, ion beam modulation has been incorporated to allow for the ion beam to be broken up into discrete packets. The modulation allows the rejection of common background interferents. This paper will present the process of using cell cross talk, ion beam modulation, and application and extension of the signal processing methodology. The application to field instrumentation will also be discussed.

  9. A Highly Sensitive and Selective Catalytic Determination of Mercury in Environmental Samples.

    PubMed

    Mohamed, Ashraf A; Ahmed, Nagat A; El-Shahat, Mohamed F

    2016-08-01

    A simple, selective and highly sensitive spectrophotometric method has been developed for mercury determination utilizing its catalytic effect on the isoniazid-hexacyanoferrate (II) reaction. The paper presents for the first time (1) the catalytic effect of Hg (I) on the cited ligand substitution reactions and (2) the activating effect of thiourea on the behavior of mercury. The reaction was monitored spectrophotometrically at 423 nm using the initial rate method. The optimized reaction conditions were 5.0 mmol L(-1) hexacyanoferrate (II), 0.5 mmol L(-1) isoniazid, 150 mmol L(-1) citrate buffer (pH 3.30 ± 0.05), and 0.2 mmol L(-1) thiourea, at 50°C. Linear calibration graphs were obtained for 1-100 and 1-55 µg L(-1) with detection limits, based on the 3Sb-criterion, of 1.2 and 1.8 µg L(-1) of Hg (II) and Hg (I), respectively. The method was conveniently applied to samples of wastewaters, inactivated vaccines, and frozen Bass fish fillet, without any prior separation or preconcentration. PMID:27168315

  10. Laser correlation velocimetry performance in diesel applications: spatial selectivity and velocity sensitivity

    NASA Astrophysics Data System (ADS)

    Hespel, Camille; Blaisot, Jean-Bernard; Gazon, Matthieu; Godard, Gilles

    2012-07-01

    The characterization of diesel jets in the near field of the nozzle exit still presents challenges for experimenters. Detailed velocity measurements are needed to characterize diesel injector performance and also to establish boundary conditions for CFD codes. The present article examines the efficiency of laser correlation velocimetry (LCV) applied to diesel spray characterization. A new optical configuration based on a long-distance microscope was tested, and special care was taken to examine the spatial selectivity of the technique. Results show that the depth of the measurement volume (along the laser beam) of LCV extends beyond the depth of field of the imaging setup. The LCV results were also found to be particularly sensitive to high-speed elements of a spray. Results from high-pressure diesel jets in a back-pressure environment indicate that this technique is particularly suited to the very near field of the nozzle exit, where the flow is the narrowest and where the velocity distribution is not too large. It is also shown that the performance of the LCV technique is controlled by the filtering and windowing parameters used in the processing of the raw signals.

  11. Selective and Sensitive Chemiluminescence Determination of MCPB: Flow Injection and Liquid Chromatography.

    PubMed

    Meseguer-Lloret, Susana; Torres-Cartas, Sagrario; Catalá-Icardo, Mónica; Gómez-Benito, Carmen

    2016-02-01

    Two new chemiluminescence (CL) methods are described for the determination of the herbicide 4-(4-chloro-o-tolyloxy) butyric acid (MCPB). First, a flow injection chemiluminescence (FI-CL) method is proposed. In this method, MCPB is photodegraded with an ultraviolet (UV) lamp and the photoproducts formed provide a great CL signal when they react with ferricyanide in basic medium. Second, a high-performance liquid chromatography chemiluminescence (HPLC-CL) method is proposed. In this method, before the photodegradation and CL reaction, the MCPB and other phenoxyacid herbicides are separated in a C18 column. The experimental conditions for the FI-CL and HPLC-CL methods are optimized. Both methods present good sensitivity, the detection limits being 0.12 µg L(-1) and 0.1 µg L(-1) (for FI-CL and HPLC-CL, respectively) when solid phase extraction (SPE) is applied. Intra- and interday relative standard deviations are below 9.9%. The methods have been satisfactorily applied to the analysis of natural water samples. FI-CL method can be employed for the determination of MCPB in simple water samples and for the screening of complex water samples in a fast, economic, and simple way. The HPLC-CL method is more selective, and allows samples that have not been resolved with the FI-CL method to be solved. PMID:26903566

  12. Sensitive and selective electrochemical detection of artemisinin based on its reaction with p-aminophenylboronic acid.

    PubMed

    Wang, Chao; Zholudov, Yuriy T; Nsabimana, Anaclet; Xu, Guobao; Li, Jianping

    2016-09-21

    The electrochemical detection of artemisinin generally requires high oxidation potential or the use of complex electrode modification. We find that artemisinin can react with p-aminophenylboronic acid to produce easily electrochemically detectable aminophenol for the first time. By making use of the new reaction, we report an alternative method to detect artemisinin through the determination of p-aminophenol. The calibration curve for the determination of artemisinin is linear in the range of 2 μmol L(-1) to 200 μmol L(-1) with the detection limit of 0.8 μmol L(-1), which is more sensitive than other reported electrochemical methods. The relative standard deviation is 4.83% for the determination of 10 μM artemisinin. Because the oxidation potential of p-aminophenol is around 0 V, the present method is high selective. When 40 μM, 90 μM and 140 μM of artemisinin were spiked to compound naphthoquine phosphate tablet samples, the recoveries are 107.6%, 105.4% and 101.7%, respectively. This detection strategy is attractive for the detection of artemisinin and its derivatives. The finding that artemisinin can react with aromatic boronic acid has the potential to be exploited for the development of other sensors, such as fluorescence artemisinin sensors. PMID:27590543

  13. A novel OFET-based biosensor for the selective and sensitive detection of lactate levels.

    PubMed

    Minami, Tsuyoshi; Sato, Tsubasa; Minamiki, Tsukuru; Fukuda, Kenjiro; Kumaki, Daisuke; Tokito, Shizuo

    2015-12-15

    Biosensors based on organic field effect transistors (OFETs) are one of the more promising device applications in organic electronics. However, OFET-based biosensors are still in their early stages of development compared to other electrochemical biosensors. This study is the first to report on an extended-gate type organic field effect transistor (OFET) for lactate detection in aqueous media. Here, the extended-gate electrode of the OFET was modified with layers of a lactate oxidase and a horseradish peroxidase osmium-redox polymer on a flexible plastic film substrate for an enzymatic redox reaction of lactate. The device exhibited both high selectivity and sensitivity. The limit of detection (LOD) and the limit of quantification (LOQ) were estimated to be 66 nM and 220 nM, respectively, which are the sufficient detection limit for practical sensor applications. The obtained results confirm that extended-gate type OFET devices are applicable to enzyme-based biosensors for detecting lactate levels. PMID:26101795

  14. A novel bi-enzyme electrochemical biosensor for selective and sensitive determination of methyl salicylate.

    PubMed

    Fang, Yi; Umasankar, Yogeswaran; Ramasamy, Ramaraja P

    2016-07-15

    An amperometric sensor based on a bi-enzyme modified electrode was fabricated to detect methyl salicylate, a volatile organic compound released by pathogen-infected plants via systemic response. The detection is based on cascadic conversion reactions that result in an amperometric electrochemical signal. The bi-enzyme electrode is made of alcohol oxidase and horseradish peroxidase enzymes immobilized on to a carbon nanotube matrix through a molecular tethering method. Methyl salicylate undergoes hydrolysis to form methanol, which is consumed by alcohol oxidase to form formaldehyde while simultaneously reducing oxygen to hydrogen peroxide. The hydrogen peroxide will be further reduced to water by horseradish peroxidase, which results in an amperometric signal via direct electron transfer. The bi-enzyme biosensor was evaluated by cyclic voltammetry and constant potential amperometry using hydrolyzed methyl salicylate as the analyte. The sensitivity of the bi-enzyme biosensor as determined by cyclic voltammetry and constant potential amperometry were 112.37 and 282.82μAcm(-2)mM(-1) respectively, and the corresponding limits of detection were 22.95 and 0.98μM respectively. Constant potential amperometry was also used to evaluate durability, repeatability and interference from other compounds. Wintergreen oil was used for real sample study to establish the application of the bi-enzyme sensor for selective determination of plant pathogen infections. PMID:26918616

  15. Realisation Of Polarisation Sensitive And Frequency Selective Surfaces On Microwave Reflectors By Laser Evaporation

    NASA Astrophysics Data System (ADS)

    Halm, R.; Kupper, Th.; Fischer, A.

    1987-01-01

    Gridded reflectors are used on communication satellites antennas to provide frequency reuse in dual linear polarisation mode of operation. The polarisation sensitive surface consists of metallic strips, forming a grid with width and spacings of the order of 0.1 mm. The use of frequency-selective surface (FSS) subreflectors allows the simultaneous generation of different microwave beams with the same main reflector. Such a reflector will require a structure of conductive arrays of either dipoles, rings, squares or square loops with typical dimensions of the order of 3-6 mm. Optimisation of the electrical design leads to critical dimensioning of these structures. By direct ablation of an aluminium surface coating by means of laser evaporation, high accuracies can be achieved. The major requirements were to minimize thermal damage of the substrate material and to produce dimensionally accurate grids. Experiments were carried out using a pulsed TEA-CO2 laser and a Q-switched Alexandrite laser. Details of the experimental set-up and conditions are described.

  16. A rapid, sensitive, and selective method for quantitation of lamprey migratory pheromones in river water.

    PubMed

    Stewart, Michael; Baker, Cindy F; Cooney, Terry

    2011-11-01

    The methodology of using fish pheromones, or chemical signatures, as a tool to monitor or manage species of fish is rapidly gaining popularity. Unequivocal detection and accurate quantitation of extremely low concentrations of these chemicals in natural waters is paramount to using this technique as a management tool. Various species of lamprey are known to produce a mixture of three important migratory pheromones; petromyzonol sulfate (PS), petromyzonamine disulfate (PADS), and petromyzosterol disulfate (PSDS), but presently there are no established robust methods for quantitation of all three pheromones. In this study, we report a new, highly sensitive and selective method for the rapid identification and quantitation of these pheromones in river water samples. The procedure is based on pre-concentration, followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. The method is fast, with unambiguous pheromone determination. Practical quantitation limits of 0.25 ng/l were achieved for PS and PADS and 2.5 ng/l for PSDS in river water, using a 200-fold pre-concentration, However, lower quantitation limits can be achieved with greater pre-concentration. The methodology can be modified easily to include other chemicals of interest. Furthermore, the pre-concentration step can be applied easily in the field, circumventing potential stability issues of these chemicals. PMID:22076684

  17. Structure sensitive selectivity of the NO-CO reaction over rhodium single crystal catalysts

    SciTech Connect

    Peden, C.H.F.; Belton, D.N.; Schmieg, S.J.

    1995-05-01

    The control of automotive emissions of nitrogen oxides (NO{sub x}) in passenger cars is accomplished by a heavy reliance on after-treatment of the engine exhaust using catalytic converters that contain a mixture of platinum (Pt), rhodium (Rh), and sometimes palladium (Pd). In this paper we examine the effect of surface structure on the NO-CO activity and selectivity by comparing the reactivity of Rh(110) and Rh(111) single crystal catalysts. Selectivity for the two possible nitrogen containing products from NO reduction, N{sub 2}O and N{sub 2}, is particularly interesting. Here we report that the selectivity of the NO-CO reaction is quite sensitive to the structure of the Rh catalyst metal surface. (A more complete description of these studies will be published elsewhere.) The more open Rh(110) surface tends to make significantly less N{sub 2}O than Rh(111) under virtually all conditions that we probed with these experiments. Furthermore, under the conditions used in this study, the NO-CO activity over Rh(110), as measured by the rate of NO loss, is somewhat faster than over Rh(111) with a lower apparent activation energy (Ea), 27.6 vs. 35.4 kcal/mol. We attribute these results to the greater tendency of the more open (110) surface to dissociate NO. Notably, more facile NO dissociation on Rh(110) would lead to greater steady-state concentrations of adsorbed N-atoms; thus, the (110) surface favors N-atom recombination over the surface reaction between adsorbed NO and N-atoms to make N{sub 2}O. In support of this, post-reaction surface analysis shows only NO on the Rh(111) surface while the Rh(110) surface contains predominantly N-atoms and much lower concentrations of adsorbed NO. NO dissociation on Rh(110) is more favorable than on Rh(111), in part, because it is less-severely poisoned by high surface concentrations of NO. In addition, the more-open (110) surface may be intrinsically more active for the elementary process of dissociating adsorbed NO.

  18. Actions of prostaglandin F2 alpha and noradrenaline on calcium exchange and contraction in rat mesenteric arteries and their sensitivity to calcium entry blockers.

    PubMed Central

    Godfraind, T.; Miller, R. C.

    1982-01-01

    1 The actions of prostaglandin F2 alpha (PGF2 alpha) and noradrenaline on contraction and 45Ca exchange have been studied in rat mesenteric arteries. 2 PGF2 alpha and noradrenaline contracted rat isolated mesenteric artery preparations to about the same extent. The PGF2 alpha-stimulated contractions, unlike those produced by noradrenaline, were completely inhibited in calcium-free physiological solution. 3 The calcium entry blocking drugs, cinnarizine and flunarizine, had little effect on the resting exchange of calcium in the arterial smooth muscle, but inhibited PGF2 alpha-stimulated contractions and 45Ca uptake to a similar extent. 4 Flunarizine was about 7 fold more potent as an inhibitor of noradrenaline- than of PGF2 alpha-mediated contraction and 45Ca uptake and this ratio was about 50 for cinnarizine. 5 EGTA (1.25 mM) produced a relaxation of noradrenaline and PGF2 alpha-induced maximal contractions. Measured over the first 2 min of EGTA contact, the rate of relaxation was much faster in noradrenaline than in PGF2 alpha-stimulated preparations. 6 Turnover of cellular calcium (influx plus efflux) during the first 2 min of noradrenaline contact was much greater than that produced by PGF2 alpha, largely due to a greater effect of noradrenaline on calcium efflux. 7 The results suggest that PGF2 alpha-but not noradrenaline-induced contractions are entirely dependent on the influx of extracellular calcium and that the agonists may stimulate calcium gating mechanisms differently. PMID:6951620

  19. A Sensitivity Study of Liric Algorithm to User-defined Input Parameters, Using Selected Cases from Thessaloniki's Measurements

    NASA Astrophysics Data System (ADS)

    Filioglou, M.; Balis, D.; Siomos, N.; Poupkou, A.; Dimopoulos, S.; Chaikovsky, A.

    2016-06-01

    A targeted sensitivity study of the LIRIC algorithm was considered necessary to estimate the uncertainty introduced to the volume concentration profiles, due to the arbitrary selection of user-defined input parameters. For this purpose three different tests were performed using Thessaloniki's Lidar data. Overall, tests in the selection of the regularization parameters, an upper and a lower limit test were performed. The different sensitivity tests were applied on two cases with different predominant aerosol types, a dust episode and a typical urban case.

  20. Increasing the selectivity and sensitivity of gas sensors for the detection of explosives

    NASA Astrophysics Data System (ADS)

    Mallin, Daniel

    Over the past decade, the use of improvised explosive devices (IEDs) has increased, domestically and internationally, highlighting a growing need for a method to quickly and reliably detect explosive devices in both military and civilian environments before the explosive can cause damage. Conventional techniques have been successful in explosive detection, however they typically suffer from enormous costs in capital equipment and maintenance, costs in energy consumption, sampling, operational related expenses, and lack of continuous and real-time monitoring. The goal was thus to produce an inexpensive, portable sensor that continuously monitors the environment, quickly detects the presence of explosive compounds and alerts the user. In 2012, here at URI, a sensor design was proposed for the detection of triacetone triperoxide (TATP). The design entailed a thermodynamic gas sensor that measures the heat of decomposition between trace TATP vapor and a metal oxide catalyst film. The sensor was able to detect TATP vapor at the part per million level (ppm) and showed great promise for eventual commercial use, however, the sensor lacked selectivity. Thus, the specific objective of this work was to take the original sensor design proposed in 2012 and to make several key improvements to advance the sensor towards commercialization. It was demonstrated that a sensor can be engineered to detect TATP and ignore the effects of interferent H2O2 molecules by doping SnO2 films with varying amounts of Pd. Compared with a pure SnO2 catalyst, a SnO2, film doped with 8 wt. % Pd had the highest selectivity between TATP and H2O2. Also, at 12 wt. % Pd, the response to TATP and H2O2 was enhanced, indicating that sensitivity, not only selectivity, can be increased by modifying the composition of the catalyst. An orthogonal detection system was demonstrated. The platform consists of two independent sensing mechanisms, one thermodynamic and one conductometric, which take measurements from

  1. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips.

    PubMed

    Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi; Hao, Fen; Wu, Ying-Song

    2015-09-01

    Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (HT) and the control line (HC); the HT/HC ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0-1000 IU mL(-1)) for AFP with a low limit of detection (0.1 IU mL(-1)) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing. PMID:26388387

  2. p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells

    PubMed Central

    Li, Zhilun; Lorent, Julie; Zhao, Chunyan; Dahlman-Wright, Karin; Strömblad, Staffan

    2015-01-01

    Estrogen receptor alpha (ERα) is highly expressed in most breast cancers. Consequently, ERα modulators, such as tamoxifen, are successful in breast cancer treatment, although tamoxifen resistance is commonly observed. While tamoxifen resistance may be caused by altered ERα signaling, the molecular mechanisms regulating ERα signaling and tamoxifen resistance are not entirely clear. Here, we found that PAK4 expression was consistently correlated to poor patient outcome in endocrine treated and tamoxifen-only treated breast cancer patients. Importantly, while PAK4 overexpression promoted tamoxifen resistance in MCF-7 human breast cancer cells, pharmacological treatment with a group II PAK (PAK4, 5, 6) inhibitor, GNE-2861, sensitized tamoxifen resistant MCF-7/LCC2 breast cancer cells to tamoxifen. Mechanistically, we identified a regulatory positive feedback loop, where ERα bound to the PAK4 gene, thereby promoting PAK4 expression, while PAK4 in turn stabilized the ERα protein, activated ERα transcriptional activity and ERα target gene expression. Further, PAK4 phosphorylated ERα-Ser305, a phosphorylation event needed for the PAK4 activation of ERα-dependent transcription. In conclusion, PAK4 may be a suitable target for perturbing ERα signaling and tamoxifen resistance in breast cancer patients. PMID:26554417

  3. In silico selection of an aptamer to estrogen receptor alpha using computational docking employing estrogen response elements as aptamer-alike molecules

    PubMed Central

    Ahirwar, Rajesh; Nahar, Smita; Aggarwal, Shikha; Ramachandran, Srinivasan; Maiti, Souvik; Nahar, Pradip

    2016-01-01

    Aptamers, the chemical-antibody substitute to conventional antibodies, are primarily discovered through SELEX technology involving multi-round selections and enrichment. Circumventing conventional methodology, here we report an in silico selection of aptamers to estrogen receptor alpha (ERα) using RNA analogs of human estrogen response elements (EREs). The inverted repeat nature of ERE and the ability to form stable hairpins were used as criteria to obtain aptamer-alike sequences. Near-native RNA analogs of selected single stranded EREs were modelled and their likelihood to emerge as ERα aptamer was examined using AutoDock Vina, HADDOCK and PatchDock docking. These in silico predictions were validated by measuring the thermodynamic parameters of ERα -RNA interactions using isothermal titration calorimetry. Based on the in silico and in vitro results, we selected a candidate RNA (ERaptR4; 5′-GGGGUCAAGGUGACCCC-3′) having a binding constant (Ka) of 1.02 ± 0.1 × 108 M−1 as an ERα-aptamer. Target-specificity of the selected ERaptR4 aptamer was confirmed through cytochemistry and solid-phase immunoassays. Furthermore, stability analyses identified ERaptR4 resistant to serum and RNase A degradation in presence of ERα. Taken together, an efficient ERα-RNA aptamer is identified using a non-SELEX procedure of aptamer selection. The high-affinity and specificity can be utilized in detection of ERα in breast cancer and related diseases. PMID:26899418

  4. Sensitive and Selective Plasmon Ruler Nanosensors for Monitoring the Apoptotic Drug Response in Leukemia

    PubMed Central

    2015-01-01

    Caspases are proteases involved in cell death, where caspase-3 is the chief executioner that produces an irreversible cutting event in downstream protein substrates and whose activity is desired in the management of cancer. To determine such activity in clinically relevant samples with high signal-to-noise, plasmon rulers are ideal because they are sensitively affected by their interparticle separation without ambiguity from photobleaching or blinking effects. A plasmon ruler is a noble metal nanoparticle pair, tethered in close proximity to one another via a biomolecule, that acts through dipole–dipole interactions and results in the light scattering to increase exponentially. In contrast, a sharp decrease in intensity is observed when the pair is confronted by a large interparticle distance. To align the mechanism of protease activity with building a sensor that can report a binary signal in the presence or absence of caspase-3, we present a caspase-3 selective plasmon ruler (C3SPR) composed of a pair of Zn0.4Fe2.6O4@SiO2@Au core–shell nanoparticles connected by a caspase-3 cleavage sequence. The dielectric core (Zn0.4Fe2.6O4@SiO2)-shell (Au) geometry provided a brighter scattering intensity versus solid Au nanoparticles, and the magnetic core additionally acted as a purification handle during the plasmon ruler assembly. By monitoring the decrease in light scattering intensity per plasmon ruler, we detected caspase-3 activity at single molecule resolution across a broad dynamic range. This was observed to be as low as 100 fM of recombinant material or 10 ng of total protein from cellular lysate. By thorough analyses of single molecule trajectories, we show caspase-3 activation in a drug-treated chronic myeloid leukemia (K562) cancer system as early as 4 and 8 h with greater sensitivity (2- and 4-fold, respectively) than conventional reagents. This study provides future implications for monitoring caspase-3 as a biomarker and efficacy of drugs. PMID:25166742

  5. Sensitive and selective plasmon ruler nanosensors for monitoring the apoptotic drug response in leukemia.

    PubMed

    Tajon, Cheryl A; Seo, Daeha; Asmussen, Jennifer; Shah, Neil; Jun, Young-wook; Craik, Charles S

    2014-09-23

    Caspases are proteases involved in cell death, where caspase-3 is the chief executioner that produces an irreversible cutting event in downstream protein substrates and whose activity is desired in the management of cancer. To determine such activity in clinically relevant samples with high signal-to-noise, plasmon rulers are ideal because they are sensitively affected by their interparticle separation without ambiguity from photobleaching or blinking effects. A plasmon ruler is a noble metal nanoparticle pair, tethered in close proximity to one another via a biomolecule, that acts through dipole-dipole interactions and results in the light scattering to increase exponentially. In contrast, a sharp decrease in intensity is observed when the pair is confronted by a large interparticle distance. To align the mechanism of protease activity with building a sensor that can report a binary signal in the presence or absence of caspase-3, we present a caspase-3 selective plasmon ruler (C3SPR) composed of a pair of Zn0.4Fe2.6O4@SiO2@Au core-shell nanoparticles connected by a caspase-3 cleavage sequence. The dielectric core (Zn0.4Fe2.6O4@SiO2)-shell (Au) geometry provided a brighter scattering intensity versus solid Au nanoparticles, and the magnetic core additionally acted as a purification handle during the plasmon ruler assembly. By monitoring the decrease in light scattering intensity per plasmon ruler, we detected caspase-3 activity at single molecule resolution across a broad dynamic range. This was observed to be as low as 100 fM of recombinant material or 10 ng of total protein from cellular lysate. By thorough analyses of single molecule trajectories, we show caspase-3 activation in a drug-treated chronic myeloid leukemia (K562) cancer system as early as 4 and 8 h with greater sensitivity (2- and 4-fold, respectively) than conventional reagents. This study provides future implications for monitoring caspase-3 as a biomarker and efficacy of drugs. PMID:25166742

  6. Optical Near Field Studies of Plasmonic and Optical Antennas For Sensitive and Selective Biosensing Applications

    NASA Astrophysics Data System (ADS)

    Gelfand, Ryan M.

    For biosensing applications a useful device needs at least two properties: high sensitivity and high selectivity. Optical spectroscopy offers unique advantages over other sensing techniques however one big challenge to overcome is the mismatch between wavelength and the size of biologically relevant molecules. In order to have high enough sensitivity to approach the single-molecule limit, the interaction between the light and the molecule should be strong. However, the diffraction limit of light is approximately half the incidence wavelength, on the order of 100 nm for the smallest nondestructive wavelengths. This presents a significant mismatch between the size of the molecule and the smallest focus spot of the light. The photo-excitation should be compressed more than 100 fold to interact strongly. We must use metallic antennas that convert the incidence radiation into plasmonic modes which can then be compressed well below the wavelength diffraction limit. Studying the near field characteristics of these metallic nanostructures will help us gain insight into this emerging field and allow us to better use them in developing next generation devices. We have developed different geometries of these antennas and simulated their performance using Finite Difference Time Domain software. We have concentrated our efforts in the mid-infrared because that is the natural molecular vibration frequency region and also the near infrared because at these frequencies there exists a mature industry for compact sources, detectors, and fiber optic components. Our simulations show a 6,000 fold mode compression for a bowtie antenna and a million fold compression for a plasmonic photonic crystal (ppc) antenna. The bull's-eye antenna does not have as a high a mode compression but it has a natural geometry for molecular sensing due to the central metallic disc. Experimentally, we have measured the near field of these antennas with a custom back reflection apertureless NSOM setup in both

  7. 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography

    SciTech Connect

    Pomper, M.G.; Katzenellenbogen, J.A.; Welch, M.J.; Brodack, J.W.; Mathias, C.J.

    1988-07-01

    We have synthesized 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone (FENP), a high affinity ligand for the progesterone receptor, labeled with the positron-emitting radionuclide fluorine-18 (t1/2 = 110 min). The synthesis proceeds in two steps from 21-hydroxy-16 alpha-ethyl-19-norprogesterone and involves (/sup 18/F)fluoride ion displacement of the 21-trifluoromethanesulfonate (21-triflate). This material is purified by HPLC and is obtained in 4-30% overall yield (decay corrected) within 40 min after the end of bombardment to produce (/sup 18/F)fluoride ion. The effective specific activity, determined by competitive radioreceptor binding assays, is 700-1400 Ci/mmol. In vivo, (/sup 18/F)FENP demonstrates highly selective, receptor-mediated uptake by the uterus of estrogen-primed rats; the uterus to blood and uterus to muscle ratios were respectively 26 and 16 at 1 h and 71 and 41 at 3 h after injection. The high target tissue selectivity of this uptake suggests that this compound may be useful for the in vivo imaging of progestin target tissues and receptor-rich tumors (such as human breast tumors) by positron emission tomography.

  8. Di-tert-butylsilylene-directed alpha-selective synthesis of p-nitrophenyl T-antigen analogues.

    PubMed

    Sato, Tetsuro; Imamura, Akihiro; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto

    2009-01-01

    Seven analogues of p-nitrophenyl T-antigen [Galbeta(1-->3)GalNAcalpha(1-->O)PNP] have been synthesized as potential substrates for elucidation of the substrate specificity of endo-alpha-N-acetylgalactosaminidase. These compounds, which are commercially unavailable, include: GlcNAcbeta(1-->3){GlcNAcbeta(1-->6)}GalNAcalpha(1-->O)PNP [core 4 type], GalNAcalpha(1-->3)GalNAcalpha(1-->O)PNP [core 5 type], GlcNAcbeta(1-->6)GalNAcalpha(1-->O)PNP [core 6 type], GalNAcalpha(1-->6)GalNAcalpha(1-->O)PNP [core 7 type], Galalpha(1-->3)GalNAcalpha(1-->O)PNP [core 8 type], Glcbeta(1-->3)GalNAcalpha(1-->O)PNP and GalNAcbeta(1-->3)GalNAcalpha(1-->O)PNP. The assembly of these synthetic probes was accomplished efficiently, based on di-tert-butylsilylene(DTBS)-directed alpha-galactosylation as a key reaction. PMID:18709455

  9. Reusable light-emitting-diode induced chemiluminescence aptasensor for highly sensitive and selective detection of riboflavin.

    PubMed

    Xu, Shuxia; Zhang, Xinfeng; Liu, Weiwei; Sun, Yonghua; Zhang, Heliang

    2013-05-15

    A novel reusable chemiluminescence aptasensor was developed based on aptamer recognition coupled with light-emitting-diode induced chemiluminescence (LED-CL) detection. The sensing approach was based on the design that the model analyte riboflavin (Rf) in sample solutions was captured by the immobilized aptamers and then eluted simply with alkaline luminol solution to catalyze the CL reaction between luminol and dissolved oxygen under high power LED irradiation. This design allowed a very simple (branch-free) flow way for the CL sensing system. The CL intensity versus the Rf concentration was linear in the range from 0.03 to 5ngmL(-1) with a limit of detection (LOD) down low to 8pgmL(-1). Without renewing the aptamer, the relative standard deviation (RSD) for seven consecutive detections is 2.33%; the sensor also showed good stability without performance deterioration after >100 times use. Up to 10000-fold of K(+), Na(+), Ca(2+), Mg(2+), and Fe(3+), 5000-fold for glucose and bovine serum albumin, 1000-fold of uric acid, 1500-fold of ascorbic acid (added with Fe(3+)), 100-fold of flavin mononucleotide and 200-fold of flavin adenine dinucleotide caused no significant interference with the determination of 0.5ngmL(-1) Rf. The sensor was applied for analysis of Rf in urine and food samples with the recovery of 94-103%. The advantages of reusability, simplicity, high sensitivity and selectivity provided by the LED-CL aptasensor will make it a good alternative tool for biological and food analysis. PMID:23298628

  10. Fluorescent Chemosensors for Selective and Sensitive Detection of Phosmet/Chlorpyrifos with Octahedral Ni(2+) Complexes.

    PubMed

    Raj, Pushap; Singh, Amanpreet; Kaur, Kamalpreet; Aree, Thammarat; Singh, Ajnesh; Singh, Narinder

    2016-05-16

    The hexadentate ligands H2L1-L3 with mixed S, N, O donor sites and possessing substituents having either "no" or electron-releasing/withdrawing nature at terminal ends are synthesized. The ligands H2L1-L3 were tested for binding with library of metal ions, wherein maximum efficiency was observed with Ni(2+), and it motivated us to prepare the Ni(2+) complexes. The ligand H2L1 underwent deprotonation and formed binuclear complex when interacted with Ni(2+) as evident from its crystal structure. The H2L2 and H2L3 having electron-withdrawing/electron releasing groups, respectively, were also deprotonated; however, they afforded mononuclear complexes with Ni(2+) ion. This signifies the importance of steric parameters instead of electronic factors in these particular cases. Impressed by differential behavior of complexes of H2L1 and H2L2/H2L3 with Ni(2+) and their photophysical and electrochemical properties, all the metal complexes were studied for their chemosensing ability. Nowadays with increased use of organophosphate, there is alarming increase of these agents in the environment, and thus we require efficient technique to estimate the level of these agents with high sensitivity and selectivity in aqueous medium. The Ni(2+) complexes with hydrophobic nature were suspended into aqueous medium for testing them as sensor for organophosphate. The (L1)2.(Ni(2+))2 could sense phosmet with detection limit of 44 nM, whereas L2.Ni(2+) and L3.Ni(2+) exhibited the detection limits of 62 and 71 nM, respectively, for chlorpyrifos. PMID:27115348

  11. Using Impact-Relevant Sensitivities to Efficiently Evaluate and Select Climate Change Scenarios

    NASA Astrophysics Data System (ADS)

    Vano, J. A.; Kim, J. B.; Rupp, D. E.; Mote, P.

    2014-12-01

    We outline an efficient approach to help researchers and natural resource managers more effectively use global climate model information in their long-term planning. The approach provides an estimate of the magnitude of change of a particular impact (e.g., summertime streamflow) from a large ensemble of climate change projections prior to detailed analysis. These estimates provide both qualitative information as an end unto itself (e.g., the distribution of future changes between emissions scenarios for the specific impact) and a judicious, defensible evaluation structure that can be used to qualitatively select a sub-set of climate models for further analysis. More specifically, the evaluation identifies global climate model scenarios that both (1) span the range of possible futures for the variable/s most important to the impact under investigation, and (2) come from global climate models that adequately simulate historical climate, providing plausible results for the future climate in the region of interest. To identify how an ecosystem process responds to projected future changes, we methodically sample, using a simple sensitivity analysis, how an impact variable (e.g., streamflow magnitude, vegetation carbon) responds locally to projected regional temperature and precipitation changes. We demonstrate our technique over the Pacific Northwest, focusing on two types of impacts each in three distinct geographic settings: (a) changes in streamflow magnitudes in critical seasons for water management in the Willamette, Yakima, and Upper Columbia River basins; and (b) changes in annual vegetation carbon in the Oregon and Washington Coast Ranges, Western Cascades, and Columbia Basin ecoregions.

  12. Optimizing Sensitization Processes in Dinuclear Luminescent Lanthanide Oligomers. Selection of Rigid Aromatic Spacers

    PubMed Central

    Lemonnier, Jean-François; Guénée, Laure; Beuchat, César; Wesolowski, Tomasz A.; Mukherjee, Prasun; Waldeck, David H.; Gogick, Kristy A.; Petoud, Stéphane; Piguet, Claude

    2011-01-01

    This work illustrates a simple approach for optimizing the lanthanide luminescence in molecular dinuclear lanthanide complexes and identifies a particular multidentate europium complex as the best candidate for further incorporation into polymeric materials. The central phenyl ring in the bis-tridentate model ligands L3–L5, which are substituted with neutral (X = H, L3), electronwithdrawing (X = F, L4), or electron-donating (X = OCH3, L5) groups, separate the 2,6-bis(benzimidazol-2-yl)pyridine binding units of linear oligomeric multi-tridentate ligand strands that are designed for the complexation of luminescent trivalent lanthanides, Ln(III). Reactions of L3–L5 with [Ln(hfac)3(diglyme)] (hfac− is the hexafluoroacetylacetonate anion) produce saturated single-stranded dumbbell-shaped complexes [Ln2(Lk)(hfac)6] (k = 3–5), in which the lanthanide ions of the two nine-coordinate neutral [N3Ln(hfac)3] units are separated by 12–14 Å. The thermodynamic affinities of [Ln(hfac)3] for the tridentate binding sites in L3–L5 are average (6.6≤log(β2,1Y,Lk)≤8.4) , but still result in 15–30% dissociation at millimolar concentrations in acetonitrile. In addition to the empirical solubility trend found in organic solvents (L4 > L3 ≫ L5), which suggests that the 1,4-difluorophenyl spacer in L4 is preferable, we have developed a novel tool for deciphering the photophysical sensitization processes operating in [Eu2(Lk)(hfac)6]. A simple interpretation of the complete set of rate constants characterizing the energy migration mechanisms provides straightforward objective criteria for the selection of [Eu2(L4)(hfac)6] as the most promising building block. PMID:21882836

  13. A sensitive amperometric immunosensor for alpha-fetoprotein based on carbon nanotube/DNA/Thi/nano-Au modified glassy carbon electrode.

    PubMed

    Ran, Xiao-Qi; Yuan, Ruo; Chai, Ya-Qin; Hong, Cheng-Lin; Qian, Xiao-Qing

    2010-09-01

    A novel amperometric immunosensor for the determination of alpha-fetoprotein (AFP) was constructed using films of multi-wall carbon nanotubes/DNA/thionine/gold nanoparticles (nano-Au). Firstly, multiwall carbon nanotubes (MWCNT) dispersed in poly(diallydimethlammonium chloride) (PDDA) were immobilized on the nano-Au film which was electrochemically deposited on the surface of glassy carbon electrode. Then a negatively charged DNA film was absorbed on the positively charged PDDA. Subsequently, thionine was attached to the electrode via the electrostatic interaction between thionine and the DNA. Finally, the nano-Au was retained on the thionine film for immobilization of AFP antibody (anti-AFP). The modification process was characterized by cyclic voltammetry (CV) and scanning electron microscope (SEM). The factors possibly influenced the performance of the proposed immunosensors were studied in detail. Under optimal conditions, the proposed immunosensor exhibited good electrochemical behavior to AFP in a two concentration ranges: 0.01-10.0 and 10.0-200.0 ng/mL with a relatively low detection limit of 0.04 ng/mL at three times the background noise. Moreover, the selectivity, repeatability and stability of the proposed immunosensor were acceptable. PMID:20627666

  14. Smooth muscle-specific switching of alpha-tropomyosin mutually exclusive exon selection by specific inhibition of the strong default exon.

    PubMed

    Gooding, C; Roberts, G C; Moreau, G; Nadal-Ginard, B; Smith, C W

    1994-08-15

    Exons 2 and 3 of alpha-tropomyosin are spliced in a strict mutually exclusive manner. Exon 3 is a default choice, being selected in almost all cell types where the gene is expressed. The default selection arises from a competition between the two exons, in which the stronger branch point/pyrimidine tract elements of exon 3 win. Exon 2 is selected predominantly or exclusively only in smooth muscle cells. We show here that the basis for the smooth muscle-specific switching of exon selection is inhibition of exon 3. Exon 3 is still skipped with smooth muscle specificity, even in the absence of exon 2. We have defined two conserved sequence elements, one in each of the introns flanking exon 3, that are essential for this regulation. Mutation of either element severely impairs regulated suppression of exon 3. No other exon or intron sequences appear to be necessary for regulation. We have also demonstrated skipping of exon 3 that is dependent upon both regulatory elements in an in vitro splicing assay. We further show that both splice sites of exon 3 must be inhibited in a concerted fashion to switch to selection of exon 2. This may relate to the requirement for negative elements on both sides of the exon. PMID:8070413

  15. Two Homoeologous Wheat Genes Confer Sensitivity to a Single Host-Selective Toxin and Susceptibility to Stagonospora nodorum blotch (SNB)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogen Stagonospora nodorum produces multiple host-selective toxins that interact with corresponding wheat sensitivity genes in an inverse gene-for-gene manner to cause the disease Stagonospora nodorum blotch (SNB) in wheat. Here, we screened accessions of Aegilops tauschii, the D-genome donor...

  16. A microporous anionic metal-organic framework for a highly selective and sensitive electrochemical sensor of Cu(2+) ions.

    PubMed

    Jin, Jun-Cheng; Wu, Ju; Yang, Guo-Ping; Wu, Yun-Long; Wang, Yao-Yu

    2016-06-28

    We first reported an anionic metal-organic framework for electrode material for the electrochemical detection of Cu(2+). The modified electrode shows an excellent selectivity, high stability and sensitivity, wide linear range and lower detection limit. This strategy for generating new electrode materials will be useful for preparing new sensors and reporters for biological systems. PMID:27315447

  17. A ferrofluid-based homogeneous assay for highly sensitive and selective detection of single-nucleotide polymorphisms.

    PubMed

    Shen, Wei; Lim, Cai Le; Gao, Zhiqiang

    2013-09-21

    A simple and low-cost colorimetric assay utilizing ferrofluidic nanoparticulate probes (FNPs) and a ligase for single-nucleotide polymorphism genotyping is described. Excellent sensitivity and selectivity were accomplished through the engagement of the FNPs and a ligase chain reaction. PMID:23923128

  18. Boronic Acid: A Bio-Inspired Strategy To Increase the Sensitivity and Selectivity of Fluorescent NADH Probe.

    PubMed

    Wang, Lu; Zhang, Jingye; Kim, Beomsue; Peng, Juanjuan; Berry, Stuart N; Ni, Yong; Su, Dongdong; Lee, Jungyeol; Yuan, Lin; Chang, Young-Tae

    2016-08-24

    Fluorescent probes have emerged as an essential tool in the molecular recognition events in biological systems; however, due to the complex structures of certain biomolecules, it remains a challenge to design small-molecule fluorescent probes with high sensitivity and selectivity. Inspired by the enzyme-catalyzed reaction between biomolecule and probe, we present a novel combination-reaction two-step sensing strategy to improve sensitivity and selectivity. Based on this strategy, we successfully prepared a turn-on fluorescent reduced nicotinamide adenine dinucleotide (NADH) probe, in which boronic acid was introduced to bind with NADH and subsequently accelerate the sensing process. This probe shows remarkably improved sensitivity (detection limit: 0.084 μM) and selectivity to NADH in the absence of any enzymes. In order to improve the practicality, the boronic acid was further modified to change the measurement conditions from alkalescent (pH 9.5) to physiological environment (pH 7.4). Utilizing these probes, we not only accurately quantified the NADH weight in a health care product but also evaluated intracellular NADH levels in live cell imaging. Thus, these bio-inspired fluorescent probes offer excellent tools for elucidating the roles of NADH in biological systems as well as a practical strategy to develop future sensitive and selective probes for complicated biomolecules. PMID:27500425

  19. The sensitizing capacity of Alstroemeria cultivars in man and guinea pig. Remarks on the occurrence, quantity and irritant and sensitizing potency of their constituents tuliposide A and tulipalin A (alpha-methylene-gamma-butyrolactone).

    PubMed

    Hausen, B M; Prater, E; Schubert, H

    1983-01-01

    Dermatitis in 8 female nursery workers handling Alstroemeria ligtu cultivars has been proven/proved in 6 cases to be of allergic origin. Epicutaneous tests with cut flower extracts as well as with the isolated and purified sensitizer were positive. Successful animal experiments corroborated the sensitising capacity of Alstroemeria cultivars. The responsible but unstable contact allergen, alpha-methylene-gamma-butyrolactone (tulipalin A), was found in short ether extracts of flower petals in concentrations up to 18%. Due to its instability, subsequent extractions were performed with methanol, yielding the sensitising constituent after purification in the glucosidic form (tuliposide A). This could be stored at room temperature for longer periods without loss of activity. Tuliposide A was determined in specimens of Alstroemeria ligtu cultivars of 14 different origins of various colours; its content varied between 1 and 2%. Direct testing of the plant material in human patients carries the risk of false positive reactions and active sensitisation, as the threshold for both forms of the allergen is very high. Only a concentration of 0.01% can be considered safe. PMID:6839738

  20. Effect of Alpha-Hederin, the active constituent of Nigella sativa, on miRNA-126, IL-13 mRNA levels and inflammation of lungs in ovalbumin-sensitized male rats

    PubMed Central

    Fallahi, Maryam; Keyhanmanesh, Rana; Khamaneh, Amir Mahdi; Ebrahimi Saadatlou, Mohammad Ali; Saadat, Saeideh; Ebrahimi, Hadi

    2016-01-01

    Objective: In previous studies the therapeutic effects of Nigella sativa have been demonstrated on asthmatic animals. In the present study, the preventive effect of single dose of alpha-hederin, its active constituent, has been evaluated on lung inflammation and some inflammatory mediators in lungs of ovalbumin sensitized rat in order to elicit its mechanism. Materials and Methods: Forty rats were randomly grouped in 4 groups; control (C), sensitized (S), sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S+TQ) and alpha-hederin (0.02 mg/kg i.p., S+AH). Levels of IL-13 mRNA and miRNA-126 in lung tissue and its pathological changes in each group were assessed. Results: Elevated levels of miRNA-126, IL-13 mRNA and pathological changes were observed in the sensitized group compared to the control group (p<0.001 to p<0.05). All of these factors were significantly reduced in S+TQ and S+AH groups in comparison to S group (p<0.001 to p<0.05). Although alpha-hederin decreased the levels of miRNA-126, IL-13 mRNA and pathological changes in comparison with thymoquinone, the results were statistically not significant. Conclusion: The results suggested that alpha-hederin had preventive effect on sensitized rats like thymoquinone. It may intervene in miRNA-126 expression, which consequently could interfere with IL-13 secretion pathway leading to a reduction in inflammatory responses. PMID:27247924

  1. Coumarin-Spiropyran Dyad with a Hydrogenated Pyran Moiety for Rapid, Selective, and Sensitive Fluorometric Detection of Cyanide Anion.

    PubMed

    Shiraishi, Yasuhiro; Nakamura, Masaya; Hayashi, Naoto; Hirai, Takayuki

    2016-07-01

    We synthesized a coumarin-spiropyran dyad with a hydrogenated pyran moiety (2), behaving as an off-on type fluorescent receptor for rapid, selective, and sensitive detection of cyanide anion (CN(-)) in aqueous media. The receptor itself shows almost no fluorescence with a quantum yield < 0.01, due to the delocalization of π-electrons over the molecule. Selective nucleophilic addition of CN(-) to the spirocarbon of the molecule rapidly promotes spirocycle opening within only 3 min. This leads to localization of π-electrons on the coumarin moiety and exhibits strong light-blue fluorescence at 459 nm with very high quantum yield (0.52). As a result of this, the receptor facilitates rapid, selective, and sensitive fluorometric detection of CN(-) as low as 1.0 μM. PMID:27268123

  2. Highly selective and sensitive detection of neurotransmitters using receptor-modified single-walled carbon nanotube sensors

    NASA Astrophysics Data System (ADS)

    Kim, Byeongju; Song, Hyun Seok; Jin, Hye Jun; Park, Eun Jin; Lee, Sang Hun; Lee, Byung Yang; Park, Tai Hyun; Hong, Seunghun

    2013-07-01

    We present receptor-modified carbon nanotube sensors for the highly selective and sensitive detection of acetylcholine (ACh), one kind of neurotransmitter. Here, we successfully expressed the M1 muscarinic acetylcholine receptor (M1 mAChR), a family of G protein-coupled receptors (GPCRs), in E. coli and coated single-walled carbon nanotube (swCNT)-field effect transistors (FETs) with lipid membrane including the receptor, enabling highly selective and sensitive ACh detection. Using this sensor, we could detect ACh at 100 pM concentration. Moreover, we showed that this sensor could selectively detect ACh among other neurotransmitters. This is the first demonstration of the real-time detection of ACh using specific binding between ACh and M1 mAChR, and it may lead to breakthroughs for various applications such as disease diagnosis and drug screening.

  3. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to {alpha}-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

    SciTech Connect

    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen; Dong, Changsheng

    2010-06-11

    Nitric oxide (NO) and {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of {alpha}-MSH to stimulate {alpha}-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to {alpha}-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm{sup 2} of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 {mu}M L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of {alpha}-MSH pathway on melanogenesis, the key gene and protein of the {alpha}-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance {alpha}-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete {alpha}-MSH to enhance the {alpha}-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  4. A GPR-protein interaction surface of Gi(alpha): implications for the mechanism of GDP-release inhibition.

    PubMed

    Natochin, Michael; Gasimov, Karim G; Artemyev, Nikolai O

    2002-01-01

    Proteins containing G-protein regulatory (GPR) motifs represent a novel family of guanine nucleotide dissociation inhibitors (GDIs) for G(alpha) subunits from the Gi family. They selectively interact with the GDP-bound conformation of Gi(alpha) and transducin-alpha (Gt(alpha)), but not with Gs(alpha). A series of chimeric proteins between Gi(alpha)(1) and Gs(alpha) has been constructed to investigate GPR-contact sites on G(alpha) subunits and the mechanism of GPR-protein GDI activity. Analysis of the interaction of two GPR-proteins-AGS3GPR and Pcp2-with the chimeric G(alpha) subunits demonstrated that the GPR-Gi(alpha)(1) interface involves the Gi(alpha)(1) switch regions and Gi(alpha)(1)-144-151, a site within the helical domain. Residues within Gi(alpha)(1)-144-151 form conformation-sensitive contacts with switch III, and may directly interact with a GPR-protein or form a GPR-binding surface jointly with switch III. The helical domain site is critical to the ability of GPR-proteins to act as GDIs. Our data suggest that a mechanism of the GDI activity of GPR-proteins is different from that of GDIs for monomeric GTPases and from the GDI-like activity of G(betagamma) subunits. The GPR-proteins are likely to block a GDP-escape route on G(alpha) subunits. PMID:11772024

  5. FA-SIFT study of reactions of protonated water and ethanol clusters with [alpha]-pinene and linalool in view of their selective detection by CIMS

    NASA Astrophysics Data System (ADS)

    Dhooghe, F.; Amelynck, C.; Rimetz-Planchon, J.; Schoon, N.; Vanhaecke, F.

    2010-02-01

    The use of protonated water clusters and protonated ethanol clusters as reagent ions has been evaluated for the resolution of an interference encountered in CIMS when measuring monoterpenes (C10H16) and linalool (C10H18O) simultaneously. To this end, the reactions of H3O+.(H2O)n (n = 1-3), (C2H5OH)mH+ (m = 1-3) and (C2H5OH.H2O)H+ with [alpha]-pinene and linalool have been characterized in a flowing afterglow-selected ion flow tube (FA-SIFT) instrument at a SIFT He buffer gas pressure of 1.43 hPa and a temperature of 298 K. All reactions with linalool were found to occur at the collision limit. The reaction of (C2H5OH)2H+ with [alpha]-pinene proceeds at half the collision rate and both the reactions of (C2H5OH)3H+ and H3O+.(H2O)3 with [alpha]-pinene have a very low rate constant. All other reactions involving [alpha]-pinene proceed at the collision rate. The reactions of H3O+.H2O, H3O+.(H2O)2, C2H5OH2+, (C2H5OH.H2O)H+ and (C2H5OH)2H+ with [alpha]-pinene mainly proceed by proton transfer. Additionally, ligand switching channels have been observed for the reactions of (C2H5OH)2H+ and H3O+.(H2O)2 with [alpha]-pinene. Protonated linalool was observed as a minor product for the reactions of (C2H5OH.H2O)H+ and H3O+.(H2O)n (n = 1-3) with linalool. For all linalool reactions, a contribution of the dissociative proton transfer product at m/z 137 was found and this ion was the main product ion for the reactions with H3O+.H2O, C2H5OH2+ and (C2H5OH.H2O)H+. For the (C2H5OH.H2O)H+/linalool reaction, ligand switching with both water and ethanol has been observed. Major ligand switching channels were observed for the reactions of (C2H5OH)2H+, (C2H5OH)3H+ and H3O+.(H2O)2 with linalool. Also, for the H3O+.(H2O)3/linalool reaction, several ligand switching channels have been observed. These results are discussed in view of their applicability for the selective detection of monoterpenes and linalool with CIMS instrumentation such as SIFT-MS, PTR-MS and APCI-MS.

  6. Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNF{alpha} in human epidermal keratinocytes (HaCaT)

    SciTech Connect

    Onda, Kenji . E-mail: knjond@ps.toyaku.ac.jp; Nagashima, Masahiro; Kawakubo, Yo; Inoue, Shota; Hirano, Toshihiko; Oka, Kitaro

    2006-12-08

    Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) {alpha} reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNF{alpha} was not accompanied by changes in mRNA expressions of GR isoforms ({alpha} or {beta}). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNF{alpha}. Additionally, we observed that TNF{alpha} reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNF{alpha}-mediated GC insensitivity. Our data suggest that overexpression of TNF{alpha} leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.

  7. Effects of cross-modal selective attention on the sensory periphery: cochlear sensitivity is altered by selective attention.

    PubMed

    Srinivasan, S; Keil, A; Stratis, K; Woodruff Carr, K L; Smith, D W

    2012-10-25

    There is increasing evidence that alterations in the focus of attention result in changes in neural responding at the most peripheral levels of the auditory system. To date, however, those studies have not ruled out differences in task demands or overall arousal in explaining differences in responding across intermodal attentional conditions. The present study sought to compare changes in the response of cochlear outer hair cells, employing distortion product otoacoustic emissions (DPOAEs), under different, balanced conditions of intermodal attention. DPOAEs were measured while the participants counted infrequent, brief exemplars of the DPOAE primary tones (auditory attending), and while counting visual targets, which were instances of Gabor gradient phase shifts (visual attending). Corroborating an earlier study from our laboratory, the results show that DPOAEs recorded in the auditory-ignoring condition were significantly higher in overall amplitude, compared with DPOAEs recorded while participants attended to the eliciting primaries; a finding in apparent contradiction with more central measures of intermodal attention. Also consistent with our previous findings, DPOAE rapid adaptation, believed to be mediated by the medial olivocochlear efferents (MOC), was unaffected by changes in intermodal attention. The present findings indicate that manipulations in the conditions of attention, through the corticofugal pathway, and its last relay to cochlear outer hair cells (OHCs), the MOC, alter cochlear sensitivity to sound. These data also suggest that the MOC influence on OHC sensitivity is composed of two independent processes, one of which is under attentional control. PMID:22871520

  8. Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells.

    PubMed

    Conrad, P W; Rust, R T; Han, J; Millhorn, D E; Beitner-Johnson, D

    1999-08-13

    Hypoxic/ischemic trauma is a primary factor in the pathology of a multitude of disease states. The effects of hypoxia on the stress- and mitogen-activated protein kinase signaling pathways were studied in PC12 cells. Exposure to moderate hypoxia (5% O(2)) progressively stimulated phosphorylation and activation of p38gamma in particular, and also p38alpha, two stress-activated protein kinases. In contrast, hypoxia had no effect on enzyme activity of p38beta, p38beta(2), p38delta, or on c-Jun N-terminal kinase, another stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation and activation of p42/p44 mitogen-activated protein kinase, although this activation was modest compared with nerve growth factor- and ultraviolet light-induced activation. Hypoxia also dramatically down-regulated immunoreactivity of cyclin D1, a gene that is known to be regulated negatively by p38 at the level of gene expression (Lavoie, J. N., L'Allemain, G., Brunet, A., Muller, R., and Pouyssegur, J. (1996) J. Biol. Chem. 271, 20608-20616). This effect was partially blocked by SB203580, an inhibitor of p38alpha but not p38gamma. Overexpression of a kinase-inactive form of p38gamma was also able to reverse in part the effect of hypoxia on cyclin D1 levels, suggesting that p38alpha and p38gamma converge to regulate cyclin D1 during hypoxia. These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific p38 signaling elements; and they also identify a downstream target of these pathways. PMID:10438538

  9. A simple highly sensitive and selective aptamer-based colorimetric sensor for environmental toxins microcystin-LR in water samples.

    PubMed

    Li, Xiuyan; Cheng, Ruojie; Shi, Huijie; Tang, Bo; Xiao, Hanshuang; Zhao, Guohua

    2016-03-01

    A simple and highly sensitive aptamer-based colorimetric sensor was developed for selective detection of Microcystin-LR (MC-LR). The aptamer (ABA) was employed as recognition element which could bind MC-LR with high-affinity, while gold nanoparticles (AuNPs) worked as sensing materials whose plasma resonance absorption peaks red shifted upon binding of the targets at a high concentration of sodium chloride. With the addition of MC-LR, the random coil aptamer adsorbed on Au NPs altered into regulated structure to form MC-LR-aptamer complexes and broke away from the surface of Au NPs, leading to the aggregation of AuNPs, and the color converted from red to blue due to the interparticle plasmon coupling. Results showed that our aptamer-based colorimetric sensor exhibited rapid and sensitive detection performance for MC-LR with linear range from 0.5 nM to 7.5 μM and the detection limit reached 0.37 nM. Meanwhile, the pollutants usually coexisting with MC-LR in pollutant water samples had not demonstrated disturbance for detecting of MC-LR. The mechanism was also proposed suggesting that high affinity interaction between aptamer and MC-LR significantly enhanced the sensitivity and selectivity for MC-LR detection. Besides, the established method was utilized in analyzing real water samples and splendid sensitivity and selectivity were obtained as well. PMID:26619046

  10. Vibration isolation technology: Sensitivity of selected classes of experiments to residual accelerations

    NASA Technical Reports Server (NTRS)

    Alexander, J. Iwan D.

    1990-01-01

    The solution was sought of a 2-D axisymmetric moving boundary problem for the sensitivity of isothermal and nonisothermal liquid columns and the sensitivity of thermo-capillary flows to buoyancy driven convection caused by residual accelerations. The sensitivity of a variety of space experiments to residual accelerations are examined. In all the cases discussed, the sensitivity is related to the dynamic response of a fluid. In some cases the sensitivity can be defined by the magnitude of the response of the velocity field. This response may involve motion of the fluid associated with internal density gradients, or the motion of a free liquid surface. For fluids with internal density gradients, the type of acceleration to which the experiment is sensitive will depend on whether buoyancy driven convection must be small in comparison to other types of fluid motion (such as thermocapillary flow), or fluid motion must be suppressed or eliminated (such as in diffusion studies, or directional solidification experiments). The effect of the velocity on the composition and temperature field must be considered, particularly in the vicinity of the melt crystal interface. As far as the response to transient disturbances is concerned the sensitivity is determined by both the magnitude and frequency the acceleration and the characteristic momentum and solute diffusion times.

  11. Highly Sensitive and Selective Photoelectrochemical Biosensor for Hg(2+) Detection Based on Dual Signal Amplification by Exciton Energy Transfer Coupled with Sensitization Effect.

    PubMed

    Zhao, Ming; Fan, Gao-Chao; Chen, Jing-Jia; Shi, Jian-Jun; Zhu, Jun-Jie

    2015-12-15

    A highly sensitive and selective photoelectrochemical (PEC) biosensor for Hg(2+) detection was developed on the basis of the synergistic effect of exciton energy transfer (EET) between CdS quantum dots (QDs) and Au nanoparticles (NPs) coupled with sensitization of rhodamine 123 (Rh123) for signal amplification. First, the TiO2/CdS hybrid structure obtained by depositing CdS QDs on TiO2 film was employed as a matrix for immobilizing probe DNA (pDNA). Next, Rh123 was introduced into the pDNA terminal, and then Au NP labeled target DNA (Au-tDNA) was hybridized with pDNA to form a rod-like double helix structure. The detection of Hg(2+) was based on a conformational change of the pDNA after incubating with Hg(2+). In the absence of Hg(2+), Rh123 was located away from the electrode surface due to the DNA hybridization, leading to inhibition of the sensitization effect, and meanwhile, the occurrence of EET between CdS QDs and Au NPs resulted in a photocurrent decrease. However, after incubating with Hg(2+), the rod-like double helix was disrupted, and the energy transfer was broken. In this case, the photocurrent recovered, and meanwhile, the folded pDNA made the labeled Rh123 move closer to the electrode surface, leading to the formation of the sensitization structure, which evidently increased the photocurrent intensity. The sensitivity of the biosensor for Hg(2+) detection was greatly enhanced for the dual signal amplification strategy. The linear range was 10 fM to 200 nM, with a detection limit of 3.3 fM. This biosensor provides a promising new platform for detecting various heavy metal ions at ultralow levels. PMID:26599580

  12. Vibration isolation technology: Sensitivity of selected classes of space experiments to residual accelerations

    NASA Technical Reports Server (NTRS)

    Alexander, J. Iwan D.; Zhang, Y. Q.; Adebiyi, Adebimpe

    1989-01-01

    Progress performed on each task is described. Order of magnitude analyses related to liquid zone sensitivity and thermo-capillary flow sensitivity are covered. Progress with numerical models of the sensitivity of isothermal liquid zones is described. Progress towards a numerical model of coupled buoyancy-driven and thermo-capillary convection experiments is also described. Interaction with NASA personnel is covered. Results to date are summarized and they are discussed in terms of the predicted space station acceleration environment. Work planned for the second year is also discussed.

  13. Calibration issues in delta alpha /alpha .

    NASA Astrophysics Data System (ADS)

    Molaro, Paolo; Centurión, Miriam; Levshakov, Sergei

    Laser Comb Wavelength calibration shows that the ThAr one is locally unreliable with possible deviations of up to 100 {m s}-1 within one order range, while delivering an overall 1 {m s}-1 accuracy (Wilken et al 2009). Such deviation corresponds to delta alpha /alpha ≈ 7* 10-6 for a Fe II-Mg II pair. Comparison of line shifts among the 5 Fe II lines, with almost identical sensitivity to fine structure constant changes, offers a clean way to directly test the presence of possible local wavelength calibration errors of whatever origin. We analyzed 5 absorption systems, with zabs ranging from 1.15 to 2.19 towards 3 bright QSOs. The results show that while some lines are aligned within 20 {m s}-1, others reveal large deviations reaching 200 {m s}-1 or higher and corresponding to a delta alpha /alpha > 10-5 level. The origin of these deviations is not clearly identified but could be related to the adaptation of wavelength calibration to CCD manufacturing irregularities. These results suggest that to draw conclusions from delta alpha /alpha analysis based on one or only few lines must be done with extreme care.

  14. Relative sensitivity of three endangered fishes, Colorado squawfish, bonytail, and razorback sucker, to selected metal pollutants

    USGS Publications Warehouse

    Buhl, K.J.

    1997-01-01

    The acute toxicity of four metal pollutants to larval and juvenile stages of endangered Colorado squawfish (Ptychocheilus lucius), bonytail (Gila elegans), and razorback sucker (Xyrauchen texanus) were determined in a water quality representative of that in the Green River, Utah. The rank order of toxicity (96-hr LC50) of the metals to all species and life stages from most toxic to least toxic was mercury (57-168 ??G/liter) > cadmium (78-168 pg/liter) > hexavalent chromium (32,000-123,000 ??g/liter) > lead (>170,000 ??G/liter). In tests with lead, a precipitate formed in all test solutions and no mortalities occurred in these treatments. The larvae of each species were as sensitive or more sensitive than the juveniles to cadmium, hexavalent chromium, and mercury. Overall, the three species exhibited similar sensitivities to cadmium, hexavalent chromium, and mercury. Comparison of test results for the juveniles with toxicity values reported for other freshwater fishes tested in different water qualities indicates that the endangered fishes are more sensitive to cadmium than other cyprinids and centrarchids and less sensitive than salmonids, whereas their sensitivity to hexavalent chromium and mercury is similar to that of other cyprinids, centrarchids, and salmonids.

  15. Genomic organization and differential signature of positive selection in the alpha and beta globin gene clusters in two cetacean species.

    PubMed

    Nery, Mariana F; Arroyo, José Ignacio; Opazo, Juan C

    2013-01-01

    The hemoglobin of jawed vertebrates is a heterotetramer protein that contains two α- and two β-chains, which are encoded by members of α- and β-globin gene families. Given the hemoglobin role in mediating an adaptive response to chronic hypoxia, it is likely that this molecule may have experienced a selective pressure during the evolution of cetaceans, which have to deal with hypoxia tolerance during prolonged diving. This selective pressure could have generated a complex history of gene turnover in these clusters and/or changes in protein structure themselves. Accordingly, we aimed to characterize the genomic organization of α- and β-globin gene clusters in two cetacean species and to detect a possible role of positive selection on them using a phylogenetic framework. Maximum likelihood and Bayesian phylogeny reconstructions revealed that both cetacean species had retained a similar complement of putatively functional genes. For the α-globin gene cluster, the killer whale presents a complement of genes composed of HBZ, HBK, and two functional copies of HBA and HBQ genes, whereas the dolphin possesses HBZ, HBK, HBA and HBQ genes, and one HBA pseudogene. For the β-globin gene cluster, both species retained a complement of four genes, two early expressed genes-HBE and HBH-and two adult expressed genes-HBD and HBB. Our natural selection analysis detected two positively selected sites in the HBB gene (56 and 62) and four in HBA (15, 21, 49, 120). Interestingly, only the genes that are expressed during the adulthood showed the signature of positive selection. PMID:24259315

  16. Genomic Organization and Differential Signature of Positive Selection in the Alpha and Beta Globin Gene Clusters in Two Cetacean Species

    PubMed Central

    Nery, Mariana F.; Arroyo, José Ignacio; Opazo, Juan C.

    2013-01-01

    The hemoglobin of jawed vertebrates is a heterotetramer protein that contains two α- and two β-chains, which are encoded by members of α- and β-globin gene families. Given the hemoglobin role in mediating an adaptive response to chronic hypoxia, it is likely that this molecule may have experienced a selective pressure during the evolution of cetaceans, which have to deal with hypoxia tolerance during prolonged diving. This selective pressure could have generated a complex history of gene turnover in these clusters and/or changes in protein structure themselves. Accordingly, we aimed to characterize the genomic organization of α- and β-globin gene clusters in two cetacean species and to detect a possible role of positive selection on them using a phylogenetic framework. Maximum likelihood and Bayesian phylogeny reconstructions revealed that both cetacean species had retained a similar complement of putatively functional genes. For the α-globin gene cluster, the killer whale presents a complement of genes composed of HBZ, HBK, and two functional copies of HBA and HBQ genes, whereas the dolphin possesses HBZ, HBK, HBA and HBQ genes, and one HBA pseudogene. For the β-globin gene cluster, both species retained a complement of four genes, two early expressed genes—HBE and HBH—and two adult expressed genes—HBD and HBB. Our natural selection analysis detected two positively selected sites in the HBB gene (56 and 62) and four in HBA (15, 21, 49, 120). Interestingly, only the genes that are expressed during the adulthood showed the signature of positive selection. PMID:24259315

  17. Alpha Particle

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Term that is sometimes used to describe a helium nucleus, a positively charged particle that consists of two protons and two neutrons, bound together. Alpha particles, which were discovered by Ernest Rutherford (1871-1937) in 1898, are emitted by atomic nuclei that are undergoing alpha radioactivity. During this process, an unstable heavy nucleus spontaneously emits an alpha particle and transmut...

  18. Selective alpha particle decay of 12C+12C resonances to excited 20Ne rotational bands observed in the 12C(12C,α)20Ne reaction

    NASA Astrophysics Data System (ADS)

    Ledoux, R. J.; Ordon¯Ez, C. E.; Bechara, M. J.; Al-Juwair, H. A.; Lavelle, G.; Cosman, E. R.

    1984-09-01

    Excitation functions of the 12C(12C,α)20Ne reaction were measured at θlab=7.5° between Ec.m.=14-40 MeV and angular distributions were measured from Ec.m.=17.8 to 20.6 MeV. Summed yields reveal prominent intermediate structure resonances over the entire range which correlate well to resonances previously observed in elastic data. The resonances show enhanced decays to excited rotational bands in 20Ne with reduced widths comparable to those for the elastic channel and an order of magnitude greater than those for the 20Ne ground state band. A discussion is given of the resonances as shape-isomeric states in a shell model secondary minimum in 24Mg, and of the selective alpha decay as being transitions to states of related configuration in 20Ne.

  19. Sensitivity and Specificity Improvement in Abdominal Obesity Diagnosis Using Cluster Analysis during Waist Circumference Cut-Off Point Selection

    PubMed Central

    Bermúdez, Valmore; Añez, Roberto; Toledo, Alexandra; Bello, Luis; Apruzzese, Vanessa; González, Robys; Chacín, Maricarmen; Cabrera, Mayela; Cano, Clímaco; Velasco, Manuel; López-Miranda, José

    2015-01-01

    Introduction. The purpose of this study was to analyze the influence of metabolic phenotypes during the construction of ROC curves for waist circumference (WC) cutpoint selection. Materials and Methods. A total of 1,902 subjects of both genders were selected from the Maracaibo City Metabolic Syndrome Prevalence Study database. Two-Step Cluster Analysis (TSCA) was applied to select metabolically healthy and sick men and women. ROC curves were constructed to determine WC cutoff points by gender. Results. Through TSCA, metabolic phenotype predictive variables were selected: HOMA2-IR and HOMA2-βcell for women and HOMA2-IR, HOMA2-βcell, and TAG for men. Subjects were classified as healthy normal weight, metabolically obese normal weight, healthy and metabolically disturbed overweight, and healthy and metabolically disturbed obese. Final WC cutpoints were 91.50 cm for women (93.4% sensitivity, 93.7% specificity) and 98.15 cm for men (96% sensitivity, 99.5% specificity). Conclusions. TSCA in the selection of the groups used in ROC curves construction proved to be an important tool, aiding in the detection of MOWN and MHO which cannot be identified with WC alone. The resulting WC cutpoints were <91.00 cm for women and <98.00 cm for men. Furthermore, anthropometry is insufficient to determine healthiness, and, biochemical analysis is needed to properly filter subjects during classification. PMID:25945356

  20. Effects of preparation variables of supported-cobalt catalysts on the selective hydrogenation of. alpha. ,. beta. -unsaturated aldehydes

    SciTech Connect

    Nitta, Yuriko; Hiramatsu, Yoshifumi; Imanaka, Toshinobu )

    1990-11-01

    The effects of starting salts, supports, added amount of Na{sub 2}CO{sub 3}, and other precipitation variables on catalytic properties of supported cobalt catalysts were studied for the hydrogenation of cinnamaldehyde and crotonaldehyde by using TGA, XRD, and XPS. The catalysts prepared from cobalt chloride always exhibited high selectivities to unsaturated alcohols irrespective of the support employed. The amount of surface chlorine remaining after H{sub 2}-reduction of the Co/SiO{sub 2} precursors prepared from cobalt chloride decreased with increasing amount of Na{sub 2}CO{sub 3} added as the precipitant, and both activity and selectivity reached maxima at around Cl/Co = 0.2 in the catalyst surface. The enhanced selectivity of the catalyst prepared from cobalt chloride was explained by the effects of residual chlorine both in the H{sub 2}-reduction stage and in the reaction stage; the former leads to a favorable crystallite size distribution (CDS) of cobalt and the latter depresses the hydrogenation of C{double bond}C double bond. The difference in activities and selectivities of various supported catalysts prepared from cobalt nitrate was discussed based on the difference in the strength of metal-support interaction which leads to different CDSs of cobalt in theses catalysts.

  1. Sensitivity and selectivity of cultivation methods to recovery a specific Salmonella serogroup from hatchery plenum samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have shown that Salmonella serotypes exhibit different growth characteristics in the same enrichment (selective or non-selective) and this can cause certain serotypes like S. Enteritidis to go undetected in a sample. The objectives of this study were to evaluate the serogroup diversity reco...

  2. Highly selective water and fat imaging applying multislice sequences without sensitivity to B1 field inhomogeneities.

    PubMed

    Schick, F; Forster, J; Machann, J; Huppert, P; Claussen, C D

    1997-08-01

    Improved selectivity to one chemical shift component was obtained using simultaneous slice-selective and chemical shift-selective excitation in sequences with usual spin-echo refocusing. The new type of sequences can be applied on modern whole-body units and permits multislice operation. Spatial-spectral excitation is based on prior research in this field, but the proposed improved version provides off-center slice excitation by the usual processing of the RF pulse envelopes. In addition, no irregular gradient shapes are necessary. The required B0 homogeneity of the new method is similar to conventional "fat-sat" techniques. In contrast to fat-sat methods, selectivity to water is not reduced by unavoidable misadjustments of the transmitter or B1 field inhomogeneities in the newly developed approach. Thus, the reported method has the potential to replace standard frequency selective fat-sat sequences for most applications. PMID:9256107

  3. Two Dimensional Host-Guest Metal-Organic Framework Sensor with High Selectivity and Sensitivity to Picric Acid.

    PubMed

    Bagheri, Minoo; Masoomi, Mohammad Yaser; Morsali, Ali; Schoedel, Alexander

    2016-08-24

    A dye-sensitized metal-organic framework, TMU-5S, was synthesized based on introducing the laser dye Rhodamine B into the porous framework TMU-5. TMU-5S was investigated as a ratiometric fluorescent sensor for the detection of explosive nitro aromatic compounds and showed four times greater selectivity to picric acid than any state-of-the-art luminescent-based sensor. Moreover, it can selectively discriminate picric acid concentrations in the presence of other nitro aromatics and volatile organic compounds. Our findings indicate that using this sensor in two dimensions leads to a greatly reduced environmental interference response and thus creates exceptional sensitivity toward explosive molecules with a fast response. PMID:27479837

  4. A label-free fluorescent aptasensor for selective and sensitive detection of streptomycin in milk and blood serum.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Nameghi, Morteza Alinezhad; Ramezani, Mohammad; Abnous, Khalil

    2016-07-15

    Sensitive and fast detection of antibiotic residues in animal derived foods and blood serum is of great interest. In this study a fluorescent aptasensor was designed for selective and sensitive detection of streptomycin (STR) based on Exonuclease III (Exo III), SYBR Gold and aptamer complimentary strand. In the absence of STR, the fluorescence intensity is weak. Upon addition of STR, the aptamer binds to its target, leading to release of complementary strand from aptamer and more protection against Exo III function. Following addition of SYBR Gold, a strong fluorescence intensity is obtained. This aptasensor showed a high selectivity toward STR with a limit of detection (LOD) as low as 54.5 nM. The validity of the procedure and applicability of the aptasensor were successfully assessed by detection of STR in a spiked milk and blood serum without interference from the sample matrix. PMID:26948599

  5. Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the "nanoquencher".

    PubMed

    Lu, Chun-Hua; Li, Juan; Liu, Jing-Jing; Yang, Huang-Hao; Chen, Xi; Chen, Guo-Nan

    2010-04-26

    Here, we report a novel, highly sensitive, selective and economical molecular beacon using graphene oxide as the "nanoquencher". This novel molecular beacon system contains a hairpin-structured fluorophore-labeled oligonucleotide and a graphene oxide sheet. The strong interaction between hairpin-structured oligonucleotide and graphene oxide keep them in close proximity, facilitating the fluorescence quenching of the fluorophore by graphene oxide. In the presence of a complementary target DNA, the binding between hairpin-structured oligonucleotide and target DNA will disturb the interaction between hairpin-structured oligonucleotide and graphene oxide, and release the oligonucleotide from graphene oxide, resulting in restoration of fluorophore fluorescence. In the present study, we show that this novel graphene oxide quenched molecular beacon can be used to detect target DNA with higher sensitivity and single-base mismatch selectivity compared to the conventional molecular beacon. PMID:20301144

  6. Redox-sensitivity and mobility of selected pharmaceutical compounds in a laboratory column experiment

    NASA Astrophysics Data System (ADS)

    Banzhaf, S.; Nödler, K.; Licha, T.; Krein, A.; Scheytt, T.

    2012-04-01

    Laboratory column experiments are suitable to investigate the sediment water interaction and to study the transport behaviour of solutes. Processes like retardation and degradation can be identified and quantified. The conducted experiment, which is closely connected to a field study in Luxembourg, investigated the transport behaviour of selected pharmaceutical compounds and their redox-dependent metabolism under water saturated conditions. Fine-grained natural sediment with a low hydraulic conductivity from a study site in Luxembourg was filled into the column. The water for the experiment was taken from a small stream at the same fieldsite. It was spiked with four pharmaceutical compounds (carbamazepine, diclofenac, ibuprofen, sulfamethoxazole) with concentrations between 170 and 300 ng/L for the different substances. The chosen pharmaceuticals were also detected in groundwater and surface water samples at the study site and used to qualify exchange/mixing of surface water and groundwater (BANZHAF et al., 2011). As some of the substances are known to exhibit redox-sensitive degradation, the redox-conditions were systematically varied throughout the experiment. This was realised by adding nitrate at the inflow of the column. During the experiment, which lasted for 2.5 months, four different nitrate concentrations (20-130 mg/L) were applied, beginning with the highest concentration. During the experiment water from the reservoir tank was sampled daily in order to detect a potential degradation of the pharmaceutical compounds before they enter the column. The effluent water was sampled every three hours to guarantee a maximum resolution for the analysis of the pharmaceuticals where necessary. In addition, major ions were analysed in the influent and effluent samples. Throughout the experiment physicochemical parameters (oxidation reduction potential (ORP), dissolved oxygen, electrical conductivity, and pH-value) were measured and logged at the outflow of the column

  7. Temperature sensitivity of the inline interferometer based on a two-core photonic crystal fiber selectively filled with polymer

    NASA Astrophysics Data System (ADS)

    Naeem, Khurram; Kim, Bok Hyeon; Kim, Bongkyun; Chung, Youngjoo

    2015-07-01

    We propose and demonstrate a highly sensitive micro-fluidic temperature sensor based on a two-core photonic crystal fiber (TCPCF). TCPCF has two cores of small asymmetry in sizes that serves as two arms in the inline Mach-Zehnder interferometer (MZI). Using manual gluing and subsequent infiltration technique, the cladding air holes near one core are selectively filled with polymer of high thermo-optic coefficient, which makes its core-mode effective index sensitive to temperature variation and induces large thermo-optic mismatch between the two cores. A high sensitivity of 1.595 nm/ oC is achieved in our experiment, which is almost 200 times improved from that of the sensor device before polymer infiltration process.

  8. Synaptic membrane responses to acute and chronic alcohol intoxication in high alcohol sensitive (HAS) and low alcohol sensitive (LAS) selectively bred rats.

    PubMed

    Beaugé, F; Kerfriden, G; Ménez, J F; Aufrère, G; Le Bourhis, B

    1994-11-01

    HAS (high alcohol sensitive) and LAS (low alcohol sensitive) lines of rats have been selectively bred based on their differences in ethanol-induced sleep time. In the present study, the two lines were compared to examine another central effect of acute alcohol intoxication: namely, hypothermia. As the disturbances in membrane microorganization have been associated with the nervous system's sensitivity and tolerance to ethanol, the synaptic plasma membrane fluidity and acute sensitivity to ethanol were also evaluated by fluorescence polarization of DPH probes in the HAS and LAS rats. The two lines did not differ in the magnitude of their hypothermic response after acute injection of ethanol (3 g/kg body wt, i.p.). Although membranes in the HAS line were slightly more rigid than in the LAS line, the level of membrane disordering after acute ethanol addition was identical for the two lines in the region examined with the DPH probe. Following the chronic intoxication of the rats, the two lines developed tolerance to the hypnotic and hypothermic effects of ethanol. In the same way, a membrane resistance (i.e. tolerance) to the disordering effect of acute ethanol addition developed in the region probed with DPH. In general, the LAS line showed a more pronounced level of tolerance than the HAS line at both the functional and membrane level. These results suggest that different measures used to assess the depressant action of ethanol, such as sleep time, hypothermia or membrane disordering, may not be related and could indicate different genetic origins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7695793

  9. Sensitivity analysis of add-on price estimate for select silicon wafering technologies

    NASA Technical Reports Server (NTRS)

    Mokashi, A. R.

    1982-01-01

    The cost of producing wafers from silicon ingots is a major component of the add-on price of silicon sheet. Economic analyses of the add-on price estimates and their sensitivity internal-diameter (ID) sawing, multiblade slurry (MBS) sawing and fixed-abrasive slicing technique (FAST) are presented. Interim price estimation guidelines (IPEG) are used for estimating a process add-on price. Sensitivity analysis of price is performed with respect to cost parameters such as equipment, space, direct labor, materials (blade life) and utilities, and the production parameters such as slicing rate, slices per centimeter and process yield, using a computer program specifically developed to do sensitivity analysis with IPEG. The results aid in identifying the important cost parameters and assist in deciding the direction of technology development efforts.

  10. FRET-based dimeric aptamer probe for selective and sensitive Lup an 1 allergen detection.

    PubMed

    Mairal, T; Nadal, P; Svobodova, M; O'Sullivan, C K

    2014-04-15

    A sensitive method for the rapid and sensitive detection of the anaphylactic food allergen Lup an 1 (β-conglutin) exploiting fluorescence resonance energy transfer (FRET) has been developed. A high affinity dimeric form of a truncated 11-mer aptamer against β-conglutin was used, with each monomeric aptamer being flanked by donor/acceptor moieties. The dimeric form in the absence of target yields fluorescence emission due to the FRET from the excited fluorophore to the proximal second fluorophore. However, upon addition of β-conglutin, the specific interaction induces a change in the bi-aptameric structure resulting in an increase in fluorescence emission. The method is highly specific and sensitive, with a detection limit of 150 pM, providing an effective tool for the direct detection of the toxic β-conglutin subunit in foodstuffs in just 1 min at room temperature. PMID:24280051

  11. Cell-Line Selectivity Improves the Predictive Power of Pharmacogenomic Analyses and Helps Identify NADPH as Biomarker for Ferroptosis Sensitivity.

    PubMed

    Shimada, Kenichi; Hayano, Miki; Pagano, Nen C; Stockwell, Brent R

    2016-02-18

    Precision medicine in oncology requires not only identification of cancer-associated mutations but also effective drugs for each cancer genotype, which is still a largely unsolved problem. One approach for the latter challenge has been large-scale testing of small molecules in genetically characterized cell lines. We hypothesized that compounds with high cell-line-selective lethality exhibited consistent results across such pharmacogenomic studies. We analyzed the compound sensitivity data of 6,259 lethal compounds from the NCI-60 project. A total of 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their median growth inhibitory GI50 profiles across the 60 cell lines, which were shown to represent distinct mechanisms of action. Further transcriptome analysis revealed a biomarker, NADPH abundance, for predicting sensitivity to ferroptosis-inducing compounds, which we experimentally validated. In summary, incorporating cell-line-selectivity filters improves the predictive power of pharmacogenomic analyses and enables discovery of biomarkers that predict the sensitivity of cells to specific cell death inducers. PMID:26853626

  12. Selective skin sensitivity changes and sensory reweighting following short-duration space flight.

    PubMed

    Lowrey, Catherine R; Perry, Stephen D; Strzalkowski, Nicholas D J; Williams, David R; Wood, Scott J; Bent, Leah R

    2014-03-15

    Skin sensory input from the foot soles is coupled with vestibular input to facilitate body orientation in a gravitational environment. Anecdotal observations suggest that foot sole skin becomes hypersensitive following space flight. The veritable level of skin sensitivity and its impact on postural disequilibrium observed post space flight have not been documented. Skin sensitivity of astronauts (n = 11) was measured as vibration perception at the great toe, fifth metatarsal and heel. Frequencies targeted four classes of receptors: 3 and 25 Hz for slow-adapting (SA) receptors and 60 and 250 Hz for fast-adapting (FA) receptors. Data were collected pre- and post-space flight. We hypothesized that skin sensitivity would increase post-space flight and correlate to balance measures. Decreased skin sensitivity was found on landing day at 3 and 25 Hz on the great toe. Hypersensitivity was found for a subset of astronauts (n = 6) with significantly increased sensitivity to 250 Hz at the heel. This subset displayed a greater reduction in computerized dynamic posturography (CDP) equilibrium (EQ) scores (-54%) on landing vs. non-hypersensitive participants (-11%). Observed hyposensitivity of SA (pressure) receptors may indicate a strategy to reduce pressure input during periods of unloading. Hypersensitivity of FAs coupled with reduced EQ scores may reflect targeted sensory reweighting. Altered gravito-inertial environments reduce vestibular function in balance control which may trigger increased weighting of FAs (that signal foot contact, slips). Understanding modulations to skin sensitivity has translational implications for mitigating postural disequilibrium following space flight and for on-Earth preventative strategies for imbalance in older adults. PMID:24458748

  13. Estimates of live-tree carbon stores in the Pacific Northwest are sensitive to model selection

    PubMed Central

    2011-01-01

    Background Estimates of live-tree carbon stores are influenced by numerous uncertainties. One of them is model-selection uncertainty: one has to choose among multiple empirical equations and conversion factors that can be plausibly justified as locally applicable to calculate the carbon store from inventory measurements such as tree height and diameter at breast height (DBH). Here we quantify the model-selection uncertainty for the five most numerous tree species in six counties of northwest Oregon, USA. Results The results of our study demonstrate that model-selection error may introduce 20 to 40% uncertainty into a live-tree carbon estimate, possibly making this form of error the largest source of uncertainty in estimation of live-tree carbon stores. The effect of model selection could be even greater if models are applied beyond the height and DBH ranges for which they were developed. Conclusions Model-selection uncertainty is potentially large enough that it could limit the ability to track forest carbon with the precision and accuracy required by carbon accounting protocols. Without local validation based on detailed measurements of usually destructively sampled trees, it is very difficult to choose the best model when there are several available. Our analysis suggests that considering tree form in equation selection may better match trees to existing equations and that substantial gaps exist, in terms of both species and diameter ranges, that are ripe for new model-building effort. PMID:21477353

  14. A Highly Sensitive Diketopyrrolopyrrole-Based Ambipolar Transistor for Selective Detection and Discrimination of Xylene Isomers.

    PubMed

    Wang, Bin; Huynh, Tan-Phat; Wu, Weiwei; Hayek, Naseem; Do, Thu Trang; Cancilla, John C; Torrecilla, Jose S; Nahid, Masrur Morshed; Colwell, John M; Gazit, Oz M; Puniredd, Sreenivasa Reddy; McNeill, Christopher R; Sonar, Prashant; Haick, Hossam

    2016-06-01

    An ambipolar poly(diketopyrrolopyrrole-terthiophene)-based field-effect transistor (FET) sensitively detects xylene isomers at low ppm levels with multiple sensing features. Combined with pattern-recognition algorithms, a sole ambipolar FET sensor, rather than arrays of sensors, can discriminate highly similar xylene structural isomers from one another. PMID:26996398

  15. Vibration isolation technology: Sensitivity of selected classes of experiments to residual accelerations

    NASA Technical Reports Server (NTRS)

    Alexander, J. Iwan D.

    1991-01-01

    Work was completed on all aspects of the following tasks: order of magnitude estimates; thermo-capillary convection - two-dimensional (fixed planar surface); thermo-capillary convection - three-dimensional and axisymmetric; liquid bridge/floating zone sensitivity; transport in closed containers; interaction: design and development stages; interaction: testing flight hardware; and reporting. Results are included in the Appendices.

  16. In vitro sensitivity of Hungarian Actinobaculum suis strains to selected antimicrobials.

    PubMed

    Biksi, I; Major, Andrea; Fodor, L; Szenci, O; Vetési, F

    2003-01-01

    In vitro antimicrobial sensitivity of 12 Hungarian isolates and the type strain ATCC 33144 of Actinobaculum suis to different antimicrobial compounds was determined both by the agar dilution and by the disc diffusion method. By agar dilution, MIC50 values in the range of 0.05-3.125 micrograms/ml were determined for penicillin, ampicillin, ceftiofur, doxycycline, tylosin, pleuromutilins, chloramphenicol, florfenicol, enrofloxacin and lincomycin. The MIC50 value of oxytetracycline and spectinomycin was 6.25 and 12.5 micrograms/ml, respectively. For ofloxacin, flumequine, neomycin, streptomycin, gentamicin, nalidixic acid, nitrofurantoin and sulphamethoxazole + trimethoprim MIC50 values were in the range of 25-100 micrograms/ml. With the disc diffusion method, all strains were sensitive to penicillin, cephalosporins examined, chloramphenicol and florfenicol, tetracyclines examined, pleuromutilins, lincomycin and tylosin. Variable sensitivity was observed for fluoroquinolones (flumequine, enrofloxacin, ofloxacin), most of the strains were susceptible to marbofloxacin. Almost all strains were resistant to aminoglycosides but most of them were sensitive to spectinomycin. A strong correlation was determined for disc diffusion and MIC results (Spearman's rho 0.789, p < 0001). MIC values of the type strain and MIC50 values of other tested strains did not differ significantly. Few strains showed a partially distinct resistance pattern for erythromycin, lincomycin and ampicillin in both methods. PMID:12688126

  17. A Novel Strategy for Gene Selection of Microarray Data Based on Gene-to-Class Sensitivity Information

    PubMed Central

    Han, Fei; Sun, Wei; Ling, Qing-Hua

    2014-01-01

    To obtain predictive genes with lower redundancy and better interpretability, a hybrid gene selection method encoding prior information is proposed in this paper. To begin with, the prior information referred to as gene-to-class sensitivity (GCS) of all genes from microarray data is exploited by a single hidden layered feedforward neural network (SLFN). Then, to select more representative and lower redundant genes, all genes are grouped into some clusters by K-means method, and some low sensitive genes are filtered out according to their GCS values. Finally, a modified binary particle swarm optimization (BPSO) encoding the GCS information is proposed to perform further gene selection from the remainder genes. For considering the GCS information, the proposed method selects those genes highly correlated to sample classes. Thus, the low redundant gene subsets obtained by the proposed method also contribute to improve classification accuracy on microarray data. The experiments results on some open microarray data verify the effectiveness and efficiency of the proposed approach. PMID:24844313

  18. The Usefulness of Selected Physicochemical Indices, Cell Membrane Integrity and Sperm Chromatin Structure in Assessments of Boar Semen Sensitivity

    PubMed Central

    Wysokińska, A.; Kondracki, S.; Iwanina, M.

    2015-01-01

    The present work describes experiments undertaken to evaluate the usefulness of selected physicochemical indices of semen, cell membrane integrity and sperm chromatin structure for the assessment of boar semen sensitivity to processes connected with pre-insemination procedures. The experiments were carried out on 30 boars: including 15 regarded as providers of sensitive semen and 15 regarded as providers of semen that is little sensitive to laboratory processing. The selection of boars for both groups was based on sperm morphology analyses, assuming secondary morphological change incidence in spermatozoa as the criterion. Two ejaculates were manually collected from each boar at an interval of 3 to 4 months. The following analyses were carried out for each ejaculate: sperm motility assessment, sperm pH measurement, sperm morphology assessment, sperm chromatin structure evaluation and cell membrane integrity assessment. The analyses were performed three times. Semen storage did not cause an increase in the incidence of secondary morphological changes in the group of boars considered to provide sperm of low sensitivity. On the other hand, with continued storage there was a marked increase in the incidence of spermatozoa with secondary morphological changes in the group of boars regarded as producing more sensitive semen. Ejaculates of group I boars evaluated directly after collection had an approximately 6% smaller share of spermatozoa with undamaged cell membranes than the ejaculates of boars in group II (p≤0.05). In the process of time the percentage of spermatozoa with undamaged cell membranes decreased. The sperm of group I boars was characterised with a lower sperm motility than the semen of group II boars. After 1 hour of storing diluted semen, the sperm motility of boars producing highly sensitive semen was already 4% lower (p≤0.05), and after 24 hours of storage it was 6.33% lower than that of the boars that produced semen with a low sensitivity. Factors

  19. Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2).

    PubMed

    Kimple, Adam J; Soundararajan, Meera; Hutsell, Stephanie Q; Roos, Annette K; Urban, Daniel J; Setola, Vincent; Temple, Brenda R S; Roth, Bryan L; Knapp, Stefan; Willard, Francis S; Siderovski, David P

    2009-07-17

    "Regulator of G-protein signaling" (RGS) proteins facilitate the termination of G protein-coupled receptor (GPCR) signaling via their ability to increase the intrinsic GTP hydrolysis rate of Galpha subunits (known as GTPase-accelerating protein or "GAP" activity). RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits. As many vasoconstrictive hormones signal via G(q) heterotrimer-coupled receptors, it is perhaps not surprising that RGS2-deficient mice exhibit constitutive hypertension. However, to date the particular structural features within RGS2 determining its selectivity for Galpha(q) over Galpha(i/o) substrates have not been completely characterized. Here, we examine a trio of point mutations to RGS2 that elicits Galpha(i)-directed binding and GAP activities without perturbing its association with Galpha(q). Using x-ray crystallography, we determined a model of the triple mutant RGS2 in complex with a transition state mimetic form of Galpha(i) at 2.8-A resolution. Structural comparison with unliganded, wild type RGS2 and of other RGS domain/Galpha complexes highlighted the roles of these residues in wild type RGS2 that weaken Galpha(i) subunit association. Moreover, these three amino acids are seen to be evolutionarily conserved among organisms with modern cardiovascular systems, suggesting that RGS2 arose from the R4-subfamily of RGS proteins to have specialized activity as a potent and selective Galpha(q) GAP that modulates cardiovascular function. PMID:19478087

  20. Selective Acylation Enhances Membrane Charge Sensitivity of the Antimicrobial Peptide Mastoparan-X

    PubMed Central

    Etzerodt, Thomas; Henriksen, Jonas R.; Rasmussen, Palle; Clausen, Mads H.; Andresen, Thomas L.

    2011-01-01

    The partitioning of the wasp venom peptide mastoparan-X (MPX) into neutral and negatively charged lipid membranes has been compared with two new synthetic analogs of MPX where the Nα-terminal of MPX was acylated with propanoic acid (PA) and octanoic acid (OA). The acylation caused a considerable change in the membrane partitioning properties of MPX and it was found that the shorter acylation with PA gave improved affinity and selectivity toward negatively charged membranes, whereas OA decreased the selectivity. Based on these findings, we hypothesize that minor differences in the embedding and positioning of the peptide in the membrane caused by either PA or OA acylation play a critical role in the fine-tuning of the effective charge of the peptide and thereby the fine-tuning of the peptide's selectivity between neutral and negatively charged lipid membranes. This finding is unique compared to previous reports where peptide acylation enhanced membrane affinity but also resulted in impaired selectivity. Our result may provide a method of enhancing selectivity of antimicrobial peptides toward bacterial membranes due to their high negative charge—a finding that should be investigated for other, more potent antimicrobial peptides in future studies. PMID:21244836

  1. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    PubMed

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  2. Carbon-fiber microelectrodes modified with 4-sulfobenzene have increased sensitivity and selectivity for catecholamines

    PubMed Central

    Hermans, Andre; Seipel, Andrew T.; Miller, Charles E.; Wightman, R. Mark

    2008-01-01

    Elliptical and cylindrical geometries of carbon-fiber microelectrodes were modified by covalent attachment of 4-sulfobenzenediazonium tetrafluoroborate following its electroreduction. Elliptical electrodes fabricated from Thornel P-55 carbon fibers show the highest amount of 4-sulfobenzene attached to the electrode. Fast-scan cyclic voltammetry was used to compare the response to dopamine and other neurochemicals at these modified carbon-fiber microelectrodes. The grafted layer causes an increased sensitivity to dopamine and other positively charged analytes that is due to increased adsorption of analyte in the grafted layer. However, this layer remains permeable to negatively charged compounds. Modified electrodes retain the increased sensitivity for dopamine during measurements in mouse brain tissue. PMID:16489775

  3. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditionaing for Allogeneic Canine Marrow Transplantion

    SciTech Connect

    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-06-15

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A”-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up.

  4. Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents.

    PubMed

    Hofmann, Mackenzie E; Andresen, Michael C

    2016-02-01

    Vanilloids, high temperature, and low pH activate the transient receptor potential vanilloid type 1 (TRPV1) receptor. In spinal dorsal root ganglia, co-activation of one of these gating sites on TRPV1 sensitized receptor gating by other modes. Here in rat brainstem slices, we examined glutamate synaptic transmission in nucleus of the solitary tract (NTS) neurons where most cranial primary afferents express TRPV1, but TRPV1 sensitization is unknown. Electrical shocks to the solitary tract (ST) evoked EPSCs (ST-EPSCs). Activation of TRPV1 with capsaicin (100 nM) increased spontaneous EPSCs (sEPSCs) but inhibited ST-EPSCs. High concentrations of the ultra-potent vanilloid resiniferatoxin (RTX, 1 nM) similarly increased sEPSC rates but blocked ST-EPSCs. Lowering the RTX concentration to 150 pM modestly increased the frequency of the sEPSCs without causing failures in the evoked ST-EPSCs. The sEPSC rate increased with raising bath temperature to 36 °C. Such thermal responses were larger in 150 pM RTX, while the ST-EPSCs remained unaffected. Vanilloid sensitization of thermal responses persisted in TTX but was blocked by the TRPV1 antagonist capsazepine. Our results demonstrate that multimodal activation of TRPV1 facilitates sEPSC responses in more than the arithmetic sum of the two activators, i.e. co-activation sensitizes TRPV1 control of spontaneous glutamate release. Since action potential evoked glutamate release is unaltered, the work provides evidence for cooperativity in gating TRPV1 plus a remarkable separation of calcium mechanisms governing the independent vesicle pools responsible for spontaneous and evoked release at primary afferents in the NTS. PMID:26471418

  5. Quantifying the Sensitivity of Energy Fluxes to Land Surface Parameter Selection Using the Active Subspace Method

    NASA Astrophysics Data System (ADS)

    Jefferson, J.; Gilbert, J. M.; Maxwell, R. M.; Constantine, P. G.

    2015-12-01

    Complex hydrologic models are commonly used as computational tools to assess and quantify fluxes at the land surface and for forecasting and prediction purposes. When estimating water and energy fluxes from vegetated surfaces, the equations solved within these models require that multiple input parameters be specified. Some parameters characterize land cover properties while others are constants used to model physical processes like transpiration. As a result, it becomes important to understand the sensitivity of output flux estimates to uncertain input parameters. The active subspace method identifies the most important direction in the high-dimensional space of model inputs. Perturbations of input parameters in this direction influence output quantities more, on average, than perturbations in other directions. The components of the vector defining this direction quantify the sensitivity of the model output to the corresponding inputs. Discovering whether or not an active subspace exists is computationally efficient compared to several other sensitivity analysis methods. Here, we apply this method to evaluate the sensitivity of latent, sensible and ground heat fluxes from the ParFlow-Common Land Model (PF-CLM). Of the 19 input parameters used to specify properties of a grass covered surface, between three and six parameters are identified as important for heat flux estimates. Furthermore, the 19-dimenision input parameter space is reduced to one active variable and the relationship between the inputs and output fluxes for this case is described by a quadratic polynomial. The input parameter weights and the input-output relationship provide a powerful combination of information that can be used to understand land surface dynamics. Given the success of this proof-of-concept example, extension of this method to identify important parameters within the transpiration computation will be explored.

  6. Nanofilm-coated photonic crystal fiber long-period gratings with modal transition for high chemical sensitivity and selectivity

    NASA Astrophysics Data System (ADS)

    Zheng, Shijie; Zhu, Yinian; Krishnaswamy, Sridhar

    2012-04-01

    Using long-period gratings (LPGs) inscribed in an endless single-mode photonic crystal fiber (PCF) and coating nanostructure film into air channels in the PCF cladding with modal transition of the LPG, we have developed a fiber-optic sensing platform for detection of chemicals. PCF-LPG possesses extremely high sensitivity to the change in refractive index and chemical selectivity by localizing binding and/or absorption events in analyte solution. In this work, we numerically and experimentally investigate the behaviors of modal transition in the PCF-LPG where the air channels of PCF cladding are azimuthally coated with two types of nanostructure polymers as primary and secondary coatings by electrostatic self-assembly (ESA) deposition technique. The primary coating does not affect PCF-LPG parameters such as grating resonance wavelengths and its intensity that can be used for sensing, but it increases the sensitivity to refractive index of chemical analytes in the air channels. The secondary coating is for selective absorption of analyte molecules of interest. Those two coatings significantly modify the cladding mode distribution of PCF-LPG and enhance the evanescent wave interaction with the external environment, leading to a highly sensitive and selective chemical sensor. The integrated sensor has potential in a variety of applications, especially for nano-liter scale measurement in situ. The functional nanostructure films which respond to different parameters can be introduced into the air channels of the PCF-LPGs as transducers with chemical selectivity. In this paper, we demonstrate a fiber-optic humidity sensor with the proposed nanofilm-coated PCF-LPG for detection of corrosion in civil infrastructural health monitoring.

  7. Brief Report: Sensitivity of Children with Autism Spectrum Disorders to Face Appearance in Selective Trust

    ERIC Educational Resources Information Center

    Li, Pengli; Zhang, Chunhua; Yi, Li

    2016-01-01

    The current study examined how children with Autism Spectrum Disorders (ASD) could selectively trust others based on three facial cues: the face race, attractiveness, and trustworthiness. In a computer-based hide-and-seek game, two face images, which differed significantly in one of the three facial cues, were presented as two cues for selective…

  8. MASS MEASUREMENTS BY AN ACCURATE AND SENSITIVE SELECTED ION RECORDING TECHNIQUE

    EPA Science Inventory

    Trace-level components of mixtures were successfully identified or confirmed by mass spectrometric accurate mass measurements, made at high resolution with selected ion recording, using GC and LC sample introduction. Measurements were made at 20 000 or 10 000 resolution, respecti...

  9. Fluorescent oligomer as a chemosensor for the label-free detection of Fe(3+) and dopamine with selectivity and sensitivity.

    PubMed

    Zhao, Lingli; Xin, Xia; Ding, Peng; Song, Aixin; Xie, Zengchun; Shen, Jinglin; Xu, Guiying

    2016-07-01

    In this article, a sensitive and selective turn-off fluorescence chemosensor, Tyloxapol (one kind of water soluble oligomer), was developed for the label-free detection of Fe(3+) ions in aqueous solution. Fluorescence (FL) experiments demonstrated that Tyloxapol was a sensitive and selective fluorescence sensor for the detection of Fe(3+) directly in water over a wide range of metal cations including Na(+), K(+), Ag(+), Hg(2+), Cd(2+), Co(2+), Cu(2+), Cr(3+), Mn(2+), Ba(2+), Zn(2+), Ni(2+), Mg(2+), Ca(2+), and Pb(2+). Moreover, the fluorescence intensity of Tyloxapol has shown a linear response to Fe(3+) in the concentration range of 0-100 μmol L(-1) with a detection limit of 2.2 μmol L(-1) in aqueous solution. Next, based on a competition mechanism, another turn-on sensing application of the Tyloxapol/Fe(3+) platform to probe dopamine (DA) against various other biological molecules such as other neurotransmitters or amino acids (norepinephrine bitartrate, acetylcholine chloride, alanine, valine, phenylalanine, tyrosine, leucine, glycine, histidine) were also investigated. It is expected that our strategy may offer a new approach for developing simple, cost-effective, rapid and sensitive sensors in biological and environmental applications. PMID:27216398

  10. Highly sensitive and selective determination of methylergometrine maleate using carbon nanofibers/silver nanoparticles composite modified carbon paste electrode.

    PubMed

    Kalambate, Pramod K; Rawool, Chaitali R; Karna, Shashi P; Srivastava, Ashwini K

    2016-12-01

    A highly sensitive and selective voltammetric method for determination of Methylergometrine maleate (MM) in pharmaceutical formulations, urine and blood serum samples has been developed based on enhanced electrochemical response of MM at carbon nanofibers and silver nanoparticles modified carbon paste electrode (CNF-AgNP-CPE). The electrode material was characterized by various techniques viz., X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy. The electrocatalytic response of MM at CNF-AgNP-CPE was studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, the proposed sensor exhibits excellent electrochemical response towards MM. The DPV study shows greatly enhanced electrochemical signal for MM at CNF-AgNP-CPE lending high sensitivity to the proposed sensor for MM detection. The peak (Ip) current for MM is found to be rectilinear in the range 4.0×10(-8)-2.0×10(-5)M with a detection limit of 7.1×10(-9)M using DPV. The feasibility of the proposed sensor in analytical applications was investigated by conducting experiments on commercial pharmaceutical formulations, human urine and blood serum samples, which yielded satisfactory recoveries of MM. The proposed electrochemical sensor offers high sensitivity, selectivity, reproducibility and practical utility. We recommend it as an authentic and productive electrochemical sensor for successful determination of MM. PMID:27612735

  11. Evaluation of cerium doped tin oxide nanoparticles as a sensitive sensor for selective detection and extraction of cobalt

    NASA Astrophysics Data System (ADS)

    Khan, Sher Bahadar; Asiri, Abdullah M.; Rahman, Mohammed M.; Marwani, Hadi M.; Alamry, Khalid A.

    2015-06-01

    Chemo-sensor technology demands to design a single, preconcentrator based sensing system having higher sensitivity, sufficient selectivity and efficient removal of metal ions with simple operating and recognition methodology. Here we effectively deliberated Ce doped SnO2 nanoparticles based sensing system which can be exploited for the recognition and extraction of Co(II) ions in a single step by strong interaction between Ce doped SnO2 nanoparticles and Co(II). The sensing ability of Ce doped SnO2 nanoparticles were deliberated for a selective removal of cobalt using inductively coupled plasma-optical emission spectrometry. The sensing ability of Ce doped SnO2 is studied for various metal ions, such as Cd(II), Co(II), Cr(III), Cu(II), Fe(III), Ni(II) and Zn(II) but the designed sensor was most selective toward Co(II) which was 5000 time more sensitive to Co(II) rather than different interfering metal ions. In addition, the desorption study for regeneration of Ce doped SnO2 nanoparticles was carried out. This novel approach provides a new route for simultaneous detection and removal of Co(II) in a single step and can be a time and cost alternative tool for environmental safety.

  12. Disperse fine equiaxed alpha alumina nanoparticles with narrow size distribution synthesised by selective corrosion and coagulation separation

    NASA Astrophysics Data System (ADS)

    Pu, Sanxu; Li, Lu; Ma, Ji; Lu, Fuliang; Li, Jiangong

    2015-07-01

    Disperse fine equiaxed α-Al2O3 nanoparticles with narrow size distribution are important materials in nanotechnology and nanomaterials, but syntheses of disperse fine equiaxed α-Al2O3 nanoparticles usually result in fine γ-Al2O3 nanoparticles or large α-Al2O3 nanoparticles larger than 15 nm. α-Al2O3 has a higher surface energy than γ-Al2O3 and becomes thermodynamically not stable with respect to γ-Al2O3 at specific surface areas larger than 100 m2/g (at sizes smaller than 15 nm for spherical particles) at room temperature. So disperse fine equiaxed α-Al2O3 nanoparticles smaller than 15 nm with narrow size distribution are extremely difficult to synthesise. Here we show the successful synthesis of disperse fine equiaxed α-Al2O3 nanoparticles with average sizes below 10 nm and narrow size distribution by selective corrosion and refined fractionated coagulation separation. An almost fully dense nanocrystalline α-Al2O3 ceramic with a relative density of 99.5% and an average grain size of 60 nm can be sintered from disperse fine equiaxed α-Al2O3 nanoparticles with narrow size distribution.

  13. Disperse fine equiaxed alpha alumina nanoparticles with narrow size distribution synthesised by selective corrosion and coagulation separation

    PubMed Central

    Pu, Sanxu; Li, Lu; Ma, Ji; Lu, Fuliang; Li, Jiangong

    2015-01-01

    Disperse fine equiaxed α-Al2O3 nanoparticles with narrow size distribution are important materials in nanotechnology and nanomaterials, but syntheses of disperse fine equiaxed α-Al2O3 nanoparticles usually result in fine γ-Al2O3 nanoparticles or large α-Al2O3 nanoparticles larger than 15 nm. α-Al2O3 has a higher surface energy than γ-Al2O3 and becomes thermodynamically not stable with respect to γ-Al2O3 at specific surface areas larger than 100 m2/g (at sizes smaller than 15 nm for spherical particles) at room temperature. So disperse fine equiaxed α-Al2O3 nanoparticles smaller than 15 nm with narrow size distribution are extremely difficult to synthesise. Here we show the successful synthesis of disperse fine equiaxed α-Al2O3 nanoparticles with average sizes below 10 nm and narrow size distribution by selective corrosion and refined fractionated coagulation separation. An almost fully dense nanocrystalline α-Al2O3 ceramic with a relative density of 99.5% and an average grain size of 60 nm can be sintered from disperse fine equiaxed α-Al2O3 nanoparticles with narrow size distribution. PMID:26166455

  14. High-sensitivity, high-selectivity detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Pushkarsky, Michael B.; Webber, Michael E.; Macdonald, Tyson; Patel, C. Kumar N.

    2006-01-01

    We report high-sensitivity detection of chemical warfare agents (nerve gases) with very low probability of false positives (PFP). We demonstrate a detection threshold of 1.2ppb (7.7μg/m3 equivalent of Sarin) with a PFP of <1:106 in the presence of many interfering gases present in an urban environment through the detection of diisopropyl methylphosphonate, an accepted relatively harmless surrogate for the nerve agents. For the current measurement time of ˜60s, a PFP of 1:106 corresponds to one false alarm approximately every 23months. The demonstrated performance satisfies most current homeland and military security requirements.

  15. Prediction of novel and selective TNF-alpha converting enzyme (TACE) inhibitors and characterization of correlative molecular descriptors by machine learning approaches.

    PubMed

    Cong, Yong; Yang, Xue-Gang; Lv, Wei; Xue, Ying

    2009-10-01

    The inhibition of TNF-alpha converting enzyme (TACE) has been explored as a feasible therapy for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Recently, large numbers of novel and selective TACE inhibitors have been reported. It is desirable to develop machine learning (ML) models for identifying the inhibitors of TACE in the early drug design phase and test the prediction capabilities of these ML models. This work evaluated four ML methods, support vector machine (SVM), k-nearest neighbor (k-NN), back-propagation neural network (BPNN) and C4.5 decision tree (C4.5 DT), which were trained and tested by using a diverse set of 443 TACE inhibitors and 759 non-inhibitors. A well-established feature selection method, the recursive feature elimination (RFE) method, was used to select the most appropriate descriptors for classification from a large pool of descriptors, and two evaluation methods, 5-fold cross-validation and independent evaluation, were used to assess the performances of these developed models. In this study, all these ML models have already achieved promising prediction accuracies. By using the RFE method, the prediction accuracies are further improved. In k-NN, the model gives the best prediction for TACE inhibitors (98.32%), and the SVM bears the best prediction for non-inhibitors (99.51%). Both the k-NN and SVM model give the best overall prediction accuracy (98.45%). To the best of our knowledge, the SVM model developed in this work is the first one for the classification prediction of TACE inhibitors with a broad applicability domain. Our study suggests that ML methods, particularly SVM, are potentially useful for facilitating the discovery of TACE inhibitors and for exhibiting the molecular descriptors associated with TACE inhibitors. PMID:19729328

  16. Error modeling and sensitivity analysis of a parallel robot with SCARA(selective compliance assembly robot arm) motions

    NASA Astrophysics Data System (ADS)

    Chen, Yuzhen; Xie, Fugui; Liu, Xinjun; Zhou, Yanhua

    2014-07-01

    Parallel robots with SCARA(selective compliance assembly robot arm) motions are utilized widely in the field of high speed pick-and-place manipulation. Error modeling for these robots generally simplifies the parallelogram structures included by the robots as a link. As the established error model fails to reflect the error feature of the parallelogram structures, the effect of accuracy design and kinematic calibration based on the error model come to be undermined. An error modeling methodology is proposed to establish an error model of parallel robots with parallelogram structures. The error model can embody the geometric errors of all joints, including the joints of parallelogram structures. Thus it can contain more exhaustively the factors that reduce the accuracy of the robot. Based on the error model and some sensitivity indices defined in the sense of statistics, sensitivity analysis is carried out. Accordingly, some atlases are depicted to express each geometric error's influence on the moving platform's pose errors. From these atlases, the geometric errors that have greater impact on the accuracy of the moving platform are identified, and some sensitive areas where the pose errors of the moving platform are extremely sensitive to the geometric errors are also figured out. By taking into account the error factors which are generally neglected in all existing modeling methods, the proposed modeling method can thoroughly disclose the process of error transmission and enhance the efficacy of accuracy design and calibration.

  17. An effective real-time colorimeteric sensor for sensitive and selective detection of cysteine under physiological conditions.

    PubMed

    Yan, Zhengquan; Guang, Shanyi; Xu, Hongyao; Liu, Xiangyang

    2011-05-01

    In this contribution, a new, real-time and sensitive colorimetric sensor, di-N-methyl-N-hydroxyethylaniline squaraine (SQ), has been identified and synthesized for cysteine analysis based on its ΔA in neutral aqueous medium (pH ≈ 7.5). The proposed method was applied to analyse synthetic amino acid samples and human serum samples. The results show that the linear range of cysteine detection in aqueous medium at pH ≈ 7.5 is 10~700 nmol L(-1) with a correlation coefficient (R) of 0.9984 and a limit of detection (3σ, n = 20) of 3.9 nmol L(-1). The relative standard deviation (RSD) for cysteine detection was lower than 4.1% (n = 5). The proposed method possesses the advantages of simplicity, rapidity, high selectivity and sensitivity. This makes it possible, for the first time, the real-time detection of cysteine under normal physiological conditions. PMID:21394346

  18. Boronic acid functionalized N-doped carbon quantum dots as fluorescent probe for selective and sensitive glucose determination

    NASA Astrophysics Data System (ADS)

    Jiang, Guohua; Jiang, Tengteng; Li, Xia; Wei, Zheng; Du, Xiangxiang; Wang, Xiaohong

    2014-04-01

    Nitrogen doped carbon quantum dots (NCQDs) of about 10 nm in diameter have been obtained by hydrothermal reaction from collagen. Because of the superiority of water dispersion, low toxicity and ease of functionlization, the NCQDs were designed as a glucose sensor after covalent grafting by 3-aminophenylboronic (APBA) (APBA-NCQDs). The as-prepared APBA-NCQDs were imparted with glucose sensitivity and selectivity from other saccharides via fluorescence (FL) quenching effect at physiological pH and at room temperature, which show high sensitivity and specificity for glucose determination with a wide range from 1 mM to 14 mM. FL quenching mechanism of APBA-NCQDs was also investigated by adding an external quencher. The APBA-NCQDs-based platform is an environmentally friendly way to substitute inorganic quantum dots containing heavy metals which offer a facile and low cost detection method.

  19. Sensitive and selective system of benzene detection based on a cataluminescence sensor.

    PubMed

    Li, Bo; Zhang, Yuejin; Liu, Juefu; Xie, Xin; Zou, Dan; Li, Minqiang; Liu, Jinhuai

    2014-06-01

    Au/La2 O3 nanomaterials were prepared through calcining Au-modified La(OH)3 precursors. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffractometry (XRD) were employed to characterize the as-prepared samples. Benzene, a common volatile organic compound, was selected as a model to investigate the cataluminescence (CTL)-sensing properties of the Au/La2 O3 nanomaterials. Results indicated that the as-prepared Au/La2 O3 exhibited outstanding CTL properties such as stable intensity, high signal-to-noise values, and short response and recovery times. Under optimized conditions, the benzene assay exhibited a broad linear range of 1-4000 ppm, with a limit of detection of 0.7 ppm, which was below the standard permitted concentrations. Furthermore, the gas sensor system showed outstanding selectivity for benzene compared with seven other types of common volatile organic compounds (VOCs). The proposed gas sensor showed good characteristics with high selectivity, fast response time and long lifetime, which suggested the promising application of the Au/La2 O3 nanomaterials as a novel highly efficient CTL-sensing material. PMID:23832690

  20. Streaming potentials reveal a short ryanodine-sensitive selectivity filter in cardiac Ca2+ release channel.

    PubMed Central

    Tu, Q; Vélez, P; Brodwick, M; Fill, M

    1994-01-01

    Single cardiac sarcoplasmic reticulum Ca2+ release channels were reconstituted into planar bilayer membranes. Streaming potentials were measured in osmotically asymmetric solutions as a shift in the reversal potential. Potential changes induced by water movement through the bilayer (concentration polarization) and reduced ion activity in the concentrated non-electrolyte solutions were determined using valinomycin. In 400 mM symmetrical CsCH3SO3, the average streaming potential was 2.74 +/- 0.2 mV (n = 5, mean +/- SE; 2 osmol/kg) and independent of the osmoticant used (sucrose or diglycine). Identical streaming potential magnitudes were obtained regardless of which side of the membrane the nonelectrolyte was placed. This suggests that the narrow part of the pore where single file diffusion occurs is relatively short (i.e., accommodates a minimum of 3 H2O molecules). This value is comparable to similar measurements in a variety of surface membrane channels. Ryanodine-modified channels had no measurable streaming potential, an increased Tris+ permeability relative to Cs+, and decreased divalent selectivity (PCs/PTris 5.1 +/- 1.1 to 1.7 +/- 0.3, n = 3; PBa/PCs 8.2 +/- 0.7 to 1.8 +/- 0.5, n = 4). Cation/anion selectivity was essentially unaltered in ryanodine-modified channels. These results suggests that the narrow region of the permeation pathway (i.e., the selectivity filter) is relatively short and widens after ryanodine modification. PMID:7696468

  1. Ion imprinted polymeric nanoparticles for selective separation and sensitive determination of zinc ions in different matrices

    NASA Astrophysics Data System (ADS)

    Shamsipur, Mojtaba; Rajabi, Hamid Reza; Pourmortazavi, Seied Mahdi; Roushani, Mahmoud

    2014-01-01

    Preparation of Zn2+ ion-imprinted polymer (Zn-IIP) nanoparticles is presented in this report. The Zn-IIP nanoparticles are prepared by dissolving stoichiometric amounts of zinc nitrate and selected chelating ligand, 3,5,7,20,40-pentahydroxyflavone, in 15 mL ethanol-acetonitrile (2:1; v/v) mixture as a porogen solvent in the presence of ethylene glycol-dimethacrylate (EGDMA) as cross-linking, methacrylic acid (MAA) as functional monomer, and 2,2-azobisisobutyronitrile (AIBN) as initiator. After polymerization, Cavities in the polymer particles corresponding to the Zn2+ ions were created by leaching the polymer in HCl aqueous solution. The synthesized IIPs were characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal analysis techniques. Also, the pH range for rebinding of Zn2+ ion on the IIP and equilibrium binding time were optimized, using flame atomic absorption spectrometry. In selectivity study, it was found that imprinting results increased affinity of the material toward Zn2+ ion over other competitor metal ions with the same charge and close ionic radius. The prepared IIPs were repeatedly used and regenerated for six times without any significant decrease in polymer binding affinities. Finally, the prepared sorbent was successfully applied to the selective recognition and determination of zinc ion in different real samples.

  2. Electrosprayed Metal Oxide Semiconductor Films for Sensitive and Selective Detection of Hydrogen Sulfide

    PubMed Central

    Ghimbeu, Camelia Matei; Lumbreras, Martine; Schoonman, Joop; Siadat, Maryam

    2009-01-01

    Semiconductor metal oxide films of copper-doped tin oxide (Cu-SnO2), tungsten oxide (WO3) and indium oxide (In2O3) were deposited on a platinum coated alumina substrate employing the electrostatic spray deposition technique (ESD). The morphology studied with scanning electron microscopy (SEM) and atomic force microscopy (AFM) shows porous homogeneous films comprising uniformly distributed aggregates of nano particles. The X-ray diffraction technique (XRD) proves the formation of crystalline phases with no impurities. Besides, the Raman cartographies provided information about the structural homogeneity. Some of the films are highly sensitive to low concentrations of H2S (10 ppm) at low operating temperatures (100 and 200 °C) and the best response in terms of Rair/Rgas is given by Cu-SnO2 films (2500) followed by WO3 (1200) and In2O3 (75). Moreover, all the films exhibit no cross-sensitivity to other reducing (SO2) or oxidizing (NO2) gases. PMID:22291557

  3. Sensitivity and Selectivity on Aptamer-Based Assay: The Determination of Tetracycline Residue in Bovine Milk

    PubMed Central

    Jeong, Sohee; Rhee Paeng, Insook

    2012-01-01

    A competitive enzyme-linked aptamer assay (ELAA) to detect tetracycline in milk was performed by using two different aptamers individually; one is 76 mer-DNA aptamer and the other is 57 mer-RNA aptamer. The best optimum condition was obtained without monovalent ion, Na+ and also by adding no Mg2+ ion in the assay buffer, along with RT incubation. The optimized ELAA showed a good sensitivity (LOD of 2.10 × 10−8 M) with a wide dynamic range (3.16 × 10−8 M ~ 3.16 × 10−4 M). In addition, the average R.S.D. across all data points of the curve was less than 2.5% with good recoveries (~101.8%) from the milk media. Thus, this method provides a good tool to monitor tetracycline in milk from MRLs' point of view. However, this ELAA method was not superior to the ELISA method in terms of specificity. This paper describes that it does not always give better sensitivity and specificity in assays even though aptamers have several advantages over antibodies and have been known to be good binders for binding assays. PMID:22547977

  4. Sensitivity and selectivity determination of bisphenol A using SWCNT-CD conjugate modified glassy carbon electrode.

    PubMed

    Gao, Yong; Cao, Yu; Yang, Duanguang; Luo, Xujun; Tang, Yiming; Li, Huaming

    2012-01-15

    In this study, we demonstrated a highly sensitive electrochemical sensor for the determination of bisphenol A (BPA) in aqueous solution by using single-walled carbon nanotubes (SWCNTs)/β-cyclodextrin (β-CD) conjugate (SWCNT-CD) modified glassy carbon electrode (GCE). The cyclic voltammetry results show that the modified GCE exhibits strong catalytic activity toward the oxidation of BPA with a well-defined cyclic voltammetric peak at 0.543 V. The response current exhibits a linear range between 10.8 nM and 18.5 μM with a high sensitivity (1256 μA mM(-1)). The detection limit of BPA is 1.0 nM (S/N=3). The enhanced performance of the fabricated sensor can be attributed to the combination of the excellent electrocatalytic properties of SWCNTs and the molecular recognition ability of β-CD. The sensor was successfully applied to determine BPA leached from real plastic samples with good recovery, ranging from 95% to 103%. PMID:22100222

  5. A highly sensitive and selective diagnostic assay based on virus nanoparticles

    NASA Astrophysics Data System (ADS)

    Park, Jin-Seung; Cho, Moon Kyu; Lee, Eun Jung; Ahn, Keum-Young; Lee, Kyung Eun; Jung, Jae Hun; Cho, Yunjung; Han, Sung-Sik; Kim, Young Keun; Lee, Jeewon

    2009-04-01

    Early detection of the protein marker troponin I in patients with a higher risk of acute myocardial infarction can reduce the risk of death from heart attacks. Most troponin assays are currently based on the conventional enzyme linked immunosorbent assay and have detection limits in the nano- and picomolar range. Here, we show that by combining viral nanoparticles, which are engineered to have dual affinity for troponin antibodies and nickel, with three-dimensional nanostructures including nickel nanohairs, we can detect troponin levels in human serum samples that are six to seven orders of magnitude lower than those detectable using conventional enzyme linked immunosorbent assays. The viral nanoparticle helps to orient the antibodies for maximum capture of the troponin markers. High densities of antibodies on the surfaces of the nanoparticles and nanohairs lead to greater binding of the troponin markers, which significantly enhances detection sensitivities. The nickel nanohairs are re-useable and can reproducibly differentiate healthy serum from unhealthy ones. We expect other viral nanoparticles to form similar highly sensitive diagnostic assays for a variety of other protein markers.

  6. Electrosprayed metal oxide semiconductor films for sensitive and selective detection of hydrogen sulfide.

    PubMed

    Ghimbeu, Camelia Matei; Lumbreras, Martine; Schoonman, Joop; Siadat, Maryam

    2009-01-01

    Semiconductor metal oxide films of copper-doped tin oxide (Cu-SnO(2)), tungsten oxide (WO(3)) and indium oxide (In(2)O(3)) were deposited on a platinum coated alumina substrate employing the electrostatic spray deposition technique (ESD). The morphology studied with scanning electron microscopy (SEM) and atomic force microscopy (AFM) shows porous homogeneous films comprising uniformly distributed aggregates of nano particles. The X-ray diffraction technique (XRD) proves the formation of crystalline phases with no impurities. Besides, the Raman cartographies provided information about the structural homogeneity. Some of the films are highly sensitive to low concentrations of H(2)S (10 ppm) at low operating temperatures (100 and 200 °C) and the best response in terms of R(air)/R(gas) is given by Cu-SnO(2) films (2500) followed by WO(3) (1200) and In(2)O(3) (75). Moreover, all the films exhibit no cross-sensitivity to other reducing (SO(2)) or oxidizing (NO(2)) gases. PMID:22291557

  7. Quantitative Evaluation of Sensitivity and Selectivity of Multiplex NanoSPR Biosensor Assays

    PubMed Central

    Yu, Chenxu; Irudayaraj, Joseph

    2007-01-01

    A new functionalization procedure was developed to replace cyltrimethylammoniumbromide coating on gold nanorods (GNRs) fabricated through seed-mediated growth with chemically active alkanethiols; antibodies were then attached to the GNRs to yield gold nanorod molecular probes (GNrMPs). The functionalization procedure was shown to minimize nonspecific binding. Multiplex sensing was demonstrated for three targets (goat anti-human IgG, goat anti-rabbit IgG, and goat anti-mouse IgG) through the distinct response of the plasmon spectra of GNrMPs to binding events. Quantification of the plasmonic binding events and estimation of ligand binding kinetics tethered to these nanoscale structures was also demonstrated through a mathematical approach. Evaluation of the experimental and theoretical data yields an affinity constant Ka = 1.34 × 107 M−1, which was in agreement with the IgG-antiIgG binding affinity reported in the literature. The GNrMP sensors were found to be highly specific and sensitive with the dynamic response in the range between 10−9 M and 10−6 M. The limit of detection of GNrMPs was found to be in the low nanomolar range, and is a function of the binding affinity: for a higher probe-target affinity pair, the limit of detection can be expected to reach femto molar levels. This technique can play a key role in developing tunable sensors for sensitive and precise monitoring of biological interactions. PMID:17660314

  8. USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics.

    PubMed

    Lee, E-W; Seong, D; Seo, J; Jeong, M; Lee, H-K; Song, J

    2015-09-01

    Given their crucial role in apoptosis suppression, inhibitor of apoptosis proteins (IAPs) have recently become attractive targets for cancer therapy. Here, we report that cellular IAP2 (cIAP2) is specifically stabilized in several cancer cell lines, leading to resistance to Smac mimetics, such as BV6 and birinapant. In particular, our results showed that cIAP2 depletion, but not cIAP1 depletion, sensitized cancer cells to Smac mimetic-induced apoptosis. Ubiquitin-specific protease 11 (USP11) is a deubiquitylase that directly stabilizes cIAP2. USP11 overexpression is frequently found in colorectal cancer and melanoma and is correlated with poor survival. In our study, cancer cell lines expressing high levels of USP11 exhibited strong resistance to Smac mimetic-induced cIAP2 degradation. Furthermore, USP11 downregulation sensitized these cells to apoptosis induced by TRAIL and BV6 and suppressed tumor growth in a xenograft model. Finally, the TNFα/JNK pathway induced USP11 expression and maintained cIAP2 stability, suggesting an alternative TNFα-dependent cell survival pathway. Collectively, our data suggest that USP11-stabilized cIAP2 may serve as a barrier against IAP-targeted clinical approaches. PMID:25613375

  9. Sensitive and selective culture medium for detection of environmental Clostridium difficile isolates without requirement for anaerobic culture conditions.

    PubMed

    Cadnum, Jennifer L; Hurless, Kelly N; Deshpande, Abhishek; Nerandzic, Michelle M; Kundrapu, Sirisha; Donskey, Curtis J

    2014-09-01

    Effective and easy-to-use methods for detecting Clostridium difficile spore contamination would be useful for identifying environmental reservoirs and monitoring the effectiveness of room disinfection. Culture-based detection methods are sensitive for detecting C. difficile, but their utility is limited due to the requirement of anaerobic culture conditions and microbiological expertise. We developed a low-cost selective broth medium containing thioglycolic acid and l-cystine, termed C. difficile brucella broth with thioglycolic acid and l-cystine (CDBB-TC), for the detection of C. difficile from environmental specimens under aerobic culture conditions. The sensitivity and specificity of CDBB-TC (under aerobic culture conditions) were compared to those of CDBB (under anaerobic culture conditions) for the recovery of C. difficile from swabs collected from hospital room surfaces. CDBB-TC was significantly more sensitive than CDBB for recovering environmental C. difficile (36/41 [88%] versus 21/41 [51%], respectively; P = 0.006). C. difficile latex agglutination, an enzyme immunoassay for toxins A and B or glutamate dehydrogenase, and a PCR for toxin B genes were all effective as confirmatory tests. For 477 total environmental cultures, the specificity of CDBB-TC versus that of CDBB based upon false-positive yellow-color development of the medium without recovery of C. difficile was 100% (0 false-positive results) versus 96% (18 false-positive results), respectively. False-positive cultures for CDBB were attributable to the growth of anaerobic non-C. difficile organisms that did not grow in CDBB-TC. Our results suggest that CDBB-TC provides a sensitive and selective medium for the recovery of C. difficile organisms from environmental samples, without the need for anaerobic culture conditions. PMID:24958803

  10. Recent approaches to improving selectivity and sensitivity of enzyme-based biosensors for organophosphorus pesticides: A review.

    PubMed

    Songa, Everlyne A; Okonkwo, Jonathan O

    2016-08-01

    Pesticide determination has attracted great attention due to the fact that they exhibit high acute toxicity and can cause long-term damage to the environment and human lives even at trace levels. Although classical analytical methods (including gas chromatography, high performance liquid chromatography, capillary electrophoresis and mass spectrometry) have been effectively used for analysis of pesticides in contaminated samples, they present certain limitations such as time-consuming sample preparation, complexity, and the requirement of expensive instrumentation and highly skilled personnel. For these reasons, there is an expanding need for analytical methods able to provide simple, rapid, sensitive, selective, low cost and reliable detection of pesticides at trace levels. Over the past decades, acetylcholinesterase (AChE) biosensors have emerged as simple, rapid and ultra-sensitive tools for toxicity detection of pesticides in the environment and food. These biosensors have the potential to complement or replace the classical analytical methods by simplifying or eliminating sample preparation and making field-testing easier and faster with significant decrease in cost per analysis. With the recent engineering of more sensitive AChE enzymes, the development of more reliable immobilization matrices and the progress in the area of microelectronics, AChE biosensors could become competitive for multi-analyte screening and soon be used for the development of portable instrumentation for rapid toxicity testing of samples. The enzymes organophosphorus hydrolase (OPH) and organophosphorus acid anhydrolase (OPAA) have also shown considerable potential in OP biosensor applications and they have been used for direct detection of OPs. This review presents the recent advances in the fabrication of enzyme biosensors for organophosphorus pesticides (OPs) and their possible applications for toxicity monitoring of organophosphorus pesticide residues in real samples. The focus will

  11. N,N-Diethylamine appended binuclear Zn(ii) complexes: highly selective and sensitive fluorescent chemosensors for picric acid.

    PubMed

    Kumar, Amit; Kumar, Ashish; Pandey, Daya Shankar

    2016-05-28

    Novel binuclear Zn(ii) complexes (1-2) derived from bis-chelating salen type ligands (H2L(1) and H2L(2)) possessing N,N-diethylamine moieties on the periphery of the molecules have been synthesized and thoroughly characterized by satisfactory elemental analyses and spectral (FT-IR, (1)H, (13)C NMR, UV-vis, fluorescence and ESI-MS) studies. The structures of H2L(1) and 1 have been authenticated by single crystal X-ray diffraction analyses. Complexes 1 and 2 strongly fluoresce and act as highly selective and sensitive chemosensors for picric acid in different organic as well as aqueous media. Both 1 and 2 showed strong potential to detect traces of PA in vapour/solid phase through contact mode analysis. Spectral and theoretical (DFT) studies suggested that the observed fluorescence quenching may be associated with ground state (GS) charge transfer as well as electrostatic interactions between 1/2 and PA. The fluorescence lifetime for the representative complex 1 displayed a double exponential curve and unaltered lifetime (τav, 0.63 nm) in the absence and presence of PA and strongly suggested that quenching follows a static mechanism. Further, DFT calculations on 1 and 2 strongly supported the static mechanism through GS charge transfer between complexes and PA. In addition, (1)H NMR spectral studies on 1-2 in the presence of PA firmly advocated strong hydrogen bonding and π-π stacking between the phenolic rings of 1-2 and the aromatic ring of PA. These complexes are capable of detecting PA either individually or in a competitive environment of other nitro- explosives. Florescence spectral studies on the model complex M lacking N,N-diethylamine groups revealed moderate selectivity and sensitivity towards PA and supported the key role of N,N-diethylamine moieties in the selectivity and sensitivity of complexes. PMID:27114325

  12. Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Yuan, Chao; Gabler, Jessica; El-Khoury, Joe M; Spatholt, Regina; Wang, Sihe

    2012-07-01

    Methylmalonic acid (MMA) is a functional biomarker of vitamin B12 deficiency. Measurement of plasma MMA is challenging due to its small molecular weight and hydrophilic nature. Several liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed for measuring plasma MMA. However, these methods involve lengthy sample preparation, long chromatographic run time, inadequate sensitivity, or interference from succinic acid (SA). Here we report a novel LC-MS/MS method for quantitation of underivatized MMA in serum or heparinized plasma with high sensitivity and selectivity. Sample preparation involved only strong anion exchange solid phase extraction. The extract was purified by online turbulent flow and analyzed on an Organic Acids column. MS/MS analysis was performed in negative electrospray mode, and the analytical time was 6 min. The use of ion ratio confirmation in combination with chromatographic resolution from SA greatly enhanced the selectivity. No interference was observed. This method was linear from 26.2 to 26,010.0 nM with an accuracy of 98-111 %. Total coefficient of variation was less than 4.6 % for three concentration levels tested. Comparison with a reference laboratory LC-MS/MS method using leftover patient serum specimens (n = 48) showed a mean bias of -2.3 nM (-0.61 %) with a Deming regression slope of 1.016, intercept of -6.6 nM, standard error of estimate of 25.3 nM, and a correlation coefficient of 0.9945. In conclusion, this LC-MS/MS method offers highly sensitive and selective quantitation of MMA in serum and plasma with simple sample preparation. PMID:22618327

  13. Highly selective and sensitive fluorescence chemosensor for the detection of palladium species based on Tsuji-Trost reaction

    NASA Astrophysics Data System (ADS)

    Xu, Zhong-Yong; Li, Jing; Guan, Su; Zhang, Lei; Dong, Chang-Zhi

    2015-09-01

    A new chemosensor 7-nitro-2,1,3-benzoxadiazole-4-allyl-N-(thiophen-2-ylmethyl)carbamate (NBDTC) was synthesized and utilized for palladium detection based on the Tsuji-Trost reaction. NBDTC displayed specific and ratiometric fluorescent responses toward palladium species. The chemosensor showed more than 50-fold enhancement in fluorescence intensity with the presence of PEG400 and palladium because NBDTC can be transformed to NBDT under palladium-catalyzing Tsuji-Trost reaction. NBDTC displayed high selectivity and sensitivity for palladium species with the detection limit of 1.13 × 10-9 M.

  14. Fabrication of bimetallic Cu/Au nanotubes and their sensitive, selective, reproducible and reusable electrochemical sensing of glucose

    NASA Astrophysics Data System (ADS)

    Tee, Si Yin; Ye, Enyi; Pan, Pei Hua; Lee, Coryl Jing Jun; Hui, Hui Kim; Zhang, Shuang-Yuan; Koh, Leng Duei; Dong, Zhili; Han, Ming-Yong

    2015-06-01

    Herein, we report a facile two-step approach to produce gold-incorporated copper (Cu/Au) nanostructures through controlled disproportionation of the Cu+-oleylamine complex at 220 °C to form copper nanowires and the subsequent reaction with Au3+ at different temperatures of 140, 220 and 300 °C. In comparison with copper nanowires, these bimetallic Cu/Au nanostructures exhibit their synergistic effect to greatly enhance glucose oxidation. Among them, the shape-controlled Cu/Au nanotubes prepared at 140 °C show the highest electrocatalytic activity for non-enzymatic glucose sensing in alkaline solution. In addition to high sensitivity and fast response, the Cu/Au nanotubes possess high selectivity against interferences from other potential interfering species and excellent reproducibility with long-term stability. By introducing gold into copper nanostructures at a low level of 3, 1 and 0.1 mol% relative to the initial copper precursor, a significant electrocatalytic enhancement of the resulting bimetallic Cu/Au nanostructures starts to occur at 1 mol%. Overall, the present fabrication of stable Cu/Au nanostructures offers a promising low-cost platform for sensitive, selective, reproducible and reusable electrochemical sensing of glucose.Herein, we report a facile two-step approach to produce gold-incorporated copper (Cu/Au) nanostructures through controlled disproportionation of the Cu+-oleylamine complex at 220 °C to form copper nanowires and the subsequent reaction with Au3+ at different temperatures of 140, 220 and 300 °C. In comparison with copper nanowires, these bimetallic Cu/Au nanostructures exhibit their synergistic effect to greatly enhance glucose oxidation. Among them, the shape-controlled Cu/Au nanotubes prepared at 140 °C show the highest electrocatalytic activity for non-enzymatic glucose sensing in alkaline solution. In addition to high sensitivity and fast response, the Cu/Au nanotubes possess high selectivity against interferences from other

  15. A naphthalene-based two-photon fluorescent probe for selective and sensitive detection of endogenous hypochlorous acid.

    PubMed

    Zhou, Xiao-Hong; Jiang, Yu-Ren; Zhao, Xiong-Jie; Guo, Dong

    2016-11-01

    An efficient naphthalene-based two-photon fluorescent probe for endogenous HClO has been reported in the present study, which consists of a 6-(2-benzothiazolyl)-2-naphthalenol fluorophore connected with a 4-aminophenol (the fluorescence quenching and response group). This probe exhibits a high selectivity and excellent sensitivity with a detection limit of 7.6nM over other reactive oxygen species and analyte species, and the fluorescence intensity enhanced 103-fold when responsed. Furthermore, it was successfully used for two-photon imaging of endogenous HClO in live cells with high-resolution. PMID:27591640

  16. Identification of a novel boronic acid as a potent, selective, and orally active hormone sensitive lipase inhibitor.

    PubMed

    Ogiyama, Tomoko; Yamaguchi, Mitsuhiro; Kurikawa, Nobuya; Honzumi, Shoko; Yamamoto, Yuka; Sugiyama, Daisuke; Inoue, Shinichi

    2016-08-15

    Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC50 value of 7nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3mg/kg. PMID:27338659

  17. An electrochemical impedimetric aptasensing platform for sensitive and selective detection of small molecules such as chloramphenicol.

    PubMed

    Pilehvar, Sanaz; Dierckx, Tarryn; Blust, Ronny; Breugelmans, Tom; De Wael, Karolien

    2014-01-01

    We report on the aptadetection of chloramphenicol (CAP) using electrochemical impedance spectroscopy. The detection principle is based on the changes of the interfacial properties of the electrode after the interaction of the ssDNA aptamers with the target molecules. The electrode surface is partially blocked due to the formation of the aptamer-CAP complex, resulting in an increase of the interfacial electron-transfer resistance of the redox probe detected by electrochemical impedance spectroscopy or cyclic voltammetry. We observed that the ratio of polarization resistance had a linear relationship with the concentrations of CAP in the range of 1.76-127 nM, and a detection limit of 1.76 nM was obtained. The covalent binding of CAP-aptamer on the electrode surface combined with the unique properties of aptamers and impedimetric transduction leads to the development of a stable and sensitive electrochemical aptasensor for CAP. PMID:25004156

  18. A sensitive and selective resonance Rayleigh scattering method for quick detection of avidin using affinity labeling Au nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Huang, Xi; Fu, Xuan; Deng, Huan; Ma, Meihu; Cai, Zhaoxia

    2016-06-01

    Avidin is a glycoprotein with antinutritional property, which should be limited in daily food. We developed an affinity biosensor system based on resonance Rayleigh scattering (RRS) and using affinity biotin labeling Au nanoparticles (AuNPs). This method was selective and sensitive for quick avidin detection due to the avidin-biotin affinitive interaction. Under optimal conditions, RRS intensity of biotin-AuNPs increase linearly with an increasing concentration of avidin from 5 to 160 ng/mL. The lower limit of detection was 0.59 ng/mL. This rapid and selective avidin detection method was used in synthetic samples and egg products with recoveries of between 102.97 and 107.92%, thereby demonstrating the feasible and practical application of this assay.

  19. Highly sensitive and selective fluorescence detection of copper (II) ion based on multi-ligand metal chelation.

    PubMed

    Zhang, Shan; Yu, Tao; Sun, Mingtai; Yu, Huan; Zhang, Zhongping; Wang, Suhua; Jiang, Hui

    2014-08-01

    A fluorescent probe was synthesized and demonstrated to be highly selective and sensitive in the reaction with copper (II) ion, generating a large variation of the fluorescence intensity in a dose-response manner. The probe contains a dansyl moiety as fluorophore and a multidentate ligand for copper (II) ion recognition. The reaction of the molecular probe with copper (II) ion proceeds rapidly and irreversibly in a 1 to 1 stoichiometric way, leading to the production of stable copper (II) complex, which subsequently results in the quenching of fluorescence. The detection limit for copper (II) ion was measured to be about 2ppb. It was also shown that the probe has high selectivity for copper (II) ion and good anti-interference ability against other transition metal ions. The herein reported very simple and reliable fluorescence probe could be employed for copper (II) ion detection in many aspects. PMID:24881551

  20. Highly sensitive and selective fluoride detection in water through fluorophore release from a metal-organic framework

    PubMed Central

    Hinterholzinger, Florian M.; Rühle, Bastian; Wuttke, Stefan; Karaghiosoff, Konstantin; Bein, Thomas

    2013-01-01

    The detection, differentiation and visualization of compounds such as gases, liquids or ions are key challenges for the design of selective optical chemosensors. Optical chemical sensors employ a transduction mechanism that converts a specific analyte recognition event into an optical signal. Here we report a novel concept for fluoride ion sensing where a porous crystalline framework serves as a host for a fluorescent reporter molecule. The detection is based on the decomposition of the host scaffold which induces the release of the fluorescent dye molecule. Specifically, the hybrid composite of the metal-organic framework NH2-MIL-101(Al) and fluorescein acting as reporter shows an exceptional turn-on fluorescence in aqueous fluoride-containing solutions. Using this novel strategy, the optical detection of fluoride is extremely sensitive and highly selective in the presence of many other anions. PMID:24008779

  1. A sensitive and selective resonance Rayleigh scattering method for quick detection of avidin using affinity labeling Au nanoparticles.

    PubMed

    Wang, Qi; Huang, Xi; Fu, Xuan; Deng, Huan; Ma, Meihu; Cai, Zhaoxia

    2016-06-01

    Avidin is a glycoprotein with antinutritional property, which should be limited in daily food. We developed an affinity biosensor system based on resonance Rayleigh scattering (RRS) and using affinity biotin labeling Au nanoparticles (AuNPs). This method was selective and sensitive for quick avidin detection due to the avidin-biotin affinitive interaction. Under optimal conditions, RRS intensity of biotin-AuNPs increase linearly with an increasing concentration of avidin from 5 to 160ng/mL. The lower limit of detection was 0.59ng/mL. This rapid and selective avidin detection method was used in synthetic samples and egg products with recoveries of between 102.97 and 107.92%, thereby demonstrating the feasible and practical application of this assay. PMID:26978788

  2. An aptasensor for selective, sensitive and fast detection of lead(II) based on polyethyleneimine and gold nanoparticles.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Lavaee, Parirokh; Ramezani, Mohammad; Abnous, Khalil

    2015-05-01

    Lead (Pb), as a major environmental contaminant, could be harmful to humans when inhaled or ingested. In this study, we developed a sensitive, selective and fast colorimetric aptasensor for Pb(+2) based on polyethylenimine (PEI) and gold nanoparticles (AuNPs). In the absence of Pb(+2), aptamer binds to PEI. So the well-dispersed AuNPs remain stable with a wine-red color. Upon the addition of Pb(+2), a conformational change happens and a G-quadruplex aptamer/Pb(+2) complex is formed, leading to the aggregation of AuNPs and a color change to blue. This sensor showed a high selectivity toward Pb(+2) with a limit of detection (LOD) as low as 702pM. Moreover, our fabricated sensor was successfully applied for Pb(+2) detection in rat serum and tap water. PMID:25989533

  3. Overcoming Selectivity and Sensitivity Issues of Direct Inject Electrospray Mass Spectrometry via DAPNe-NSI-MS

    NASA Astrophysics Data System (ADS)

    Clemons, Kristina; Nnaji, Chinyere; Verbeck, Guido F.

    2014-05-01

    Direct inject electrospray mass spectrometry offers minimal sample preparation and a "shotgun" approach to analyzing samples. However, complex matrix effects often make direct inject an undesirable sample introduction technique, particularly for trace level analytes. Highlighted here is our solution to the pitfalls of direct inject mass spectrometry and other ambient ionization methods with a focus on trace explosives. Direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry solves selectivity issues and reduces matrix effects while maintaining minimal sample preparation requirements. With appropriate solvent conditions, most explosive residues can be analyzed with this technique regardless of the nature of the substance (i.e., nitroaromatic, oxidizing salt, or peroxide).

  4. Tailoring Dye-sensitized Upconversion Nanoparticles Excitation Bands towards Excitation Wavelength Selective Imaging

    PubMed Central

    Wu, Xiang; Lee, Hyungseok; Bilsel, Osman; Zhang, Yuanwei; Li, Zhanjun; Chen, Teresa; Liu, Yi; Duan, Chunying; Shen, Jie; Punjabi, Amol; Han, Gang

    2015-01-01

    One of key roadblocks in UCNP development is its extremely limited choices of excitation wavelengths. We report a generic design to program UCNPs to possess highly tunable dye characteristic excitation bands. Using such distinctive properties, we were able to develop a new excitation wavelength selective security imaging. This work unleashed the greater freedom of the excitation wavelengths of the upconversion nanoparticles and we believe it is a game-changer in the field and this method will enable numerous applications that are currently limited by existing UCNPs. PMID:26499208

  5. Tailoring dye-sensitized upconversion nanoparticle excitation bands towards excitation wavelength selective imaging

    DOE PAGESBeta

    Wu, Xiang; Lee, Hyungseok; Bilsel, Osman; Zhang, Yuanwei; Li, Zhanjun; Chen, Teresa; Liu, Yi; Duan, Chunying; Shen, Jie; Punjabi, Amol; et al

    2015-01-01

    One of the key roadblocks in UCNP development is its extremely limited choices of excitation wavelengths. We report a generic design to program UCNPs to possess highly tunable dye characteristic excitation bands. Using such distinctive properties, we were able to develop a new excitation wavelength selective security imaging. Finally, this work unleashed the greater freedom of the excitation wavelengths of the upconversion nanoparticles and we believe it is a game-changer in the field and this method will enable numerous applications that are currently limited by existing UCNPs.

  6. Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection.

    PubMed

    MacLeod, J A; Nemeth, A C; Dicke, W C; Wang, D; Manalili Wheeler, S; Hannis, J C; Collier, G B; Drader, J J

    2016-07-01

    Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT® system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis. PMID:27280174

  7. Simple and sensitive colorimetric sensors for the selective detection of Cu2+ in aqueous buffer.

    PubMed

    Huo, Jianzhong; Liu, Kai; Zhao, Xiaojun; Zhang, Xingxing; Wang, Ying

    2014-01-01

    Simple chromogenic sensor for the selective detection of Cu(2+) was described. With the addition of Cu(2+), a bathochromic shift about 82 nm was observed in the UV-VIS spectra, with the color change from colorless to bright yellow. This suggested that the coordination between receptor and Cu(2+) was formed, and the strong push-pull system occurred. The followed IR spectra indicated that Cu(2+) coordinated to the two phenolic oxygen atoms and one of two azomethines in the receptor. PMID:24161519

  8. Improving the prediction of chemotherapeutic sensitivity of tumors in breast cancer via optimizing the selection of candidate genes.

    PubMed

    Jiang, Lina; Huang, Liqiu; Kuang, Qifan; Zhang, Juan; Li, Menglong; Wen, Zhining; He, Li

    2014-04-01

    Estrogen receptor status and the pathologic response to preoperative chemotherapy are two important indicators of chemotherapeutic sensitivity of tumors in breast cancer, which are used to guide the selection of specific regimens for patients. Microarray-based gene expression profiling, which is successfully applied to the discovery of tumor biomarkers and the prediction of drug response, was suggested to predict the cancer outcomes using the gene signatures differentially expressed between two clinical states. However, many false positive genes unrelated to the phenotypic differences will be involved in the lists of differentially expressed genes (DEGs) when only using the statistical methods for gene selection, e.g. Student's t test, and subsequently affect the performance of the predictive models. For the purpose of improving the prediction of clinical outcomes, we optimized the selection of DEGs by using a combined strategy, for which the DEGs were firstly identified by the statistical methods, and then filtered by a similarity profiling approach that used for candidate gene prioritization. In our study, we firstly verified the molecular functions of the DEGs identified by the combined strategy with the gene expression data generated in the microarray experiments of Si-Wu-Tang, which is a popular formula in traditional Chinese medicine. The results showed that, for Si-Wu-Tang experimental data set, the cancer-related signaling pathways were significantly enriched by gene set enrichment analysis when using the DEG lists generated by the combined strategy, confirming the potentially cancer-preventive effect of Si-Wu-Tang. To verify the performance of the predictive models in clinical application, we used the combined strategy to select the DEGs as features from the gene expression data of the clinical samples, which were collected from the breast cancer patients, and constructed models to predict the chemotherapeutic sensitivity of tumors in breast cancer. After

  9. Audit Report on "Management Controls over the Department's Excess Weapons Inventories and Selected Sensitive Equipment used by Protective Forces"

    SciTech Connect

    2009-01-01

    Since September 11, 2001, the Department of Energy has, on several occasions, revised its security posture based on identified threats and adversaries. These revisions in security posture have driven Departmental sites to upgrade their defensive and tactical equipment. Subsequent changes in the perceived threats have, in some cases, led to a reduction in the need for certain types of weapons, thus creating a pool of surplus equipment. These surplus weapons could potentially be used by other Department sites and Federal law enforcement agencies. Recent Office of Inspector General reports have raised concerns with the adequacy of controls related to defensive and tactical equipment. For example, our report on Management Controls Over Defense Related High Risk Property (OAS-M-08-06, April 2008) found that administrative controls over certain defense related high risk property were not sufficient for providing accountability over these items. Because of prior reported weaknesses in controls over defensive and tactical equipment, we initiated this audit to determine whether the Department and its contractors were properly managing excess weapons inventories and selected sensitive equipment used by protective forces. Our review disclosed that the Department was not always properly managing its inventories of excess weapons and selected sensitive equipment. We identified issues with the retention of unneeded weapons at many locations and with the identification and tracking of sensitive items. More specifically: Sites maintained large inventories of weapons that were no longer needed but had not been made available for use by either other Departmental sites or other Federal law enforcement agencies. For instance, at six of the locations included in our review we identified a total of 2,635 unneeded weapons with a total acquisition value of over $2.8 million that had not been officially declared as excess - an action that would have made them available for others to use

  10. The Remote Detection of Alpha-Radioactive Nucleus Decay

    NASA Astrophysics Data System (ADS)

    Gurkovskiy, Boris; Miroshnichenko, Vladimir; Onishchenko, Evgeny; Simakov, Andrey; Streil, Thomas

    Results of the new device design for the alpha-radiation remote detection are presented. Negative ions from the alpha particle tracks are detected by the discharge wire counter opened to air. Ion clusters being transferred from the particle tracks to the detector volume by an air flux. The detector works in a counting mode that provides sharp selectivity and accuracy of measurements. The basic parameters of the device are: detecting distance -0.5 m; measurement time -30 s; the square sensitivity -0.05 Bq/cm2.

  11. A ratiometric fluorescence nanosensor for highly selective and sensitive detection of selenite.

    PubMed

    Chen, Linfeng; Tian, Xike; Zhao, Yuan; Li, Yong; Yang, Chao; Zhou, Zhaoxin; Liu, Xiangwen

    2016-08-01

    The instant and on-site detection of selenium still remains a challenge for environmental monitoring and medical prevention. We herein developed a ratiometric fluorescent nanosensor for accurate and on-site sensing of SeO3(2-) by linking the recognition molecule 3,3'-diaminobenzidine (DAB) onto the surface of carboxyl group modified CdTe@SiO2. The fluorescence of DAB on the surface of silica nanospheres could be selectively and efficiently enhanced by SeO3(2-) through a surface chelating reaction between DAB and SeO3(2-). Thus, in the presence of SeO3(2-), the nanosensor would show two characteristic fluorescence emissions of Se-DAB and CdTe QDs under a single excitation wavelength. The selectivity and the optimal conditions for the detection of SeO3(2-) were carefully investigated. The ratio of F530/F635 linearly increased with increasing SeO3(2-) concentration in the range of 0 to 2.5 μM and the detection limit reaches as low as 6.68 nM (0.53 ppb). This developed nanosensor has the capability of on-site detection in an aqueous system without any separation step. The Se concentrations in selenium-rich food were detected and the results were consistent with the values determined by ICP-AES. PMID:27241591

  12. Molecularly imprinted upconversion nanoparticles for highly selective and sensitive sensing of Cytochrome c.

    PubMed

    Guo, Ting; Deng, Qiliang; Fang, Guozhen; Liu, Cuicui; Huang, Xuan; Wang, Shuo

    2015-12-15

    A novel method combined the high selectivity of molecular imprinting technology with the strong fluorescence property of upconversion nanoparticles (UCNPs) for sensing of Cytochrome c (Cyt c) was proposed. The molecularly imprinted material-coated upconversion nanoparticles (UCNPs@MIP) were obtained by in situ coating Cyt c imprinted materials to the surface of the carboxyl modified UCNPs through sol-gel technique. The structure and component of the prepared UCNPs@MIP was investigated by transmission electron microscopy (TEM), power X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDXA) and X-ray photoelectron spectroscopic (XPS). The TEM showed the diameter of UCNPs was 40 nm, and thickness of MIP was 5-10nm. The fluorescence intensity of UCNPs@MIP reduced gradually with the increase of Cyt c concentration. Under optimum conditions, the imprinting factor is 3.19, and the UCNPs@MIP showed selective recognition for Cyt c among other proteins such as bovine serum albumin (BSA) and Lysozyme (Lyz). Therefore, this new method for sensing protein is very promising for future applications. PMID:26176210

  13. Highly sensitive and selective electrochemical detection of Hg(2+) through surface-initiated enzymatic polymerization.

    PubMed

    Mei, Chenyang; Lin, Dajie; Fan, Chengchao; Liu, Aili; Wang, Shun; Wang, Jichang

    2016-06-15

    A Hg(2+) electrochemical biosensor is developed by integrating thymine-Hg(2+)-thymine (T-Hg(2+)-T) base pairs for the high selectivity with surface-initiated enzymatic polymerization (SIEP) for signal amplification. The fabrication begins with the covalent conjugation of capture DNA probe labeled with thiol at its 3'terminal onto the gold electrode. The presence of Hg(2+) leads to DNA hybridization, in which complementary DNA was captured onto the biosensor surface, which subsequently catalyzed the addition of deoxynucleotides (dNTP) containing biotinlated 2'-deoxyadenosine 5'-triphosphate (biotin-dATP) by terminal deoxynucleotidyl transferase (TdT). The binding between biotin and strepavidin leads to the attachment of a large number of strepavidin functionalized silver nanoparticles (strepavidin-AgNPs), which could generate electrochemical stripping signal of silver to monitor the concentration of Hg(2+) in KCl solution. Through utilizing the T-Hg(2+)-T selectivity and SIEP amplification, this assay method can detect aqueous Hg(2+) with a wide linear range from 0.05nM to 100nM and a detection limit of 0.024nM. The application of this sensor in the analysis of drinking water demonstrates that the proposed method works well for real samples. PMID:26807524

  14. Molecularly imprinted polymer decorated nanoporous gold for highly selective and sensitive electrochemical sensors

    NASA Astrophysics Data System (ADS)

    Li, Yingchun; Liu, Yuan; Liu, Jie; Liu, Jiang; Tang, Hui; Cao, Cong; Zhao, Dongsheng; Ding, Yi

    2015-01-01

    Electrochemical nanosensors based on nanoporous gold leaf (NPGL) and molecularly imprinted polymer (MIP) are developed for pharmaceutical analysis by using metronidazole (MNZ) as a model analyte. NPGL, serving as the loading platform for MIP immobilization, possesses large accessible surface area with superb electric conductivity, while electrochemically synthesized MIP thin layer affords selectivity for specific recognition of MNZ molecules. For MNZ determination, the hybrid electrode shows two dynamic linear range of 5 × 10-11 to 1 × 10-9 mol L-1 and 1 × 10-9 to 1.4 × 10-6 mol L-1 with a remarkably low detection limit of 1.8 × 10-11 mol L-1 (S/N = 3). In addition, the sensor exhibits high binding affinity and selectivity towards MNZ with excellent reproducibility and stability. Finally, the reliability of MIP-NPGL for MNZ detection is proved in real fish tissue samples, demonstrating the potential for the proposed electrochemical sensors in monitoring drug and biological samples.

  15. Molecularly imprinted polymer decorated nanoporous gold for highly selective and sensitive electrochemical sensors

    PubMed Central

    Li, Yingchun; Liu, Yuan; Liu, Jie; Liu, Jiang; Tang, Hui; Cao, Cong; Zhao, Dongsheng; Ding, Yi

    2015-01-01

    Electrochemical nanosensors based on nanoporous gold leaf (NPGL) and molecularly imprinted polymer (MIP) are developed for pharmaceutical analysis by using metronidazole (MNZ) as a model analyte. NPGL, serving as the loading platform for MIP immobilization, possesses large accessible surface area with superb electric conductivity, while electrochemically synthesized MIP thin layer affords selectivity for specific recognition of MNZ molecules. For MNZ determination, the hybrid electrode shows two dynamic linear range of 5 × 10−11 to 1 × 10−9 mol L−1 and 1 × 10−9 to 1.4 × 10−6 mol L−1 with a remarkably low detection limit of 1.8 × 10−11 mol L−1 (S/N = 3). In addition, the sensor exhibits high binding affinity and selectivity towards MNZ with excellent reproducibility and stability. Finally, the reliability of MIP-NPGL for MNZ detection is proved in real fish tissue samples, demonstrating the potential for the proposed electrochemical sensors in monitoring drug and biological samples. PMID:25572290

  16. Molecularly imprinted polymer decorated nanoporous gold for highly selective and sensitive electrochemical sensors.

    PubMed

    Li, Yingchun; Liu, Yuan; Liu, Jie; Liu, Jiang; Tang, Hui; Cao, Cong; Zhao, Dongsheng; Ding, Yi

    2015-01-01

    Electrochemical nanosensors based on nanoporous gold leaf (NPGL) and molecularly imprinted polymer (MIP) are developed for pharmaceutical analysis by using metronidazole (MNZ) as a model analyte. NPGL, serving as the loading platform for MIP immobilization, possesses large accessible surface area with superb electric conductivity, while electrochemically synthesized MIP thin layer affords selectivity for specific recognition of MNZ molecules. For MNZ determination, the hybrid electrode shows two dynamic linear range of 5 × 10(-11) to 1 × 10(-9) mol L(-1) and 1 × 10(-9) to 1.4 × 10(-6) mol L(-1) with a remarkably low detection limit of 1.8 × 10(-11) mol L(-1) (S/N = 3). In addition, the sensor exhibits high binding affinity and selectivity towards MNZ with excellent reproducibility and stability. Finally, the reliability of MIP-NPGL for MNZ detection is proved in real fish tissue samples, demonstrating the potential for the proposed electrochemical sensors in monitoring drug and biological samples. PMID:25572290

  17. Criteria for Sample Selection to Maximize Planet Sensitivity and Yield from Space-Based Microlens Parallax Surveys

    NASA Astrophysics Data System (ADS)

    Yee, Jennifer C.; Gould, Andrew; Beichman, Charles; Calchi Novati, Sebastiano; Carey, Sean; Gaudi, B. Scott; Henderson, Calen B.; Nataf, David; Penny, Matthew; Shvartzvald, Yossi; Zhu, Wei

    2015-09-01

    Space-based microlens parallax measurements are a powerful tool for understanding planet populations, especially their distribution throughout the Galaxy. However, if space-based observations of the microlensing events must be specifically targeted, it is crucial that microlensing events enter the parallax sample without reference to the known presence or absence of planets. Hence, it is vital to define objective criteria for selecting events where possible and to carefully consider and minimize the selection biases where not possible so that the final sample represents a controlled experiment. We present objective criteria for initiating observations and determining their cadence for a subset of events, and we define procedures for isolating subjective decision making from information about detected planets for the remainder of events. We also define procedures to resolve conflicts between subjective and objective selections. These procedures maximize the planet sensitivity of the sample as a whole by allowing for planet detections even if they occur before satellite observations for objectively selected events and by helping to trigger fruitful follow-up observations for subjectively chosen events. This paper represents our public commitment to these procedures, which is a necessary component of enforcing objectivity on the experimental protocol. They will be implemented for the 2015 Spitzer microlensing campaign.

  18. Nicosulfuron application in agricultural soils drives the selection towards NS-tolerant microorganisms harboring various levels of sensitivity to nicosulfuron.

    PubMed

    Petric, Ines; Karpouzas, Dimitrios G; Bru, David; Udikovic-Kolic, Nikolina; Kandeler, Ellen; Djuric, Simonida; Martin-Laurent, Fabrice

    2016-03-01

    The action mode of sulfonylurea herbicides is the inhibition of the acetohydroxyacid synthase (AHAS) required for the biosynthesis of amino acids valine and isoleucine in plants. However, this enzyme is also present in a range of non-targeted organisms, among which soil microorganisms are known for their pivotal role in ecosystem functioning. In order to assess microbial toxicity of sulfonylurea herbicide nicosulfuron (NS), a tiered microcosm (Tier I) to field (Tier II) experiment was designed. Soil bacteria harboring AHAS enzyme tolerant to the herbicide nicosulfuron were enumerated, isolated, taxonomically identified, and physiologically characterized. Results suggested that application of nicosulfuron drives the selection towards NS-tolerant bacteria, with increasing levels of exposure inducing an increase in their abundance and diversity in soil. Tolerance to nicosulfuron was shown to be widespread among the microbial community with various bacteria belonging to Firmicutes (Bacillus) and Actinobacteria (Arthrobacter) phyla representing most abundant and diverse clusters. While Arthrobacter bacterial population dominated community evolved under lower (Tier II) nicosulfuron selection pressure, it turns out that Bacillus dominated community evolved under higher (Tier I) nicosulfuron selection pressure. Different NS-tolerant bacteria likewise showed different levels of sensitivity to the nicosulfuron estimated by growth kinetics on nicosulfuron. As evident, Tier I exposure allowed selection of populations able to better cope with nicosulfuron. One could propose that sulfonylureas-tolerant bacterial community could constitute a useful bioindicator of exposure to these herbicides for assessing their ecotoxicity towards soil microorganisms. PMID:26517995

  19. A carbon dot-based "off-on" fluorescent probe for highly selective and sensitive detection of phytic acid.

    PubMed

    Gao, Zhao; Wang, Libing; Su, Rongxin; Huang, Renliang; Qi, Wei; He, Zhimin

    2015-08-15

    We herein report a facile, one-step pyrolysis synthesis of photoluminescent carbon dots (CDs) using citric acid as the carbon source and lysine as the surface passivation reagent. The as-prepared CDs show narrow size distribution, excellent blue fluorescence and good photo-stability and water dispersivity. The fluorescence of the CDs was found to be effectively quenched by ferric (Fe(III)) ions with high selectivity via a photo-induced electron transfer (PET) process. Upon addition of phytic acid (PA) to the CDs/Fe(III) complex dispersion, the fluorescence of the CDs was significantly recovered, arising from the release of Fe(III) ions from the CDs/Fe(III) complex because PA has a higher affinity for Fe(III) ions compared to CDs. Furthermore, we developed an "off-on" fluorescence assay method for the detection of phytic acid using CDs/Fe(III) as a fluorescent probe. This probe enables the selective detection of PA with a linear range of 0.68-18.69 μM and a limit of detection (signal-to-noise ratio is 3) of 0.36 μM. The assay method demonstrates high selectivity, repeatability, stability and recovery ratio in the detection of the standard and real PA samples. We believe that the facile operation, low-cost, high sensitivity and selectivity render this CD-based "off-on" fluorescent probe an ideal sensing platform for the detection of PA. PMID:25829220

  20. Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells.

    PubMed

    Sundar, Shyam N; Marconett, Crystal N; Doan, Victor B; Willoughby, Jamin A; Firestone, Gary L

    2008-12-01

    MCF7 cells are an estrogen-responsive human breast cancer cell line that expresses both estrogen receptor (ER) alpha and ERbeta. Treatment of MCF7 cells with artemisinin, an antimalarial phytochemical from the sweet wormwood plant, effectively blocked estrogen-stimulated cell cycle progression induced by either 17beta-estradiol (E(2)), an agonist for both ERs, or by propyl pyrazole triol (PPT), a selective ERalpha agonist. Artemisinin strongly downregulated ERalpha protein and transcripts without altering expression or activity of ERbeta. Transfection of MCF7 cells with ERalpha promoter-linked luciferase reporter plasmids revealed that the artemisinin downregulation of ERalpha promoter activity accounted for the loss of ERalpha expression. Artemisinin treatment ablated the estrogenic induction of endogenous progesterone receptor (PR) transcripts by either E(2) or PPT and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (EREs). Chromatin immunoprecipitation assays revealed that artemisinin significantly downregulated the level of endogeneous ERalpha bound to the PR promoter, whereas the level of bound endogeneous ERbeta was not altered. Treatment of MCF7 cells with artemisinin and the pure antiestrogen fulvestrant resulted in a cooperative reduction of ERalpha protein levels and enhanced G(1) cell cycle arrest compared with the effects of either compound alone. Our results show that artemisinin switches proliferative human breast cancer cells from expressing a high ERalpha:ERbeta ratio to a condition in which ERbeta predominates, which parallels the physiological state linked to antiproliferative events in normal mammary epithelium. PMID:18784357

  1. Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor [alpha] Selective Agonist 2-((3-((2-(4-Chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic Acid (BMS-687453)

    SciTech Connect

    Li, Jun; Kennedy, Lawrence J.; Shi, Yan; Tao, Shiwei; Ye, Xiang-Yang; Chen, Stephanie Y.; Wang, Ying; Hernndez, Andrs S.; Wang, Wei; Devasthale, Pratik V.; Chen, Sean; Lai, Zhi; Zhang, Hao; Wu, Shung; Smirk, Rebecca A.; Bolton, Scott A.; Ryono, Denis E.; Zhang, Huiping; Lim, Ngiap-Kie; Chen, Bang-Chi; Locke, Kenneth T.; O’Malley, Kevin M.; Zhang, Litao; Srivastava, Rai Ajit; Miao, Bowman; Meyers, Daniel S.; Monshizadegan, Hossain; Search, Debra; Grimm, Denise; Zhang, Rongan; Harrity, Thomas; Kunselman, Lori K.; Cap, Michael; Kadiyala, Pathanjali; Hosagrahara, Vinayak; Zhang, Lisa; Xu, Carrie; Li, Yi-Xin; Muckelbauer, Jodi K.; Chang, Chiehying; An, Yongmi; Krystek, Stanley R.; Blanar, Michael A.; Zahler, Robert; Mukherjee, Ranjan; Cheng, Peter T.W.; Tino, Joseph A.

    2010-04-12

    An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and 410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.

  2. Climate change signal over the Alpine region - sensitivity to GCM selection

    NASA Astrophysics Data System (ADS)

    Zubler, Elias M.; Fischer, Andreas M.; Liniger, Mark A.

    2015-04-01

    The use of multi-model ensembles has become a common and widely accepted practice to evaluate climate change signals and various aspects of the associated uncertainties. However, for regional analysis of climate change, it is not always feasible to use all of the available model simulations. Some models do not sufficiently represent processes that are important for a particular region, or they lack crucial topographic details to represent the corresponding climate in a realistic manner. When relying on regional climate model projections, a GCM selection is implicitly done, as not all of the available GCM simulations are being dynamically downscaled. Specifically, within EURO-CORDEX, more than 30 RCM simulations and more than 10 GCMs are provided for the strongest emission scenario RCP8.5 from the CMIP5 ensemble. Simulations with other emission scenarios are also provided. However, many RCMs in EURO-CORDEX are driven by one of only five of the available GCMs (CNRM-CM5, MPI-ESM, HadGEM, IPSL and EC-EARTH). It was shown previously that in particular RCM temperature responses tend to cluster according to their driving GCM. Therefore, it is important to better understand the relation among the GCMs. In multi-model ensembles as large as CMIP5, in which models tend to correlate due to their similar origin, model selection or weighting becomes an important issue. This study evaluates the distribution of climate change signals in the CMIP5 ensemble for temperature and precipitation over the Greater Alpine region and shows that different methods of model selection considerably influences the resulting temperature spread in the climate change signals at the end of the century relative to 1980-2009: excluding those GCMs with a poor representation of Alpine climate leads to a spread-difference of more than 1°C compared to a choice where all models are included and given the same weight. Furthermore, it is highlighted that the largest amount of spread can be retained with a

  3. Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

    PubMed

    Vitale, Alessandro; Farinati, Fabio; Burra, Patrizia; Trevisani, Franco; Giannini, Edoardo G; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Di Marco, Mariella; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Felder, Martina; Sacco, Rodolfo; Morisco, Filomena; Missale, Gabriele; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Chiaramonte, Maria; Spolverato, Gaya; Cillo, Umberto

    2015-10-01

    The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using the alpha-fetoprotein (AFP) model on the basis of AFP values and radiological size and number of nodules. The primary endpoint was the net health benefit (NHB), defined as LT survival benefit in quality-adjusted life years minus incremental costs (US $)/willingness to pay. The calculated median cost of non-LT therapies per patient was US $53,042 in Italy and US $62,827 in the United States. On Monte Carlo simulation, the NHB of LT was always positive for AFP model values ≤ 3 and always negative for values > 7 in both countries. A multivariate model showed that nontumor variables (patient's age, Child-Turcotte-Pugh [CTP] class, and alternative therapies) had the potential to shift the AFP model threshold of LT cost-ineffectiveness from 3 to 7. LT proved always cost-effective for HCC patients with AFP model values ≤ 3, whereas the cost-ineffectiveness threshold ranged between 3 and 7 using nontumor variables. PMID:26183802

  4. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) induces cell cycle arrest and apoptosis selectively in Survivin-overexpressing breast cancer cells.

    PubMed

    Neophytou, Christiana M; Constantinou, Constantina; Papageorgis, Panagiotis; Constantinou, Andreas I

    2014-05-01

    D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is a vitamin E derivative that has been intensively applied as a vehicle for drug delivery systems to enhance drug solubility and increase the oral bioavailability of anti-cancer drugs. Recently, it has been reported that TPGS acts as an anti-cancer agent alone or synergistically with chemotherapeutic drugs and increases the efficacy of nanoparticle formulations. In this study, we investigated the antitumor efficacy and the molecular mechanism of action of TPGS in breast cancer cell lines. Our results show that TPGS can induce G1/S cell cycle arrest and apoptosis in breast cancer cell lines (MCF-7 and MDA-MB-231) but not in "normal" (non-tumorigenic) immortalized cells (MCF-10A and MCF-12F). An investigation of the molecular mechanism of action of TPGS reveals that induction of G1/S phase cell cycle arrest is associated with upregulation of P21 and P27Kip1 proteins. Induction of apoptosis by TPGS involves the inhibition of phospho-AKT and the downregulation of the anti-apoptotic proteins Survivin and Bcl-2. Interestingly, our results also suggest that TPGS induces both caspase -dependent and -independent apoptotic signaling pathways and that this vitamin E derivative is selectively cytotoxic in breast cancer cell lines. When compared to the Survivin inhibitor YM155, TPGS was shown to be more selective for cancer cell growth inhibition. Overall our results suggest that TPGS may not only be useful as a carrier molecule for drug delivery, but may also exert intrinsic therapeutic effects suggesting that it may promote a synergistic interaction with formulated chemotherapeutic drugs. PMID:24560876

  5. Highly selective and sensitive fluorescent probe for the detection of nitrite.

    PubMed

    Gu, Biao; Huang, Liyan; Hu, Jiali; Liu, Jingjing; Su, Wei; Duan, Xiaoli; Li, Haitao; Yao, Shouzhuo

    2016-05-15

    A simple and reliable fluorescent nitrite (NO2(-)) probe, 2-(1H-phenanthro[9,10-d] imidazol-2-yl)aniline (PA), was rationally developed based on a novel NO2(-)-mediated diazozation and subsequent cyclization. The new sensing mechanism of the probe was confirmed by using NMR, IR spectra, control experiments and DFT calculations. The synthesized probe showed low pH dependence, fast and highly selective fluorescence response to NO2(-) over other species. Under the optimized conditions, the linear response of the probe toward NO2(-) was in the range of 0.1-10 μM with a low detection limit of 4.3×10(-8) M. Moreover, PA was successfully applied for the determination of NO2(-) in environmental samples and food products. PMID:26992506

  6. Functionalized polymeric magnetic nanoconstructs for selective capturing and sensitive detection of Salmonella typhimurium.

    PubMed

    Chattopadhyay, Sruti; Kaur, Avneet; Jain, Swati; Sabharwal, Prabhjot K; Singh, Harpal

    2016-09-21

    Rapid detection and enumeration of pathogens is essential for monitoring contamination and spoilage of food products to ensure improved quality control management. Functionalized polymeric magnetic nanoconstructs (FPMNCs) were developed as an effective immunomagnetic separator and sensing platform for the selective capturing of Salmonella typhimurium. Novel FPMNCs were prepared in three stages involving synthesis of iron oxide (IO) dispersion, capping with sodium oleate and encapsulation of preformed IO nanoparticles by in-situ free radical emulsion polymerization of styrene (St), methyl methacrylate (MMA) and acetoacetoxy ethylmethacrylate (AAEM). PMMA improves the stability of FPMNCs by bridging extremely hydrophobic PS and hydrophilic PAAEM. Core-shell morphology of hydrophobic core of IO, PS & PMMA and hydrophilic shell of PAAEM was demonstrated by SEM, TEM and FTIR studies. FPMNCs with surface functionalized acetoacetoxy groups were covalently attached with polyclonal antibodies against Salmonella common structural antigen (CSA-1-Ab) without using any linker and catalyst. Colorimetric readout signal was acquired using CSA-1-Ab-HRP as secondary antibody after formation of sandwich immunocomplex with bacteria where the optical density of the samples were recorded using ELISA plate reader at 450 nm. The developed immunoassay was specific and selective which captures only targeted S. typhimurium with a detection limit of 10 cells/mL lower than infectious dose of salmonellosis infection. Minimal interference of food matrix with high signal to noise ratio was shown by various food samples. In addition, the performance of developed FPMNC based immunoassay was superior to commercially available immunomagnetic microbeads demonstrating undisputed advantage for capturing and detecting specific bacteria without any pre-enrichment of sample. PMID:27590554

  7. Microglial brain region-dependent diversity and selective regional sensitivities to ageing

    PubMed Central

    Grabert, Kathleen; Michoel, Tom; Karavolos, Michail H; Clohisey, Sara; Baillie, J Kenneth; Stevens, Mark P; Freeman, Tom C; Summers, Kim M; McColl, Barry W

    2015-01-01

    Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration. PMID:26780511

  8. Microglial brain region-dependent diversity and selective regional sensitivities to aging.

    PubMed

    Grabert, Kathleen; Michoel, Tom; Karavolos, Michail H; Clohisey, Sara; Baillie, J Kenneth; Stevens, Mark P; Freeman, Tom C; Summers, Kim M; McColl, Barry W

    2016-03-01

    Microglia have critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific, spatially restricted patterns, the origins of which are unknown. We performed to our knowledge the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse, and found that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune-vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during aging. Microglial diversity may enable regionally localized homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration. PMID:26780511

  9. Highly Sensitive and Selective Label-Free Optical Detection of Mercuric Ions Using Photon Upconverting Nanoparticles

    PubMed Central

    Kumar, Manoj; Zhang, Peng

    2010-01-01

    We demonstrate a fluorescence-based, label-free detection scheme that reports the presence of Hg(II) ion using photon upconverting nanoparticles. A single-stranded DNA containing a number of thymine bases to be used as the Hg2+-capturing element is covalently attached to the photon upconverting NaYF4:Yb3+,Tm3+ nanoparticles. Under the illumination of 980 nm laser, energy transfer takes place between the NaYF4:Yb3+,Tm3+ nanoparticles as the donor and SYBR green I, a DNA intercalating dye, as the acceptor. By monitoring the ratio of the acceptor emission to the donor emission, we can quantitatively detect the presence of the mercuric ions with a directly observed detection limit of 0.06 nM. The remarkably high signal-to-noise ratio of photon upconverting particles leads to very high sensitivity and specificity without the need of fluorophore labeling. The sensor also does not suffer from photobleaching. PMID:20456935

  10. High-sensitivity high-selectivity detection of CWAs and TICs using tunable laser photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Pushkarsky, Michael; Webber, Michael; Patel, C. Kumar N.

    2005-03-01

    We provide a general technique for evaluating the performance of an optical sensor for the detection of chemical warfare agents (CWAs) in realistic environments and present data from a simulation model based on a field deployed discretely tunable 13CO2 laser photoacoustic spectrometer (L-PAS). Results of our calculations show the sensor performance in terms of usable sensor sensitivity as a function of probability of false positives (PFP). The false positives arise from the presence of many other gases in the ambient air that could be interferents. Using the L-PAS as it exists today, we can achieve a detection threshold of about 4 ppb for the CWAs while maintaining a PFP of less than 1:106. Our simulation permits us to vary a number of parameters in the model to provide guidance for performance improvement. We find that by using a larger density of laser lines (such as those obtained through the use of tunable semiconductor lasers), improving the detector noise and maintaining the accuracy of laser frequency determination, optical detection schemes can make possible CWA sensors having sub-ppb detection capability with <1:108 PFP. We also describe the results of a preliminary experiment that verifies the results of the simulation model. Finally, we discuss the use of continuously tunable quantum cascade lasers in L-PAS for CWA and TIC detection.

  11. CHEF induced highly selective and sensitive turn-on fluorogenic and colorimetric sensor for Fe3+.

    PubMed

    Goswami, Shyamaprosad; Das, Sangita; Aich, Krishnendu; Sarkar, Deblina; Mondal, Tapan Kumar; Quah, Ching Kheng; Fun, Hoong-Kun

    2013-11-14

    A new fluorescent probe was synthesized from rhodamine-6G and 6-(hydroxymethyl) picolinohydrazide for the sensing of Fe(3+) in an aqueous environment. The structure of the sensor was confirmed through its single crystal X-ray study. It exhibits a high specificity and sensitivity towards Fe(3+) over other interfering heavy and transition metal ions (HTM). The turn-on greenish-yellow fluorescence and a colorimetric change from colourless to pink were observed upon addition of Fe(3+) which evokes almost 116- and 23-fold enhancement in absorbance and emission intensity respectively in an acetonitrile-water (1:1, v/v, 25 °C) solution at a neutral pH (pH = 7.2). The Fe(3+) promoted ring opening of the spirolactam framework to the open chain amide platform of the sensor is responsible for its visible colour change and turn-on fluorescence activity. It also exhibits an excellent performance in the "dip stick" method. Moreover the limit of detection of the probe is in the 10(-8) M range. PMID:24000084

  12. A recyclable chitosan-based QCM biosensor for sensitive and selective detection of breast cancer cells in real time.

    PubMed

    Zhang, Shaolian; Bai, Haihua; Luo, Jinmei; Yang, Peihui; Cai, Jiye

    2014-12-01

    A highly sensitive and recyclable quartz crystal microbalance (QCM) biosensor was developed using chitosan (CS) and folic acid (FA), generating conjugates that are selectively recognized by MCF-7 cancer cell over-expressed folic acid receptors. The prepared CS-FA conjugate was characterized by UV-vis spectroscopy and Fourier transform infrared spectroscopy. Atomic force microscopy and scanning electron microscopy further presented the morphology of the CS-FA conjugate interface. The hydrophilicity of films was characterized by measuring the contact angle. The recognition of MCF-7 cancer cells was investigated in situ using QCM. Captured by FA, the concentration of the MCF-7 cell was determined on-line using a quartz crystal microbalance and a wide linear range of 4.5 × 10(2) to 1.01 × 10(5) cells per mL was obtained, with a detection limit of 430 cells per mL. The fluorescence microscope further confirmed the specificity and biocompatibility of the constructed biosensor. In addition, the regeneration of the QCM biosensor was studied by using lysozyme. This receptor-bound ligand based QCM biosensor also showed good selectivity, and repeatability in the cell mixture. For the first time, this simple, economical and label-free chitosan-based QCM sensing was demonstrated, and such design could provide a promising detection strategy for sensitive detection of cancer cell over-expressed folic acid receptors. PMID:25313373

  13. DNA-based detection of mercury(ii) ions through characteristic current signals in nanopores with high sensitivity and selectivity

    NASA Astrophysics Data System (ADS)

    Zeng, Tao; Li, Ting; Li, Yuru; Liu, Lei; Wang, Xingyong; Liu, Quansheng; Zhao, Yuliang; Wu, Hai-Chen

    2014-07-01

    We report single-molecule detection of Hg2+ by threading an Hg2+-mediated DNA duplex through α-hemolysin nanopores, which generates characteristic three-level current patterns and enables the unambiguous detection of Hg2+. This strategy precludes any background interference and features high sensitivity and selectivity. Moreover, the platform could be readily integrated with aptamers and molecular beacons, offering extended possibilities for the construction of a new DNA-based nanopore sensing system.We report single-molecule detection of Hg2+ by threading an Hg2+-mediated DNA duplex through α-hemolysin nanopores, which generates characteristic three-level current patterns and enables the unambiguous detection of Hg2+. This strategy precludes any background interference and features high sensitivity and selectivity. Moreover, the platform could be readily integrated with aptamers and molecular beacons, offering extended possibilities for the construction of a new DNA-based nanopore sensing system. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02062f

  14. Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations

    PubMed Central

    Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir

    2012-01-01

    The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate. PMID:22412190

  15. Recent Results on the CKM Angle Alpha

    SciTech Connect

    Mihalyi, A.; /Wisconsin U., Madison

    2005-10-18

    The method to measure the CKM angle {alpha} and the modes sensitive to it are discussed. It is shown that the B {yields} {rho}{rho} decays provide the most stringent constraint on {alpha}, which is found to be {alpha} = 96{sup o} {+-} 10{sup o}(stat) {+-} 4{sup o}(syst){+-} 13{sup o}(penguin).

  16. Oxygen-evoked changes in transcriptional activity of the 5'-flanking region of the human amiloride-sensitive sodium channel (alphaENaC) gene: role of nuclear factor kappaB.

    PubMed Central

    Baines, Deborah L; Janes, Mandy; Newman, David J; Best, Oliver G

    2002-01-01

    Expression of the alpha-subunit of the amiloride-sensitive sodium channel (alphaENaC) is regulated by a number of factors in the lung, including oxygen partial pressure (PO2). As transcriptional activation is a mechanism for raising cellular mRNA levels, we investigated the effect of physiological changes in PO2 on the activity of the redox-sensitive transcription factor nuclear factor kappaB (NF-kappaB) and transcriptional activity of 5'-flanking regions of the human alphaENaC gene using luciferase reporter-gene vectors transiently transfected into human adult alveolar carcinoma A549 cells. By Western blotting we confirmed the presence of NF-kappaB p65 but not p50 in these cells. Transiently increasing PO2 from 23 to 42 mmHg for 24 h evoked a significant increase in NF-kappaB DNA-binding activity and transactivation of a NF-kappaB-driven luciferase construct (pGLNF-kappaBpro), which was blocked by the NF-kappaB activation inhibitor sulphasalazine (5 mM). Transcriptional activity of alphaENaC-luciferase constructs containing 5'-flanking sequences (including the NF-kappaB consensus) were increased by raising PO2 from 23 to 142 mmHg if they contained transcriptional initiation sites (TIS) for exons 1A and 1B (pGL3E2.2) or the 3' TIS of exon 1B alone (pGL3E0.8). Sulphasalazine had no significant effect on the activity of these constructs, suggesting that the PO2-evoked rise in activity was not a direct consequence of NF-kappaB activation. Conversely, the relative luciferase activity of a construct that lacked the 3' TIS, a 3' intron and splice site but still retained the 5' TIS and NF-kappaB consensus sequence was suppressed significantly by raising PO2. This effect was reversed by sulphasalazine, suggesting that activation of NF-kappaB mediated PO2-evoked suppression of transcription from the exon 1A TIS of alphaENaC. PMID:12023897

  17. Measurement of the L. beta. to L. cap alpha. intensity ratio through a selective excitation of L/sub III/ subshell in elements of Zgreater than or equal to70

    SciTech Connect

    Murty, G.S.K.; Chandrasekhar Rao, M.V.S.; Raghavaiah, C.V.; Reddy, S.B.; Satyanarayana, G.; Sastry, D.L.

    1989-02-01

    The intensity ratio of L..beta../sub 2/+L..beta../sub 5/+L..beta../sub 6/ to L..cap alpha../sub 1/+L..cap alpha../sub 2/ was measured in seven elements (Zgreater than or equal to70) through a selective excitation of the L/sub III/ subshell using an x-ray tube. A high-resolution Si(Li) detector system coupled to a computer controlled multichannel analyzer was used in these measurements. The results show that the relative transition probabilities L..beta.. and L..cap alpha.. agree with the relativistic Hartree-Fock-Slater calculations in the case of Yb and U, while a discrepancy of 3.1--8.7 % between experiment and theory is found for the other elements.

  18. Urchin-like polypyrrole nanoparticles for highly sensitive and selective chemiresistive sensor application

    NASA Astrophysics Data System (ADS)

    Lee, Jun Seop; Jun, Jaemoon; Shin, Dong Hoon; Jang, Jyongsik

    2014-03-01

    Urchin-like polypyrrole (U_PPy) nanoparticles with various diameters were fabricated using a dual-nozzle electrospray and vapor deposition polymerization (VDP). Metal oxide nanoneedle-decorated PPy (FePPy) particles were fabricated as starting materials for deposition of a PPy layer on the metal oxide surface. The FePPy particles were prepared by heating and stirring an aqueous solution of the metal precursor and electrosprayed PPy (E_PPy) particles with nucleated sites on the surface. U_PPys with a maximized surface area were then formed by soaking in an initiator solution followed by VPD. The U_PPy particles were evaluated in various hazardous chemical gas sensors at room temperature. Because of their larger surface area, U_PPy based chemiresistive sensors exhibited greater sensitivity and ca. 10-100 times higher minimum detectable levels (MDLs) of common analytes than pristine PPy particle-based sensors. For example, the MDL of NH3 was approximately 0.01 ppm, which is better than that observed for other conducting polymer nanostructures. Our new fabrication methodology promises to be an effective approach for fabrication of hybrid nanostructures for future sensing technologies.Urchin-like polypyrrole (U_PPy) nanoparticles with various diameters were fabricated using a dual-nozzle electrospray and vapor deposition polymerization (VDP). Metal oxide nanoneedle-decorated PPy (FePPy) particles were fabricated as starting materials for deposition of a PPy layer on the metal oxide surface. The FePPy particles were prepared by heating and stirring an aqueous solution of the metal precursor and electrosprayed PPy (E_PPy) particles with nucleated sites on the surface. U_PPys with a maximized surface area were then formed by soaking in an initiator solution followed by VPD. The U_PPy particles were evaluated in various hazardous chemical gas sensors at room temperature. Because of their larger surface area, U_PPy based chemiresistive sensors exhibited greater sensitivity

  19. EEG Alpha Power and Intelligence.

    ERIC Educational Resources Information Center

    Doppelmayr, M.; Klimesch, W.; Stadler, W.; Pollhuber, D.; Heine, C.

    2002-01-01

    Tested whether alpha power in different sub-bands is selectively related to intelligence. For 74 Austrian subjects, the EEG was recorded during a resting session and 2 different intelligence tests were performed. Findings show a strong positive correlation between intelligence and alpha power. (SLD)

  20. The sensitive and selective adsorption of aromatic compounds with highly crosslinked polymer nanoparticles.

    PubMed

    Liu, Shuqin; Chen, Darui; Zheng, Juan; Zeng, Lewei; Jiang, Jijun; Jiang, Ruifeng; Zhu, Fang; Shen, Yong; Wu, Dingcai; Ouyang, Gangfeng

    2015-10-28

    This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar organic pollutants by means of solid-phase microextraction (SPME). Owing to its high hydrophobicity, diverse pore size distribution and highly conjugated structure, a 10 μm HCP coating exhibited excellent adsorption abilities towards benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP-nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five PAHs in environmental water samples and satisfactory recoveries were achieved. The findings could provide a new benchmark for the exploitation of superb HCPs as effective adsorbents for SPME or other adsorption applications. PMID:26416568

  1. Unnatural amino acids increase sensitivity and provide for the design of highly selective caspase substrates.

    PubMed

    Poreba, M; Kasperkiewicz, P; Snipas, S J; Fasci, D; Salvesen, G S; Drag, M

    2014-09-01

    Traditional combinatorial peptidyl substrate library approaches generally utilize natural amino acids, limiting the usefulness of this tool in generating selective substrates for proteases that share similar substrate specificity profiles. To address this limitation, we synthesized a Hybrid Combinatorial Substrate Library (HyCoSuL) with the general formula of Ac-P4-P3-P2-Asp-ACC, testing the approach on a family of closely related proteases - the human caspases. The power of this library for caspase discrimination extends far beyond traditional PS-SCL approach, as in addition to 19 natural amino acids we also used 110 diverse unnatural amino acids that can more extensively explore the chemical space represented by caspase-active sites. Using this approach we identified and employed peptide-based substrates that provided excellent discrimination between individual caspases, allowing us to simultaneously resolve the individual contribution of the apical caspase-9 and the executioner caspase-3 and caspase-7 in the development of cytochrome-c-dependent apoptosis for the first time. PMID:24832467

  2. Asteroid Target Selection and Orbital Manipulation Sensitivity for Deflection Demonstration Missions

    NASA Astrophysics Data System (ADS)

    Sanchez, J. P.

    2015-06-01

    In recent years, space agencies have begun to seriously consider launching demonstration missions to test some of the asteroid orbital deflection technologies and methods that have been studied and discussed in the scientific literature. Consequently, several mission studies have already been carried out. This paper attempts to gain new insights into the target selection process by analyzing the orbital evolution of a large set of notional accessible asteroids that cover all types of Near Earth Object families. The evolution of their unperturbed orbits and their anthropogenically modified trajectories was compared, and a measure of the resilience of a given orbit to anthropogenic manipulation was taken (i.e., orbital innocuity). The results show that pruning criteria such as considering only Amor objects (i.e., non-Earth-crossers) reduce unnecessarily the population of potential suitable targets and that within large regions of Earth-crossing orbital space asteroids can be found that are both accessible and safe to manipulate from the standpoint of the Earth impact risk.

  3. Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin

    PubMed Central

    Prueksaritanont, Thomayant; Chu, Xiaoyan; Evers, Raymond; Klopfer, Stephanie O; Caro, Luzelena; Kothare, Prajakti A; Dempsey, Cynthia; Rasmussen, Scott; Houle, Robert; Chan, Grace; Cai, Xiaoxin; Valesky, Robert; Fraser, Iain P; Stoch, S Aubrey

    2014-01-01

    Aims Rosuvastatin and pitavastatin have been proposed as probe substrates for the organic anion-transporting polypeptide (OATP) 1B, but clinical data on their relative sensitivity and selectivity to OATP1B inhibitors are lacking. A clinical study was therefore conducted to determine their relative suitability as OATP1B probes using single oral (PO) and intravenous (IV) doses of the OATP1B inhibitor rifampicin, accompanied by a comprehensive in vitro assessment of rifampicin inhibitory potential on statin transporters. Methods The clinical study comprised of two separate panels of eight healthy subjects. In each panel, subjects were randomized to receive a single oral dose of rosuvastatin (5 mg) or pitavastatin (1 mg) administered alone, concomitantly with rifampicin (600 mg) PO or IV. The in vitro transporter studies were performed using hepatocytes and recombinant expression systems. Results Rifampicin markedly increased exposures of both statins, with greater differential increases after PO vs. IV rifampicin only for rosuvastatin. The magnitudes of the increases in area under the plasma concentration–time curve were 5.7- and 7.6-fold for pitavastatin and 4.4- and 3.3-fold for rosuvastatin, after PO and IV rifampicin, respectively. In vitro studies showed that rifampicin was an inhibitor of OATP1B1 and OATP1B3, breast cancer resistance protein and multidrug resistance protein 2, but not of organic anion transporter 3. Conclusions The results indicate that pitavastatin is a more sensitive and selective and thus preferred clinical OATP1B probe substrate than rosuvastatin, and that a single IV dose of rifampicin is a more selective OATP1B inhibitor than a PO dose. PMID:24617605

  4. Highly selective and sensitive detection of glutathione using mesoporous silica nanoparticles capped with disulfide-containing oligo(ethylene glycol) chains.

    PubMed

    El Sayed, Sameh; Giménez, Cristina; Aznar, Elena; Martínez-Máñez, Ramón; Sancenón, Félix; Licchelli, Maurizio

    2015-01-28

    Mesoporous silica nanoparticles loaded with safranin O and capped with disulfide-containing oligo(ethylene glycol) chains were used for the selective and sensitive fluorimetric detection of glutathione. PMID:25482517

  5. The influence of worm age, duration of exposure and endpoint selection on bioassay sensitivity for Neanthes arenaceodentata (Annelida: Polychaeta)

    SciTech Connect

    Bridges, T.S.; Farrar, J.D.

    1997-08-01

    The influence of worm age, duration of exposure, and endpoint selection on bioassay sensitivity were evaluated for Neanthes arenaceodentata. Worms were exposed to contaminated sediment collected from Black Rock Harbor (BRH) near Bridgeport, Connecticut, USA. This sediment was diluted with clean control sediment to result in five experimental treatments: 0, 25, 50, 75, and 100% BRH. Three exposure scenarios were employed: (1) a 4-week exposure beginning with newly emerged juveniles (EJ-4w), (2) a 7-week exposure beginning with newly emerged juveniles (EJ-7w), and (3) a 4-week exposure beginning with 3-week-old juveniles (3WO-4w). Six measures of worm size were recorded at the conclusion of each exposure to evaluate differences among measurement endpoints. Survival was significantly reduced at the 25% BRH level for the EJ-7w scenario and at the 100% BRH level for the EJ-4w and 3WO-4w scenarios. Growth was significantly reduced at the 25% BRH level in each exposure scenario. Estimates based on the calculated minimum detectable difference indicated that considerably lower concentrations of BRH (6--10%) should be distinguishable by measuring effects on Neanthes growth. Worm size measured in terms of projected area, dry weight, and ash-free dry weight provided the most sensitive measures of effects. Increasing the length of exposure from 4 to 7 weeks and initiating exposures with emergent juveniles rather than 3-week-old worms increased the sensitivity of the bioassay. The results of this study demonstrate that N. arenacedentata is sensitive to the presence of sediment-associated contaminants and that test animal age, duration of exposure, and choice of endpoint can have a large effect on the magnitude of the toxic response observed.

  6. A sensitive, selective, and portable detector for contraband: The compact integrated narcotics detection instrument

    SciTech Connect

    Tuemer, T.O.; Doan, L.; Su, C.W.; Baritelle, J.; Rhoton, B.

    2000-07-01

    A Compact Integrated Narcotics Detection Instrument (CINDI) has been developed at NOVA R and D, Inc., in cooperation with the US Coast Guard. This detector utilizes neutrons emitted from {sup 252}Cf. Neutrons emitted from the front face of CINDI penetrate dense compartment barrier materials with little change in energy but are backscattered by hydrogen-rich materials such as drugs. The backscattered neutrons are detected, and the rate is displayed by a microprocessor-controller integrated into CINDI. The operator guides the detector along a suspected area and receives immediate feedback from the state-of-the-art electronics. For user safety, the device incorporates a highly sensitive detection scheme to permit the use of a very weak radioactive source, without compromising detectability. CINDI is capable of detecting narcotics effectively behind panels made of steel, wood, fiberglass, or even lead-lined materials. This makes it useful for inspecting marine vessels, ship bulkheads, automobiles, structure walls, or small sealed containers. Figure 2 shows three views of the CINDI instrument. CINDI responds strongly to hydrogen-rich materials such as narcotics. It has been tested at NOVA, the US Coast Guard, and Brewt Power Systems. The results of the tests show excellent response and specificity to narcotics. CINDI has led to a new technology that shows promise for identifying the concealed contraband. The new technique uses a fusion of two independent but complementary signals for detecting and possibly identifying concealed drugs in a variety of carriers such as vehicles, marine vessels, airplanes, containers, cargo, and luggage. The carriers will be scanned using both neutron and gamma-ray sources. The signal from both the neutron and gamma-ray backscattering and/or transmission can be used simultaneously to detect and possibly identify the contrabands it has been trained for. A system that can produce three-dimensional images for both signals may also be developed

  7. Gold nanoprobe functionalized with specific fusion protein selection from phage display and its application in rapid, selective and sensitive colorimetric biosensing of Staphylococcus aureus.

    PubMed

    Liu, Pei; Han, Lei; Wang, Fei; Petrenko, Valery A; Liu, Aihua

    2016-08-15

    Staphylococcus aureus (S. aureus) is one of the most ubiquitous pathogens in public healthcare worldwide. It holds great insterest in establishing robust analytical method for S. aureus. Herein, we report a S. aureus-specific recognition element, isolated from phage monoclone GQTTLTTS, which was selected from f8/8 landscape phage library against S. aureus in a high-throughput way. By functionalizing cysteamine (CS)-stabilized gold nanoparticles (CS-AuNPs) with S. aureus-specific pVIII fusion protein (fusion-pVIII), a bifunctional nanoprobe (CS-AuNPs@fusion-pVIII) for S. aureus was developed. In this strategy, the CS-AuNPs@fusion-pVIII could be induced to aggregate quickly in the presence of target S. aureus, resulting in a rapid colorimetric response of gold nanoparticles. More importantly, the as-designed probe exhibited excellent selectivity over other bacteria. Thus, the CS-AuNPs@fusion-pVIII could be used as the indicator of target S. aureus. This assay can detect as low as 19CFUmL(-1)S. aureus within 30min. Further, this approach can be applicable to detect S. aureus in real water samples. Due to its sensitivity, specificity and rapidness, this proposed method is promising for on-site testing of S. aureus without using any costly instruments. PMID:27085951

  8. The sensitive and selective adsorption of aromatic compounds with highly crosslinked polymer nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Shuqin; Chen, Darui; Zheng, Juan; Zeng, Lewei; Jiang, Jijun; Jiang, Ruifeng; Zhu, Fang; Shen, Yong; Wu, Dingcai; Ouyang, Gangfeng

    2015-10-01

    This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar organic pollutants by means of solid-phase microextraction (SPME). Owing to its high hydrophobicity, diverse pore size distribution and highly conjugated structure, a 10 μm HCP coating exhibited excellent adsorption abilities towards benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP-nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five PAHs in environmental water samples and satisfactory recoveries were achieved. The findings could provide a new benchmark for the exploitation of superb HCPs as effective adsorbents for SPME or other adsorption applications.This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the

  9. Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection

    PubMed Central

    Chang, Chia Lin; Semyonov, Jenia; Cheng, Po Jen; Huang, Shang Yu; Park, Jae Il; Tsai, Huai-Jen; Lin, Cheng-Yung; Grützner, Frank; Soong, Yung Kuei; Cai, James J.; Hsu, Sheau Yu Teddy

    2013-01-01

    In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies. PMID:23613906

  10. Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies.

    PubMed

    Briscoe, Adriana D; Bybee, Seth M; Bernard, Gary D; Yuan, Furong; Sison-Mangus, Marilou P; Reed, Robert D; Warren, Andrew D; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

    2010-02-23

    The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)-a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with lambda(max) = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate. PMID:20133601

  11. Reaction-Driven Self-Assembled Micellar Nanoprobes for Ratiometric Fluorescence Detection of CS2 with High Selectivity and Sensitivity.

    PubMed

    Lu, Wei; Xiao, Peng; Liu, Zhenzhong; Gu, Jincui; Zhang, Jiawei; Huang, Youju; Huang, Qing; Chen, Tao

    2016-08-10

    The detection of highly toxic CS2, which is known as a notorious occupational hazard in various industrial processes, is important from both environmental and public safety perspectives. We describe here a robust type of chemical-reaction-based supramolecular fluorescent nanoprobes for ratiometric determination of CS2 with high selectivity and sensitivity in water medium. The micellar nanoprobes self-assemble from amphiphilic pyrene-modified hyperbranched polyethylenimine (Py-HPEI) polymers with intense pyrene excimer emission. Selective sensing is based on a CS2-specific reaction with hydrophilic amino groups to produce hydrophobic dithiocarbamate moieties, which can strongly quench the pyrene excimer emission via a known photoinduced electron transfer (PET) mechanism. Therefore, the developed micellar nanoprobes are free of the H2S interference problem often encountered in the widely used colorimetric assays and proved to show high selectivity over many potentially competing chemical species. Importantly, the developed approach is capable of CS2 sensing even in complex tap and river water samples. In addition, in view of the modular design principle of these powerful micellar nanoprobes, the sensing strategy used here is expected to be applicable to the development of various sensory systems for other environmentally important guest species. PMID:27419849

  12. Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies

    PubMed Central

    Briscoe, Adriana D.; Bybee, Seth M.; Bernard, Gary D.; Yuan, Furong; Sison-Mangus, Marilou P.; Reed, Robert D.; Warren, Andrew D.; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

    2010-01-01

    The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)—a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with λmax = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate. PMID:20133601

  13. Thiacalix[4]arene-tetra-(quinoline-8- sulfonate): a Sensitive and Selective Fluorescent Sensor for Co (II).

    PubMed

    Modi, Krunal; Panchal, Urvi; Dey, Shuvankar; Patel, Chirag; Kongor, Anita; Pandya, Himanshu A; Jain, V K

    2016-09-01

    A novel fluorescent thiacalix[4]arene-tetra-(quinoline-8-sulfonate) (TCTQ8S) was synthesized by condensation of thiacalix[4]arene (TCA) and 8-quinoline sulfonyl chloride(8QSC). TCTQ8S was characterized by ESI-MS, (1)H-NMR and (13)C-NMR spectroscopic methods. TCTQ8S was found to be an efficient "turn-off" fluorescent sensor for the selective and sensitive recognition of Co(II) ions. The Job's plot measurement reveals a 1:1 stoichiometric ratio. The designed chemosensor exhibited high selectivity toward Co(II) ions vs. other tested metal ions, with a detection limit of up to 1.038 × 10(-9) M. The binding constant and quantum yield for the complex were also determined. Molecular docking studies have been successfully performed to support 1:1 binding of TCTQ8S with the Co(II) metal ion. TCTQ8S was evaluated for real sample analysis on water sample for the detection of Co(II). Graphical Abstract Thiacalix derivatized fluorescent sensor for the selective detection of Co(II). PMID:27392975

  14. Alpha Thalassemia

    MedlinePlus

    ... an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia minor. It can ... gene on one chromosome 25% 25% 25% 25% hemoglobin H disease there is a 25% chance with ...

  15. Two distinct abnormalities in patients with C8 alpha-gamma deficiency. Low level of C8 beta chain and presence of dysfunctional C8 alpha-gamma subunit.

    PubMed Central

    Tedesco, F; Roncelli, L; Petersen, B H; Agnello, V; Sodetz, J M

    1990-01-01

    The sera from three C8 alpha-gamma deficient patients previously reported to have a selective C8 alpha-gamma defect were analyzed by SDS-PAGE and Western blot using two polyclonal antisera to C8 alpha-gamma and a monoclonal antibody to C8 alpha. All three sera exhibited C8 alpha-gamma bands that dissociated into alpha and gamma chains under reducing conditions. Quantitation of the alpha-gamma subunit in these sera by a sensitive ELISA revealed an amount approximately 1% of that found in normal human serum. A similar assay performed with a specific antiserum to C8 beta showed unexpectedly low levels of C8 beta in these sera, which were confirmed by hemolytic titration of C8 beta. The remarkable differences between C8 alpha-gamma and C8 beta in the C8 alpha-gamma deficient sera was that in spite of their comparable immunochemical levels, C8 beta still exhibited functional activity whereas C8 alpha-gamma was totally inactive. That the residual C8 alpha-gamma was inactive was also proved by its inability to show lytic bands in an overlay system after SDS-PAGE and subsequent removal of SDS. The implications of these findings for a novel concept of C8 deficiency are discussed. Images PMID:2394837

  16. Sensitized spectrophotometric determination of Cr(III) ion for speciation of chromium ion in surfactant media using alpha-benzoin oxime.

    PubMed

    Ghaedi, Mehrorang; Asadpour, Enayat; Vafaie, Azam

    2006-01-01

    A simple and accurate micellanized spectrophotometric method for determination of trace amounts of Cr(III) ion in tab and top water and a synthetic mixture has been described. The micellar method is based on effect of organized molecular assemblies such as micelles in spectrophotometric measurement due to their effect on the systems of interest. The ability of micellar system in solubilizing of sparingly soluble ligand or complexes has been used for increasing figures of merit of an analytical method. Due to solubility increasing in aqueous media requirement for a primary extraction can be eliminated. Using the alpha-benzoin oxime (alpha-BO) spectrophotometric determination of Cr(III) ion has been performed and results are compared. The spectrophotometric determination of Cr(III) ion using alpha-BO in the presence of non-ionic surfactant Triton X-100 has been performed. The influence of type and amount of surfactant, pH, complexation time and amount of ligand were examined. Finally, the repeatability, accuracy and the effect of interfering ions on the determination of Cr(III) ion was evaluated. The proposed methods successfully with recovery yield of almost 100% have been applied to the rapid and simple determination of Cr(III) ion in the real samples. There is a good agreement between methods and atomic absorption spectrometry. The Beers law is obeyed over the concentration range of 0.1-13.7 microg mL(-1) for micellar media. The detection limit is 0.8 ng mL(-1). The molar absorptivity of complex is 5350 L mol(-1) cm(-1). PMID:16344251

  17. Sensitive and selective detection of Hg2+ and Cu2+ ions by fluorescent Ag nanoclusters synthesized via a hydrothermal method

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Ren, Xiangling; Meng, Xianwei; Fang, Zheng; Tang, Fangqiong

    2013-09-01

    An easily prepared fluorescent Ag nanoclusters (Ag NCs) probe for the sensitive and selective detection of Hg2+ and Cu2+ ions was developed here. The Ag NCs were synthesized by using polymethacrylic acid sodium salt as a template via a convenient hydrothermal process. The as-prepared fluorescent Ag NCs were monodispersed, uniform and less than 2 nm in diameter, and can be quenched in the presence of mercury (Hg2+) or copper (Cu2+) ions. Excellent linear relationships existed between the quenching degree of the Ag NCs and the concentrations of Hg2+ or Cu2+ ions in the range of 10 nM to 20 μM or 10 nM to 30 μM, respectively. By using ethylenediaminetetraacetate (EDTA) as the masking agent of Cu2+, Hg2+ was exclusively detected in coexistence with Cu2+ with high sensitivity (LOD = 10 nM), which also provided a reusable detection method for Cu2+. Furthermore, the different quenching phenomena caused by the two metals ions such as changes in visible colour, shifts of UV absorbance peaks and changes in size of Ag NCs make it easy to distinguish between them. Therefore the easily synthesized fluorescent Ag NCs may have great potential as Hg2+ and Cu2+ ions sensors.An easily prepared fluorescent Ag nanoclusters (Ag NCs) probe for the sensitive and selective detection of Hg2+ and Cu2+ ions was developed here. The Ag NCs were synthesized by using polymethacrylic acid sodium salt as a template via a convenient hydrothermal process. The as-prepared fluorescent Ag NCs were monodispersed, uniform and less than 2 nm in diameter, and can be quenched in the presence of mercury (Hg2+) or copper (Cu2+) ions. Excellent linear relationships existed between the quenching degree of the Ag NCs and the concentrations of Hg2+ or Cu2+ ions in the range of 10 nM to 20 μM or 10 nM to 30 μM, respectively. By using ethylenediaminetetraacetate (EDTA) as the masking agent of Cu2+, Hg2+ was exclusively detected in coexistence with Cu2+ with high sensitivity (LOD = 10 nM), which also provided a

  18. The role of the central L- or D-Pro residue on structure and mode of action of a cell-selective alpha-helical IsCT-derived antimicrobial peptide.

    PubMed

    Lim, Shin Saeng; Kim, Yangmee; Park, Yoonkyung; Kim, Jae Il; Park, Il-Seon; Hahm, Kyung-Soo; Shin, Song Yub

    2005-09-01

    IsCT-P (ILKKIWKPIKKLF-NH2) is a novel alpha-helical antimicrobial peptide with bacterial cell selectivity designed from a scorpion-derived peptide IsCT. To investigate the role of L- or D-Pro kink on the structure and the mode of action of a short alpha-helical antimicrobial peptide with bacterial cell selectivity, we synthesized IsCT-p, in which D-Pro is substituted for L-Pro8 of IsCT-P. CD spectra revealed that IsCT-P adopted a typical alpha-helical structure in various membrane-mimicking conditions, whereas IsCT-p showed a random structure. This result indicated that D-Pro in the central position of a short alpha-helical peptide provides more remarkable structural flexibility than L-Pro. Despite its higher antibacterial activity, IsCT-p was much less effective at inducing dye leakage in the negatively charged liposome mimicking bacterial membrane and induced no or little membrane potential depolarization of Staphylococcus aureus. Confocal laser scanning microscopy showed that IsCT-p penetrated the bacterial cell membrane and accumulated in the cytoplasm, whereas IsCT-P remained outside or on the cell membrane. These results suggested that the major target of IsCT-P and IsCT-p is the bacterial membranes and intracellular components, respectively. Collectively, our results demonstrated that the central D-Pro kink in alpha-helical antimicrobial peptides plays an important role in penetrating bacterial membrane as well as bacterial cell selectivity. PMID:16040002

  19. Selective Inhibition of Alpha/Beta-Hydrolase Domain 6 Attenuates Neurodegeneration, Alleviates Blood Brain Barrier Breakdown, and Improves Functional Recovery in a Mouse Model of Traumatic Brain Injury

    PubMed Central

    Tchantchou, Flaubert

    2013-01-01

    Abstract 2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central nervous system and is elevated after brain injury. Because of its rapid hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short-lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2-AG degradation, causes a robust increase of brain levels of 2-AG, it also leads to cannabinoid receptor desensitization and behavioral tolerance. Alpha/beta hydrolase domain 6 (ABHD6) is a novel 2-AG hydrolytic enzyme that accounts for a small portion of 2-AG hydrolysis, but its inhibition is believed to elevate the levels of 2-AG within the therapeutic window without causing side effect. Using a mouse model of traumatic brain injury (TBI), we found that post-insult chronic treatment with a selective ABHD6 inhibitor WWL70 improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. This study indicates that the fine-tuning of 2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and neuroprotective effects in TBI. PMID:23151067

  20. Protective effect of PNU-120596, a selective alpha7 nicotinic acetylcholine receptor-positive allosteric modulator, on myocardial ischemia-reperfusion injury in rats.

    PubMed

    Li, Hui; Zhang, Zong-Ze; Zhan, Jia; He, Xiang-Hu; Song, Xue-Min; Wang, Yan-Lin

    2012-06-01

    The cholinergic anti-inflammatory pathw