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1

Ambrosino, Fabrizio, Lenka Thinová, Miroslav Hýža, and Carlo Sabbarese. "214Bi/214Pb radioactivity ratio three-year monitoring in rainwater in Prague." Nukleonika 65, no. 2 (June 1, 2020): 115–19. http://dx.doi.org/10.2478/nuka-2020-0018.

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AbstractContinuous monitoring of natural gamma radiation in air has been carried out, during December 2014 – January 2018, with 1-min cyclic measurement in Prague, Czech Republic using a NaI(Tl) probe. The 214Bi/214Pb ratio as a tracer in rainwater has been investigated to study its variations related to both the ambient dose equivalent rate per hour and the amount of rainfall. A hybrid methodology for time series analysis, composed of the aggregation of two signal decomposition methods (multiple linear regression and empirical mode decomposition) and one forecasting method (support vector regression), has been applied to identify the anomalies in the studied signals in order to better find correlations among them. The results show a strong correlation between the ambient dose equivalent rate and the 214Bi/214Pb ratio values and between both these signals and rainfall amount ≥5 mm/h. Furthermore, the considered descendants of radon are mainly responsible for the overall ambient dose equivalent rate.
2

Giokaris, N. D., D. F. Anderson, and B. J. Kross. "Signal from the natural radioactivity of depleted uranium in liquid argon." Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 248, no. 2-3 (August 1986): 389–92. http://dx.doi.org/10.1016/0168-9002(86)91023-5.

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3

Bellotti, E., C. Broggini, G. Di Carlo, M. Laubenstein, and R. Menegazzo. "STUDY OF THE TIME DEPENDENCE OF RADIOACTIVITY." Acta Polytechnica 53, A (December 18, 2013): 524–27. http://dx.doi.org/10.14311/ap.2013.53.0524.

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The activity of a <sup>137</sup>Cs source was measured using a germanium detector installed deep underground in the Gran Sasso Laboratory. In total about 5100 energy spectra, one hour measuring time each, were collected and used to search for time variations of the decay constant with periods from a few hours to 1 year. No signal with amplitude larger than 9.6 × 10<sup>−5</sup> at 95% C.L. was detected. These limits are more than one order of magnitude lower than the values on the oscillation amplitude reported in the literature. The same data give a value of 29.96±0.08 years for the <sup>137</sup>Cs half life, which is in good agreement with the world mean value of 30.05 ± 0.08 years.
4

Smith, John N., Robin M. Brown, William J. Williams, Marie Robert, Richard Nelson, and S. Bradley Moran. "Arrival of the Fukushima radioactivity plume in North American continental waters." Proceedings of the National Academy of Sciences 112, no. 5 (December 29, 2014): 1310–15. http://dx.doi.org/10.1073/pnas.1412814112.

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The large discharge of radioactivity into the northwest Pacific Ocean from the 2011 Fukushima Dai-ichi nuclear reactor accident has generated considerable concern about the spread of this material across the ocean to North America. We report here the first systematic study to our knowledge of the transport of the Fukushima marine radioactivity signal to the eastern North Pacific. Time series measurements of 134Cs and 137Cs in seawater revealed the initial arrival of the Fukushima signal by ocean current transport at a location 1,500 km west of British Columbia, Canada, in June 2012, about 1.3 y after the accident. By June 2013, the Fukushima signal had spread onto the Canadian continental shelf, and by February 2014, it had increased to a value of 2 Bq/m3 throughout the upper 150 m of the water column, resulting in an overall doubling of the fallout background from atmospheric nuclear weapons tests. Ocean circulation model estimates that are in reasonable agreement with our measured values indicate that future total levels of 137Cs (Fukushima-derived plus fallout 137Cs) off the North American coast will likely attain maximum values in the 3–5 Bq/m3 range by 2015–2016 before declining to levels closer to the fallout background of about 1 Bq/m3 by 2021. The increase in 137Cs levels in the eastern North Pacific from Fukushima inputs will probably return eastern North Pacific concentrations to the fallout levels that prevailed during the 1980s but does not represent a threat to human health or the environment.
5

Koo, Kil-Mo, Jin-Ho Song, Sang-Baik Kim, Kwang-Il Ahn, Won-Pil Baek, Kil-Nam Oh, and Gyu-Tae Kim. "Response Analysis on Electrical Pulses under Severe Nuclear Accident Temperature Conditions Using an Abnormal Signal Simulation Analysis Module." Science and Technology of Nuclear Installations 2012 (2012): 1–15. http://dx.doi.org/10.1155/2012/656590.

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Unlike design basis accidents, some inherent uncertainties of the reliability of instrumentations are expected while subjected to harsh environments (e.g., high temperature and pressure, high humidity, and high radioactivity) occurring in severe nuclear accident conditions. Even under such conditions, an electrical signal should be within its expected range so that some mitigating actions can be taken based on the signal in the control room. For example, an industrial process control standard requires that the normal signal level for pressure, flow, and resistance temperature detector sensors be in the range of 4~20 mA for most instruments. Whereas, in the case that an abnormal signal is expected from an instrument, such a signal should be refined through a signal validation process so that the refined signal could be available in the control room. For some abnormal signals expected under severe accident conditions, to date, diagnostics and response analysis have been evaluated with an equivalent circuit model of real instruments, which is regarded as the best method. The main objective of this paper is to introduce a program designed to implement a diagnostic and response analysis for equivalent circuit modeling. The program links signal analysis tool code to abnormal signal simulation engine code not only as a one body order system, but also as a part of functions of a PC-based ASSA (abnormal signal simulation analysis) module developed to obtain a varying range of theR-Ccircuit elements in high temperature conditions. As a result, a special function for abnormal pulse signal patterns can be obtained through the program, which in turn makes it possible to analyze the abnormal output pulse signals through a response characteristic of a 4~20 mA circuit model and a range of the elements changing with temperature under an accident condition.
6

Mebinck, K., H. Middelkoop, N. van Diepen, E. R. van der Graaf, and R. J. de Meijer. "Radiometric fingerprinting of fluvial sediments in the Rhine-Meuse delta, the Netherlands – a feasibility test." Netherlands Journal of Geosciences 86, no. 3 (September 2007): 229–40. http://dx.doi.org/10.1017/s0016774600077829.

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AbstractThe deposits of the Rhine and the Meuse in the Netherlands alternate in their delta in a complex way. This paper discusses a method to distinguish the deposits of the Rhine and the Meuse based on the differences in natural radioactivity of 40K, 238U and 232Th, and the effect of the age of the deposits on the radiometrie signal. In total, six channel belts of the Rhine and the Meuse were selected for sampling with an approximate age of about 2000, 4000 and 6000 14C years B.P. Of each channel belt 5 samples of different lithology were taken: clay (C), clay leads (CL), sandy clay loam (sCL), sandy loam (sL) and sand (S). All samples were analysed on organic matter content, grain size, geochemistry and radioactivity of the radionuclides 40K, 238U and 232Th. The radioactivity of the sample is mainly influenced by the grain size of the sample. Therefore, this signal is divided in partial radioactivities for three grain size fractions – clay (<16 μm), silt (16 – 63 μm) and sand (>63 μm) – to make the radiometric fingerprint, which is independent of the grain size of the sample. These fingerprints show a difference between the Rhine and the Meuse. Additionally, the radiometric signal strongly depends on the age of the deposits. Remarkably, this trend with age is opposite in the deposits of the Rhine and the Meuse and opposite in the clay and silt fraction. Because the radiometrie differences between the samples seem more distinct than the geochemical differences, the radiometric fingerprints are more suitable to distinguish the deposits of the Rhine and the Meuse. A method is presented to derive the contribution of the Rhine and the Meuse in a deposit of unknown origin, assuming that the radiometric fingerprints found are consistent and valid for the Rhine-Meuse delta. To distinguish the deposits of the Rhine and the Meuse, both the grain size composition and the age of the deposits have to be known.
7

Harte, Robert J. A., Julian C. Matthews, Susan M. O'Reilly, D. W. Owen Tilsley, Safiye Osman, Gavin Brown, Sajinder J. Luthra, Frank Brady, Terry Jones, and Patricia M. Price. "Tumor, Normal Tissue, and Plasma Pharmacokinetic Studies of Fluorouracil Biomodulation With N-Phosphonacetyl-l-aspartate, Folinic Acid, and Interferon Alfa." Journal of Clinical Oncology 17, no. 5 (May 1999): 1580. http://dx.doi.org/10.1200/jco.1999.17.5.1580.

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PURPOSE: To evaluate the effect of N-phosphonacetyl-l-aspartate (PALA), folinic acid (FA), and interferon alfa (IFN-α) biomodulation on plasma fluorouracil (5FU) pharmacokinetics and tumor and liver radioactivity uptake and retention after [18F]-fluorouracil (5-[18F]-FU) administration. PATIENTS AND METHODS: Twenty-one paired pharmacokinetic studies were completed on patients with colorectal, gastric, and hepatocellular cancer, utilizing positron emission tomography (PET), which allowed the acquisition of tumor, normal tissue, and plasma pharmacokinetic data and tumor blood flow (TBF) measurements. The first PET study was completed when the patient was biomodulator-naive and was repeated on day 8 after the patient had been treated with either PALA, FA, or IFN-α in recognized schedules. RESULTS: TBF was an important determinant of tumor radioactivity uptake (r = .90; P < .001) and retention (r = .96; P < .001), for which radioactivity represents a composite signal of 5-[18F]-FU and [18F]-labeled metabolites and catabolites. After treatment with PALA, TBF decreased (four of four patients; P = .043), as did tumor radioactivity exposure (five of five patients; P = .0437), with no change in plasma 5FU clearance. With FA treatment, there were no differences observed in whole-body metabolism, plasma 5FU clearance, or tumor and liver pharmacokinetics. IFN-α had measurable effects on TBF and 5-[18F]-FU metabolism but had no apparent affect on liver blood flow. CONCLUSION: The administration of PALA and IFN-α produced measurable changes in plasma, tumor, and liver pharmacokinetics after 5-[18F]-FU administration. No changes were observed after FA administration. In vivo effects may negate the anticipated therapeutic advantage of 5FU biomodulation with some agents.
8

Szemraj, Janusz, Khalid N. I. Al-Nedawi, Ewa Chabielska, Wlodzimierz Buczko, and Zofia Pawlowska. "Tissue distribution of a menthyl-conjugated oligodeoxyribonucleotide antisense to PAI-1 mRNA." Acta Biochimica Polonica 52, no. 4 (November 21, 2005): 849–56. http://dx.doi.org/10.18388/abp.2005_3397.

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The inhibitory effect of numerous analogues of PO-16, an hexadecadeoxyribonucleotide antisense to sequences -22 to -17 of PAI-1 mRNA coding for a fragment of the signal peptide, on the expression of PAI-1 in endothelial cells, and physiological consequences of the subsequently reduced PAI-1 activity tested in vitro and in vivo, were described in our previous studies. Of particular interest was PO-16 5'-O-conjugated with menthyl phosphorothioate (MPO-16R). In this work, tissue localisation of MPO-16R labelled with [(35)S] phosphorothioate at the 3'-end, was determined. [(35)S]MPO-16R and control [(35)S]MPO-16R-SENSE oligonucleotides were administered intravenously into 22 rats and organ distribution of the labelled bioconjugates was assessed after 24 and 48 h. For this purpose, tissue sections were subjected to autoradiography, and quantitated by liquid scintillation after solubilisation. Overall clearance of radioactivity was already seen after 24 h, with the radioactivity recovered mainly in the kidney and liver. A smaller fraction of radioactivity was also retained in the spleen and heart. The kidney concentration of the labelled probe was higher than that of liver by 50%. The distribution of PAI-1 mRNA in untreated rat kidney, liver, spleen and heart established by two independent techniques: Ribonuclease Protection Assay and Real-Time PCR, shows the same pattern as that observed for [(35)S]MPO-16R antisense.
9

MacPhee, C. H. "Granulocyte/macrophage colony-stimulating factor affects myo-inositol metabolism in a novel manner. Implications for its priming action on human neutrophils." Biochemical Journal 286, no. 2 (September 1, 1992): 535–40. http://dx.doi.org/10.1042/bj2860535.

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Little is known about the signal transduction processes involved in the priming action of granulocyte/macrophage colony-stimulating factor (GM-CSF) on neutrophils. This study has used myo-[3H]inositol-labelled human neutrophils to determine whether preincubation with GM-CSF influences myo-inositol (Ins) metabolism in control cells, or in cells stimulated with the bacterial chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMetLeuPhe). GM-CSF pretreatment did not influence the total cellular 3H radioactivity content, demonstrating that the cytokine had no effect on Ins uptake. However, neutrophils pretreated with GM-CSF showed a dramatic 25-40% fall in the free [3H]Ins content of the cell, which was almost quantitatively recovered in a 2-4-fold increase in radioactivity within PtdIns. The remainder of the 3H radioactivity was found proportionately distributed throughout all other [3H]Ins-containing metabolites. Interestingly, in comparison with controls, the GM-CSF-stimulated increases in [3H]polyphosphoinositide (including 3-phosphorylated lipids) and [3H]Ins polyphosphate contents were consistently higher than that observed with PtdIns. This observation suggests that GM-CSF influences the hormone-sensitive pool of PtdIns, possibly through the activation of a PtdIns synthase which is rate-limiting to subsequent metabolic pathways. This is the first report of an action of GM-CSF on Ins metabolism, and highlights the conversion of Ins to PtdIns as a key regulatory metabolic step.
10

Franchini, P. "DarkSide-20k Veto Photon-Detector Units: construction and characterization." Journal of Instrumentation 19, no. 05 (May 1, 2024): C05013. http://dx.doi.org/10.1088/1748-0221/19/05/c05013.

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Abstract DarkSide-20k is a global direct dark matter search experiment situated underground at LNGS (Italy), designed to reach a total exposure of 200 tonne-years nearly free from instrumental backgrounds. The core of the detector is a dual-phase Time Projection Chamber (TPC) filled with 50 tonne of low-radioactivity liquid argon. The entire TPC wall is surrounded by a gadolinium-loaded polymethylmethacrylate (Gd-PMMA), which acts as a neutron veto, immersed in a second low-radioactivity liquid argon bath enclosed in a stainless steel vessel. The neutron veto is equipped with large-area Silicon PhotoMultiplier (SiPM) array detectors, placed on the outside of the TPC wall. SiPMs are arranged in a compact design meant to minimize the material used for PCBs, cables and connectors: the so-called Veto Photon-Detector Units (vPDUs). A vPDU comprises 16 vTiles, each containing 24 SIPMs, together with front-end electronics, and a motherboard, which distributes voltage and control signals, sums vTiles channels, and drives the electrical signal transmission. The neutron veto will be equipped with 120 vPDUs. The paper will focus on the production of the first vPDUs, describing the assembly chain in the U.K. institutes, in order to underline the rigorous QA/QC procedures, up to the final characterization of the first completed prototypes. Tests will be extensively performed in liquid nitrogen baths either for the single vTiles and for the assembled vPDUs, with the purpose of assigning a “quality passport” to each component.
11

Lefauconnier, Bernard, Jon Ove Hagen, Jean Francis Pinglot, and Michel Pourchet. "Mass-balance estimates on the glacier complex Kongsvegen and Sveabreen, Spitsbergen, Svalbard, using radioactive layers." Journal of Glaciology 40, no. 135 (1994): 368–76. http://dx.doi.org/10.1017/s0022143000007450.

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AbstractAnalyses of total β and γ radioactivity have been carried out on ten shallow ice cores collected in 1989 and 1990 on Kongsvegen and Sveabreen, Spitsbergen. No peak of total β radioactivity, corresponding to the Chernobyl accident (1986), can be identified. Chernobyl layers were identified by137Cs and134Cs activities, and a signal from the nuclear tests in Novaya Zemlya (1961–62), was detected at one location by137Cs activity. The mean net accumulation for the periods 1986–89 and 1962–88 was estimated for both glaciers. Using topographic data, the mean net ablation on Kongsvegen was estimated for the period 1964–90 and the mean net balances were calculated. The results agree with recent direct glaciological balance measurements. For the period 1986–89, the net accumulation was higher on Sveabreen than on Kongsvegen, and the equilibrium-line altitudes (ELA) were around 450 and 520 m a.s.l., respectively. Kongsvegen had a positive balance of 0.11 m w.eq. and Sveabreen was in equilibrium, whereas for the last 26 years the balance of Kongsvegen was slightly negative (−0.10 m w.eq.) and the ELA was around 560 m a.s.l.
12

Naor, Z., J. Molcho, H. Zakut, and E. Yavin. "Calcium-independent phosphatidylinositol response in gonadotropin-releasing-hormone-stimulated pituitary cells." Biochemical Journal 231, no. 1 (October 1, 1985): 19–23. http://dx.doi.org/10.1042/bj2310019.

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This paper describes the effect of gonadotropin-releasing hormone (GnRH, gonadoliberin) on phospholipid metabolism in cultured rat pituitary cells. The cells were incubated with [32P]Pi to label endogenous phospholipids (10-60 min) and then stimulated with GnRH for up to 60 min. Cellular phospholipids were separated by two-dimensional t.l.c. and the radioactivity was determined. Phosphatidylinositol (PI), a minor constituent of cellular phospholipids (7.7%), was the major labelled phospholipid, accounting for 45% of the total radioactivity, at early periods after pulse labelling. On the other hand, phosphatidylcholine, the major cellular phospholipid (37%), was labelled only to 32% of the total radioactivity. The remaining label was distributed among phosphatidylethanolamine (4.2%), cardiolipin (3.4%), phosphatidic acid (PA, 2.5%), and phosphatidylserine (1.8%). GnRH doubled 32P labelling of PA and PI significantly at 1 and 5 min of incubation respectively in the presence or absence of extracellular Ca2+. Labelling of other phospholipids was not affected by GnRH treatment. The half-maximal stimulating dose (ED50) for PI labelling and lutropin release was 0.75 nM and 0.5 nM respectively, and the stimulatory effect was blocked by the potent GnRH antagonist [D-Glp1,pClPhe2,D-Trp3,6]GnRH. GnRH-stimulated PA and PI labelling could not be demonstrated after 1 and 45 min of incubation respectively, or when the prelabelling was conducted for 60 min rather than 10 min. These results suggest heterogeneous compartmentalization of gonadotroph PA and PI pools and that increased PI turnover might be a transducing signal for Ca2+ gating that follows gonadotroph GnRH-receptor activation.
13

Saleem, Azeem, Graham Searle, Laura M. Kenny, Mickael Huiban, Adam Waldman, Louise Downie, Mike Lau, et al. "Brain and tumor penetration of carbon-11–labeled lapatinib ([11C]Lap) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 635. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.635.

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635 Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [11C]Lap. Methods: Pts with HER2+ MBC with an ECOG of <3 were grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases and underwent 90-minute dynamic cranial PET-CT scans after IV administration of a microdose (<1 mg) of [11C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [11C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [11C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [11C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [11C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [11C]Lap contributed to >80% of activity in plasma at 60 minutes. Tissue data revealed [11C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [11C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [11C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [11C]Lap uptake in brain metastases was higher than in normal brain. [11C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.
14

Manek, Hirva, and Foram Gala. "Brown adipose tissue – magnetic resonance imaging (MRI) appearance of these physiological fat deposits in a newborn." Wadia Journal of Women and Child Health 2 (February 1, 2024): 140–43. http://dx.doi.org/10.25259/wjwch_36_2023.

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Brown adipose tissue (BAT) is responsible for thermogenesis in neonates and infants in response to cold environment. 18F-fluorodeoxyglucose positron emission tomography is the reference for imaging of BAT, but it is a functional imaging modality and hence lacks sensitivity due to varying patient and environmental factors. Magnetic resonance imaging (MRI) lacks the use of radioactivity and ionizing radiation and can prove to be an excellent imaging modality to study the distribution of BAT. We report a neonate with sepsis whose MRI study of the neck and upper chest done to look for infective focus revealed classical distribution and signal intensity of BAT.
15

Lefauconnier, Bernard, Jon Ove Hagen, Jean Francis Pinglot, and Michel Pourchet. "Mass-balance estimates on the glacier complex Kongsvegen and Sveabreen, Spitsbergen, Svalbard, using radioactive layers." Journal of Glaciology 40, no. 135 (1994): 368–76. http://dx.doi.org/10.3189/s0022143000007450.

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AbstractAnalyses of total β and γ radioactivity have been carried out on ten shallow ice cores collected in 1989 and 1990 on Kongsvegen and Sveabreen, Spitsbergen. No peak of total β radioactivity, corresponding to the Chernobyl accident (1986), can be identified. Chernobyl layers were identified by 137Cs and 134Cs activities, and a signal from the nuclear tests in Novaya Zemlya (1961–62), was detected at one location by 137Cs activity. The mean net accumulation for the periods 1986–89 and 1962–88 was estimated for both glaciers. Using topographic data, the mean net ablation on Kongsvegen was estimated for the period 1964–90 and the mean net balances were calculated. The results agree with recent direct glaciological balance measurements. For the period 1986–89, the net accumulation was higher on Sveabreen than on Kongsvegen, and the equilibrium-line altitudes (ELA) were around 450 and 520 m a.s.l., respectively. Kongsvegen had a positive balance of 0.11 m w.eq. and Sveabreen was in equilibrium, whereas for the last 26 years the balance of Kongsvegen was slightly negative (−0.10 m w.eq.) and the ELA was around 560 m a.s.l.
16

Strasser, Heiner, Christina Hoffmann, Hans Grisebach, and Ulrich Matern. "Are Polyphosphoinositides Involved in Signal Transduction of Elicitor-Induced Phytoalexin Synthesis in Cultured Plant Cells ?" Zeitschrift für Naturforschung C 41, no. 7-8 (August 1, 1986): 717–24. http://dx.doi.org/10.1515/znc-1986-7-810.

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Abstract The phospholipids of cultured parsley and soybean cells were labelled with myo-[2-3H]inositol, [2-3H]glycerol or [32P]orthophosphate. By one-and two-dimensional chromatographic comparison of the labelled phospholipids with reference substances, the presence of 1-(3-sn-phosphatidyl)-ᴅ-myo-inositol 4-phosphate and 1-(3-sn-phosphatidyl)-ᴅ-myo-inositol 4,5-bisphosphate was demonstrated in these cultures. These results were corroborated by analysis of the deacylation products. Cells were labelled with either myo-[2-3H]inositol, [2-3H]glycerol or [32P]orthophosphate and subsequently challenged with elicitor for various lengths of time. Radioactivity in individual phosphoinositides from these cells was determined. No significant influence of elicitor-challenge of either soybean or parsley cells on incorporation of 3H or 32P into polyphospho­inositides was found between 0.5 and 20 min after elicitor addition.
17

Freudenberg, R., M. Andreeff, J. Kotzerke, and H. Hartmann. "Radioaktivität mit dem Smartphone messen." Nuklearmedizin 52, no. 02 (2013): 64–70. http://dx.doi.org/10.3413/nukmed-0526-12-08.

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SummaryThe interest in the detection of radioactive materials has strongly increased after the accident in the nuclear power plant Fukushima and has led to a bottleneck of suitable measuring instruments. Smartphones equipped with a commercially available software tool could be used for dose rate measurements following a calibration according to the specific camera module. Aim: We examined whether such measurements provide reliable data for typical activities and radionuclides in nuclear medicine. Methods: For the nuclides 99mTc (10 – 1000 MBq), 131I (3.7 – 1800 MBq, therapy capsule) and 68Ga (50 – 600 MBq) radioactivity with defined geo metry in different distances was measured. The smartphones Milestone Droid 1 (Motorola) and HTC Desire (HTC Corporation) were compared with the standard instruments AD6 (automess) and DoseGUARD (AEA Technology). Results: Measurements with the smartphones and the other devices show a good agreement: linear signal increase with rising activity and dose rate. The long time measurement (131I, 729 MBq, 0.5 m, 60 min) demonstrates a considerably higher variation (by 20%) of the measured smartphone data values compared with the AD6. For low dose rates (< 1 μGy/h), the sensitivity decreases so that measurements of e. g. the natural radiation exposure do not lead to valid results. The calibration of the camera responsivity for the smartphone has a big influence on the results caused by the small detector surface of the camera semiconductor. Conclusions: With commercial software the camera module of a smartphone can be used for the measurement of radioactivity. Dose rates resulting from typical nuclear medicine procedures can be measured reliably (e. g., dismissal dose after radioiodine therapy). The signal shows a high correlation to measured values of conventional dose measurement devices.
18

Khalaf, Salah Q., and Hayder S. Hussien. "Radon concentration measurement in water reservoirs for some areas of north Baghdad by RAD7." Journal of Physics: Conference Series 2114, no. 1 (December 1, 2021): 012062. http://dx.doi.org/10.1088/1742-6596/2114/1/012062.

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Abstract Radon is a naturally occurring, odorless, colorless, radioactive, tasteless, and noble gas. Radon concentrations have been measured by the usage of alpha spectroscopy (RAD-7). The RAD-7 measuring process is based on detecting alpha particles produced from the disintegration of radon and its products using a solid-state alpha detector (usually silicon), and then converting alpha radiation directly to an electrical signal. The radioactivity of radon gas was measured in forty-two samples from reservoir water for different areas north of Baghdad utilizing a RAD7 detector. This study proved that the high value of radon concentrations was less than the permissible limit as recorded by the World Health Organization.
19

Tordoff, M. G., N. Rawson, and M. I. Friedman. "2,5-anhydro-D-mannitol acts in liver to initiate feeding." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 2 (August 1, 1991): R283—R288. http://dx.doi.org/10.1152/ajpregu.1991.261.2.r283.

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We determined the site at which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) acts to increase food intake in rats. Rats began eating sooner and ate more food during hepatic portal than during jugular infusions of 2,5-AM (50, 100, or 150 mg/h). After rats were intubated with 2,5-[14C]AM (1.15 microCi in 200 mg/kg), significant quantities of radioactivity were found in liver but not in brain. Hepatic vagotomy prevented the eating response to 200 mg/kg 2,5-AM without altering the effect of the analogue on plasma fuels. These results indicate that low doses of 2,5-AM act in the liver to increase food intake and suggest that the signal for feeding generated in the liver is transmitted to the brain through the hepatic vagus nerve. Taken together, this work provides the strongest evidence to date that a signal initiating feeding behavior originates in the liver.
20

Paragas, Violette B., Yu-Zhong Zhang, Richard P. Haugland, and Victoria L. Singer. "The ELF-97 Alkaline Phosphatase Substrate Provides a Bright, Photostable, Fluorescent Signal Amplification Method for FISH." Journal of Histochemistry & Cytochemistry 45, no. 3 (March 1997): 345–57. http://dx.doi.org/10.1177/002215549704500302.

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We used the ELF-97 (Enzyme-Labeled Fluorescence) phosphatase substrate, 2-(5'-chloro-2-phosphoryloxyphenyl)-6-chloro-4(3H)-quinazolinone, with alkaline phosphatase conjugates of streptavidin and appropriate antibodies to amplify signals from biotinylated and haptenylated hybridization probes. The dephosphorylated product, ELF-97 alcohol, is a bright yellow-green fluorescent precipitate optimally excited at ∼360 nm, with emission centered at ∼530 nm. This large Stokes shift allows ELF-97 signals to be easily distinguished from sample autofluorescence and signals arising from counterstains or other fluorophores. The ELF-97 precipitate was extremely photostable compared to fluorescein, allowing multiple photographic exposures of samples without significant signal intensity loss. For RNA in situ hybridization, labeling was specific and localized well to targets in cultured cells, tissue sections, and whole-mount zebrafish embryos. ELF-97 signals developed in seconds to minutes and were easily distinguished from pigmented tissues or cells, unlike those obtained using colorimetric substrates. We used the substrate with singly biotinylated short oligonucleotides to detect actin mRNA in MDCK cells and actin and β-galactosidase mRNA in LacZ+ mouse fibroblasts. We also used a biotinylated cDNA, complementary to the mRNA encoded by the constant region of the T-cell receptor β-chain, to specifically identify T-cells in mouse lymph node tissue sections. With digoxigenin-labeled probes, we detected several developmentally expressed mRNAs in whole-mount zebrafish embryos. Hybridization to centromere repeat regions in human metaphase and interphase chromosomes was also detected; ELF-97 signals were manyfold brighter than signals obtained with fluorescein conjugates. Finally, Southern blot hybridization using singly labeled oligonucleotide probes yielded a sensitivity similar to that obtained with radioactivity. (J Histochem Cytochem 45:345–357, 1997)
21

Edwards, Y. S., and A. W. Murray. "Accumulation of phosphatidylalcohol in cultured cells: use of subcellular fractionation to investigate phospholipase D activity during signal transduction." Biochemical Journal 308, no. 2 (June 1, 1995): 473–80. http://dx.doi.org/10.1042/bj3080473.

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Phosphatidylalcohol accumulates as a product of a phospholipase D (PLD)-catalysed transphosphatidylation reaction in cells incubated in the presence of a primary alcohol. In the presence of ethanol the phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated the accumulation of [3H]phosphatidylethanol (PEth) in HeLa cells prelabelled with [3H]palmitic acid. Radioactivity associated with PEth increased linearly during a 30 min incubation, indicating that a sustained activation of PLD is caused by PMA in these cells. This was accompanied by the membrane association of protein kinase C-alpha (PKC-alpha), the PKC isoform that recent studies indicate is involved in the activation of PLD. In similar experiments, the neuropeptide bradykinin stimulated an accumulation of PEth in 3T3 Li cells. The radioactivity associated with PEth increased to a maximal level at 30 s and plateaued after this time, suggesting that bradykinin induces only a transient activation of PLD in these cells. This is consistent with the effects of bradykinin on PKC-alpha, which underwent a rapid and transient association with cell membranes. The subcellular localization of PEth was examined using the technique of subcellular fractionation on Percoll density gradients to isolate organelle-enriched fractions from HeLa and 3T3 Li cells. An accumulation of [3H]PEth was measured in the plasma-membrane (PM)-enriched fractions of both HeLa and 3T3 Li cells after incubation with PMA and bradykinin respectively. This was accompanied by a time-dependent accumulation of [3H]PEth in the combined mitochondrial and endoplasmic reticulum (MER)-enriched fractions of both cell lines. PMA was also found to cause translocation of PKC-alpha to both the PM- and MER-enriched fractions in HeLa cells. However, bradykinin stimulated the translocation of PKC-alpha to the PM-enriched fractions only of 3T3 Li cells. The results show that PLD activation leads to the accumulation of PEth in both the PM and MER fractions. We therefore propose that either bradykinin activates a PM-associated PLD and the PLD reaction product is rapidly translocated to other membrane systems or it activates an MER-associated PLD by a mechanism that does not involve PKC-alpha.
22

Ahmad, Waqar, Bushra Gull, Jasmin Baby, and Farah Mustafa. "A Comprehensive Analysis of Northern versus Liquid Hybridization Assays for mRNAs, Small RNAs, and miRNAs Using a Non-Radiolabeled Approach." Current Issues in Molecular Biology 43, no. 2 (June 22, 2021): 457–84. http://dx.doi.org/10.3390/cimb43020036.

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Northern blotting (NB), a gold standard for RNA detection, has lost its charm due to its hands-on nature, need for good quality RNA, and radioactivity. With the emergence of the field of microRNAs (miRNAs), the necessity for sensitive and quantitative NBs has again emerged. Here, we developed highly sensitive yet non-radiolabeled, fast, economical NB, and liquid hybridization (LH) assays without radioactivity or specialized reagents like locked nucleic acid (LNA)- or digoxigenin-labeled probes for mRNAs/small RNAs, especially miRNAs using biotinylated probes. An improvised means of hybridizing oligo probes along with efficient transfer, cross-linking, and signal enhancement techniques was employed. Important caveats of each assay were elaborated upon, especially issues related to probe biotinylation, use of exonuclease, and bioimagers not reported earlier. We demonstrate that, while the NBs were sensitive for mRNAs and small RNAs, our LH protocol could efficiently detect these and miRNAs using less than 10–100 times the total amount of RNA, a sensitivity comparable to radiolabeled probes. Compared to NBs, LH was a faster, more sensitive, and specific approach for mRNA/small RNA/miRNA detection. A comparison of present work with six seminal studies is presented along with detailed protocols for easy reproducibility. Overall, our study provides effective platforms to study large and small RNAs in a sensitive, efficient, and cost-effective manner.
23

Mosley-Thompson, E., P. D. Kruss, L. G. Thompson, M. Pourchet, and P. Grootes. "Snow Stratigraphic Record at South Pole: Potential for Paleoclimatic Reconstruction." Annals of Glaciology 7 (1985): 26–33. http://dx.doi.org/10.3189/s0260305500005863.

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An extensive investigation of the visible stratigraphy, microparticle concentration, liquid conductivity, oxygen isotopes and beta-radioactivity was conducted in pits excavated at Amundsen-Scott South Pole station. The objectives of the investigation were to assess the spatial representativeness of the geochemical and physical records preserved within the snow strata and to ascertain the temporal resolution which can be obtained from such ice-core records. Accurate interpretation of the time scale and reconstruction of climatic conditions from these time series requires (1) the analysis of as many stratigraphic parameters as possible and (2) the synthesis of data from a suite of cores in the study area. For periods of 10 a or less, regionally representative accumulation rates cannot be obtained from annual accumulation time series reconstructed at a single site. Although the microparticle concentrations, liquid conductivity and oxygen isotopic abundances all exhibit a seasonal cycle in the firn, the construction of an accurate time scale requires all three parameters in conjunction with the beta-radioactivity. Absolute dating will be impossible for cores from South Pole where entire accumulation years may be missing. Nevertheless, for East Antarctica, where accumulation rates are low (<0.1 m a−1 water equivalent), the good temporal resolution and the preservation of a distinct annual signal in some geochemical parameters makes the South Pole a very attractive site for deep ice-core drilling.
24

Mosley-Thompson, E., P. D. Kruss, L. G. Thompson, M. Pourchet, and P. Grootes. "Snow Stratigraphic Record at South Pole: Potential for Paleoclimatic Reconstruction." Annals of Glaciology 7 (1985): 26–33. http://dx.doi.org/10.1017/s0260305500005863.

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An extensive investigation of the visible stratigraphy, microparticle concentration, liquid conductivity, oxygen isotopes and beta-radioactivity was conducted in pits excavated at Amundsen-Scott South Pole station. The objectives of the investigation were to assess the spatial representativeness of the geochemical and physical records preserved within the snow strata and to ascertain the temporal resolution which can be obtained from such ice-core records. Accurate interpretation of the time scale and reconstruction of climatic conditions from these time series requires (1) the analysis of as many stratigraphic parameters as possible and (2) the synthesis of data from a suite of cores in the study area. For periods of 10 a or less, regionally representative accumulation rates cannot be obtained from annual accumulation time series reconstructed at a single site. Although the microparticle concentrations, liquid conductivity and oxygen isotopic abundances all exhibit a seasonal cycle in the firn, the construction of an accurate time scale requires all three parameters in conjunction with the beta-radioactivity. Absolute dating will be impossible for cores from South Pole where entire accumulation years may be missing. Nevertheless, for East Antarctica, where accumulation rates are low (&lt;0.1 m a−1 water equivalent), the good temporal resolution and the preservation of a distinct annual signal in some geochemical parameters makes the South Pole a very attractive site for deep ice-core drilling.
25

Dougniaux, Grégoire, William Soerjady, Kelvin Ankrah, and Diane Mauclère. "Numerical Simulation of a CAM-Measured Spectra Influenced by Coarse Aerosol." Atmosphere 13, no. 12 (December 16, 2022): 2113. http://dx.doi.org/10.3390/atmos13122113.

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In nuclear facilities, the mandatory atmosphere surveillance is operated by Continuous Air Monitors. This standalone instrument is designed to measure the airborne aerosol activity concentration and to trig an alarm signal when a predetermined activity concentration is exceeded. However, a rapid resuspension event of coarse aerosol leads to a measurement error: the airborne aerosol activity concentration is over-evaluated. Prior results have shown that the coarse aerosol deposit disturbs the background evaluation for the radioactivity measurement. The interactions between radioactive aerosols (with radon daughters) and coarse non-radioactive aerosols have to be investigated by running together aerosol models and nuclear simulations. Therefore, this paper investigates different ways to represent an aerosol deposit in numerical simulations. We developed two numerical aerosol deposit models that we integrated into Geant4, a tool for the simulation of the passage of radiations through matter, and then compared these to experimental results. The simplest model was discarded, and by using the second model, we managed to correctly frame our simulation results as an experimental measurement: an aerosol has been correctly considered in a nuclear simulation. By combining theory, simulations, and experimentations on both aerosol science and nuclear physics, this research will be able to improve the comprehension of monitors’ behaviour in delicate situations and, more broadly, the filtration of aerosols using radioactivity.
26

Law, R. E., J. B. Stimmel, M. A. Damore, C. Carter, S. Clarke, and R. Wall. "Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions." Molecular and Cellular Biology 12, no. 1 (January 1992): 103–11. http://dx.doi.org/10.1128/mcb.12.1.103-111.1992.

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We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.
27

Law, R. E., J. B. Stimmel, M. A. Damore, C. Carter, S. Clarke, and R. Wall. "Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions." Molecular and Cellular Biology 12, no. 1 (January 1992): 103–11. http://dx.doi.org/10.1128/mcb.12.1.103.

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We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.
28

Herzog, Eva, Stephen Harris, Andrew McEwen, Ingo Pragst, Gerhard Dickneite, Stefan Schulte, and Sabine Zollner. "Biodistribution of the Recombinant Fusion Protein Linking the Human Factor IX to Human Albumin (rIX-FP) in Rats." Blood 120, no. 21 (November 16, 2012): 1117. http://dx.doi.org/10.1182/blood.v120.21.1117.1117.

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Abstract Abstract 1117 The recombinant fusion protein linking the human coagulation factor IX to human albumin, rIX-FP, developed by CSL Behring GmbH, is currently undergoing investigation in clinical phase II/III trials (PROLONG - 9FP) for prophylaxis and on-demand treatment of bleeding in haemophilia B patients. The present study has been conducted to evaluate the biodistribution of rIX-FP in comparison to the marketed recombinant factor IX product BeneFIX®. Therefore, [3H]-rIX-FP or [3H]-BeneFIX®, labeled at lysine or terminal NH2 residues using the N-Succinimidyl [2,3,-3H] propionate (NSP) method, were administered intravenously to male Sprague Dawley (SD) rats at a single dose leading to a radioactive dose of 400 μCi/kg. Using whole-body autoradiography (QWBA), tissue radioactivity was determined at 0.25, 1, 3, 8, 24, 72, 120 and 240 hours following [3H]-rIX-FP, and at 0.25, 1, 3 and 24 hours following [3H]-BeneFIX® administration. In addition to full body sections, the hind limbs were separately subjected to QWBA to obtain more detailed information on the product distribution within the bone marrow, articular capsule and synovial region of the knee joints. In parallel, plasma, urine and faeces were collected at pre-dose and at several sampling points throughout the 24 and 240 hour study period, respectively, to calculate excretion balance and assess physiological elimination pathways. The radioactivity associated with the purified [3H]-labelled protein was determined by quantitative radiochemical analysis (QRA) and high performance liquid chromatography (HPLC). Biological activity of [3H]-labelled rIX-FP and BeneFIX® was confirmed using a chromogenic assay for factor IX activity. The radioactivity associated with plasma, urine and faeces samples was determined by QRA. HPLC-mass spectrometry (MS) techniques were employed to further characterize individual components identified following profiling of plasma and urine samples by size exclusion chromatography (SEC). Overall, the tissue distribution of [3H]-rIX-FP and [3H]-BeneFIX® was comparable, both penetrating predominantly into well perfused tissues and organs. Both products are also rapidly present in synovial and mineralized regions of knee joint sections and seem to mostly localize to the zone of calcified cartilage within the growth plate regions of long bones. For both, the longest retention time was observed in the bone marrow and endosteum of long bones. However, whereas [3H]-rIX-FP was detectable over 120 hours after administration, [3H]-BeneFIX® signal could only be detected until 24 hours post dosing. This is also reflected in the pharmacokinetic parameters determined based on the QRA of plasma and urine samples which suggested a terminal half life of 20.4 and 6.1 hours for [3H]-rIX-FP and [3H]-BeneFIX®, respectively, following correction for total radioactivity attributable to intact product. For both proteins, the major route of elimination was urinary. In case of [3H]-rIX-FP 73% of radioactivity was recovered in urine at 240 hours, the latest sampling point investigated. Less than 5% of radioactivity was eliminated in faeces and approximately 20% of radioactivity was present in tissues after 240 hours. Plasma profiling showed that up to 8 hours, 100% of the radioactivity could be assigned to unchanged [3H]-rIX-FP. From 24 to 240 hours, increasing levels of low molecular weight components (LMW) could be observed in plasma. Intriguingly, no high molecular protein components like [3H]-rIX-FP or albumin were detected in urine. Only LMW [3H]-components were found to be renally excreted. Such LMW components could be either be free [3H]-Lysine or bigger peptide fragments derived from [3H]-rIX-FP, which occur as a result of physiological protein catabolism. An exact identification of such renally excreted fragments is currently underway using HPLC-MS. Overall, the observed data are consistent with the hypothesis, that recycling via FcRn receptor is likely to be the physiological retention route for [3H]-rIX-FP. Consequently, this study shows that rIX-FP exhibits equal biodistribution compared to other marketed recombinant factor IX products such as BeneFIX®, but clearly distinguishes itself from BeneFIX® by its extended plasma half-life allowing a reduction in dosing frequency leading to increased therapeutic convenience and compliance. Disclosures: Herzog: CSL Behring GmbH: Employment. Harris:Quotient Bioresearch Metabolic Chemistry: Commercial Research Organisation Other. McEwen:Quotient Bioresearch Metabolic Chemistry: Commercial Research Organisation Other. Pragst:CSL Behring GmbH: Employment. Dickneite:CSl Behring GmbH: Employment. Schulte:CSL Behring GmbH: Employment. Zollner:CSL Behring GmbH: Employment.
29

Nikolaev, A. V., E. I. Starovoitov, D. V. Fedosov, A. V. Kolesnikov, and M. A. Filin. "Navigation Technology of Unmanned Vehicles Based on Electromagnetic Induction." Mekhatronika, Avtomatizatsiya, Upravlenie 24, no. 11 (November 1, 2023): 583–89. http://dx.doi.org/10.17587/mau.24.583-589.

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The article deals with the issues of determining the position of unmanned vehicles (UV) in tunnels in the absence of signals from global navigation satellite systems (GNSS) and unfavorable operating conditions, such as low light, high humidity, radioactivity and others. The authors proposes a method for navigating unmanned vehicles based on the phenomenon of electromagnetic induction. On board the unmanned vehicle there is a high-frequency generator, a radio transmitting unit, a radio receiving unit, an information management system, and under the bearing or supporting surface of the unmanned vehicle propulsion unit there is a single-wire radio transmission line coordinated with the environment by means of an active load. The high-frequency generator transmits high-frequency current to the radio transmitting unit, which excites a single-wire radio transmission line, the single-wire radio transmission line emits a high-frequency radio signal supplied to the radio receiving unit for further conversion by the information management system into electrical control signals of an unmanned vehicle. Magnetic loops or electrical vibrators can be used as radiating antenna from the radio transmitting unit, and magnetic loops or ferrite probe excited by the high-frequency magnetic field of the radio transmission line can be used as receiving antenna. The article deals with the influence of the environment on the processes of radiation and reception of radio signals. Computer testing of the developed method was carried out with using three-dimensional electromagnetic modeling. Electrically small loop antennas located orthogonally were used to transmit and receive the radio signal. It was shown that the phase analysis of the transmission gain in both cases can provide ample information about the direction and deviation rate from the path which is set using the radio transmission line. The results of the study can be useful for the development of navigation systems for unmanned vehicles in conditions of limited availability of signals from GNSS.
30

Agnes, P., I. F. M. Albuquerque, T. Alexander, A. K. Alton, M. Ave, H. O. Back, G. Batignani, et al. "Long-term temporal stability of the DarkSide-50 dark matter detector." Journal of Instrumentation 19, no. 05 (May 1, 2024): P05057. http://dx.doi.org/10.1088/1748-0221/19/05/p05057.

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Abstract The stability of a dark matter detector on the timescale of a few years is a key requirement due to the large exposure needed to achieve a competitive sensitivity. It is especially crucial to enable the detector to potentially detect any annual event rate modulation, an expected dark matter signature. In this work, we present the performance history of the DarkSide-50 dual-phase argon time projection chamber over its almost three-year low-radioactivity argon run. In particular, we focus on the electroluminescence signal that enables sensitivity to sub-keV energy depositions. The stability of the electroluminescence yield is found to be better than 0.5%. Finally, we show the temporal evolution of the observed event rate around the sub-keV region being consistent to the background prediction.
31

Fragoso, Yara Dadalti, Arnfinn Seim, Lars Jacob Stovner, Merete Mack, Kristian S. Bjerve, and Ottar Sjaastad. "Arachidonic Acid Metabolism in Polymorphonuclear Cells in Headaches: A Methodologic Study." Cephalalgia 8, no. 3 (September 1988): 149–55. http://dx.doi.org/10.1046/j.1468-2982.1988.0803149.x.

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Prostaglandins and leukotrienes have been implicated in the pathogenesis of various types of headache, mainly because some, but not all, cyclo-oxygenase inhibitors are effective in their treatment. We have therefore investigated whether a pathologically changed turnover of arachidonic acid (AA)-containing phospholipids can be seen in headache patients, using isolated polymorphonuclear cells (PMNs) from healthy controls and patients with chronic paroxysmal hemicrania (CPH) and cluster headache. PMNs from healthy controls incorporated 55% of the added (1-14C)AA into total lipids, and 0.5% ± 0.14% of this radioactivity was found in the phosphatidylserine (PS) fraction. PMNs from a cluster headache and a CPH patient showed 300% and 900% increase in PS labeling from AA, respectively. No other phospholipids showed any difference between controls and patients. The results are discussed in connection with membrane signal transduction via the PS-dependent protein kinase C.
32

Chang, Yu-Fen, Pavel Struchalin, Bodil Næss, Tom Christian Holm Adamsen, and Boris V. Balakin. "Development of an imaging method for in vivo single-cell tracking under high-noise conditions: a proof of principle." Journal of Physics: Conference Series 2675, no. 1 (December 1, 2023): 012009. http://dx.doi.org/10.1088/1742-6596/2675/1/012009.

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Abstract This paper reports the development of a positron imaging method for in vivo single-cell tracking under high-noise conditions. Following biological processes spatially and temporally at a single-cell level in a living organism is desirable for inquiring into the relationships between the behaviours and properties of cells. Positron-emitting radionuclides enable detecting and following radioactivity-labelled substances deep inside living organisms. However, positron imaging has several challenges, such as the distribution of high noise in other areas close to the cell under investigation. In this work, an algorithm for locating a cell with millisecond resolution to combat the strong interference of nearby noise is developed. The feasibility of the method is verified by the demonstration of particle tracking and detection of behavioural changes in an environment with the signal-to-noise ratio of 1:9.
33

PEYROT, Fabienne, Catherine GRILLON, Catherine VERGELY, Luc ROCHETTE, and Claire DUCROCQ. "Pharmacokinetics of 1-nitrosomelatonin and detection by EPR using iron dithiocarbamate complex in mice." Biochemical Journal 387, no. 2 (April 5, 2005): 473–78. http://dx.doi.org/10.1042/bj20040828.

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The N-nitroso-derivative of melatonin, NOM (1-nitrosomelatonin), which has been demonstrated to be a NO• [oxidonitrogen(•)] donor in buffered solutions, is a new potential drug particularly in neurological diseases. The advantage of NOM, a very lipophilic drug, is its ability to release both melatonin and NO•, an easily diffusible free radical. In order to evaluate the distribution and the pharmacokinetics of NOM, [O-methyl-3H]NOM was administered to and followed in mice. A complementary method for monitoring NOM, EPR, was performed in vitro and ex vivo with (MGD)2–Fe2+ (iron–N-methyl-D-glucamine dithiocarbamate) complex as a spin trap. The behaviour of NOM was compared with that of GSNO (S-nitrosoglutathione), a hydrophilic NO• donor. In the first minutes following [O-methyl-3H]NOM intraperitoneal injection, the radioactivity was found in organs (6% in the liver, 1% in the kidney and 0.6% in the brain), but not in the blood. In both liver and brain, the radioactivity content decreased over time with similar kinetics reflecting the diffusion and metabolism of NOM and of its metabolites. Based on the characterization and the quantification of the EPR signal in vitro with NOM or GSNO using (MGD)2–Fe2+ complex in phosphate-buffered solutions, the detection of these nitroso compounds was realized ex vivo in mouse tissue extracts. (MGD)2–Fe2+–NO was observed in the brain of NOM-treated mice in the first 10 min following injection, revealing that NOM was able to cross the blood–brain barrier, while GSNO was not.
34

Giovacchini, Giampiero, Michael C. J. Chang, Michael A. Channing, Maria Toczek, Alicja Mason, Arun L. W. Bokde, Catherine Connolly, et al. "Brain Incorporation of [11C]Arachidonic Acid in Young Healthy Humans Measured with Positron Emission Tomography." Journal of Cerebral Blood Flow & Metabolism 22, no. 12 (December 2002): 1453–62. http://dx.doi.org/10.1097/01.wcb.0000033209.60867.7a.

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Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A2. The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K*of [11C]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [11C]CO2. K* and cerebral blood volume ( Vb) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6 ± 1.2 and 2.6 ± 0.5 μL · min−1 · mL−1 in gray and white matter, respectively. K* and Vb values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [11C]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A2-signaling, PET and [11C]AA may be useful to measure signal transduction in the human brain.
35

Roychoudhury, Siddhartha, Susan M. Collins, Barbara A. Hynd, and Christian N. Parker. "High Throughput Autophosphorylation Assay for Bacterial Protein Histidine Kinases." Journal of Biomolecular Screening 2, no. 2 (March 1997): 85–90. http://dx.doi.org/10.1177/108705719700200206.

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Protein histidine kinases play a major role in bacteria as sensor components in the so-called "two-component" systems involved in signal transduction. We describe a high throughput assay for these kinases using CheA, the bacterial chemotaxis-regulating kinase from Escherichia coil. The purpose of the assay was to monitor ATP-dependent autophosphorylation of the kinase resulting in the phosphorylation of the conserved histidine residue. Unlike most eukaryotic protein kinases, "two-component" kinases are not known to phosphorylate histones and small peptide substrates. This limits the level of phosphorylation and consequently the signal generated in these assays. We, therefore, established the desirable reaction conditions first using the conventional method involving the radio labeling of CheA by [y-32P]ATP followed by gel electrophoresis-based analysis. Next, we converted the assay to a high throughput format in which CheA, autophosphorylated and radiolabeled with [y-33P]ATP, was trapped in a filter via anionic or hydrophobic interaction using diethyl aminoethyl or nitrocellulose-based 96-well filter plates, respectively. Free [y-33P]ATP was removed by washing the wells with high salt buffers. The dried plates were then analyzed for radioactivity associated with the wells by scintillation counting. Finally, we performed and validated the assay in a partially automated format using nitrocellulose-based filter plates.
36

Amartey, John K., Yufei Shi, Ibrahim Al-Jammaz, Celestina Esguerra, Basem Al-Otaibi, and Futwan Al-Mohanna. "Radioiodinated Naphthylalanine Derivatives Targeting Pancreatic Beta Cells in Normal and Nonobese Diabetic Mice." Experimental Diabetes Research 2008 (2008): 1–8. http://dx.doi.org/10.1155/2008/371716.

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An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P< .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies showed colocalization of insulin and the conjugate radioligand in the pancreas. The results demonstrated that pancreatic uptake is receptor-mediated, and that beta cells are the primary target.
37

Ebibuloami, Biere, Ogunremi Ayorinde, Aina Oluwagbenga, Emumejaye Kugbere, Olaoye Adeola, and Mustapha Olalekan. "Detection Efficiency of a NaI (Tl) Gamma Spectrometry System for Measurement of Low Level Radioactivity." Physics Access 01, no. 01 (September 6, 2021): 61–65. http://dx.doi.org/10.47514/phyaccess.2021.1.1.010.

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Qualitative analysis of radionuclides requires the use of reliable gamma-ray detection system. The NaI(Tl) detector has been widely used and still one of the most used detectors today. It is therefore imperative to validate the reliability of the 5x5 cm2 NaI(Tl) gamma spectrometry system used in carrying out gamma-ray analysis of soil samples in the Radiation and Health Laboratory, Federal University of Agriculture Abeokuta, Nigeria. The gamma ray spectrometer is housed in a 5 cm thick cylindrical lead shield. Calibration was executed using standard materials produced under the auspices of the International Atomic Energy Agency (IAEA). Resolution and detection limit (LD) of the detector were determined using full width at half the maximum of the energy peak of 137Cs and background signal level of the reference materials respectively. Counting efficiencies of the detector was calculated using energies of 1460 keV, 1764keV and 2615 keV for 40K, 226Ra and 232Th respectively. Secondary samples, RGMIX1 and RGMIX2 were formulated and counted to calculate activity concentrations using the NaI(Tl) detector. Resolution of the detector was calculated to be 7.8% of 137Cs, which is good for a NaI(Tl) detector. The counting efficiency of the detector is seen to depend on the gamma ray energy. The results from this work shows that the detector system is suitable gamma spectrometry, and will give quality measurements when used for quantitative determination of radionuclides in environmental samples. The efficiency and resolution of the NaI(Tl) detector should also be determined using photon energies obtained from other radioactive sources.
38

Vicentini, L. M., A. Ambrosini, F. Di Virgilio, J. Meldolesi, and T. Pozzan. "Activation of muscarinic receptors in PC12 cells. Correlation between cytosolic Ca2+ rise and phosphoinositide hydrolysis." Biochemical Journal 234, no. 3 (March 15, 1986): 555–62. http://dx.doi.org/10.1042/bj2340555.

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The intracellular signals generated by carbachol activation of the muscarinic receptor [release of inositol phosphates as a consequence of phosphoinositide hydrolysis and rise of the cytosolic Ca2+ concentration ([Ca2+]i, measured by quin2)] were studied in intact PC12 pheochromocytoma cells that had been differentiated by treatment with nerve growth factor. When measured in parallel samples of the same cell preparation 30 s after receptor activation, the release of inositol trisphosphate and of its possible metabolites, inositol bis- and mono-phosphate, and the [Ca2+]i rise were found to occur with almost superimposable carbachol concentration curves. At the same time carbachol caused a decrease in the radioactivity of preloaded phosphatidylinositol 4,5-bisphosphate, the precursor of inositol trisphosphate. Neither the inositol phosphate nor the [Ca2+]i signal was modified by preincubation of the cells with either purified Bordetella pertussis toxin or forskolin, the direct activator of adenylate cyclase. Both signals were partially inhibited by dibutyryl cyclic AMP, especially when the nucleotide analogue was applied in combination with the phosphodiesterase inhibitors RO 201724 and theophylline. The latter drug alone profoundly inhibited the carbachol-induced [Ca2+]i rise, with only minimal effect on phosphoinositide hydrolysis. Because of the diverging results obtained with forskolin on the one hand, dibutyryl cyclic AMP and phosphodiesterase inhibitors on the other, the effects of the latter drugs are considered to be pharmacological, independent of the intracellular cyclic AMP concentration. Two further drugs tested, mepacrine and MY5445, inhibited phosphoinositide hydrolysis at the same time as the 45Ca2+ influx stimulated by carbachol. Taken together, our results concur with previous evidence obtained with permeabilized cells and cell fractions to indicate phosphatidylinositol 4,5-bisphosphate hydrolysis and [Ca2+]i rise as two successive events in the intracellular transduction cascade initiated by receptor activation. The strict correlation between the carbachol concentration curves for inositol trisphosphate generation and [Ca2+]i rise, and the inhibition by theophylline of the Ca2$ signal without major effects on inositol phosphate generation, satisfy important requirements of the abovementioned interpretation.
39

Stroet, Marcus C. M., Erik de Blois, Joost Haeck, Yann Seimbille, Laura Mezzanotte, Marion de Jong, Clemens W. G. M. Löwik, and Kranthi M. Panth. "In Vivo Evaluation of Gallium-68-Labeled IRDye800CW as a Necrosis Avid Contrast Agent in Solid Tumors." Contrast Media & Molecular Imaging 2021 (December 13, 2021): 1–8. http://dx.doi.org/10.1155/2021/2853522.

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Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, is an important biomarker. Tumor necrosis occurs in most solid tumors due to improperly functioning blood vessels that cannot keep up with the rapid growth, especially in aggressively growing tumors. The amount of necrosis per tumor volume is often correlated to rapid tumor proliferation and can be used as a diagnostic tool. Furthermore, efficient therapy against solid tumors will directly or indirectly lead to necrotic tumor cells, and detection of increased tumor necrosis can be an early marker for therapy efficacy. We propose the application of necrosis avid contrast agents to detect therapy-induced tumor necrosis. Herein, we advance gallium-68-labeled IRDye800CW, a near-infrared fluorescent dye that exhibits excellent necrosis avidity, as a potential PET tracer for in vivo imaging of tumor necrosis. We developed a reliable labeling procedure to prepare [68Ga]Ga-DOTA-PEG4-IRDye800CW ([68Ga]Ga-1) with a radiochemical purity of >96% (radio-HPLC). The prominent dead cell binding of fluorescence and radioactivity from [68Ga]Ga-1 was confirmed with dead and alive cultured 4T1-Luc2 cells. [68Ga]Ga-1 was injected in 4T1-Luc2 tumor-bearing mice, and specific fluorescence and PET signal were observed in the spontaneously developing tumor necrosis. The ip injection of D-luciferin enabled simultaneous bioluminescence imaging of the viable tumor regions. Tumor necrosis binding was confirmed ex vivo by colocalization of fluorescence uptake with TUNEL dead cell staining and radioactivity uptake in dichotomized tumors and frozen tumor sections. Our presented study shows that [68Ga]Ga-1 is a promising PET tracer for the detection of tumor necrosis.
40

Jonker, Ard, Piet A. J. de Boer, Maurice J. B. van den Hoff, Wouter H. Lamers, and Antoon F. M. Moorman. "Towards Quantitative In Situ Hybridization." Journal of Histochemistry & Cytochemistry 45, no. 3 (March 1997): 413–23. http://dx.doi.org/10.1177/002215549704500309.

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In situ hybridization analysis of tissue mRNA concentrations remains to be accepted as a quantitative technique, even though exposure of tissue sections to photographic emulsion is equivalent to Northern blot analysis. Because of the biological importance of in situ quantification of RNA sequences within a morphological context, we evaluated the quantitative aspects of this technique. In calibrated microscopic samples, autoradiographic signal (density of silver grains) was proportionate to the radioactivity present, to the exposure time, and to time of development of the photographic emulsion. Similar results were obtained with tissue sections, showing that all steps of the in situ hybridization protocol, before and including the detection of the signal, can be reproducibly performed. Furthermore, the integrated density of silver grains produced in liver and intestinal sections by the in situ hybridization procedure using 35S-labeled riboprobes is directly proportionate to the signal obtained by quantitative Northern blot analysis. The significance of this finding is that in situ quantification of RNA can be realized with high sensitivity and with the additional advantage of the possibility of localizing mRNA within the cells of interest. Application of this procedure on fetal and adult intestinal tissue showed that the carbamoylphosphate synthetase (CPS)-expressing epithelial cells of both tissues accumulated CPS mRNA to the same level but that whole-organ CPS mRNA levels decreased four- to fivefold in the same period, owing to a comparable decrease in the number of CPS-expressing cells in total intestinal tissue. (J Histochem Cytochem 45:413–423, 1997)
41

Ramesh Babu, V., Subhash Ram, and N. Sundararajan. "Modeling and inversion of magnetic and VLF-EM data with an application to basement fractures: A case study from Raigarh, India." GEOPHYSICS 72, no. 5 (September 2007): B133—B140. http://dx.doi.org/10.1190/1.2759921.

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We present modeling of magnetic and very low frequency electromagnetic (VLF-EM) data to map the spatial distribution of basement fractures where uranium is reported in Sambalpur granitoids in the Raigarh district, Chhattisgarh, India. Radioactivity in the basement fractures is attributed to brannerite, [Formula: see text] complex, and uranium adsorbed on ferruginous matter. The amplitude of the 3D analytical signal of the observed magnetic data indicates the trend of fracture zones. Further, the application of Euler 3D deconvolution to magnetic data provides the spatial locations and depth of the source. Fraser-filtered VLF-EM data and current density pseudosections indicate the presence of shallow and deep conductive zones along the fractures. Modeling of VLF-EM data yields the subsurface resistivity distribution of the order of less than 100 ohm-m of the fractures. The interpreted results of both magnetic and VLF-EM data agree well with the geologic section obtained from drilling.
42

Akindele, O. A., A. Bernstein, S. Boyd, J. Burns, M. Calle, J. Coleman, R. Collins, et al. "Acceptance tests of Hamamatsu R7081 photomultiplier tubes." Journal of Instrumentation 18, no. 08 (August 1, 2023): P08015. http://dx.doi.org/10.1088/1748-0221/18/08/p08015.

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Abstract Photomultiplier tubes (PMTs) are traditionally an integral part of large underground experiments as they measure the light emission from particle interactions within the enclosed detection media. The BUTTON experiment will utilise around 100 PMTs to measure the response of different media suitable for rare event searches. A subset of low-radioactivity 10-inch Hamamatsu R7081 PMTs were tested, characterised, and compared to manufacture certification. This manuscript describes the laboratory tests and analysis of gain, peak-to-valley ratio and dark rate of the PMTs to give an understanding of the charge response, signal-to-noise ratio and dark noise background as an acceptance test of the suitability of these PMTs for water-based detectors. Following the evaluation of these tests, the PMT performance agreed with the manufacturer specifications. These results are imperative for modeling the PMT response in detector simulations and providing confidence in the performance of the devices once installed in the detector underground.
43

Oprea, A., F. Gunsing, P. Schillebeeckx, O. Aberle, M. Bacak, E. Berthoumieux, D. Cano-Ott та ін. "Measurement of the 241Am(n,γ) cross section at the n_TOF facility at CERN". EPJ Web of Conferences 284 (2023): 01036. http://dx.doi.org/10.1051/epjconf/202328401036.

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The neutron capture cross section of 241Am is an important quantity for nuclear energy production and fuel cycle scenarios. Several measurements have been performed in recent years with the aim to reduce existing uncertainties in evaluated data. Two previous measurements, performed at the 185 m flight-path station EAR1 of the neutron time-of-flight facility n_TOF at CERN, have permitted to substantially extend the resolved resonance region, but suffered in the near-thermal energy range from the unfavorable signal-to-background ratio resulting from the combination of the high radioactivity of 241Am and the rather low thermal neutron flux. The here presented 241Am(n,γ) measurement, performed with C6D6 liquid scintillator gamma detectors at the 20 m flight-path station EAR2 of the n_TOF facility, took advantage of the much higher neutron flux. The current status of the analysis of the data, focussed on the low-energy region, will be described here.
44

CARROLL, LEWIS. "ACHIEVING A LINEAR DOSE RATE RESPONSE IN PULSE-MODE SILICON PHOTODIODE SCINTILLATION DETECTORS OVER A WIDE RANGE OF EXCITATIONS." International Journal of Modern Physics: Conference Series 27 (January 2014): 1460136. http://dx.doi.org/10.1142/s2010194514601367.

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We are developing a new dose calibrator for nuclear pharmacies that can measure radioactivity in a vial or syringe without handling it directly or removing it from its transport shield “pig”. The calibrator's detector comprises twin opposing scintillating crystals coupled to Si photodiodes and current-amplifying trans-resistance amplifiers. Such a scheme is inherently linear with respect to dose rate over a wide range of radiation intensities, but accuracy at low activity levels may be impaired, beyond the effects of meager photon statistics, by baseline fluctuation and drift inevitably present in high-gain, current-mode photodiode amplifiers. The work described here is motivated by our desire to enhance accuracy at low excitations while maintaining linearity at high excitations. Thus, we are also evaluating a novel “pulse-mode” analog signal processing scheme that employs a linear threshold discriminator to virtually eliminate baseline fluctuation and drift. We will show the results of a side-by-side comparison of current-mode versus pulse-mode signal processing schemes, including perturbing factors affecting linearity and accuracy at very low and very high excitations. Bench testing over a wide range of excitations is done using a Poisson random pulse generator plus an LED light source to simulate excitations up to ∼106 detected counts per second without the need to handle and store large amounts of radioactive material.
45

Remaury, A., D. Larrouy, D. Daviaud, B. Rouot та H. Paris. "Coupling of the α2-adrenergic receptor to the inhibitory G-protein Gi and adenylate cyclase in HT29 cells". Biochemical Journal 292, № 1 (15 травня 1993): 283–88. http://dx.doi.org/10.1042/bj2920283.

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Previous studies have established that the human colon carcinoma cell line HT29 expresses an alpha 2-adrenergic receptor of the alpha 2A subtype, which is negatively coupled to adenylate cyclase. The purpose of the present study was to examine the mechanisms of alpha 2-adrenergic signal transduction in these cells. [32P]ADP-ribosylation with pertussis toxin and immunoblots using antibodies specific for the Gi alpha-subunits indicated that two distinct Gi-proteins (Gi2 and Gi3) were present in HT29-cell membranes. Treatment of intact cells with pertussis toxin resulted in a time-dependent decrease in the amount of [32P]ADP-ribosylatable Gi2 and Gi3, which coincided with a diminution in the number of alpha 2-adrenergic receptors in high-affinity state for agonists and with a progressive loss of ability of UK14304 to inhibit forskolin-stimulated accumulation of cyclic AMP. When membranes were [32P]ADP-ribosylated with cholera toxin in the absence of exogenous added guanine nucleotides, radioactivity was incorporated into a 45 kDa polypeptide representing Gs, as well as into 40-41 kDa polypeptides corresponding to Gi3 and Gi2. The amount of radioactivity incorporated into the two GiS under basal conditions was decreased by addition of the alpha 2-antagonist RX821002. It was not significantly affected by addition of clonidine (partial alpha 2-agonist), but was doubled by the addition of UK14304 (full alpha 2-agonist). This effect was blocked by RX821002. Study of adenylate cyclase activity indicated that preincubation of HT29 membranes with the antibody AS/7 (anti-alpha i1/alpha i2), but not with the antibody EC/2 (anti-alpha i3), attenuated the inhibitory effect of UK14304 on forskolin-stimulated adenylate cyclase. These data demonstrate that the alpha 2A-adrenergic receptor is coupled to both Gi2 and Gi3, and identify Gi2 as the major mediator of inhibition of adenylate cyclase in HT29 cells.
46

Saini, Deepak Kumar, and Jaya Sivaswami Tyagi. "High-Throughput Microplate Phosphorylation Assays Based on DevR-DevS/Rv2027c 2-Component Signal Transduction Pathway to Screen for Novel Antitubercular Compounds." Journal of Biomolecular Screening 10, no. 3 (April 2005): 215–24. http://dx.doi.org/10.1177/1087057104272090.

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DevR-DevS (Rv3133c-Rv3132c) and DevR-Rv2027c have been established through their autophosphorylation and phospho-transfer properties to constitute bonafide regulatory 2-component systems of Mycobacterium tuberculosis. DevR has also been shown by others to play a key regulatory role in the expression of M. tuberculosis genes comprising the dormancy regulon. The authors describe high-throughput phosphorylation assays in a microplate format using DevS and Rv2027c histidine kinases and DevR response regulator proteins from M. tuberculosis. The assays were designed to measure [γ-32P]ATP-dependent autophosphorylation of DevS/Rv2027c and also the phosphotransfer reaction to DevR. First, the optimal reaction conditions were established using the conventional method of radiolabeling the 2-component proteins by [γ-32P]ATP and followed by gel electrophoresis-based analysis. Next, the assays were converted to a high-throughput format in which the radiolabeled protein retained on a filter using mixed cellulose ester-based 96-well filter plates was analyzed for radioactivity retention by scintillation counting. The utility of these assays to screen for inhibitors is illustrated using 2-mercaptobenzimidazole, ethidium bromide, and EDTA. The high quality and flexibility of these assays will enable their use in high-throughput screening for new antitubercular compounds directed against 2-component systems that comprise a novel target in dormant mycobacteria.
47

Kiraga, Łukasz, Gabriele Cerutti, Agata Braniewska, Damian Strzemecki, Zuzanna Sas, Alberto Boffi, Carmelinda Savino, et al. "Biodistribution PET/CT Study of Hemoglobin-DFO-89Zr Complex in Healthy and Lung Tumor-Bearing Mice." International Journal of Molecular Sciences 21, no. 14 (July 15, 2020): 4991. http://dx.doi.org/10.3390/ijms21144991.

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Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine β93 is the sole attachment moiety to the αβ-protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells.
48

Nosjean, Olivier, Sophie Souchaud, Clarisse Deniau, Olivier Geneste, Nicolas Cauquil, and Jean A. Boutin. "A Simple Theoretical Model for Fluorescence Polarization Binding Assay Development." Journal of Biomolecular Screening 11, no. 8 (December 2006): 949–58. http://dx.doi.org/10.1177/1087057106294841.

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Fluorescence polarization is a screening technology that is radioactivity free, homogeneous, and ratiometric. The signal measured with this technology is a weighted value of free and bound ligand. As a consequence, saturation curves are accessible only after calculation of the corresponding concentrations of free and bound ligand. To make this technology more accessible to assay development, the authors propose a simple mathematical model that predicts fluorescence polarization values from ligand and receptor total concentrations, depending on the corresponding dissociation constant. This model was validated using data of Bodipy-NDP-αMSH binding to MC5, obtained after either ligand saturation of a receptor preparation or, conversely, receptor saturation of a ligand solution. These experimental data were also used to calculate the actual concentration of free and bound ligand and receptor and to obtain pharmacological constants by Scatchard analysis. A general method is proposed, which facilitates the design of fluorescence polarization binding assays by relying on the representation of theoretical polarization values. This approach is illustrated by the application to 2 systems of very different affinities.
49

Malysheva, A. O., G. E. Kodina, E. A. Lyamtseva, N. A. Taratonenkova, and A. S. Lunev. "Experience in Validation of Methods for Determination of Radiochemical Impurities in Radiopharmaceuticals." Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 10, no. 4 (December 11, 2020): 244–56. http://dx.doi.org/10.30895/1991-2919-2020-10-4-244-256.

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Most important quality attributes of any radiopharmaceutical (RPh) are its radiochemical purity (RCP) or content of radiochemical impurities (RCIs) that have to comply with respective norms and limits. However, at present, there is no unified approach to validation of analytical methods in the context of highly radioactive samples.The aim of the study was to develop an approach to validation of methods for determination of RCI content in RPhs.Materials and methods: the authors determined the content of RCIs in a radiopharmaceutical formulation containing a complex of technetium-99m and methylenediphosphonic acid by the radiometric method after isolation of impurities from the main compound by thin-layer chromatography using silica gel and methyl ethyl ketone (for sodium pertechnetate determination) and silica gel and 13.6% sodium acetate solution (for determination of hydrolysed reduced technetium-99m). The radioactivity was registered by a chromatogram scanner with a detector of gamma-rays with energies from 0.05 to 1.5 MeV.Results: the paper analyses existing official approaches to validation of analytical procedures and compares them with the results of experimental studies described in available publications. It assesses the validation parameters for compliance with the acceptance criteria set forth in the current regulations and substantiates selectivity of chromatographic determination of impurities under the selected test conditions. Coefficients of variation for repeatability, reproducibility, and accuracy did not exceed 4.5, 2.8, and 8.9%, respectively, given the relative error of not more than 10.5%. The study demonstrated signal linearity for the 10-fold dilution of the standardised sodium pertechnetate solution, it also demonstrated correspondence between the applied and detected radioactivity when performing the test in the impurity content range of 0.5–5%. The validation procedure was associated with significant radiation burden for the personnel of the quality control laboratory.Conclusions: the authors suggested a methodological approach to validation of methods for determination of RCI content in technetium-99m-based RPhs. This approach may be used in the development of a guideline on validation of analytical methods for RCP/RCI determination in RPhs, or for introduction of relevant sections into existing documents.
50

Matovic, Milovan, Miroslav Ravlic, Marija Jeremic, Slobodan Jankovic, and Marina Vlajkovic. "Alarm system for surveillance of patients receiving high doses of radioiodine (131I) therapy in the case of unauthorised abandoning of a controlled area." Nuclear Technology and Radiation Protection 33, no. 2 (2018): 223–29. http://dx.doi.org/10.2298/ntrp1802223m.

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After receiving high doses of radioiodine the patients have to remain isolated within the ?restricted area?, until the radioactivity of the body drops below a certain level. The aim of this paper was to present our alarming system designed to discover patients who attempt to abandon the ?restricted area? and inform medical staff about the event. The system consists of a survey-meter with a pancake probe directed towards the corridor. The survey-meter is connected to a trigger circuit which gives a signal in the case when the measured count rate exceeds a preset value. This signal sets ?on? the alarm device, blinking light, programmable siren and IP camera, in order to warn the patient and inform the personnel when such a case occurs. In order to test the consistency and sensitivity of our system we measured ten times the ambient dose equivalent, H*(10), from the source of 925 MBq (25 mCi) 131I, kept at a distance of 1 m. The average ambient dose equivalent was 77.73 ? 31.57 (0.084 mSvh-1 per MBq, or 3.1 mSvh-1 per mCi). We measured ten times the same source at various distances (1-2.25 m) from the probe. In each position, the system was triggered. Also we tested the system on 40 patients treated with radioiodine instructed to pass through the corridor. Each of their attempts triggered the system. According to our experience gained over the past few years, this alarm system intended for patients receiving radionuclide therapy ensures a high level of safety for both the patients and medical staff.

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