Half-life of Xe120

Science.gov (United States)

Phillips, A. A.; Andreoiu, C.; Ball, G. C.; Bandyopadhyay, D.; Behr, J. A.; Chupp, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hayden, M. E.; Hyland, B.; Nuss-Warren, S. R.; Pearson, M. R.; Schumaker, M. A.; Smith, M. B.; Svensson, C. E.; Tardiff, E. R.; Valiente-Dobón, J. J.; Warner, T.

2006-08-01

We have measured the half-life of Xe120 using a high-purity germanium (HPGe) detector to monitor the 176, 178, and 762 keV γ rays from Xe120 β+ decay. The result, 46±0.6 min, differs significantly from the value 40±1 min reported by Andersson [Ark. Fys. 28, 37 (1964)]. We have also measured the half-lives of Cs120 and I120 to be 60±0.7 s and 82.1±0.6 min, respectively, both of which are consistent with previous measurements.

A new determination of the 209Po half-life

International Nuclear Information System (INIS)

Collé, R; Fitzgerald, R P; Laureano–Perez, L

2014-01-01

A substantial 25% error in the then-known and accepted (102 ± 5) year half-life of 209 Po was reported on in 2007. This error was detected from decay data from two separate primary standardizations of a 209 Po solution standard, which were performed approximately 12 years apart. Despite author claims that this observation was not a new half-life determination, it was nevertheless included in subsequent nuclear data evaluations and compilations to obtain a currently tabulated value of (115 ± 13) a, computed from the median and range of the two half-life reports. A third primary standardization on the identical 209 Po solution has since been performed to derive a new half-life value of (125.2 ± 3.3) a. This half-life determination was obtained from 30 distinct data sets over a period of 20.7 years, encompassing over 700 liquid scintillation measurements with nearly 50 counting sources all prepared from the same solution, and as obtained over a very broad range of measurement conditions (composition of cocktails, characteristics of counters, time sequencing) during five periods in 1993, 1994, 2005, and 2013. (paper)

Measurement of the 20F half-life

Science.gov (United States)

Hughes, M.; George, E. A.; Naviliat-Cuncic, O.; Voytas, P. A.; Chandavar, S.; Gade, A.; Huyan, X.; Liddick, S. N.; Minamisono, K.; Paulauskas, S. V.; Weisshaar, D.

2018-05-01

The half-life of the 20F ground state was measured using a radioactive beam implanted in a plastic scintillator and recording β γ coincidences together with four CsI(Na) detectors. The result, T1 /2=11.0011 (69) stat(30) sys s, is at variance by 17 combined standard deviations with the two most precise results. The present value revives the poor consistency of results for this half-life and calls for a new measurement, with a technique having different sources of systematic effects, to clarify the discrepancy.

Precise half-life measurement of the superallowed emitter 30S

Science.gov (United States)

Iacob, V. E.; Hardy, J. C.; Chen, L.; Horvat, V.; Bencomo, M.; Nica, N.; Park, H. I.; Roeder, B. T.; Saastamoinen, A.

2018-03-01

We have measured the half-life of 30S, the parent of a superallowed 0+→0+β transition, to a high precision using very pure sources and a 4 π proportional gas counter to detect the decay positrons. Our result for the half-life is 1.179 92(34) s. As a by-product of this measurement, we determine the half-life of its daughter, 30P, to be 2.501(2) min.

Beryllium-10: Half-life and AMS-standards

International Nuclear Information System (INIS)

Hofmann, H.J.; Beer, J.; Bonani, G.; von Gunten, H.R.; Raman, S.; Suter, M.; Walker, R.L.; Woelfli, W.; Zimmermann, D.

1987-01-01

Absolute AMS measurements of 10 Be require reliable standards for calibration. Among the existing standards, rather large differences have been observed. These differences were found partially to be due to the different half-life values which were assumed. Also for comparison of AMS data with activity measurements, it is necessary to know the 10 Be half-life as precisely as possible. Starting with 5 ml of the standardized ORNL-MASTER solution, a working solution with a well-defined 10 Be content was prepared. Its specific activity was determined by liquid scintillation counting. This measurement yielded a new value of (1.52 +- 0.05) My for the 10 Be half-life, which is in agreement with the previously reported values but is about three times more accurate. Two independent dilution series produced new AMS standards with 10 Be/ 9 Be ratios of the order of 10 -10 and 10 -11 . These standards were measured at the ETH/SIN AMS facility with high accuracy and are compared with other available 10 Be standards. 15 refs, 2 figs., 3 tabs

Experimental study of half-life determinations using 60Co

International Nuclear Information System (INIS)

Rutledge, A.R.; Smith, L.V.; Merritt, J.S.

1983-01-01

The half-life of 60 Co was determined by two methods, (i) the 4π#betta# ionization chamber method and (ii) the 4π #betta#-#betta# coincidence method. The first is a relative counting method in which the only rate-dependent correction is for background, whereas the second is an 'absolute' counting method which involves several rate-dependent corrections. In addition, various methods of calculation of the results were tested. The half-life values for the two counting systems were in good agreement and the weighted mean value for the half-life of 60 Co was found to be 1925.02+-0.47 d. (orig.)

Determination of plutonium-241 half-life by mass spectrometric measurement

International Nuclear Information System (INIS)

Hiyama, Takashi; Wada, Yukio; Onishi, Koichi

1982-01-01

Much data for Pu-241 half-life have been reported, but these values range from 13.8 years to 15.1 years depending on investigators. In order to define the half-life of Pu-241, the half-life was calculated by analyzing the mass spectrometry data obtained in the author's laboratory over the past six years on Plutonium Isotopic Standard Reference Materials prepared at the National Bureau of Standards (NBS). The sample used for this work consisted of SRM-947 and SRM-948 prepared at NBS. Before mass spectrometric analysis, the plutonium aliquot was separated from its Am-241 daughter by anion exchange chromatography, since Am-241 is not distinguished from Pu-241 in the mass spectrometer. 241 Pu/ 239 Pu and 241 Pu/ 240 Pu ratios were calculated from the values of mass spectrometric measurement. From the relation of log N to time, the half-life of Pu-241 was determined, based on the slope using a least squares fit. The half-life of Pu-241 was estimated to be 14.29+-0.15 years. (Yoshitake, I.)

Half-life evaluations for 3H, 90Sr, and 90Y

International Nuclear Information System (INIS)

MacMahon, Desmond

2006-01-01

A recent paper has reviewed methods for the evaluation of discrepant sets of data and demonstrated the results of applying these methods to the published half-life data of 90 Sr and 137 Cs [MacMahon, T.D., Pearce, A., Harris, P., 2004. Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281]. The half-life data for 3 H has been subject to a comprehensive review and critical evaluation by Lucas and Unterweger [2000. Comprehensive review and critical evaluation of the half-life of tritium. J. Res. Natl. Inst. Stand. Technol. 105, 541-549]. The current paper reports the results of applying the various evaluation procedures of MacMahon et al. Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281] to the data of Lucas and Unterweger [Comprehensive review and critical evaluation of the half-life of tritium. J. Res. Natl. Inst. Stand. Technol. 105, 541-549], resulting in a recommended half-life of 4497(4) days. MacMahon et al. [Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281] highlighted problems in the evaluation of the discrepant half-life data of 90 Sr, in particular the worrying upward trend in the data, where the weighted mean of all the measurements increases, on average, by 35 days each time a new measurement result is added. The current paper reports on further analyses of these data. New measurements of the half-life of 90 Y have been reported by Kossert and Schrader [2004. Standardization by liquid scintillation counting and half-life measurements of 90 Y. Appl. Radiat. Isot. 60, 741]. This has prompted a new evaluation of all available published 90 Y half-life data. The data are fairly consistent, and a value of 64.063(16) h is recommended

Half-life of the superallowed β+ emitter Ne18

Science.gov (United States)

Grinyer, G. F.; Smith, M. B.; Andreoiu, C.; Andreyev, A. N.; Ball, G. C.; Bricault, P.; Chakrawarthy, R. S.; Daoud, J. J.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Valiente-Dobón, J. J.; Williams, S. J.; Zganjar, E. F.

2007-08-01

The half-life of Ne18 has been determined by detecting 1042-keV γ rays in the daughter F18 following the superallowed-Fermi β+ decay of samples implanted at the center of the 8πγ-ray spectrometer, a spherical array of 20 HPGe detectors. Radioactive Ne18 beams were produced on-line, mass-separated, and ionized using an electron-cyclotron-resonance ionization source at the ISAC facility at TRIUMF in Vancouver, Canada. This is the first high-precision half-life measurement of a superallowed Fermi β decay to utilize both a large-scale HPGe spectrometer and the isotope separation on-line technique. The half-life of Ne18, 1.6656 ± 0.0019 s, deduced following a 1.4σ correction for detector pulse pile-up, is four times more precise than the previous world average. As part of an investigation into potential systematic effects, the half-life of the heavier isotope Ne23 was determined to be 37.11 ± 0.06 s, a factor of 2 improvement over the previous precision.

Topology and Oligomerization of Mono- and Oligomeric Proteins Regulate Their Half-Lives in the Cell.

Science.gov (United States)

Mallik, Saurav; Kundu, Sudip

2018-06-05

To find additional structural constraints (besides disordered segments) that regulate protein half-life in the cell, we herein assess the influence of native topology of monomeric and sequestration of oligomeric proteins into multimeric complexes in yeast, human, and mouse. Native topology acts as a molecular marker of globular protein's mechanical resistance and consequently captures their half-life variations on genome scale. Sequestration into multimeric complexes elongates oligomeric protein half-life in the cell, presumably by burying ubiquitinoylation sites and disordered segments required for proteasomal recognition. The latter effect is stronger for proteins associated with multiple complexes and for those binding early during complex self-assembly, including proteins that oligomerize with large proportions of surface buried. After gene duplication, diversification of topology and sequestration into non-identical sets of complexes alter half-lives of paralogous proteins during the course of evolution. Thus, native topology and sequestration into multimeric complexes reflect designing principles of proteins to regulate their half-lives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measurement of the half-life of 68Ga

International Nuclear Information System (INIS)

García-Toraño, Eduardo; Peyrés Medina, Virginia; Romero, Eduardo; Roteta, Miguel

2014-01-01

The half-life of the positron-emitter 68 Ga has been measured by following the decay rate with two systems based on ionization chamber and Ge detectors. The decay rate was measured for periods of time up to 10 half-lives. The combination of the 6 results obtained with both systems gives a value of T 1/2 =67.845(18) min, in good agreement with recommended data and with an uncertainty lower than any other previously reported value. - Highlights: • The half-life of the positron-emitter radionuclide 68 Ga was measured. • Two measurement setups (ionization chamber and Ge detector) were used. • Results agree with evaluated data but exhibit lower uncertainty

Half-life predictions for decay modes of superheavy nuclei

International Nuclear Information System (INIS)

Duarte, S.B.; Tavares, O.A.P.; Goncalves, M.; Rodriguez, O.; Guzman, F.; Barbosa, T.N.; Garcia, F.; Dimarco, A.

2004-09-01

We applied the Effective Liquid Drop Model (ELDM) to predict the alpha-decay, cluster emission and cold fission half-life-values of nuclei in the region of Superheavy Elements (SHE). The present calculations have been made in the region of the ZN-plane defined by 155 <=N <=220 and 110<=Z<=135. Shell effects are included via the Q-value of the corresponding decay case. We report the results of a systematic calculation of the half-life for the three nuclear decay modes in a region of the ZN-plane where superheavy elements are expected to be found. Results have shown that, among the decay modes investigated here, the alpha decay is the dominant one. i.e, the decay mode of smallest half-lives. Half-life predictions for alpha decay, cluster emission and cold fission for the isotopic family of the most recent SHE detected of Z=115 and for the isotopic family of the already consolidated SHE of Z=111 are presented. (author)

Intrinsically disordered segments and the evolution of protein half-life

Science.gov (United States)

Babu, M.

2013-03-01

Precise turnover of proteins is essential for cellular homeostasis and is primarily mediated by the proteasome. Thus, a fundamental question is: What features make a protein an efficient substrate for degradation? Here I will present results that proteins with a long terminal disordered segment or internal disordered segments have a significantly shorter half-life in yeast. This relationship appears to be evolutionarily conserved in mouse and human. Furthermore, upon gene duplication, divergence in the length of terminal disorder or variation in the number of internal disordered segments results in significant alteration of the half-life of yeast paralogs. Many proteins that exhibit such changes participate in signaling, where altered protein half-life will likely influence their activity. We suggest that variation in the length and number of disordered segments could serve as a remarkably simple means to evolve protein half-life and may serve as an underappreciated source of genetic variation with important phenotypic consequences. MMB acknowledges the Medical Research Council for funding his research program.

Real-time RT-PCR analysis of mRNA decay: half-life of Beta-actin mRNA in human leukemia CCRF-CEM and Nalm-6 cell lines

Directory of Open Access Journals (Sweden)

Barredo Julio C

2002-03-01

Full Text Available Abstract Background We describe an alternative method to determine mRNA half-life (t1/2 based on the Real-Time RT-PCR procedure. This approach was evaluated by using the β-actin gene as a reference molecule for measuring of mRNA stability. Results Human leukemia Nalm-6 and CCRF-CEM cells were treated with various concentrations of Actinomycin D to block transcription and aliquots were removed periodically. Total RNA was isolated and quantified using the RiboGreen® fluorescent dye with the VersaFluor Fluorometer System. One μg of total RNA was reverse transcribed and used as template for the amplification of a region of the β-actin gene (231 bp. To generate the standard curve, serial ten-fold dilutions of the pBactin-231 vector containing the cDNA amplified fragment were employed, β-actin mRNAs were quantified by Real-Time RT-PCR using the SYBR® Green I fluorogenic dye and data analyzed using the iCycle iQ system software. Using this method, the β-actin mRNA exhibited a half-life of 6.6 h and 13.5 h in Nalm-6 and CCRF-CEM cells, respectively. The t1/2 value obtained for Nalm-6 is comparable to those estimated from Northern blot studies, using normal human leukocytes (5.5 h. Conclusions We have developed a rapid, sensitive, and reliable method based on Real-Time RT-PCR for measuring mRNA half-life. Our results confirm that β-actin mRNA half-life can be affected by the cellular growth rate.

On the 209Po half-life error and its confirmation. A critique

International Nuclear Information System (INIS)

Colle, R.; Colle, A.M.

2016-01-01

A recent report on 209 Po claimed to have made a determination of the 125-a half-life from measurements made over 0.8 % of one half-life. A careful reanalysis of the original data with a more complete and rigorous consideration of the underlying uncertainties demonstrates that this claim cannot withstand critical scrutiny. More importantly, this critique examines the larger issue as to what constitutes a valid half-life determination, and highlights that a careful and realistic analysis beyond the mere fitting of decay data to an exponential function is required for the measurement and reporting of half-life values. (author)

Determination of the {sup 151}Sm half-life

Energy Technology Data Exchange (ETDEWEB)

Be, Marie-Martine; Cassette, Philippe [CEA, LIST, Gif sur Yvette (France). LNE-Laboratoire National Henri Becquerel; Isnard, Helene [CEA-LANIE, Gif sur Yvette (France); and others

2015-07-01

New measurements have been undertaken to determine the half-life of {sup 151}Sm. A pure {sup 151}Sm solution was obtained after chemical separation from a samarium solution resulting from the dissolution of an irradiated samarium sample. The concentration of {sup 151}Sm in the solution was measured by mass spectrometry, combined with the isotope dilution technique. The activity of the solution was measured by liquid scintillation counting by six European laboratories as part of an international comparison. These combined results lead to a half-life of T{sub 1/2} = 94.6(6)a.

18F half-life measurement using a high-purity germanium detector

International Nuclear Information System (INIS)

Han, Jubong; Lee, K.B.; Park, T.S.; Lee, J.M.; Oh, P.J.; Lee, S.H.; Kang, Y.S.; Ahn, J.K.

2012-01-01

The half-life of 18 F has been measured using HPGe detectors with a 137 Cs reference source. The counting ratio of 511 keV γ-rays from 18 F to 622 keV γ-rays from 137 Cs was fitted for the half-life with a weighted least-square method. Uncertainties due to the systematic effects arising from the measurement of a high activity 18 F source were studied in detail. The half-life of 18 F was found to be (109.72±0.19) min. The result is in a good agreement with the recommended value of (109.728±0.019) min evaluated at the Laborotaire National Henri Becquerel (LNHB). - Highlights: ► The 18 F half-life was measured with a reference source and without it using HPGe detectors. ► We found the systematic effect ‘activity dynamic range effect’ by monitoring the counts of the reference source. ► This activity dynamic range effect was corrected by using the reference source method. ► The 18 F half-life using the reference source method was in a good agreement with the recommended value of LNHB.

Using gamma distribution to determine half-life of rotenone, applied in freshwater

Energy Technology Data Exchange (ETDEWEB)

Rohan, Maheswaran, E-mail: mrohan@aut.ac.nz [Department of Biostatistics and Epidemiology, Auckland University of Technology, Auckland (New Zealand); Fairweather, Alastair; Grainger, Natasha [Science and Capability, Department of Conservation, Hamilton (New Zealand)

2015-09-15

Following the use of rotenone to eradicate invasive pest fish, a dynamic first-order kinetic model is usually used to determine the half-life and rate at which rotenone dissipated from the treated waterbody. In this study, we investigate the use of a stochastic gamma model for determining the half-life and rate at which rotenone dissipates from waterbodies. The first-order kinetic and gamma models produced similar values for the half-life (4.45 days and 5.33 days respectively) and days to complete dissipation (51.2 days and 52.48 days respectively). However, the gamma model fitted the data better and was more flexible than the first-order kinetic model, allowing us to use covariates and to predict a possible range for the half-life of rotenone. These benefits are particularly important when examining the influence that different environmental factors have on rotenone dissipation and when trying to predict the rate at which rotenone will dissipate during future operations. We therefore recommend that in future the gamma distribution model is used when calculating the half-life of rotenone in preference to the dynamic first-order kinetics model. - Highlights: • We investigated the use of the gamma model to calculate the half-life of rotenone. • Physical and environmental variables can be incorporated into the model. • A method for calculating the range around a mean half-life is presented. • The model is more flexible than the traditionally used first-order kinetic model.

High-precision half-life determination for the superallowed β+ emitter Ga62

Science.gov (United States)

Grinyer, G. F.; Finlay, P.; Svensson, C. E.; Ball, G. C.; Leslie, J. R.; Austin, R. A. E.; Bandyopadhyay, D.; Chaffey, A.; Chakrawarthy, R. S.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kanungo, R.; Leach, K. G.; Mattoon, C. M.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Sarazin, F.; Savajols, H.; Schumaker, M. A.; Wong, J.

2008-01-01

The half-life of the superallowed β+ emitter Ga62 has been measured at TRIUMF's Isotope Separator and Accelerator facility using a fast-tape-transport system and 4π continuous-flow gas proportional counter to detect the positrons from the decay of Ga62 to the daughter Zn62. The result, T1/2=116.100±0.025 ms, represents the most precise measurement to date (0.022%) for any superallowed β-decay half-life. When combined with six previous measurements of the Ga62 half-life, a new world average of T1/2=116.121±0.021 ms is obtained. This new half-life measurement results in a 20% improvement in the precision of the Ga62 superallowed ft value while reducing its mean by 0.9σ to ft=3074.3(12) s. The impact of this half-life measurement on precision tests of the CVC hypothesis and isospin symmetry breaking corrections for A⩾62 superallowed decays is discussed.

Precision half-life measurement of 17F

Science.gov (United States)

Brodeur, M.; Nicoloff, C.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Gupta, Y. K.; Hall, M. R.; Hall, O.; Hu, J.; Kelly, J. M.; Kolata, J. J.; Long, J.; O'Malley, P.; Schultz, B. E.

2016-02-01

Background: The precise determination of f t values for superallowed mixed transitions between mirror nuclide are gaining attention as they could provide an avenue to test the theoretical corrections used to extract the Vu d matrix element from superallowed pure Fermi transitions. The 17F decay is particularly interesting as it proceeds completely to the ground state of 17O, removing the need for branching ratio measurements. The dominant uncertainty on the f t value of the 17F mirror transition stems from a number of conflicting half-life measurements. Purpose: A precision half-life measurement of 17F was performed and compared to previous results. Methods: The life-time was determined from the β counting of implanted 17F on a Ta foil that was removed from the beam for counting. The 17F beam was produced by transfers reaction and separated by the TwinSol facility of the Nuclear Science Laboratory of the University of Notre Dame. Results: The measured value of t1/2 new=64.402 (42) s is in agreement with several past measurements and represents one of the most precise measurements to date. In anticipation of future measurements of the correlation parameters for the decay and using the new world average t1/2 world=64.398 (61) s, we present a new estimate of the mixing ratio ρ for the mixed transition as well as the correlation parameters based on assuming Standard Model validity. Conclusions: The relative uncertainty on the new world average for the half-life is dominated by the large χ2=31 of the existing measurements. More precision measurements with different systematics are needed to remedy to the situation.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

Directory of Open Access Journals (Sweden)

Martha M. C. Elwenspoek

2017-10-01

Full Text Available Early life adversity (ELA increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59 or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18. No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57 in ELA. In addition, senescent T cells (CD57+ in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

A half-life the divided life of Bruno Pontecorvo, physicist or spy

CERN Document Server

Close, Frank

2015-01-01

Bruno Pontecorvo dedicated his career to hunting for the Higgs boson of his day: the neutrino, a nearly massless particle considered essential to the process of nuclear fission. His work on the Manhattan project under Enrico Fermi confirmed his reputation as a brilliant physicist and helped usher in the nuclear age. He should have won a Nobel Prize, but late in the summer of 1950 he vanished. At the height of the Cold War, Pontecorvo had disappeared behind the Iron Curtain. In Half-Life, physicist and historian Frank Close offers a heretofore untold history of Pontecorvo’s life, based on unprecedented access to his friends, family, and colleagues. With all the elements of a Cold War thriller—classified atomic research, an infamous double agent, a kidnapping by Soviet operatives—Half-Life is a history of particle physics at perhaps its most powerful: when it created the bomb.

Radionuclide biological half-life values for terrestrial and aquatic wildlife

International Nuclear Information System (INIS)

Beresford, N.A.; Beaugelin-Seiller, K.; Burgos, J.; Cujic, M.; Fesenko, S.; Kryshev, A.; Pachal, N.; Real, A.; Su, B.S.; Tagami, K.; Vives i Batlle, J.; Vives-Lynch, S.; Wells, C.; Wood, M.D.

2015-01-01

The equilibrium concentration ratio is typically the parameter used to estimate organism activity concentrations within wildlife dose assessment tools. Whilst this is assumed to be fit for purpose, there are scenarios such as accidental or irregular, fluctuating, releases from licensed facilities when this might not be the case. In such circumstances, the concentration ratio approach may under- or over-estimate radiation exposure depending upon the time since the release. To carrying out assessments for such releases, a dynamic approach is needed. The simplest and most practical option is representing the uptake and turnover processes by first-order kinetics, for which organism- and element-specific biological half-life data are required. In this paper we describe the development of a freely available international database of radionuclide biological half-life values. The database includes 1907 entries for terrestrial, freshwater, riparian and marine organisms. Biological half-life values are reported for 52 elements across a range of wildlife groups (marine = 9, freshwater = 10, terrestrial = 7 and riparian = 3 groups). Potential applications and limitations of the database are discussed. - Highlights: • 1907 biological half-life values have been collated for wildlife species. • Data cover 52 elements. • 27 marine, freshwater, riparian and terrestrial organisms are included.

HALO--a Java framework for precise transcript half-life determination.

Science.gov (United States)

Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf

2010-05-01

Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo.

Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

Science.gov (United States)

Hindmarsh, Peter C; Charmandari, Evangelia

2015-04-01

Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

Calculation of the biological half-life of radioactive isotopes

International Nuclear Information System (INIS)

Szabo, S.A.

1982-01-01

The biological half-life of 137 Cs and 90 Sr was determined based on K and Ca metabolism and on the considerable chemical similarity of K and Ca, carriers of Cs and Sr, resp. The tsub(1/2)=a/bxln2 formula was used for the calculation, where a is the quantity of the element in question, while b is the daily need of the animal for the given element. The biological half-life for cattle of both 137 Cs and 90 Sr was found to be 30 days, while that for swine 20 days and 35 days respectively. (Sz.J.)

Re-measurement of the half-life of sup 7 sup 9 Se

CERN Document Server

Jiang Song Sheng; Diao Li Jun; Li Chun Shen; GouJingRu; Wu Shao Yon

2002-01-01

A new attempt has been made for the re-measurement of the half-life of sup 7 sup 9 Se. We made two major improvements over our earlier sup 7 sup 9 Se half-life determination (Nucl. Instr. and Meth. B 123 (1997) 403). Firstly, the half-life of sup 7 sup 9 Se was measured relative to the precisely known half-life of sup 7 sup 5 Se, rather than an absolute measurement of sup 7 sup 9 Se/Se. Secondly, the Projectile X-ray Detection technique was used for the separation of sup 7 sup 9 Se from its isobar, sup 7 sup 9 Br, rather than measuring sup 8 sup 1 Br for the deduction of sup 7 sup 9 Br interference, and this technique was also used for separation of sup 7 sup 5 Se and its isobar, sup 7 sup 5 As. A detailed description of the sample preparations, experimental setup and measurements are given. The re-measured half-life of sup 7 sup 9 Se was (2.95+-0.38)x10 sup 5 a, about a factor of 3 lower than the previous value, 1.1x10 sup 6 a. The problems in the previous measurement are discussed.

The half-life of 207Bi and decays of 211At and 211Po

International Nuclear Information System (INIS)

Yanokura, M.; Kudo, H.; Nakahara, H.; Miyano, K.; Ohya, S.; Nitoh, O.

1978-01-01

The half-life of 207 Bi was obtained from the genetic relation between 207 Po and 207 Bi, and between 211 At and 207 Bi. The half-life was found to be 33.4 +- 0.8 y. The half-life of 207 Po was determined to be 5.81 +- 0.04 h by following the decay of the characteristic γ-rays from 207 Po. The half-life of 211 At was determined to be 7.23 +- 0.02 h by following the decay of γ-rays and α-particles from 211 At and 211 Po. The half-lives determined in the present work for 207 Po and 211 At agree with the literature although the half-life of 207 Bi differs considerably from the currently accepted value of 38 y. The branching ratio of 211 At decaying through EC and α-decay modes was determined together with the branching ratios of the three α-particles emitted from 211 Po. (Auth.)

Influence of ethacrynic acid on glutathione S-transferase pi transcript and protein half-lives in human colon cancer cells.

Science.gov (United States)

Shen, H; Ranganathan, S; Kuzmich, S; Tew, K D

1995-10-12

Ethacrynic acid (EA) is a plant phenolic acid that is both an inhibitor and an inducer of glutathione S-transferase (GST) activity. To determine contributory factors in the increased GST activity caused by EA treatment, human colon carcinoma HT29 cells were compared with a cloned EA-resistant population (HT6-8) maintained in medium containing 72 microM EA. Several factors are involved in the increased expression of GST pi in HT6-8. For example, nuclear run-on experiments showed an approximately 2-fold increase in the rate of transcription of GST pi. In addition, the half-life of GST pi transcript was increased from 4.1 (wild type, HT29, HT4-1) to 8.4 hr. The half-life of GST pi protein was 1-2 hr in HT4-1 cells versus 8-9 hr in HT6-8 cells. When either human ovarian carcinoma cells (SKOV3) or human prostatic carcinoma cells (DU145) were treated with EA, the half-life of the GST pi transcript was also increased. The transcript half-lives of another thiol-metabolism enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and a phase II detoxification enzyme, dihydrodiol dehydrogenase (DDH), were also increased in HT6-8, SKOV3 and DU145 cells treated with EA. However, the half-lives of transcripts from "housekeeping genes," such as glyceraldehyde 3-phosphate dehydrogenase (G3PDH), beta-actin and beta-tubulin, were not changed in these cell lines following EA. Apparently, a number of coordinated factors are involved in EA-enhanced expression of GST pi and other detoxification enzymes.

Update of NIST half-life results corrected for ionization chamber source-holder instability

International Nuclear Information System (INIS)

Unterweger, M.P.; Fitzgerald, R.

2014-01-01

As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties. - Highlights: • The NIST half-life data is corrected for sample positioning variations and refitted. • These results are reported and increased errors in the reported values are given. • Longer lived radionuclides are discussed

Validation of effective half-life of tritium and computation of dose at Madras Atomic Power Station

International Nuclear Information System (INIS)

Moolya, L.L.; Kannan, R.K.; Sreekumaran Nair, B.; Mohandas, P.G.; Rajan, R.

2001-01-01

In Pressurised Heavy Water Reactors (PHWRs) tritium is produced by the activation of deuterium present in the moderator and coolant system. Hence, the inventory of tritium in PHWR is high and it contributes about 20 percent of the Station Dose. Tritium enters body by inhalation, ingestion and skin absorption. Dose received by an individual depends on its elimination rate from the body and hence the effective half-life. It is found that the effective half-life varies from person to person. The effective half-life also depends on the weather condition. The variation of effective half-life is taken care of in dose estimation by average method. However, in case of dose calculation for single uptake cases, there is a need to take fixed effective half-life. ICRP has taken the effective half-life as 10 days. The effective half-life is taken as 6 days in Indian conditions based on the studies conducted earlier in MAPS and elsewhere. Now with available data for about 16 years a fresh study was conducted to validate the effective half-life. This paper gives the study of effective half-life of tritium and its variation during different seasons of the year in MAPS. This paper also gives methods used for computing dose due to tritium. (author)

Influence of sex and age on the biological half-life of cadmium in mice

International Nuclear Information System (INIS)

Taguchi, T.; Suzuki, S.

1981-01-01

The influence of age on the whole-body biological half-life of 109 Cd was studied in male mice following ip injection. The influence of sex on whole-body and organ retention was ascertained after sc injection. The whole-body biological half-life of 109 Cd of the older mice was more than twice that of the younger mice, and that of the female mice was longer than that of the males. These differences demonstrate a biological difference between males and females with respect to whole-body half-life of 109 Cd. The effects of age and sex on the biological half-life of Cd in mice are assessed quantitatively

Measurement of the 8Li half-life

International Nuclear Information System (INIS)

Flechard, X.; Lienard, E.; Naviliat-Cuncic, O.; Ban, G.; Carniol, B.; Etasse, D.; Fontbonne, J. M.; Rodriguez, D.; Lallena, A. M.; Alvarez, M. A. G.; Praena, J.

2010-01-01

We report a new measurement of the 8 Li half-life using a plastic scintillator and an ultrafast waveform digitizing module. The result, T 1/2 =(838.40±0.36) ms, improves by a factor of 2.5 the most precise result obtained so far and is furthermore deduced with negligible corrections due to dead time.

Half-life distribution table of radioactive nuclei

International Nuclear Information System (INIS)

Gugenberger, P.

1954-01-01

This table allows to identify an element if its period is known. Data for this table were taken from the half-life values adopted by Hollander, PERLMAN and SEABORG (Rev. mod. Phys., 1953, 22 number 2). Moreover for each nucleus, the mass number, the charge number and the type of decay are given in the table. (author) [fr

Potential fitness benefits of the half-pounder life history in Klamath River steelhead

Science.gov (United States)

Hodge, Brian W.; Wilzbach, Peggy; Duffy, Walter G.

2014-01-01

Steelhead Oncorhynchus mykiss from several of the world's rivers display the half-pounder life history, a variant characterized by an amphidromous (and, less often, anadromous) return to freshwater in the year of initial ocean entry. We evaluated factors related to expression of the half-pounder life history in wild steelhead from the lower Klamath River basin, California. We also evaluated fitness consequences of the half-pounder phenotype using a simple life history model that was parameterized with our empirical data and outputs from a regional survival equation. The incidence of the half-pounder life history differed among subbasins of origin and smolt ages. Precocious maturation occurred in approximately 8% of half-pounders and was best predicted by individual length in freshwater preceding ocean entry. Adult steelhead of the half-pounder phenotype were smaller and less fecund at age than adult steelhead of the alternative (ocean contingent) phenotype. However, our data suggest that fish of the half-pounder phenotype are more likely to spawn repeatedly than are fish of the ocean contingent phenotype. Models predicted that if lifetime survivorship were equal between phenotypes, the fitness of the half-pounder phenotype would be 17–28% lower than that of the ocean contingent phenotype. To meet the condition of equal fitness between phenotypes would require that first-year ocean survival be 21–40% higher among half-pounders in freshwater than among their cohorts at sea. We concluded that continued expression of the half-pounder phenotype is favored by precocious maturation and increased survival relative to that of the ocean contingent phenotype.

On the half-life of luminescence signals in dosimetric applications: A unified presentation

Science.gov (United States)

Pagonis, V.; Kitis, G.; Polymeris, G. S.

2018-06-01

Luminescence signals from natural and man-made materials are widely used in dosimetric and dating applications. In general, there are two types of half-lives of luminescence signals which are of importance to experimental and modeling work in this research area. The first type of half-life is the time required for the population of the trapped charge in a single trap to decay to half its initial value. The second type of half-life is the time required for the luminescence intensity to drop to half of its initial value. While there a handful of analytical expressions available in the literature for the first type of half-life, there are no corresponding analytical expressions for the second type. In this work new analytical expressions are derived for the half-life of luminescence signals during continuous wave optical stimulation luminescence (CW-OSL) or isothermal luminescence (ITL) experiments. The analytical expressions are derived for several commonly used luminescence models which are based on delocalized transitions involving the conduction band: first and second order kinetics, empirical general order kinetics (GOK), mixed order kinetics (MOK) and the one-trap one-recombination center (OTOR) model. In addition, half-life expressions are derived for a different type of luminescence model, which is based on localized transitions in a random distribution of charges. The new half-life expressions contain two parts. The first part is inversely proportional to the thermal or optical excitation rate, and depends on the experimental conditions and on the cross section of the relevant luminescence process. The second part is characteristic of the optical and/or thermal properties of the material, as expressed by the parameters in the model. A new simple and quick method for analyzing luminescence signals is developed, and examples are given of applying the new method to a variety of dosimetric materials. The new test allows quick determination of whether a set of

ISABELLE half-cell control system

International Nuclear Information System (INIS)

Buxton, W.; Frankel, R.; Humphrey, J.W.

1977-01-01

The primary function of the ISABELLE half-cell control system is to monitor and control the magnet power supplies of the half-cell. In addition, the control system must be flexible enough that it can be expanded to become involved in additional areas such as vacuum and magnetic measurements. A control system based upon AGS control standards, but modified into a development tool for research and electrical engineering support was constructed. Special attention was given to the inherent differences between controlling an ISABELLE and a conventional fast cycling accelerator. The use of FORTRAN and BASIC networks, and microprocessors is reviewed insofar as they pertain to this system. Some general opinions on model control systems, based upon experience, are presented

Radioactive source simulation for half-life experiment

International Nuclear Information System (INIS)

Wanitsuksombut, Warapon; Decthyothin, Chanti

1999-01-01

A simulation of radioactivity decay by using programmable light source with a few minutes half-life is suggested. A photodiode with digital meter label in cps is use instead of radiation detector. Both light source and photodiode are installed in a black box to avoid surrounding room light. The simulation set can also demonstrate Inverse Square Law experiment of radiation penetration. (author)

The half-life of 125I

International Nuclear Information System (INIS)

Simpson, B.R.S.; Meyer, B.R.

1989-01-01

The Bureau International des Poids et Mesures (BIPM) organized an international comparison of activity measurements of a solution of 125 I. The half-life value adopted was 59.5±0.4d. The large uncertainty took account of a recently published value (Schrader, 1986) which is considerably lower than the widely used value of 60.0±0.1d. The present work, which was undertaken at the suggestion of the BIPM, has yielded a value which confirms the lower measurement. (author)

Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells.

Science.gov (United States)

Di Scala, Coralie; Mazzarino, Morgane; Yahi, Nouara; Varini, Karine; Garmy, Nicolas; Fantini, Jacques; Chahinian, Henri

2017-06-01

Anandamide (AEA) is a ubiquitous lipid that exerts neurotransmitter functions but also controls important biological functions such as proliferation, survival, or programmed cell death. The latter effects are also regulated by ceramide, a lipid enzymatically generated from sphingomyelin hydrolysis by sphingomyelinase. Ceramide has been shown to increase the cellular toxicity of AEA, but the mechanisms controlling this potentiating effect remained unclear. Here we have used a panel of in silico, physicochemical, biochemical and cellular approaches to study the crosstalk between AEA and ceramide apoptotic pathways. Molecular dynamics simulations indicated that AEA and ceramide could form a stable complex in phosphatidylcholine membranes. Consistent with these data, we showed that AEA can specifically insert into ceramide monolayers whereas it did not penetrate into sphingomyelin membranes. Then we have studied the effects of ceramide on AEA-induced toxicity of human neuroblastoma cells. In these experiments, the cells have been either naturally enriched in ceramide by neutral sphingomyelinase pre-incubation or treated with C2-ceramide, a biologically active ceramide analog. Both treatments significantly increased the cytotoxicity of AEA as assessed by the MTS mitochondrial toxicity assay. This effect was correlated with the concomitant accumulation of natural ceramide (or its synthetic analog) and AEA in the cells. A kinetic study of AEA hydrolysis showed that ceramide inhibited the fatty acid amino hydrolase (FAAH) activity in cell extracts. Taken together, these data suggested that ceramide binds to AEA, increases its half-life and potentiates its cytotoxicity. Overall, these mechanisms account for a functional cross-talk between AEA and ceramide apoptotic pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of disintegration half-life of 252Cf

International Nuclear Information System (INIS)

Chen Keliang; Liu Guoxing; Wang Sufang; Zheng Jiwen

1991-01-01

The follow-up measurements have been made by using a Si(Au) detector with small solid angle geometry for α disintegration of 252 Cf. The measured half-life of disintegration is 2.638 ± 0.009 year. This value is in accordance with other previous results

Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life.

Science.gov (United States)

Adams, Ralph; Griffin, Laura; Compson, Joanne E; Jairaj, Mark; Baker, Terry; Ceska, Tom; West, Shauna; Zaccheo, Oliver; Davé, Emma; Lawson, Alastair Dg; Humphreys, David P; Heywood, Sam

2016-10-01

We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds HSA with similar affinity within the physiologically relevant range of pH 5.0 - pH 7.4, and does not have a deleterious effect on the binding of HSA to neonatal Fc receptor (FcRn). A crystal structure of humanized CA645 Fab in complex with HSA was solved and showed that CA645 Fab binds to domain II of HSA. Superimposition with the crystal structure of FcRn bound to HSA confirmed that CA645 does not block HSA binding to FcRn. In mice, the serum half-life of humanized CA645 Fab is 84.2 h. This is a significant extension in comparison with Fab variant. The Fab-HSA structure was used to design a series of mutants with reduced affinity to investigate the correlation between the affinity for albumin and serum half-life. Reduction in the affinity for MSA by 144-fold from 2.2 nM to 316 nM had no effect on serum half-life. Strikingly, despite a reduction in affinity to 62 µM, an extension in serum half-life of 26.4 h was still obtained. CA645 Fab and the CA645 Fab-HSA complex have been deposited in the Protein Data Bank (PDB) with accession codes, 5FUZ and 5FUO, respectively.

Update of NIST half-life results corrected for ionization chamber source-holder instability.

Science.gov (United States)

Unterweger, M P; Fitzgerald, R

2014-05-01

As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties. © 2013 Published by Elsevier Ltd.

Neutron activation analyses and half-life measurements at the usgs triga reactor

Science.gov (United States)

Larson, Robert E.

Neutron activation of materials followed by gamma spectroscopy using high-purity germanium detectors is an effective method for making measurements of nuclear beta decay half-lives and for detecting trace amounts of elements present in materials. This research explores applications of neutron activation analysis (NAA) in two parts. Part 1. High Precision Methods for Measuring Decay Half-Lives, Chapters 1 through 8 Part one develops research methods and data analysis techniques for making high precision measurements of nuclear beta decay half-lives. The change in the electron capture half-life of 51Cr in pure chromium versus chromium mixed in a gold lattice structure is explored, and the 97Ru electron capture decay half-life are compared for ruthenium in a pure crystal versus ruthenium in a rutile oxide state, RuO2. In addition, the beta-minus decay half-life of 71mZn is measured and compared with new high precision findings. Density Functional Theory is used to explain the measured magnitude of changes in electron capture half-life from changes in the surrounding lattice electron configuration. Part 2. Debris Collection Nuclear Diagnostic at the National Ignition Facility, Chapters 9 through 11 Part two explores the design and development of a solid debris collector for use as a diagnostic tool at the National Ignition Facility (NIF). NAA measurements are performed on NIF post-shot debris collected on witness plates in the NIF chamber. In this application NAA is used to detect and quantify the amount of trace amounts of gold from the hohlraum and germanium from the pellet present in the debris collected after a NIF shot. The design of a solid debris collector based on material x-ray ablation properties is given, and calculations are done to predict performance and results for the collection and measurements of trace amounts of gold and germanium from dissociated hohlraum debris.

Susceptibility of Primary Human Choroid Plexus Epithelial Cells and Meningeal Cells to Infection by JC Virus.

Science.gov (United States)

O'Hara, Bethany A; Gee, Gretchen V; Atwood, Walter J; Haley, Sheila A

2018-04-15

JC polyomavirus (JCPyV) establishes a lifelong persistence in roughly half the human population worldwide. The cells and tissues that harbor persistent virus in vivo are not known, but renal tubules and other urogenital epithelial cells are likely candidates as virus is shed in the urine of healthy individuals. In an immunosuppressed host, JCPyV can become reactivated and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system. Recent observations indicate that JCPyV may productively interact with cells in the choroid plexus and leptomeninges. To further study JCPyV infection in these cells, primary human choroid plexus epithelial cells and meningeal cells were challenged with virus, and their susceptibility to infection was compared to the human glial cell line, SVG-A. We found that JCPyV productively infects both choroid plexus epithelial cells and meningeal cells in vitro Competition with the soluble receptor fragment LSTc reduced virus infection in these cells. Treatment of cells with neuraminidase also inhibited both viral infection and binding. Treatment with the serotonin receptor antagonist, ritanserin, reduced infection in SVG-A and meningeal cells. We also compared the ability of wild-type and sialic acid-binding mutant pseudoviruses to transduce these cells. Wild-type pseudovirus readily transduced all three cell types, but pseudoviruses harboring mutations in the sialic acid-binding pocket of the virus failed to transduce the cells. These data establish a novel role for choroid plexus and meninges in harboring virus that likely contributes not only to meningoencephalopathies but also to PML. IMPORTANCE JCPyV infects greater than half the human population worldwide and causes central nervous system disease in patients with weakened immune systems. Several recent reports have found JCPyV in the choroid plexus and leptomeninges of patients with encephalitis. Due to their role in forming the blood

The impact of extended half-life versus conventional factor product on hemophilia caregiver burden.

Science.gov (United States)

Schwartz, Carolyn E; Powell, Victoria E; Su, Jun; Zhang, Jie; Eldar-Lissai, Adi

2018-05-01

Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been investigated. This study aimed to evaluate caregiver burden in extended half-life versus conventional factor products for hemophilia A and B. This cross-sectional web-based study of caregivers of people with hemophilia A or B was recruited from a panel research company and by word of mouth. Participants completed the Hemophilia Caregiver Impact measure, the PedsQL Family Impact Module (PedsQL), and the Work Productivity and Activity Impairment Questionnaire (WPAI). We also collected demographic, insurance coverage, and medical information related to the hemophilia patient(s). Burden differences were assessed using linear regression and matched cohort analyses. The sample (n = 448) included 49 people who were caring for people on extended half-life factor products. Worse caregiver burden was associated with more infusions per week and more bleeds in the past 6 months. Regression analyses suggested that caring for someone who is on a extended half-life factor product is associated with lower emotional impact (β = - 0.11, p factor product had lower Emotional Impact and Practical Impact scores (t = - 2.95 and - 2.94, respectively, p factor product infusions of extended half-life factor products appears to reduce the emotional distress and practical burden of caregiving. Future work should evaluate the longitudinal impact.

Superior serum half life of albumin tagged TNF ligands

International Nuclear Information System (INIS)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

2010-01-01

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

On the biological half-life of caesium in pregnant women and infants

International Nuclear Information System (INIS)

Rundo, J.; Turner, F.M.

1992-01-01

In the 1960s, changes were observed in the levels of 137 Cs in women who were pregnant or who had recently given birth. These were not associated with changes in the rate of fall-out, and were interpreted as the consequences of changes in the biological half-life. It was deduced that the biological half-life of caesium just before parturition averaged 59% of the value (87±33 days) after the birth of the baby; and that there was a step change at parturition. The behaviour of the levels during pregnancy suggested there was a gradual decrease in the biological half-life. Similar measurements were made in very young children. The concentration of the radionuclide in a breast-fed baby was usually a little less than that in the mother, indicating some discrimination in the transfer from plasma to milk; the concentration in a bottle-fed baby increased substantially and rapidly from the level at or shortly after birth. Data for three babies were sufficiently extensive to permit determination of the biological half-life in each. Values of 8.7±0.6 days, 15.4±1.1 days, and 14.9±3.6 days were derived. (author)

Improving the control of systematic uncertainties in precision measurements of radionuclide half-life

International Nuclear Information System (INIS)

Towers, S.

2013-01-01

Many experiments designed to precisely determine the half-life of a radionuclide employ a long lived reference source to help determine the impact on the data of any systematic variation in the detector and associated electronics. The half-life of the radionuclide of interest is determined from the ratio of its decay rate data to the decay rate data from the reference source. This correction procedure assumes that any underlying systematic affects the data and reference measurements in exactly the same way. In this paper we show that when some systematic effects affect the two differently, the ratio procedure can leave artifacts in the corrected data that can compromise an unbiased and precise assessment of the radionuclide half-life. We describe two methods that can help overcome this problem. We also describe several statistical tests that help determine which effects may underlie systematic variations in the data. We discuss an illustrative example based on previously published 32 Si and 36 Cl data recorded by an experiment at Brookhaven National Laboratory. We correct the data for systematic variation related to climate variation and estimate the 32 Si half-life to be T 1/2 =171.8±1.8. The reduction in uncertainty in the 32 Si half-life, relative to the previous estimate based upon this data, is equivalent to that which would be achieved through increasing the size of the data set by almost 3.5 times. - Author-Highlights: • Isotope decay data and reference source data can have differing systematics. • Differing systematics can inflate uncertainty of isotope half-life estimate. • We describe two methods to overcome this problem. • We describe statistical tests to determine which variables cause systematics. • We analyze Brookhaven 32Si/36Cl decay data as an illustrative example

High-precision half-life determination for 21Na using a 4 π gas-proportional counter

Science.gov (United States)

Finlay, P.; Laffoley, A. T.; Ball, G. C.; Bender, P. C.; Dunlop, M. R.; Dunlop, R.; Hackman, G.; Leslie, J. R.; MacLean, A. D.; Miller, D.; Moukaddam, M.; Olaizola, B.; Severijns, N.; Smith, J. K.; Southall, D.; Svensson, C. E.

2017-08-01

A high-precision half-life measurement for the superallowed β+ transition between the isospin T =1 /2 mirror nuclei 21Na and 21Ne has been performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1 /2=22.4506 (33 ) s, a result that is a factor of 4 more precise than the previous world-average half-life for 21Na and represents the single most precisely determined half-life for a transition between mirror nuclei to date. The contribution to the uncertainty in the 21Na F tmirror value due to the half-life is now reduced to the level of the nuclear-structure-dependent theoretical corrections, leaving the branching ratio as the dominant experimental uncertainty.

Half-life and intensities of photons of 103Pd isotope

International Nuclear Information System (INIS)

Popov, Yu.S.; Zakharova, L.V.; Kupriyanov, V.N.; Andreev, O.I.; Pakhomov, A.N.; Vakhetov, F.Z.

2001-01-01

Half-life and intensities of photons forming during 103 Pd isotope decay are determined by the methods of semiconductor x-ray and γ-spectrometry. 103 Pd is applied in nuclear medicine for preparation of 103m Rh isomer (T 1/2 =56 min) being used in irradiation of prostate neoplasms. Half-life of 103 Pd isotope is 16±0.6 days, relative intensities of x-ray and γ-photons are: K α /Kβ=5.1±0.4; 358 keV - 100 rel.units; 295 keV - 12.3±0.4 rel.units; 497 keV - 17.6±0.6 rel.units. Errors are represented for confidence probability 95 % [ru

Establishment of human papillomavirus infection requires cell cycle progression.

Directory of Open Access Journals (Sweden)

Dohun Pyeon

2009-02-01

Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

Beyond effective half-life characterization of radionuclide dynamics

International Nuclear Information System (INIS)

Hermanska, J.; Blazek, T.; Karny, M.

1996-01-01

A refined model was set up and tested of the effective radionuclide half-life in nuclear medicine, making allowance for the fact that the basic assumption that the observed data can be fitted by a mono-exponential, as well as some other assumptions, is not true. The results are discussed. (P.A.). 1 tab., 32 refs

Acute or chronic life-threatening diseases associated with Epstein-Barr virus infection.

Science.gov (United States)

Okano, Motohiko; Gross, Thomas G

2012-06-01

Infectious mononucleosis (IM) is one of the representative, usually benign, acute diseases associated with primary Epstein-Barr virus (EBV) infection. IM is generally self-limiting and is characterized mostly by transient fever, lymphadenopathy and hepatosplenomegaly. However, very rarely primary EBV infection results in severe or fatal conditions such as hemophagocytic lymphohistiocytosis together with fulminant hepatitis designated as severe or fatal IM or EBV-associated hemophagocytic lymphohistiocytosis alone. In addition, chronic EBV-associated diseases include Burkitt's lymphoma, undifferentiated nasopharyngeal carcinoma, Hodgkin lymphoma, T-cell lymphoproliferative disorder (LPD)/lymphoma, natural killer-cell LPD including leukemia or lymphoma, gastric carcinoma, pyothorax-associated lymphoma and senile B-cell LPD as well as chronic active EBV infection and LPD/lymphoma in patients with immunodeficiency. The number of chronic life-threatening diseases linked to the EBV infection is increasingly reported and many of these diseases have a poor prognosis. This review will focus on the historical, pathogenetic, diagnostic, therapeutic and prophylactic issues of EBV-associated life-threatening diseases.

Half-life data--a critical review of TECDOC-619 update

International Nuclear Information System (INIS)

Woods, M.J.; Collins, S.M.

2004-01-01

An accurate knowledge of selected nuclear decay data is critical to a wide range of processes involving radionuclides. An IAEA publication in 1991 was dedicated to the evaluation of half-lives and specific gamma-ray emission probabilities for 39 selected radionuclides considered to be important for detector efficiency calibrations. A new exercise was initiated in December 1998 to update this previous evaluation and to include a number of new radionuclides of interest; 62 radionuclides were considered along with specific parent-daughter combinations (to give a total of 64 radionuclides). That work is now being completed and a new set of recommended data is being prepared for publication. A critical comparison of the 1991 and 2003 half-life data suggests that there has not been any significant improvement in the accuracy of the recommended data. The possible reasons for this situation are discussed together with the evaluation procedure and the quality of the available data. Proposals are made for concerted actions that could lead to a significant improvement in these recommended half-life data

Effect of change in half-life of Se-79 on the safety of HLW geological disposal system

International Nuclear Information System (INIS)

Ishihara, Yoshinao; Ishiguro, Katsuhiko; Umeki, Hiroyuki

1999-11-01

Se-79 is one of key radionuclides in the performance assessment of the geological disposal system. Based on recent measurements, it is possible that the half-life of Se-79 will be changed longer than the present value in most handbooks and tables of isotopes. This study presents performance assessment calculations to investigate the overall effect of change in half-life of Se-79 on the repository system safety. The total system performance analyses for Se-79 were carried out, which focussed on the Reference-Case of the safety assessment in the H12 Project. As results, the maximum release rate in Becquerel unit of Se-79 from the engineered barrier system with new half-life decreases about one order of magnitude than that with half-life used so far. It is, however, that the maximum release rate in Becquerel unit of Se-79 from the natural barrier system is almost same for both half-life because of the channelling effects of groundwater flow. Consequently, the calculated maximum dose rate of Se-79 with new half-life does not change. It can be concluded that the change in half-life of Se-79 does not affect overall safety of the H12 disposal concept. (author)

Standardization of 40 K by liquid scintillation counting. Determination of the half-life

International Nuclear Information System (INIS)

Grau Carles, A.; Grau Malonda, A.

1997-01-01

The relative abundance of the natural radioisotope ''40 K in environmental samples frequently generates interferences in low activity measurements. In the present study we propose the determination of ''40 K by the CIEMAT/NIST method. On this context, the verification of ''40 K half-life is required. We present a half-life value obtained by liquid scintillation counting in excellent agreement with those reported in the literature. (Author)

Tests of a Fast Plastic Scintillator for High-Precision Half-Life Measurements

Science.gov (United States)

Laffoley, A. T.; Dunlop, R.; Finlay, P.; Leach, K. G.; Michetti-Wilson, J.; Rand, E. T.; Svensson, C. E.; Grinyer, G. F.; Thomas, J. C.; Ball, G.; Garnsworthy, A. B.; Hackman, G.; Orce, J. N.; Triambak, S.; Williams, S. J.; Andreoiu, C.; Cross, D.

2013-03-01

A fast plastic scintillator detector is evaluated for possible use in an ongoing program of high-precision half-life measurements of short lived β emitters. Using data taken at TRI-UMF's Isotope Separator and Accelerator Facility with a radioactive 26Na beam, a detailed investigation of potential systematic effects with this new detector setup is being performed. The technique will then be applied to other β-decay half-life measurements including the superallowed Fermi β emitters 10C, 14O, and T = 1/2 decay of 15O.

Near-optimum procedure for half-life measurement by high-resolution gamma-ray spectrometry

International Nuclear Information System (INIS)

Parker, J.L.

1989-01-01

A near-optimum procedure for using high-resolution γ-ray spectrometry to measure the half-lives of appropriate γ-ray- emitting-nuclides is presented. Among the important points of the procedure are the employment of the reference source method for implicit correction of pileup and deadtime losses; the use of full-energy peak-area ratios as the fundamental measured quantities; and continuous, high-rate data acquisition to obtain good results in a fraction of a half-life if desired. Equations are given for estimating the precision of the computed half-lives in terms of total measurement time, number of spectral acquisitions, and the precision of peak-area ratios. Results of 169 Yb half-life measurements are given as an example of the procedure's application. 3 refs., 2 tabs

Precision half-life measurement of 11C: The most precise mirror transition F t value

Science.gov (United States)

Valverde, A. A.; Brodeur, M.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Blankstein, D.; Brown, G.; Burdette, D. P.; Frentz, B.; Gilardy, G.; Hall, M. R.; King, S.; Kolata, J. J.; Long, J.; Macon, K. T.; Nelson, A.; O'Malley, P. D.; Skulski, M.; Strauss, S. Y.; Vande Kolk, B.

2018-03-01

Background: The precise determination of the F t value in T =1 /2 mixed mirror decays is an important avenue for testing the standard model of the electroweak interaction through the determination of Vu d in nuclear β decays. 11C is an interesting case, as its low mass and small QE C value make it particularly sensitive to violations of the conserved vector current hypothesis. The present dominant source of uncertainty in the 11CF t value is the half-life. Purpose: A high-precision measurement of the 11C half-life was performed, and a new world average half-life was calculated. Method: 11C was created by transfer reactions and separated using the TwinSol facility at the Nuclear Science Laboratory at the University of Notre Dame. It was then implanted into a tantalum foil, and β counting was used to determine the half-life. Results: The new half-life, t1 /2=1220.27 (26 ) s, is consistent with the previous values but significantly more precise. A new world average was calculated, t1/2 world=1220.41 (32 ) s, and a new estimate for the Gamow-Teller to Fermi mixing ratio ρ is presented along with standard model correlation parameters. Conclusions: The new 11C world average half-life allows the calculation of a F tmirror value that is now the most precise value for all superallowed mixed mirror transitions. This gives a strong impetus for an experimental determination of ρ , to allow for the determination of Vu d from this decay.

Lymphocytes and macrophages are infected by Theileria equi, but T cells and B cells are not required to establish infection in vivo.

Directory of Open Access Journals (Sweden)

Joshua D Ramsay

Full Text Available Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata, the intraleukocyte stage (schizont of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID, which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis

Pre-Clinical Intravenous Serum Pharmacokinetics of Albumin Binding and Non-Half-Life Extended Nanobodies®

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Sven Hoefman

2015-07-01

Full Text Available Nanobodies are antigen-binding, single variable domain proteins derived from naturally-occurring, heavy chain only antibodies. They are highly soluble, stable, and can be linked to build multi-specific formats. Several Nanobodies are currently in clinical development in different therapeutic areas, for both chronic and acute applications. For the former, prolonged exposure is achieved by half-life extending moieties that target endogenous albumin, while for the latter, non-half-life extended constructs are preferable. To demonstrate the general pharmacokinetic behavior of both formats, serum levels of seven intravenously administered Nanobodies were analyzed in cynomolgus monkeys, mice or rabbits. In monkeys, the total clearance of a monomeric irrelevant Nanobody was rapid (2.0 mL/(min*kg and approximated the species glomerular filtration rate, indirectly suggesting that the Nanobody was mainly eliminated via the kidneys. When linked to an anti-albumin Nanobody, a 376-fold decrease in clearance was observed, resulting in a terminal half-life of 4.9 days, corresponding to the expected species albumin half-life. Similar conclusions were drawn for (non- half-life extended mono-, bi- and trimeric Nanobodies in mice or rabbits, suggesting that these kinetic principles apply across species. Applying this knowledge to species translation and study design is crucial for successful pre-clinical development of novel therapeutic Nanobody candidates.

Targeted and Untargeted Lipidomics of Emiliania huxleyi Viral Infection and Life Cycle Phases Highlights Molecular Biomarkers of Infection, Susceptibility, and Ploidy

Directory of Open Access Journals (Sweden)

Jonathan Eliott Hunter

2015-10-01

Full Text Available Marine viruses that infect phytoplankton strongly influence the ecology and evolution of their hosts. Emiliania huxleyi is characterized by a biphasic life cycle composed of a diploid (2N and haploid (1N phase; diploid cells are susceptible to infection by specific coccolithoviruses, yet haploid cells are resistant. Glycosphingolipids (GSLs play a role during infection, but their molecular distribution in haploid cells is unknown. We present mass spectrometric analyses of lipids from cultures of uninfected diploid, infected diploid, and uninfected haploid E. huxleyi. Known viral GSLs were present in the infected diploid cultures as expected, but surprisingly, trace amounts of viral GSLs were also detected in the uninfected haploid cells. Sialic-acid GSLs have been linked to viral susceptibility in diploid cells, but were found to be absent in the haploid cultures, suggesting a mechanism of haploid resistance to infection. Additional untargeted high-resolution mass spectrometry data processed via multivariate analysis unveiled a number of novel biomarkers of infected, non-infected, and haploid cells. These data expand our understanding on the dynamics of lipid metabolism during E. huxleyi host/virus interactions and highlight potential novel biomarkers for infection, susceptibility, and ploidy.

Half-life of each dioxin and PCB congener in the human body

Energy Technology Data Exchange (ETDEWEB)

Ogura, Isamura [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)

2004-09-15

It is well known that dioxin and PCB congeners accumulate in the human body. For assessing their toxicological risk, it is important to know the half-life of each congener in the human body. This study summarizes the overall half-lives of congeners in humans as reported in the literature, and compares them with the half-lives due to fecal and sebum excretions, as estimated by data on the concentrations of congeners in feces and sebum in the literature. In addition, the overall half-lives of congeners for the general Japanese population were estimated from the data on dietary intakes and concentrations in the human body reported by the municipalities.

Advances in therapeutic Fc engineering - modulation of IgG associated effector functions and serum half-life

Directory of Open Access Journals (Sweden)

Abhishek Saxena

2016-12-01

Full Text Available Today monoclonal immunoglobulin gamma (IgG antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs are achieved through both its antigen binding fragment (Fab and crystallizable fragment (Fc. Fab can specifically recognize tumor associated antigen (TAA and thus modulate TAA-linked downstream signaling pathways that may lead to inhibition of tumor growth, induction of tumor apoptosis and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity (ADCC, complement-dependent cytotoxicity (CDC and antibody dependent cell-mediated phagocytosis (ADCP. Moreover, Fc is the region interacting with the neonatal Fc receptor (FcRn in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anti-cancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering based mAbs under clinical trials.

An albumin-oligonucleotide assembly for potential combinatorial drug delivery and half-life extension applications

DEFF Research Database (Denmark)

Kuhlmann, Matthias; Hamming, Jonas Bohn Refslund; Voldum, Anders

2017-01-01

The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in wh...... technology platform that offers potential combinatorial drug delivery and half-life extension applications.......The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach......, in which the 3' or 5' end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays...

Designing of peptides with desired half-life in intestine-like environment

KAUST Repository

Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh

2014-01-01

hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical

Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

Science.gov (United States)

Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa

2016-06-01

The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Biological Half-Life Measurements of Radioactive Strontium in Hormonal-Resistant Prostate Cancer Patients

International Nuclear Information System (INIS)

Haquin, G.; Riemer, T.; Kaniun, N.; Datz, H.; Yungreiss, Z.; Vexler, A.; Ben-Yosef, R.; Pelled, O.; German, U.; Marko, R.; Teshuva, A.; Kol, R.

2004-01-01

Therapy for metastatic bone pain in Hormonal-Resistant Prostate Cancer (HRPC) patients is performed by administering systemic radioisotope therapy [1]. The beta radiation emitted by the radioactive strontium 89 Sr [T 1/2 =50.5 d, E β (max)=1.49 MeV], an adequate radionuclide for this therapy procedure, irradiates the metastatic cells in the bone, producing the desired palliative effect. The beta disintegration of 89 Sr is followed by a low abundance (0.00945%) gamma ray with energy of 909 keV. The commercially available 89 Sr is in the form of Sr Cl and contains an impurity of less than 0.5% of 85 Sr [T 1/2 =64.8 d] ,which decays by electron capture, emitting gamma rays at 511 keV (95.71%). The radiation dose to the metastatic cells due to the gamma rays is negligible compared to the dose given by the beta radiation, assuming that the 89 Sr is concentrated at the metastatic bony lesions. Accurate information about retention and excretion of Sr in the patient's body will contribute to better evaluate the effectiveness of the treatment. he effective half-life of 89 Sr can be calculated either from Whole Body Counting (WBC) measurements or by measuring 85 Sr and/or 89 Sr in urine/blood. WBC measurements, using collimated HPGe detectors, allow the follow-up of 89 Sr and 85 Sr at different sites in the skeletal bones of the patient. Biological half-lives of Sr in different body sections measured by WBC and the correlation with excretion-rate-based biological half-lives are presented

ESOL facility for the generation and radiochemical separation of short half-life fission products

International Nuclear Information System (INIS)

Gehrke, R.J.; Meikrantz, D.H.; Baker, J.D.; Anderl, R.A.; Novick, V.J.; Greenwood, R.C.

1988-01-01

A facility has been developed at the Idaho National Engineering Laboratory (INEL) for the generation and rapid radiochemical separation of short half-life mixed fission products. This facility, referred to as the Idaho Elemental Separation On Line (ESOL), consists of electro-plated sources of spontaneously fissioning 252 Cf with a helium jet transport arrangement to continuously deliver short half-life, mixed fission products to the radiochemistry laboratory for rapid, computer controlled, radiochemical separations. 18 refs., 13 figs

A formula for half-life of proton radioactivity

Science.gov (United States)

Zhang, Zhi-Xing; Dong, Jian-Min

2018-01-01

We present a formula for proton radioactivity half-lives of spherical proton emitters with the inclusion of the spectroscopic factor. The coefficients in the formula are calibrated with the available experimental data. As an input to calculate the half-life, the spectroscopic factor that characterizes the important information on nuclear structure should be obtained with a nuclear many-body approach. This formula is found to work quite well, and in better agreement with experimental measurements than other theoretical models. Therefore, it can be used as a powerful tool in the investigation of proton emission, in particular for experimentalists. Supported by National Natural Science Foundation of China (11435014, 11405223, 11675265, 11575112), the 973 Program of China (2013CB834401, 2013CB834405), National Key Program for S&T Research and Development (2016YFA0400501), the Knowledge Innovation Project (KJCX2-EW-N01) of Chinese Academy of Sciences, the Funds for Creative Research Groups of China (11321064) and the Youth Innovation Promotion Association of Chinese Academy of Sciences

Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA.

Directory of Open Access Journals (Sweden)

Jana Ferdin

Full Text Available To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort. We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

Crystalline structure and microstructural characteristics of the cathode/electrolyte solid oxide half-cells

International Nuclear Information System (INIS)

Chiba, Rubens; Vargas, Reinaldo Azevedo; Andreoli, Marco; Santoro, Thais Aranha de Barros; Seo, Emilia Satoshi Miyamaru

2009-01-01

The solid oxide fuel cell (SOFC) is an electrochemical device generating of electric energy, constituted of cathode, electrolyte and anode; that together they form a unity cell. The study of the solid oxide half-cells consisting of cathode and electrolyte it is very important, in way that is the responsible interface for the reduction reaction of the oxygen. These half-cells are ceramic materials constituted of strontium-doped lanthanum manganite (LSM) for the cathode and yttria-stabilized zirconia (YSZ) for the electrolyte. In this work, two solid oxide half-cells have been manufactured, one constituted of LSM cathode thin film on YSZ electrolyte substrate (LSM - YSZ half-cell), and another constituted of LSM cathode and LSM/YSZ composite cathode thin films on YSZ electrolyte substrate (LSM - LSM/YSZ - YSZ half cell). The cathode/electrolyte solid oxide half-cells were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results have been presented with good adherence between cathode and electrolyte and, LSM and YSZ phases were identified. (author)

Precision half-life measurement of .sup.140 La with Ge-detector

Czech Academy of Sciences Publication Activity Database

Adam, Jindřich; Belov, A. G.; Brandt, R.; Chaloun, P.; Honusek, Milan; Kalinnikov, V. G.; Krivopustov, M. I.; Kulakov, B. A.; Langrock, E. J.; Pronskikh, V. S.; Sosnin, A. N.; Stegailov, V. I.; Tsoupko-Sitnikov, V. M.; Wan, J. S.; Westmeier, W.

2002-01-01

Roč. 187, - (2002), s. 419-426 ISSN 0168-583X R&D Projects: GA AV ČR KSK1048102 Keywords : radioastive nuclei * Ge-detectors * half-life measurements Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.158, year: 2002

High-Precision Half-Life Measurement for the Superallowed β+ Emitter Alm26

Science.gov (United States)

Finlay, P.; Ettenauer, S.; Ball, G. C.; Leslie, J. R.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Bandyopadhyay, D.; Cross, D. S.; Demand, G.; Djongolov, M.; Garrett, P. E.; Green, K. L.; Grinyer, G. F.; Hackman, G.; Leach, K. G.; Pearson, C. J.; Phillips, A. A.; Sumithrarachchi, C. S.; Triambak, S.; Williams, S. J.

2011-01-01

A high-precision half-life measurement for the superallowed β+ emitter Alm26 was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1/2=6346.54±0.46stat±0.60systms, consistent with, but 2.5 times more precise than, the previous world average. The Alm26 half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed β decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for Alm26, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi β-decay studies used to test the conserved vector current hypothesis and determine the Vud element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life.

Directory of Open Access Journals (Sweden)

Yu-Hang Zhang

Full Text Available A drug's biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347, monoamine transmembrane transporter activity (GO:0008504, negative regulation of synaptic transmission (GO:0050805, neuroactive ligand-receptor interaction (hsa04080, serotonergic synapse (hsa04726, and linoleic acid metabolism (hsa00591, among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

Differentially-Expressed Pseudogenes in HIV-1 Infection

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Aditi Gupta

2015-09-01

Full Text Available Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these “functional” pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

Differentially-Expressed Pseudogenes in HIV-1 Infection.

Science.gov (United States)

Gupta, Aditi; Brown, C Titus; Zheng, Yong-Hui; Adami, Christoph

2015-09-29

Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these "functional" pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

Application of genetic algorithms for determination biological half-life of 137 Cs in milk

International Nuclear Information System (INIS)

Pantelic, G.

1998-01-01

Genetic algorithm an optimization method involving natural selection mechanisms, was used to determine biological half-life of sup 1 sup 3 sup 7 Cs in the milk, after the Chernobyl accident, based on a two compartment linear system model. Genetic algorithms operate on populations of strings. Reproduction, crossover and mutation are applied to successive string population to create new string population. A model parameter estimation is performed by minimizing square differences between fitting function and experimental data. The calculated biological half-life of sup 1 sup 3 sup 7 Cs in milk is (32(+(-) days (author)

High-precision half-life measurements of the T =1 /2 mirror β decays 17F and 33Cl

Science.gov (United States)

Grinyer, J.; Grinyer, G. F.; Babo, M.; Bouzomita, H.; Chauveau, P.; Delahaye, P.; Dubois, M.; Frigot, R.; Jardin, P.; Leboucher, C.; Maunoury, L.; Seiffert, C.; Thomas, J. C.; Traykov, E.

2015-10-01

Background: Measurements of the f t values for T =1 /2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the f t values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T =1 /2 β+ emitters, 17F and 33Cl, in order to eliminate the half-life as the leading source of uncertainty in their f t values. Method: Half-lives of 17F and 33Cl were determined using β counting of implanted radioactive ion beam samples on a moving tape transport system at the Système de Production d'Ions Radioactifs Accélérés en Ligne low-energy identification station at the Grand Accélérateur National d'Ions Lourds. Results: The 17F half-life result, 64.347 (35) s, precise to ±0.05 % , is a factor of 5 times more precise than the previous world average. The half-life of 33Cl was determined to be 2.5038 (22) s. The current precision of ±0.09 % is nearly 2 times more precise compared to the previous world average. Conclusions: The precision achieved during the present measurements implies that the half-life no longer dominates the uncertainty of the f t values for both T =1 /2 mirror decays 17F and 33Cl.

$\\beta$-decay half-life of $^{70}$Kr a bridge nuclide for the rp-process beyond A = 70

CERN Document Server

Oinonen, M; Jokinen, A; Baumann, P; Didierjean, François; Huck, A; Knipper, A; Ramdhane, M; Walter, G; Van Duppen, P; Huyse, M; Marguier, G; Novikov, Yu N; Popov, A; Seliverstov, D M; Schatz, H

2000-01-01

The $\\beta$-decay half-life of $^{70}$Kr has been measured for the first time at the ISOLDE PSB Facility at CERN. Mass separated $^{70}$Kr ions were produced by 1 GeV proton induced spallation reactions in a Nb foil. The measured half-life is 57(21) ms. This value is consistent with the half-life calculated assuming a pure Fermi decay, but is clearly lower than the value used in a recent rp-process reaction flow calculation. The result shows that the reaction flow via two-proton-capture of $^{68}$Se is 2.5 times faster than previously calculated assuming an astrophysical temperature of 1.5 GK and a density of 10$^{6}$g/cm$^{3}$.

Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).

Science.gov (United States)

Russell, Mark H; Waterland, Robert L; Wong, Fiona

2015-06-01

Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cells in Dengue Virus Infection In Vivo

Directory of Open Access Journals (Sweden)

Sansanee Noisakran

2010-01-01

Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

High-Precision Half-life Measurements for the Superallowed β+ Emitter 14O

Science.gov (United States)

Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E. R.; Thomas, J. C.; Unsworth, C.

2014-03-01

The half-life of 14O, a superallowed Fermi β+ emitter, has been determined via simultaneous γ and β counting experiments at TRIUMF's Isotope Separator and Accelerator facility. Following the implantation of 14O samples at the center of the 8π spectrometer, a γ counting measurement was performed by detecting the 2313 keV γ-rays emitted from the first excited state of the daughter 14N using 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned directly behind the implantation site. The results, T½(γ) = 70:632 ± 0:094 s and T½(β) = 70:610 ± 0:030 s, are consistent with one another and, together with eight previous measurements, establish a new average for the 14O half-life of T½ = 70:619 ± 0:011 s with a reduced χ2 of 0.99.

A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

Science.gov (United States)

Li, Z. X.; Zhao, W. W.

2015-01-01

The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

Determination of {sup 126}Sn half-life from ICP-MS and gamma spectrometry measurements

Energy Technology Data Exchange (ETDEWEB)

Bienvenu, P.; Arnal, N.; Comte, J. [CEA Cadarache DEN/DEC/SA3C/LARC, Paul Lez Durance (France); Ferreux, L.; Lepy, M.C.; Be, M.M. [CEA Saclay LIST LNE/LNHB, Gif sur Yvette (France); Andreoletti, G. [AREVA Cogema SL/UP2-800, Beaumont Hague (France)

2009-07-01

A new value of {sup 126}Sn half-life was determined by combination of inductively coupled plasma-mass spectrometry (ICP-MS) and gamma spectrometry measurements on purified sample solutions collected from nuclear fuel reprocessing. {sup 126}Sn was isolated through dissolution of fission product precipitates and liquid-liquid extraction with N-benzoyl-N-phenyl-hydroxylamine (BPHA). The abundance of {sup 126}Sn atoms together with the absence of interfering species in the analysed solutions made it possible to measure both mass concentration and nuclide activity with high precision and accuracy. This led to a {sup 126}Sn half-life value of 1.980 (57) x 10{sup 5} a. (orig.)

Number of infection events per cell during HIV-1 cell-free infection.

Science.gov (United States)

Ito, Yusuke; Remion, Azaria; Tauzin, Alexandra; Ejima, Keisuke; Nakaoka, Shinji; Iwasa, Yoh; Iwami, Shingo; Mammano, Fabrizio

2017-07-26

HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q. Dang et al., Proc. Natl. Acad. Sci. USA 101:632-7, 2004: K. M. Law et al., Cell reports 15:2711-83, 2016). Here, we build on these notions and provide a more detailed and extensive quantitative framework. We developed a novel mathematical model explicitly considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Particularly, in contrast to the previous studies, we took into account the different susceptibility of the target cells as a continuous distribution. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our model reproduces these datasets.

Increased Functional Half-life of Fibroblast Growth Factor-1 by Recovering a Vestigial Disulfide Bond

Directory of Open Access Journals (Sweden)

Jihun Lee

2010-12-01

Full Text Available The fibroblast growth factor (FGF family of proteins contains an absolutely conserved Cys residue at position 83 that is present as a buried free cysteine. We have previously shown that mutation of the structurally adjacent residue, Ala66, to cysteine results in the formation of a stabilizing disulfide bond in FGF-1. This result suggests that the conserved free cysteine residue at position 83 in the FGF family of proteins represents a vestigial half-cystine. Here, we characterize the functional half-life and mitogenic activity of the oxidized form of the Ala66Cys mutation to identify the effect of the recovered vestigial disulfide bond between Cys83 and Cys66 upon the cellular function of FGF-1. The results show that the mitogenic activity of this mutant is significantly increased and that its functional half-life is greatly extended. These favorable effects are conferred by the formation of a disulfide bond that simultaneously increases thermodynamic stability of the protein and removes a reactive buried thiol at position 83. Recovering this vestigial disulfide by introducing a cysteine at position 66 is a potentially useful protein engineering strategy to improve the functional half-life of other FGF family members.

A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

Science.gov (United States)

Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Myers, Julia E; Keiffer, Timothy R; DiGiuseppe, Stephen; Polk, Paula; Bodily, Jason M; Scott, Rona S; Sapp, Martin

2018-03-01

Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

Directory of Open Access Journals (Sweden)

Malgorzata Bienkowska-Haba

2018-03-01

Full Text Available Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16. This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

Measurements of Actual Effective Half - Life in 131I Therapy for Graves' Hyperthyroidism

International Nuclear Information System (INIS)

So, Yong Seon; Kim, Myung Seon; Kwon, Ki Hyun; Kim, Seok Whan; Kim, Tae Hyung; Han, Sang Woong; Kim, Eun Sil; Kim, Chong Soon

1996-01-01

Radioiodine[131I] has been used for the treatment of Graves' hyperthyroidism since the late 1940's and is now generally regarded as the treatment of choice for Graves' hyperthyroidism who does not remit following a course of antithyroid drugs. But for the dose given, several different protocols have been described by different centers, each attempting to reduce the incidence of long-term hypothyroidism while maintaining an acceptable rate control of Graves' hyperthyroidism. Our goals were to evaluate effective half-life and predict absorbed dose in Graves' hyperthyroidism patients, therefore, to calculate and read minister radioiodine activity needed to achieve aimed radiation dose. Our data showed that the mean effective 131I half-life for Graves' disease is 5.3 days(S.D=0.88) and mean biologic half-life is 21 days, range 9.5-67.2 days. The mean administered activity and the mean values of absorbed doses wet: 532 MBq(S.D.=254), 112 Gy (S.D.=50.9), respectively. The mean activity needed to achieve aimed radiation dose were 51 MBq and marked differences of 131I thyroidal uptake between tracer and therapy occurred in our study. We are sure that the dose calculation method that uses 5 days thyroidal 131I uptake measurements after tracer and therapy dose, provides sufficient data about the effective treatment in Graves' hyperthyroidism.

Half Life - The divided life of Bruno Maximovitch Pontecorvo

CERN Multimedia

CERN. Geneva

2016-01-01

When Bruno Pontecorvo fled to the USSR at the height of the Cold War in 1950, half way through his life, the British Government, MI5 and FBI tried to portray him as scientifically insignificant, and to imply that his disappearance posed no threat to the West. In reality Pontecorvo was already one of the leading experts in nuclear physics, and recently declassified papers reveal that a prime agenda of FBI and MI5 was to cover up their errors. . During his time in the USSR he made major contributions to physics, and justified the sobriquet: "Mr Neutrino". This talk will reveal the background to his sudden flight, and also evaluate his work in theoretical physics in the aftermath of his arrival in Dubna. Previously secret documents now show that he proposed the concept of associated production before Gell Mann and Pais, and he had an idea to discover the neutrino at a reactor. He may be considered the father of neutrino astronomy with his successful prediction that neutrinos from a supernova could be detected, b...

Curvature and Strength of Ni-YSZ Solid Oxide Half-Cells After Redox Treatments

DEFF Research Database (Denmark)

Faes, Antonin; Frandsen, Henrik Lund; Pihlatie, Mikko

2010-01-01

One of the main drawbacks of anode-supported solid oxide fuel cell technology is the limited capability to withstand reduction and oxidation (“RedOx”) of the Ni phase. This study compares the effect of RedOx cycles on curvature and strength of half-cells, composed of a nickel-yttria-stabilized-zi......One of the main drawbacks of anode-supported solid oxide fuel cell technology is the limited capability to withstand reduction and oxidation (“RedOx”) of the Ni phase. This study compares the effect of RedOx cycles on curvature and strength of half-cells, composed of a nickel...... it is calculated analytically from the force. In this calculation the thermal stresses are estimated from the curvature of the half-cell. For each treatment, more than 30 samples are tested. About 20 ball-on-ring samples are laser cut from one original 12×12 cm2 half-cell. Curvature and porosity are measured...

High-precision half-life and branching-ratio measurements for superallowed Fermi β+ emitters at TRIUMF - ISAC

Science.gov (United States)

Laffoley, A. T.; Dunlop, R.; Finlay, P.; Grinyer, G. F.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Blank, B.; Bouzomita, H.; Chagnon-Lessard, S.; Chester, A.; Cross, D. S.; Demand, G.; Diaz Varela, A.; Djongolov, M.; Ettenauer, S.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Glister, J.; Green, K. L.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Pearson, C. J.; Phillips, A. A.; Rand, E. T.; Starosta, K.; Sumithrarachchi, C. S.; Svensson, C. E.; Tardiff, E. R.; Thomas, J. C.; Towner, I. S.; Triambak, S.; Unsworth, C.; Williams, S. J.; Wong, J.; Yates, S. W.; Zganjar, E. F.

2014-03-01

A program of high-precision half-life and branching-ratio measurements for superallowed Fermi β emitters is being carried out at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. Recent half-life measurements for the superallowed decays of 14O, 18Ne, and 26Alm, as well as branching-ratio measurements for 26Alm and 74Rb are reported. These results provide demanding tests of the Standard Model and the theoretical isospin symmetry breaking (ISB) corrections in superallowed Fermi β decays.

Determination of half life of tellurium isotopes: a proposal for the teaching of nuclear physics

International Nuclear Information System (INIS)

Ruivo, Julio C.; Zamboni, Cibele B.; Batista, Wagner F.

2013-01-01

This work aimed at the development of courseware for teaching nuclear physics, using experimental data of half-life measurement (T1/2) of Tellurium isotopes (A=127 and 131). The choice of Tellurium was established for providing nuclear data, which are fundamental in related investigations of nuclear structure and its use in various areas such as geochemistry, chemical and pharmaceutical industries, astrophysics etc. For evaluation of the proposal performance, the material was made available, bringing a lot of information about nuclear safety, production and storage of radioactive material and concepts of radioactive decay, subatomic particles, emission of gamma radiation, half-life, etc.

Determination of half life of tellurium isotopes: a proposal for the teaching of nuclear physics

Energy Technology Data Exchange (ETDEWEB)

Ruivo, Julio C.; Zamboni, Cibele B.; Batista, Wagner F., E-mail: julio.ruivo.costa@usp.br, E-mail: czamboni@ipen.br, E-mail: fisicawagner@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

This work aimed at the development of courseware for teaching nuclear physics, using experimental data of half-life measurement (T1/2) of Tellurium isotopes (A=127 and 131). The choice of Tellurium was established for providing nuclear data, which are fundamental in related investigations of nuclear structure and its use in various areas such as geochemistry, chemical and pharmaceutical industries, astrophysics etc. For evaluation of the proposal performance, the material was made available, bringing a lot of information about nuclear safety, production and storage of radioactive material and concepts of radioactive decay, subatomic particles, emission of gamma radiation, half-life, etc.

Study of the half-life of 123I and the determination of possible radionuclidic impurities

International Nuclear Information System (INIS)

Delgado, Jose Ubiratan; Araujo, Miriam Taina Ferreira de; Silva, Carlos Jose da; Araujo, Camila Cristina Cunha; Candido, Marcos Antonio; Pereira, Wagner do Prado

2013-01-01

During the process of production of the radiopharmaceutical nuclear reactor or cyclotron, impurities can be generated from biological, chemical and radionuclidic. The development of the present work was to study the half-life of Na 123 I sample produced in IEN (Institute of Nuclear Engineering) using the technique of gamma-ray spectrometry with germanium detector in order to Identify such impurities. The results Indicate values of half-life consistent with recent publications with a deviation of 0,08% and 0:11% of uncertainty as well as the identification of impurities to radionuclides 95m Tc, 96 Tc and 121 Te. (author)

The HP 9825 A program for the determination of an isotope half-life

International Nuclear Information System (INIS)

Jujuratisbela, Uju.

1980-01-01

Determination of half life of gold 198, indium 116, manganese 56, copper 64 are presented, using least squares method in HP 9825 A. This method is more accurate and needs less time than graphic method. (author tr.)

Work Dissatisfaction and Sleep Problems among Canadians in the Latter Half of Life.

Science.gov (United States)

Brown, Kyla; Bierman, Alex

2017-09-01

This study examined the relationship between work dissatisfaction and sleep problems among Canadian adults in the latter half of life, as well as how gender and social contact moderate this relationship. Data were obtained from the Canadian General Social Survey, Cycle 21 (2007), which sampled adults aged 45 and older in 2007. Analyses focused on individuals with employment as their main activity. Analyses show that work dissatisfaction positively predicts trouble sleeping. There are no significant gender differences in this relationship. Social contact with friends buffers this relationship, but social contact with family does not, and buffering does not vary significantly between men and women. This research contributes to knowledge on sleep problems by showing that work dissatisfaction is adversely associated with sleep problems among Canadians in the latter half of life, but social contact with friends can weaken this deleterious relationship.

New evaluation of alpha decay half-life of 190Pt isotope for the Pt-Os dating system

International Nuclear Information System (INIS)

Tavares, O.A.P.; Medeiros, E.L.; Terranova, M.L.

2005-08-01

A semiempirical model based on the quantum mechanical tunnelling mechanism of alpha emission from nuclei has been used to evaluate the half-life of the Pt isotopes. For the important naturally occurring 190 Pt isotope, the radiogenic parent in the 190 Pt → 186 Os dating system, the model yielded a half-life value of (3.7± 0.3) versus 10 11 y. This is comparable to (3.2±0.1) versus 10 11 y which was obtained in the last direct counting experiment to measure the alpha activity of 190 Pt (Tavares and Terranova, Rad. Measurem. 27 (1997) 19). A literature survey of available alpha decay half-life values for 190 Pt isotope is also reported. The significant discrepancies found between data obtained by direct counting, indirect geological methods and different calculation models are analysed and discussed. (author)

High-precision half-life measurements of the T=1/2 mirror beta decays F-17 and Cl-33

OpenAIRE

Grinyer, J; Grinyer, G. F; Babo, Mathieu; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J. C; Traykov, E

2015-01-01

Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, 17F and 33Cl, in order to eliminate the half-life as th...

High-precision half-life measurements of the T=1/2 mirror β decays F17 and Cl33

OpenAIRE

Grinyer, J; Grinyer, G F; Babo, M; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J C; Traykov, E

2015-01-01

Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, F17 and Cl33, in order to eliminate the half-life as the le...

Apoptosis in HEp-2 cells infected with Ureaplasma diversum.

Science.gov (United States)

Amorim, Aline Teixeira; Marques, Lucas Miranda; Santos, Angelita Maria Oliveira Gusmão; Martins, Hellen Braga; Barbosa, Maysa Santos; Rezende, Izadora Souza; Andrade, Ewerton Ferraz; Campos, Guilherme Barreto; Lobão, Tássia Neves; Cortez, Beatriz Araujo; Monezi, Telma Alvez; Machado-Santelli, Glaucia Maria; Timenetsky, Jorge

2014-09-04

Bacterial pathogens have many strategies for infecting and persisting in host cells. Adhesion, invasion and intracellular life are important features in the biology of mollicutes. The intracellular location of Ureaplasma diversum may trigger disturbances in the host cell. This includes activation or inhibition of pro and anti-apoptotic factors, which facilitate the development of host damage. The aim of the present study was to associate U. diversum infection in HEp-2 cells and apoptosis induction. Cells were infected for 72hs with four U. diversum clinical isolates and an ATCC strain. The U. diversum invasion was analyzed by Confocal Laser Scanning Microscopy and gentamicin invasion assay. The apoptosis was evaluated using pro-apoptotic and anti-apoptotic gene expression, and FITC Annexin V/Dead Cell Apoptosis Kit. The number of internalized ureaplasma in HEp-2 cells increased significantly throughout the infection. The flow cytometry analysis with fluorochromes to detect membrane depolarization and gene expression for caspase 2, 3 and 9 increased in infected cells after 24 hours. However, after 72 hours a considerable decrease of apoptotic cells was observed. The data suggests that apoptosis may be initially induced by some isolates in association with HEp-2 cells, but over time, there was no evidence of apoptosis in the presence of ureaplasma and HEp-2 cells. The initial increase and then decrease in apoptosis could be related to bacterial pathogen-associated molecular pattern (PAMPS). Moreover, the isolates of U. diversum presented differences in the studied parameters for apoptosis. It was also observed that the amount of microorganisms was not proportional to the induction of apoptosis in HEp-2 cells.

Dendritic cells as Achilles' heel and Trojan horse during varicella zoster virus infection

Directory of Open Access Journals (Sweden)

Günther eSchönrich

2015-05-01

Full Text Available Varicella zoster virus (VZV, a human alphaherpesvirus, causes varicella and subsequently estab-lishes latency within sensory nerve ganglia. Later in life VZV can reactivate to cause herpes zoster. A reduced frequency of VZV-specific T cells is strongly associated with herpes zoster illustrating that these immune cells are central to control latency. Dendritic cells (DCs are required for the generation of VZV-specific T cells. However, DCs can also be infected in vitro and in vivo allowing VZV to evade the antiviral immune response. Thus, DCs represent the immune systems’ Achilles heel. Uniquely among the human herpesviruses, VZV infects both DCs and T cells, and exploits both as Trojan horses. During primary infection VZV-infected DCs traffic to the draining lymph nodes and tonsils, where the virus is transferred to T cells. VZV-infected T cells subsequently spread infection throughout the body to give the typical varicella skin rash. The delicate interplay between VZV and DCs and its consequences for viral immune evasion and viral dissemination will be discussed in this article.

Effect of parent and daughter deformation on half-life time in exotic ...

Indian Academy of Sciences (India)

Shi and Swiatecki [6] put forward a model for exotic decay studies that uses Coulomb and proximity potential as interacting barrier for post-scission region and uses simple power law for overlap region. These authors [7] studied the effect of deformation of parent, daughter and shell attenuation on half-life time treating ...

Half-life and mass measurement of the short-lived {sup 215}Po isotope (1.78 ms) at the FRS ion catcher

Energy Technology Data Exchange (ETDEWEB)

Rink, Ann-Kathrin; Bergmann, Julian; Ebert, Jens; Hornung, Christine; Miskun, Ivan; Reiter, Moritz P. [Justus-Liebig Universitaet Giessen (Germany); Ayet San Andres, Samuel; Dickel, Timo; Plass, Wolfgang R.; Scheidenberger, Christoph [Justus-Liebig Universitaet Giessen (Germany); GSI, Darmstadt (Germany); Geissel, Hans; Purushothaman, Sivaji [GSI, Darmstadt (Germany)

2016-07-01

At the Low-Energy Branch (LEB) of the Super-FRS at FAIR, precision experiments with exotic nuclei will be performed using ion traps and lasers. The nuclei will be produced at relativistic energies, slowed down, thermalised in a cryogenic stopping cell (CSC) and made available to various experiments. The thermalisation is a challenging task because of the large energy straggling of the nuclei after production, which requires a stopping cell with large areal densities. Also, the process needs to be performed on a millisecond time scale in order to give access to short-lived nuclides. This method has already been successfully applied at the FRS Ion Catcher at GSI using a prototype CSC. Recently the potential of the method has been demonstrated by the mass and half-life measurement of the {sup 215}Po nuclide with a half-life of 1.78 ms only. The multiple-reflection time-of-flight mass spectrometer at the FRS Ion Catcher has been used to determine the mass to a sub-ppm accuracy and to provide a mass-selected beam for alpha spectroscopy. Furthermore, experiments have been performed with the prototype CSC in order to test novel concepts to be used with the final version of the CSC for the LEB.

Going Beyond the Binary : The body, Sexuality and Identity in Shelley Jackson’s Half Life: a novel

OpenAIRE

Liu, Linjing

2012-01-01

The thesis focuses on Shelley Jackson’s Half Life: a Novel with efforts directed towards a literary interpretation considering relevant issues within the context of gender and feminist theory. The argument rests upon four basic units: the theoretical framework at the outset, the question of the body next, thirdly an investigation of sexuality, and finally a consideration of identity. In Jackson’s Half Life: a Novel the non-dualist thinking underlies a deliberate play of dualism. To go beyond ...

Efferocytosis of Pathogen-Infected Cells

Directory of Open Access Journals (Sweden)

Niloofar Karaji

2017-12-01

Full Text Available The prompt and efficient clearance of unwanted and abnormal cells by phagocytes is termed efferocytosis and is crucial for organism development, maintenance of tissue homeostasis, and regulation of the immune system. Dying cells are recognized by phagocytes through pathways initiated via “find me” signals, recognition via “eat me” signals and down-modulation of regulatory “don’t eat me” signals. Pathogen infection may trigger cell death that drives phagocytic clearance in an immunologically silent, or pro-inflammatory manner, depending on the mode of cell death. In many cases, efferocytosis is a mechanism for eliminating pathogens and pathogen-infected cells; however, some pathogens have subverted this process and use efferocytic mechanisms to avoid innate immune detection and assist phagocyte infection. In parallel, phagocytes can integrate signals received from infected dying cells to elicit the most appropriate effector response against the infecting pathogen. This review focuses on pathogen-induced cell death signals that drive infected cell recognition and uptake by phagocytes, and the outcomes for the infected target cell, the phagocyte, the pathogen and the host.

Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

Science.gov (United States)

Fan, Kelong; Jiang, Bing; Guan, Zhe; He, Jiuyang; Yang, Dongling; Xie, Ni; Nie, Guohui; Xie, Can; Yan, Xiyun

2018-04-10

Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

Improved half-life determination and β-delayed γ-ray spectroscopy for 18Ne decay

Science.gov (United States)

Grinyer, G. F.; Ball, G. C.; Bouzomita, H.; Ettenauer, S.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Green, K. L.; Hackman, G.; Leslie, J. R.; Pearson, C. J.; Rand, E. T.; Sumithrarachchi, C. S.; Svensson, C. E.; Thomas, J. C.; Triambak, S.; Williams, S. J.

2013-04-01

The half-life of the superallowed Fermi β+ emitter 18Ne has been determined to ±0.07% precision by counting 1042 keV delayed γ rays that follow approximately 8% of all β decays. The deduced half-life, T1/2=1.6648(11) s, includes a 0.7% correction that accounts for systematic losses associated with rate-dependent detector pulse pileup that was determined using a recently developed γ-ray photopeak-counting technique. This result is a factor of two times more precise than, and in excellent agreement with, a previous lower-statistics measurement that employed the same experimental setup. High-resolution β-delayed γ-ray spectroscopy results for the relative γ-ray intensities and β-decay branching ratios to excited states in the daughter 18F are also presented.

Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

DEFF Research Database (Denmark)

Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

2017-01-01

BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

Research of the impact of coupling between unit cells on performance of linear-to-circular polarization conversion metamaterial with half transmission and half reflection

Science.gov (United States)

Guo, Mengchao; Zhou, Kan; Wang, Xiaokun; Zhuang, Haiyan; Tang, Dongming; Zhang, Baoshan; Yang, Yi

2018-04-01

In this paper, the impact of coupling between unit cells on the performance of linear-to-circular polarization conversion metamaterial with half transmission and half reflection is analyzed by changing the distance between the unit cells. An equivalent electrical circuit model is then built to explain it based on the analysis. The simulated results show that, when the distance between the unit cells is 23 mm, this metamaterial converts half of the incident linearly-polarized wave into reflected left-hand circularly-polarized wave and converts the other half of it into transmitted left-hand circularly-polarized wave at 4.4 GHz; when the distance is 28 mm, this metamaterial reflects all of the incident linearly-polarized wave at 4.4 GHz; and when the distance is 32 mm, this metamaterial converts half of the incident linearly-polarized wave into reflected right-hand circularly-polarized wave and converts the other half of it into transmitted right-hand circularly-polarized wave at 4.4 GHz. The tunability is realized successfully. The analysis shows that the changes of coupling between unit cells lead to the changes of performance of this metamaterial. The coupling between the unit cells is then considered when building the equivalent electrical circuit model. The built equivalent electrical circuit model can be used to perfectly explain the simulated results, which confirms the validity of it. It can also give help to the design of tunable polarization conversion metamaterials.

High-precision half-life measurements for the superallowed Fermi β+ emitter 14O

Science.gov (United States)

Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E.; Thomas, J. C.; Unsworth, C.

2013-07-01

The half-life of the superallowed Fermi β+ emitter 14O has been determined via simultaneous direct β and γ counting experiments at TRIUMF's Isotope Separator and Accelerator (ISAC) facility. A γ-ray counting measurement was performed by detecting the 2312.6-keV γ rays emitted from an excited state of the daughter 14N following the implantation of samples at the center of the 8π γ-ray spectrometer, a spherical array of 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned behind the implantation site with a solid angle coverage of ˜20%. The results, T1/2(β)=70.610±0.030s and T1/2(γ)=70.632±0.094s, form a consistent set and, together with eight previous measurements, establish a new average for the 14O half-life of T1/2=70.619±0.011s with a reduced χ2 of 0.99.

Hour Glass Half-Full or Half-Empty? Future Time Perspective and Preoccupation with Negative Events Across the Life Span

Science.gov (United States)

Strough, JoNell; de Bruin, Wändi Bruine; Parker, Andrew M.; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-01-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having limited future time perspective that motivates them to maximize well-being in the “here and now.” Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a US national adult life-span sample (N= 3,933, 18-93 yrs), we found that a two-factor model of future time perspective (focus on future opportunities; focus on limited time) fit the data better than a one-factor model. Through middle age, people perceived the life-span hourglass as half full—they focused more on future opportunities than limited time. Around age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty—they focused less on future opportunities and more on limited time. This pattern held even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared to men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as two dimensions are discussed. PMID:27267222

Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span.

Science.gov (United States)

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-09-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Precise half-life measurement of the superallowed β+ emitter 38Km

International Nuclear Information System (INIS)

Ball, G. C.; Boisvert, G.; Bricault, P.; Churchman, R.; Dombsky, M.; Lindner, T.; Macdonald, J. A.; Vandervoort, E.; Bishop, S.; D'Auria, J. M.; Hardy, J. C.; Iacob, V. E.; Leslie, J. R.; Mak, H.-B.

2010-01-01

The half-life of 38 K m has been measured to be 924.46(14) ms, a result that is a factor of two more precise than any of the five previous measurements of this quantity. The previous results are not consistent with one another, but our result agrees well with the two most recent ones. The derived ft value for 38 K m is now one of the three most precisely known superallowed ft values.

Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

Science.gov (United States)

Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

2015-09-01

A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

Examination of the biological half-life and organ d;stribution of tritiated lysin-vasopressin in Brattleboro rats

International Nuclear Information System (INIS)

Laczi, F.; Laszlo, F.

1980-01-01

15 μCi tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin. (L.E.)

Examination of the biological half-life and organ d; stribution of tritiated lysin-vasopressin in Brattleboro rats

Energy Technology Data Exchange (ETDEWEB)

Laczi, F; Laszlo, F [Szegedi Orvostudomanyi Egyetem Szeged (Hungary). 1. Belgyogyaszati Klinika; Keri, Gy; Teplan, I [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary)

1980-04-01

15 ..mu..Ci tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin.

High-Precision Half-Life Measurements for the Superallowed Fermi β+ Emitters 14O and 18Ne

Science.gov (United States)

Laffoley, A. T.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bender, P. C.; Bidaman, H.; Bildstein, V.; Blank, B.; Bouzomita, H.; Cross, D. S.; Deng, G.; Diaz Varela, A.; Dunlop, M. R.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P.; Giovinazzo, J.; Grinyer, G. F.; Grinyer, J.; Hadinia, B.; Jamieson, D. S.; Jigmeddorj, B.; Ketelhut, S.; Kisliuk, D.; Leach, K. G.; Leslie, J. R.; MacLean, A.; Miller, D.; Mills, B.; Moukaddam, M.; Radich, A. J.; Rajabali, M. M.; Rand, E. T.; Svensson, C. E.; Tardiff, E.; Thomas, J. C.; Turko, J.; Voss, P.; Unsworth, C.

High-precision half-life measurements, at the level of ±0.04%, for the superallowed Fermi emitters 14O and 18Ne have been performed at TRIUMF's Isotope Separator and Accelerator facility. Using 3 independent detector systems, a gas-proportional counter, a fast plastic scintillator, and a high-purity germanium array, a series of direct β and γ counting measurements were performed for each of the isotopes. In the case of 14O, these measurements were made to help resolve an existing discrepancy between detection methods, whereas for 18Ne the half-life precision has been improved in anticipation of forthcoming high-precision branching ratio measurements.

Comparison of isotope dilution and excretion methods for determining the half-life of ascorbic acid in the guinea pig

International Nuclear Information System (INIS)

Kipp, D.E.; Rivers, J.M.

1984-01-01

The half-life of ascorbic acid (AA) in guinea pigs was investigated by the isotope dilution and excretion methods. The dilution method measures [1-14C]AA disappearance from the plasma, whereas the excretion method measures the elimination of [1-14C]AA and the metabolites from the body. Two groups of animals underwent both isotope studies in reverse order. Animals were conditioned to the experimental procedures and fed 2.5 mg AA/100 g body weight orally to maintain a daily intake of the vitamin independent of food consumption. The two isotope procedures imposed similar stress on the animals, as determined by plasma cortisol levels and body weight changes. The AA half-life calculations of the rapidly exchangeable pool by the isotope dilution method yielded values of 1.23 and 0.34 hours for the two groups, respectively. The half-life of the slowly exchangeable pool for the two groups was 60.2 and 65.8 hours, respectively. The half-life of AA in the rapidly exchangeable pool, as measured by the excretion studies, was 4.57-8.75 hours. For the slowly exchangeable pool, it was 146-149 hours. The longer half-life of both pools obtained with the excretion method indicates that the isotope is disappearing from the plasma more rapidly than it is being excreted. This suggests that a portion of the [1-14C]AA leaving the plasma is removed to a body pool that is not sampled by the isotope excretion method

Towards a measurement of the half-life of {sup 60}Fe for stellar and early Solar System models

Energy Technology Data Exchange (ETDEWEB)

Ostdiek, K.; Anderson, T. [University of Notre Dame, Notre Dame, IN 46556 (United States); Bauder, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Bowers, M.; Collon, P. [University of Notre Dame, Notre Dame, IN 46556 (United States); Dressler, R. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Greene, J. [Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Kutschera, W. [Vienna Environmental Research Accelerator Laboratory, Waehringer Strasse 17, 1090 Vienna (Austria); Lu, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Robertson, D. [University of Notre Dame, Notre Dame, IN 46556 (United States); Schumann, D. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Skulski, M. [University of Notre Dame, Notre Dame, IN 46556 (United States); Wallner, A. [The Australian National University, Canberra, ACT 0200 (Australia)

2015-10-15

Radioisotopes, produced in stars and ejected into the Interstellar Medium, are important for constraining stellar and early Solar System (ESS) models. In particular, the half-life of the radioisotope, {sup 60}Fe, can have an impact on calculations for the timing for ESS events, the distance to nearby Supernovae, and the brightness of individual, non-steady-state {sup 60}Fe gamma ray sources in the Galaxy. A half-life measurement has been undertaken at the University of Notre Dame and measurements of the {sup 60}Fe/{sup 56}Fe concentration of our samples using Accelerator Mass Spectrometry has begun. This result will be coupled with an activity measurement of the isomeric decay in {sup 60}Co, which is the decay product of {sup 60}Fe. Preliminary half-life estimates of (2.53 ± 0.24) × 10{sup 6} years seem to confirm the recent measurement by Rugel et al. (2009).

Half-life, branching-ratio, and Q-value measurement for the superallowed 0+→0+β+ emitter 42Ti

International Nuclear Information System (INIS)

Nieto, T. Kurtukian; Souin, J.; Audirac, L.; Blank, B.; Giovinazzo, J.; Eronen, T.; Aeystoe, J.; Elomaa, V.-V.; Hager, U.; Hakala, J.; Jokinen, A.; Kankainen, A.; Karvonen, P.; Kessler, T.; Moore, I. D.; Penttilae, H.; Rahaman, S.; Reponen, M.; Rissanen, J.; Saastamoinen, A.

2009-01-01

The half-life, the branching ratio, and the decay Q value of the superallowed β emitter 42 Ti were measured in an experiment performed at the JYFLTRAP facility of the Accelerator Laboratory of the University of Jyvaeskylae. 42 Ti is the heaviest T z =-1 nucleus for which high-precision measurements of these quantities have been tried. The half-life (T 1/2 =208.14±0.45 ms) and the Q value [Q EC =7016.83(25) keV] are close to or reach the required precision of about 0.1%. The branching ratio for the superallowed decay branch [BR=47.7(12)%], a by-product of the half-life measurement, does not reach the necessary precision yet. Nonetheless, these results allow one to determine the experimental ft value and the corrected Ft value to be 3114(79) and 3122(79) s, respectively.

The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection

Directory of Open Access Journals (Sweden)

Nicolas eRuffin

2012-01-01

Full Text Available HIV-1 infection is characterized by continuous antigenic stimulation, chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells has previously been reported to occur in both children and adults infected with HIV-1; these cells are responsible for mounting and maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development which are impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

Tests of the methods of analysis of picosecond lifetimes and measurement of the half-life of the 569.6 keV level in 207Pb

International Nuclear Information System (INIS)

Lima, E. de; Kawakami, H.; Lima, A. de; Hichwa, R.; Ramayya, A.V.; Hamilton, J.H.; Dunn, W.; Kim, H.J.

1978-01-01

Customarily one extracts the half-life of the nuclear state from a delayed time spectrum by an analysis of the centroid shift, the slope and lately by the convolution method. Recently there have been two formulas relating the centroid shift to the half-life of the nuclear state. These two procedures can give different results for the half-life when Tsub(1/2) the same order or less than the time width of one channel. An extensive investigation of these two formulas and precedures has been made by measuring the half-life of the first excited state in 207 Pb at 569.6 keV. This analysis confirms Bay's formula relating the centroid shift to the half-life of the state. The half-life of the 569.6 keV level in 207 Pb is measured to be (129+-3) ps in excellent agreement with Weisskopf's single particle estimate of 128 ps for an E2 transition. (Auth.)

Measurements of Actual Effective Half - Life in {sup 131}I Therapy for Graves' Hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

So, Yong Seon; Kim, Myung Seon; Kwon, Ki Hyun; Kim, Seok Whan; Kim, Tae Hyung; Han, Sang Woong; Kim, Eun Sil; Kim, Chong Soon [Hanil General Hospital, Seoul (Korea, Republic of)

1996-03-15

Radioiodine[131I] has been used for the treatment of Graves' hyperthyroidism since the late 1940's and is now generally regarded as the treatment of choice for Graves' hyperthyroidism who does not remit following a course of antithyroid drugs. But for the dose given, several different protocols have been described by different centers, each attempting to reduce the incidence of long-term hypothyroidism while maintaining an acceptable rate control of Graves' hyperthyroidism. Our goals were to evaluate effective half-life and predict absorbed dose in Graves' hyperthyroidism patients, therefore, to calculate and read minister radioiodine activity needed to achieve aimed radiation dose. Our data showed that the mean effective 131I half-life for Graves' disease is 5.3 days(S.D=0.88) and mean biologic half-life is 21 days, range 9.5-67.2 days. The mean administered activity and the mean values of absorbed doses wet: 532 MBq(S.D.=254), 112 Gy (S.D.=50.9), respectively. The mean activity needed to achieve aimed radiation dose were 51 MBq and marked differences of 131I thyroidal uptake between tracer and therapy occurred in our study. We are sure that the dose calculation method that uses 5 days thyroidal 131I uptake measurements after tracer and therapy dose, provides sufficient data about the effective treatment in Graves' hyperthyroidism.

[Quality of life of pregnant women infected with the human immunodeficiency virus (HIV) in the city of São Paulo].

Science.gov (United States)

Tirado, Maria do Carmo Braga do Amaral; Bortoletti, Fátima Ferrreira; Nakamura, Mary Uchiyama; Souza, Eduardo de; Soárez, Patrícia Coelho de; Castelo Filho, Adauto; Amed, Abês Mahmed

2014-05-01

It was to assess the quality of life (QOL) of HIV-infected pregnant women using the HIV/AIDS - Targeted Quality of Life (HAT-QoL) questionnaire. A descriptive study of 60 pregnant women attended at the Multidisciplinary Nucleus of Infectious Diseases During Pregnancy (NUPAIG) - UNIFESP/EPM and in the referral network of the Municipal Office of São Paulo, conducted from February 2011 to October 2012. Sociodemographic and clinical variables were collected from 60 HIV-infected pregnant women who answered the HAT-QoL questionnaire, which included 34 questions about quality of life. The average age was 30 years and the average period of HIV infection was 5.7 years. Only 8.3% of patients had a CD4 cell score of ≤200 cells/mm³ and 45% showed undetectable viral load. The average domain scores ranged from 47.5 to 83.7. The domains with the lowest scores were financial concerns and concerns about secrecy. The domains with the highest scores and lower impact on quality of life were concerns about medication and confidence in the professional. In this initial study with 60 pregnant women, we concluded that the HAT-QOL can contribute to the assessment of quality of life in the population of HIV-infected pregnant women in Brazil.

Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma.

Science.gov (United States)

Ito, Katsuki; Hibi, Kenji; Ando, Hideyuki; Hidemura, Kazuhiko; Yamazaki, Taiji; Akiyama, Seiji; Nakao, Akimasa

2002-02-01

Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p Clearance (k) showed a significant difference between the groups (p time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.

Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.

Science.gov (United States)

Costa, Vivian Vasconcelos; Ye, Weijian; Chen, Qingfeng; Teixeira, Mauro Martins; Preiser, Peter; Ooi, Eng Eong; Chen, Jianzhu

2017-08-01

Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo , identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control

Schrödinger's Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

Science.gov (United States)

Mordecai, Gideon J; Verret, Frederic; Highfield, Andrea; Schroeder, Declan C

2017-03-18

Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV); a double stranded DNA (dsDNA) virus belonging to the family Phycodnaviridae . E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the "Cheshire Cat" escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA) that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR) and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger's cat; of being simultaneously both dead and alive.

Phenytoin shortens the half-life of the hypoxic cell radiosensitizer misonidazole in man: implications for possible reduced toxicity

International Nuclear Information System (INIS)

Workman, P.; Bleehen, N.M.; Wiltshire, C.R.; Cambridge Univ.

1980-01-01

Results are described of a preliminary study of the effects of phenytoin, (commonly used as an anticonvulsant in the treatment of patients with brain tumours), on the plasma pharmacokinetics of misonidazole (MISO) in man. Previous studies have shown that pretreatment with phenytoin shortens the half-life of MISO in dogs and mice by induction of drug metabolizing enzymes, and also reduces the acute lethal effects of MISO in mice. In this study patients with various types of malignancy and with cerebral metastases were given MISO before and after a course of phenytoin. Others were assessed as controls without phenytoin administration. Plasma concentrations of MISO were determined in blood samples taken before and at various times after administration. A summary of the pharmacokinetic data obtained is given. (author)

Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

Science.gov (United States)

Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Grinyer, G. F.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.

2009-10-01

The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada. A beam of ˜10^5 ^26Al^m/s was delivered in October 2007 and its decay was observed using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [4pt] [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 79, 055502 (2009).

Helicobacter pylori impairs murine dendritic cell responses to infection.

Directory of Open Access Journals (Sweden)

Ya-Hui Wang

Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.

Science.gov (United States)

Kulinski, Joseph M; Darrah, Eric J; Broniowska, Katarzyna A; Mboko, Wadzanai P; Mounce, Bryan C; Malherbe, Laurent P; Corbett, John A; Gauld, Stephen B; Tarakanova, Vera L

2015-09-01

Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell-cell transmission of VSV-G pseudotyped lentivector particles.

Directory of Open Access Journals (Sweden)

Amy M Skinner

Full Text Available Many replicating viruses, including HIV-1 and HTLV-1, are efficiently transmitted from the cell surface of actively infected cells upon contact with bystander cells. In a previous study, we reported the prolonged cell surface retention of VSV-G replication-deficient pseudotyped lentivector prior to endocytic entry. However, the competing kinetics of cell surface versus dissociation, neutralization or direct transfer to other cells have received comparatively little attention. Here we demonstrate that the relative efficiency of cell-cell surface transmission can outpace "cell-free" transduction at limiting vector input. This coincides with the prolonged half-life of cell bound vector but occurs, unlike HTLV-1, without evidence for particle aggregation. These studies suggest that cell-surface attachment stabilizes particles and alters neutralization kinetics. Our experiments provide novel insight into the underexplored cell-cell transmission of pseudotyped particles.

Parvovirus B19 infection during pregnancy and risks to the fetus.

Science.gov (United States)

Ornoy, Asher; Ergaz, Zivanit

2017-03-15

Parvovirus B19 infects 1 to 5% of pregnant women, generally with normal pregnancy outcomes. During epidemics, the rate of infection is higher. Major congenital anomalies among offspring of infected mothers are rare, as the virus does not appear to be a significant teratogen. However, parvovirus B19 infection may cause significant fetal damage, and in rare cases, brain anomalies and neurodevelopmental insults, especially if infection occurs in the first 20 weeks of pregnancy. Parvovirus B19 is also an important cause of fetal loss, especially in the second half of pregnancy when spontaneous fetal loss from other causes is relatively rare. Parvovirus B19 infection may affect many fetal organs and can cause severe anemia, following fetal erythroid progenitor cells infection and apoptosis, especially in fetuses, that have shortened half-life of erythrocytes. Severe anemia may cause high output cardiac failure and nonimmune hydrops fetalis. In addition, parvovirus B19 may directly infect myocardial cells and produce myocarditis that further aggravates the cardiac failure. Intrauterine fetal transfusion is commonly used for the treatment of severe fetal anemia with survival rates of 75 to 90% and significant reduction of fetal morbidity. Only 66 cases were evaluated neurodevelopmentally, of which 10 (16%) had slight or severe neurodevelopmental problems. Because parvovirus B19 infection can cause severe fetal morbidity and mortality, it should be part of the routine work-up of pregnant women who have been exposed to the virus or of pregnancies with suspected fetal hydrops. Assessment for maternal infection during pregnancy is especially important during epidemics, when sero-conversion rates are high. Birth Defects Research 109:311-323, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Plasmonic Photovoltaic Cells with Dual-Functional Gold, Silver, and Copper Half-Shell Arrays.

Science.gov (United States)

Wu, Ling; Kim, Gyu Min; Nishi, Hiroyasu; Tatsuma, Tetsu

2017-09-12

Solid-state photovoltaic cells based on plasmon-induced charge separation (PICS) have attracted growing attention during the past decade. However, the power conversion efficiency (PCE) of the previously reported devices, which are generally loaded with dispersed metal nanoparticles as light absorbers, has not been sufficiently high. Here we report simpler plasmonic photovoltaic cells with interconnected Au, Ag, and Cu half-shell arrays deposited on SiO 2 @TiO 2 colloidal crystals, which serve both as a plasmonic light absorber and as a current collector. The well-controlled and easily prepared plasmonic structure allows precise comparison of the PICS efficiency between different plasmonic metal species. The cell with the Ag half-shell array has higher photovoltaic performance than the cells with Au and Cu half-shell arrays because of the high population of photogenerated energetic electrons, which gives a high electron injection efficiency and suppressed charge recombination probability, achieving the highest PCE among the solid-state PICS devices even without a hole transport layer.

Magnet power supply system for the ISABELLE half-cell prototype

International Nuclear Information System (INIS)

Nawrocky, R.J.

1977-01-01

Due to stringent requirements on the spatial harmonic content of ISABELLE's magnetic field, the magnet power supplies for the half-cell prototype must be dynamically accurate and stable to within 0.01% of their full-scale rating. Depending on the application, the full-scale current of various units comprising the system ranges from +-50 A to 4000 A. The system, as constructed is fully controllable and programmable either manually or with a control computer. The magnet power supply system described was constructed and interconnected with the half-cell computer control equipment. A number of power supply units were tested with inductive test loads in both the manual and the computer control modes. Test results on stability and speed of response indicate that all systems perform according to specifications

A Half-Life Measurement of the 343.4 keV Level in {sup 175}Lu

Energy Technology Data Exchange (ETDEWEB)

Hoejeberg, M; Malmskog, S G

1969-05-15

Great theoretical interest has recently been shown in the asymptotically forbidden 5/2 5/2+ [402] - 7/2 7/2+ [404] M1-transitions in {sup 181}Ta and {sup 175}Lu . Half-lives of the 5/2 5/2+ [402] level in {sup 175}Lu have been reported which differ by more than a factor of 10. Using an electron-electron coincidence spectrometer the half-life of this level has been re-measured and a value of (0.26 {+-} 0.02) nsec has been established.

Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

International Nuclear Information System (INIS)

Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

2003-01-01

Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

Merkel cell polyomavirus infection and Merkel cell carcinoma.

Science.gov (United States)

Liu, Wei; MacDonald, Margo; You, Jianxin

2016-10-01

Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

Dependence of the half-life of ²²¹Fr on the implantation environment

DEFF Research Database (Denmark)

Olaizola, B.; Fraile, L.M.; Riisager, Karsten

2010-01-01

The possible dependence of the half-life of 221Fr on the solid-state environment has been investigated by the simultaneous measurement of implanted 221Fr ions in an insulator (Si) and a metallic substrate (Au) at the ISOLDE facility at CERN. Our results indicate that, if existing, the difference ...

The analysis of predictability of α-decay half-life formulae and the α partial half-lives of some exotic nuclei

International Nuclear Information System (INIS)

Dasgupta-Schubert, N.; Reyes, M.A.; Tamez, V.A.

2009-01-01

The predictabilities of the three α-decay half-life formulae, the Royer GLDM, the Viola-Seaborg and the Sobiczewski-Parkhomenko formulae, have been evaluated by developing a method based on the ansatz of standard experimental benchmarking. The coefficients of each formula were re-derived using the reliable data of the α -standards nuclei. The modified formulae that resulted were used to evaluate the accuracies of the formulae towards the prediction of half-lives of a set of nuclides with well-studied α spectroscopic data as well as a set of exotic α emitters. Further, a simple linear optimisation of the modified formulae allowed adjustments for the insufficient statistics of the primary data set without changing the modified formulae. While the three modified formulae showed equivalent results for all the medium heavy nuclei except the odd-odd, the modified GLDM showed relatively the best figures of merit for the odd-odd and superheavy nuclides. (orig.)

A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ling; Wang, Lin; Meng, Zhiyun; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Gao, Lei; Zhu, Xiaoxia; Sun, Wenzhong; Li, Jian; Zheng, Ying; Dou, Guifang, E-mail: douguifang@vip.163.com

2014-03-07

Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy.

Systematics of half-lives for proton radioactivity

International Nuclear Information System (INIS)

Medeiros, E.L.; Rodrigues, M.M.N.; Duarte, S.B.; Tavares, O.A.P.

2007-01-01

Half-life measurements for both ground-state and isomeric transitions in proton radioactivity are systematized by using a semiempirical, one-parameter model based on tunneling through a potential barrier, where the centrifugal and overlapping effects are taken into account within the spherical nucleus approximation. This approach, which has been successfully applied to alpha decay cases covering ∼ 30 orders of magnitude in half-life, has shown, in addition, very adequate at fitting all existing data on partial half-life, T 1/2p , of proton emission from nuclei. Nearly 70 measured half-life values have been analysed, and the data could be described by two straight lines relating the pure Coulomb contribution to half life with the quantity Z d (μ 0 /Q p ) 1/2 (Z d is the atomic number of the daughter nucleus, μ 0 is the reduced mass, and Q p is the total nuclear energy available for decay). These straight lines are shown to correspond to different degrees of deformation, namely, very prolate (δ> approx. 0.1), and other shaped (delta < approx. 0.1) parent nuclei. The goodness in reproducing the data attained in the present systematics allows for half-life predictions for a few possible cases of proton radioactivity not yet experimentally accessed. (author)

HCV Infection and B-Cell Lymphomagenesis

Directory of Open Access Journals (Sweden)

Masahiko Ito

2011-01-01

Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

High-Precision Half-Life and Branching Ratio Measurements for the Superallowed β+ Emitter 26Alm

Science.gov (United States)

Finlay, P.; Svensson, C. E.; Demand, G. A.; Garrett, P. E.; Green, K. L.; Leach, K. G.; Phillips, A. A.; Rand, E. T.; Ball, G.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Sumithrarachchi, C. S.; Williams, S. J.; Triambak, S.

2013-03-01

High-precision half-life and branching-ratio measurements for the superallowed β+ emitter 26Alm were performed at the TRIUMF-ISAC radioactive ion beam facility. An upper limit of ≤ 15 ppm at 90% C.L. was determined for the sum of all possible non-analogue β+/EC decay branches of 26Alm, yielding a superallowed branching ratio of 100.0000+0-0.0015%. A value of T1/2 = 6:34654(76) s was determined for the 26Alm half-life which is consistent with, but 2.5 times more precise than, the previous world average. Combining these results with world-average measurements yields an ft value of 3037.58(60) s, the most precisely determined for any superallowed emitting nucleus to date. This high-precision ft value for 26Alm provides a new benchmark to refine theoretical models of isospin-symmetry-breaking effects in superallowed β decays.

Schrödinger’s Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

Directory of Open Access Journals (Sweden)

Gideon J. Mordecai

2017-03-01

Full Text Available Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV; a double stranded DNA (dsDNA virus belonging to the family Phycodnaviridae. E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the “Cheshire Cat” escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger’s cat; of being simultaneously both dead and alive.

Schrödinger’s Cheshire Cat: Are Haploid Emiliania huxleyi Cells Resistant to Viral Infection or Not?

Science.gov (United States)

Mordecai, Gideon J.; Verret, Frederic; Highfield, Andrea; Schroeder, Declan C.

2017-01-01

Emiliania huxleyi is the main calcite producer on Earth and is routinely infected by a virus (EhV); a double stranded DNA (dsDNA) virus belonging to the family Phycodnaviridae. E. huxleyi exhibits a haplodiploid life cycle; the calcified diploid stage is non-motile and forms extensive blooms. The haploid phase is a non-calcified biflagellated cell bearing organic scales. Haploid cells are thought to resist infection, through a process deemed the “Cheshire Cat” escape strategy; however, a recent study detected the presence of viral lipids in the same haploid strain. Here we report on the application of an E. huxleyi CCMP1516 EhV-86 combined tiling array (TA) that further confirms an EhV infection in the RCC1217 haploid strain, which grew without any signs of cell lysis. Reverse transcription polymerase chain reaction (RT-PCR) and PCR verified the presence of viral RNA in the haploid cells, yet indicated an absence of viral DNA, respectively. These infected cells are an alternative stage of the virus life cycle deemed the haplococcolithovirocell. In this instance, the host is both resistant to and infected by EhV, i.e., the viral transcriptome is present in haploid cells whilst there is no evidence of viral lysis. This superimposed state is reminiscent of Schrödinger’s cat; of being simultaneously both dead and alive. PMID:28335465

Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis.

Science.gov (United States)

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L; Wu, Hui; Kitten, Todd

2009-11-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified-a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (approximately 2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

Science.gov (United States)

Hannemann, Sebastian; Galán, Jorge E

2017-07-01

Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

Propose of a model for dose and hazard calculation due the Rn-222, Rn-220 and its short half-life daugthers inhalation

International Nuclear Information System (INIS)

Mauricio, C.L.P.

1982-01-01

The compartimental dosimetric model is used to simulate, by computer, the interactions of the inhalated radon atom radiations and its short half-life daugthers with cells. The metabolic trajectory of these radionuclides is described by differential equations of continuous medium dynamics, where the elements transform by radioactive decay. This work permits to determine the individual retenction function, beeing useful in radioprotection routines or emergence situations. The results of internal dosimetry are consistent with the new I.C.R.P. - 32 international recommendations. (L.C.) [pt

Mechanisms of cell death in canine parvovirus-infected cells provide intuitive insights to developing nanotools for medicine

Directory of Open Access Journals (Sweden)

Jonna Nykky

2010-06-01

Full Text Available Jonna Nykky, Jenni E Tuusa, Sanna Kirjavainen, Matti Vuento, Leona GilbertNanoscience Center and Department of Biological and Environmental Science, University of Jyväskylä, FinlandAbstract: Viruses have great potential as nanotools in medicine for gene transfer, targeted gene delivery, and oncolytic cancer virotherapy. Here we have studied cell death mechanisms of canine parvovirus (CPV to increase the knowledge on the CPV life cycle in order to facilitate the development of better parvovirus vectors. Morphological studies of CPV-infected Norden laboratory feline kidney (NLFK cells and canine fibroma cells (A72 displayed characteristic apoptotic events. Apoptosis was further confirmed by activation of caspases and cellular DNA damage. However, results from annexin V-propidium iodide (PI labeling and membrane polarization assays indicated disruption of the plasma membrane uncommon to apoptosis. These results provide evidence that secondary necrosis followed apoptosis. In addition, two human cancer cell lines were found to be infected by CPV. This necrotic event over apoptotic cell death and infection in human cells provide insightful information when developing CPV as a nanotool for cancer treatments.Keywords: canine parvovirus, apoptosis, necrosis, nanoparticle, virotherapy

Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-life Versus Extended Half-life Products and Those Switching from Standard Half-life to Extended Half-life Products.

Science.gov (United States)

Tortella, Bartholomew J; Alvir, José; McDonald, Margaret; Spurden, Dean; Fogarty, Patrick F; Chhabra, Amit; Pleil, Andreas M

2018-01-24

Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while

ORIGEN-S Decay Data Library and Half-Life Uncertainties

International Nuclear Information System (INIS)

Hermann, O.W.

1998-01-01

The results of an extensive update of the decay data of the ORIGEN-S library are presented in this report. The updated decay data were provided for both the ORIGEN-S and ORIGEN2 libraries in the same project. A complete edit of the decay data plus the available half-life uncertainties are included in Appendix A. A detailed description of the types of data contained in the library, the format of the library, and the data sources are also presented. Approximately 24% of the library nuclides are stable, 66% were updated from ENDF/B-VI, about 8% were updated from ENSDF, and the remaining 2% were not updated. Appendix B presents a listing of percentage changes in decay heat from the old to the updated library for all nuclides containing a difference exceeding 1% in any parameter

Half-life of the 3/2/sup +/ level of /sup 119/Sn

Energy Technology Data Exchange (ETDEWEB)

Abreu, M C; Gil, F B [Faculdade de Ciencias da Universidade de Lisboa, Lisbon (Portugal). Grupo de Espectroscopia Nuclear, Laboratorio de Fisica

1976-01-01

The half-life of the 3/2/sup +/, 23.87 keV level of /sup 119/Sn is measured by the delayed coincidence technique. Magnetic spectrometry associated with scintillation techniques and scintillation spectrometry only have been used. The results obtained with these techniques were respectively Tsub(1/2) = 17.87 +- 0.11 ns and Tsub(1/2) = 18.48 +- 0.30 ns. The measured reduced M1 transition probability is compared with the single-particle and Kisslinger and Sorensen model predictions.

Pile-up corrections for high-precision superallowed β decay half-life measurements via γ-ray photopeak counting

Science.gov (United States)

Grinyer, G. F.; Svensson, C. E.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Chakrawarthy, R. S.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kulp, W. D.; Leach, K. G.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Sarazin, F.; Schumaker, M. A.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Williams, S. J.; Wong, J.; Wood, J. L.; Zganjar, E. F.

2007-09-01

A general technique that corrects γ-ray gated β decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of Na26 implanted at the center of the 8π γ-ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The β-decay half-life of Na26 obtained from counting 1809-keV γ-ray photopeaks emitted by the daughter Mg26 was determined to be T=1.07167±0.00055 s following a 27σ correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct β counting and demonstrates the feasibility of high-precision β-decay half-life measurements through the use of high-purity germanium γ-ray detectors. The technique presented here, while motivated by superallowed-Fermi β decay studies, is general and can be used for all half-life determinations (e.g. α-, β-, X-ray, fission) in which a γ-ray photopeak is used to select the decays of a particular isotope.

Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice

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Asquith Kelly L

2010-02-01

Full Text Available Abstract Background Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV, increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. Methods We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR and host immunological responses. Results Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice

Biological half-life of bromide in the rat depends primarily on the magnitude of sodium intake

Czech Academy of Sciences Publication Activity Database

Pavelka, Stanislav; Babický, Arnošt; Vobecký, Miloslav

2005-01-01

Roč. 54, č. 6 (2005), s. 639-644 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50110509 Keywords : biological half-life * bromide * sodium Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

Science.gov (United States)

Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D; Heywood, Sam; Humphreys, David P

2016-10-01

An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG.

Thyroid fractional deposition and half life of radioiodine

International Nuclear Information System (INIS)

Fujita, Minoru

1974-01-01

In order to measure the absorbed dose of radioiodine in the thyroid gland, which was incorporated by halation or ingestion, iodine intake (fa), 131 I thyroid uptake rate(fw), 131 I thyroid uptake rate compared to the rate in the whole body (f 2 ) and the half life of iodine in the thyroid gland(Teff) were examined. Thyroid fractional deposition of 131 I was compared between Japanese and European. The rate of 131 I which moved from the blood into the thyroid gland in children (f 2 ') and the effect of the iodine in meals on 131 I thyroid uptake (fw) were also studied. In Japanese, f 2 was 0.28 and the mean Teff was 6.9 +- 0.7 days in 11 Japanese adults. There was an individual difference in these biological parameter and the values in adults were different from those in children. A little difference in value between Japanese and European suggested to be caused by the greater amount of stable iodine in meals in Japanese. (Serizawa, K.)

Influence of antithyroid medication on effective half-life and uptake of 131 I following radioiodine therapy

International Nuclear Information System (INIS)

Moka, D.; Voth, E.; Schicha, H.

1997-01-01

Aim: A radioiodine therapy (RIT) in thyrotoxic patients receiving antithyroid drugs (ATD) leads in comparison to nonpretreated patients either to higher therapeutic doses or to higher treatment failure rates. Aim of this study was to optimize the effect of RIT in patients pretreated with ATD. Methods: Therefore, the influence of ATD was assessed in 109 patients with shortened effective half-life of 131 I. RIT was performed under stationary conditions. Radioiodine activity of the thyroid gland was stopped three days after RIT. The patients antithyroid medication was stopped three days after RIT. The progress of the first RIT and of a second radioiodine application, which still was necessary in 29 patients, was compared to 32 patients receiving ATD, continuously. Results: Values of effective half-life for 131 I rose significantly from 3.2±0.2 to 5.7±0.2 days (Graves' disease: 3.4 to 5.7 days; toxic goiters' disease: Multifocal autonomy 3.2 to 6.2 days; unifocal autonomy 2.5 auf 5.0 days) 2-3 days after stopping ATD. There was an increase of the 131 I-uptake of a second RIT decreased significantly in patients receiving ATD, continuously. Conclusion: Effective half-life and uptake of 131 I was affected significantly by ATD. The stop taking of ATD after RIT is useful to improve an apparent insufficient RIT in thyrotoxic patients receiving ATD. (orig.) [de

Congenital Cytomegalovirus Infection: Child Development, Quality of Life and Impact on Daily Life.

NARCIS (Netherlands)

Korndewal, Marjolein J; Oudesluys-Murphy, Anne Marie; Kroes, Aloys C M; Vossen, Ann C T M; de Melker, Hester E

2017-01-01

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection worldwide and can lead to long-term impairments such as developmental delay. It is currently unknown how this affects the daily life of children and their parents. Children For this study, children with cCMV were

Study on the biological half-life and organ-distribution of tritiated lysine-vasopressin in Brattleboro rats

International Nuclear Information System (INIS)

Laczi, F.; Laszlo, F.A.; Keri, Gy.; Teplan, I.

1980-01-01

The biological half-life and organ-distribution of tritiated lysine-vasopressin were determined in R-Amsterdam rats, and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-life of the tritiated lysin-vasopressin in the Brattleboro rats did not differ significantly from that found in the R-Amsterdam rats. The highest radioactivities were observed in the neuro- and adenohypophyses and in the kidneys of both the R-Amsterdam and the Brattleboro rats. The accumulation of tritiated LVP was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ-accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary hypothalamic diabetes insipidus. (author)

Fast renal trapping of porcine Luteinizing Hormone (pLH shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life

Directory of Open Access Journals (Sweden)

Locatelli Alain

2003-10-01

Full Text Available Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH and equine CG (eCG which exhibit respectively a short and a long half-life. This was done first by following half-lives of pLH in piglets with hepatic portal circulation shunted or not. It was expected that such a shunt would enhance the short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and 123I-eCG was performed in intact rats to compare their routes and rates of distribution and elimination. Methods Native pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anæsthetized piglet. Blood samples were recovered sequentially over one hour time and the hormone concentrations were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and 123I-eCG was performed in rats using a OPTI-CGR gamma camera. Results In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min. In the rat, the half-life of pLH was also found to be very short (3–6 min and 123I-pLH was found to accumulate in high quantity in less than 10 min post injection at the level of kidneys but not in the liver. 123I-eCG didn't accumulate in any organ in the rats during the first hour, plasma concentrations of this gonadotropin being still elevated (80% at this time. Conclusion In both the porcine and rat species, the liver is not responsible for the rapid elimination of pLH from the circulation compared to eCG. Our scintigraphic experiments suggest that the very short circulatory half-life of LH is due to rapid renal trapping.

Oral epithelial cells are susceptible to cell-free and cell-associated HIV-1 infection in vitro

International Nuclear Information System (INIS)

Moore, Jennifer S.; Rahemtulla, Firoz; Kent, Leigh W.; Hall, Stacy D.; Ikizler, Mine R.; Wright, Peter F.; Nguyen, Huan H.; Jackson, Susan

2003-01-01

Epithelial cells lining the oral cavity are exposed to HIV-1 through breast-feeding and oral-genital contact. Genital secretions and breast milk of HIV-1-infected subjects contain both cell-free and cell-associated virus. To determine if oral epithelial cells can be infected with HIV-1 we exposed gingival keratinocytes and adenoid epithelial cells to cell-free virus and HIV-1-infected peripheral blood mononuclear cells and monocytes. Using primary isolates we determined that gingival keratinocytes are susceptible to HIV-1 infection via cell-free CD4-independent infection only. R5 but not X4 viral strains were capable of infecting the keratinocytes. Further, infected cells were able to release infectious virus. In addition, primary epithelial cells isolated from adenoids were also susceptible to infection; both cell-free and cell-associated virus infected these cells. These data have potential implications in the transmission of HIV-1 in the oral cavity

Experimental infection of Leishmania (L. chagasi in a cell line derived from Lutzomyia longipalpis (Diptera:Psychodidae

Directory of Open Access Journals (Sweden)

Felio J Bello

2005-10-01

Full Text Available The present work describes the in vitro infection of a cell line Lulo, derived from Lutzomyia longipalpis embryonic tissue, by Leishmania chagasi promastigotes. This infection process is compared with a parallel one developed using the J774 cell line. The L. chagasi MH/CO/84/CI-044B strain was used for experimental infection in two cell lines. The cells were seeded on glass coverslips in 24-well plates to reach a final number of 2 x 10(5 cells/well. Parasites were added to the adhered Lulo and J774 cells in a 10:1 ratio and were incubated at 28 and 37ºC respectively. After 2, 4, 6, 8, and 10 days post-infection, the cells were extensively washed with PBS, fixed with methanol, and stained with Giemsa. The number of internalized parasites was determined by counting at least 400 cultured cells on each coverslip. The results showed continuous interaction between L. chagasi promastigotes with the cell lines. Some ultrastructural characteristics of the amastigote forms were observed using transmission electron microscopy. The highest percentage of infection in Lulo cells was registered on day 6 post-infection (29.6% and on day 4 in the J774 cells (51%. This work shows similarities and differences in the L. chagasi experimental infection process in the two cell lines. However, Lulo cells emerge as a new model to study the life-cycle of this parasite.

Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells

International Nuclear Information System (INIS)

Suhrbier, A.; Winger, L.A.; Castellano, E.; Sinden, R.E.

1990-01-01

Exoerythrocytic (EE) stages of Plasmodium berghei derived from irradiated sporozoites were cultured in vitro in HepG2 cells. They synthesized several antigens, predominantly but not exclusively those expressed by normal early erythrocytic schizonts. After invasion, over half the intracellular sporozoites, both normal and irradiated, appeared to die. After 24 h, in marked contrast to the normal parasites, EE parasites derived from irradiated sporozoites continued to break open, shedding their antigens into the cytoplasm of the infected host cells. Increasing radiation dosage, which has previously been shown to reduce the ability of irradiated sporozoites to protect animals, correlated with reduced de novo antigen synthesis by EE parasites derived from irradiated sporozoites

Methodology for Assessing the Probability of Corrosion in Concrete Structures on the Basis of Half-Cell Potential and Concrete Resistivity Measurements

OpenAIRE

Sadowski, Lukasz

2013-01-01

In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpos...

Absorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant origin

International Nuclear Information System (INIS)

Johnson, P.E.; Lykken, G.I.; Korynta, E.D.

1991-01-01

Absorption and biological half-life of 54 Mn were measured in adult men and women fed foods labeled intrinsically or extrinsically with 54 Mn. Each subject consumed a series of three test meals consisting of a food labeled intrinsically, a food labeled extrinsically or MnCl 2 (control) served in random order. The foods tested were lettuce, spinach, wheat and sunflower seeds. Lettuce meals and their controls contained 9.65 mumol Mn; other meals contained 22.50 mumol Mn. In addition to the test food or MnCl 2 , each meal consisted of vegetable oil (5 g), salt (NaCl, 0.15 g) and crackers (10 g), which provided 0.55 mumol Mn. There were no differences in percentage of Mn absorption or biological half-life of 54 Mn for any of the intrinsically/extrinsically labeled food pairs. Absorption of 54 Mn from MnCl 2 (8.90%) was greater than from lettuce (5.20%), spinach (3.81%), wheat (2.16%) or sunflower seeds (1.71%), but the biological half-life did not vary with the source of Mn. Absorption of 54 Mn from lettuce was significantly (P less than 0.05) greater than from wheat or sunflower seeds. Although the Mn dose in the test meal was less for lettuce than for the other foods, there was no difference in Mn absorption from MnCl 2 between the subjects fed lettuce and subjects fed other foods. There was no correlation of either 54 Mn absorption or biological half-life with whole blood or plasma Mn

Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection.

Science.gov (United States)

Shan, Liang; Deng, Kai; Gao, Hongbo; Xing, Sifei; Capoferri, Adam A; Durand, Christine M; Rabi, S Alireza; Laird, Gregory M; Kim, Michelle; Hosmane, Nina N; Yang, Hung-Chih; Zhang, Hao; Margolick, Joseph B; Li, Linghua; Cai, Weiping; Ke, Ruian; Flavell, Richard A; Siliciano, Janet D; Siliciano, Robert F

2017-10-17

The latent reservoir for HIV-1 in resting memory CD4 + T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4 + T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4 + T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4 + T cells. Establishment of latent HIV-1 infection in CD4 + T could be inhibited by viral-specific CD8 + T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. Copyright © 2017. Published by Elsevier Inc.

Comprehensive Evaluation of Streptococcus sanguinis Cell Wall-Anchored Proteins in Early Infective Endocarditis▿ †

Science.gov (United States)

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L.; Wu, Hui; Kitten, Todd

2009-01-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified—a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (∼2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention. PMID:19703977

The beta(+) decay and cosmic-ray half-life of Mn-54

Science.gov (United States)

Dacruz, M. T. F.; Norman, E. B.; Chan, Y. D.; Garcia, A.; Larimer, R. M.; Lesko, K. T.; Stokstad, R. G.; Wietfeldt, F. E.

1993-03-01

We performed a search for the beta(+) branch of Mn-54 decay. As a cosmic ray, Mn-54, deprived of its atomic electrons, can decay only via beta(+) and beta(-) decay, with a half-life of the order of 106 yr. This turns Mn-54 into a suitable cosmic chronometer for the study of cosmic-ray confinement times. We searched for coincident back-to-back 511-keV gamma-rays using two germanium detectors inside a Nal(Tl) annulus. An upper limit of 2 x 10-8 was found for the beta(+) decay branch, corresponding to a lower limit of 13.7 for the log ft value.

Murid herpesvirus-4 exploits dendritic cells to infect B cells.

Directory of Open Access Journals (Sweden)

Miguel Gaspar

2011-11-01

Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

Energy dependence of average half-life of delayed neutron precursors in fast neutron induced fission of 235U and 236U

International Nuclear Information System (INIS)

Isaev, S.G.; Piksaikin, L.E.; Kazakov, L.E.; Tarasko, M.Z.

2000-01-01

The measurements of relative abundances and periods of delayed neutrons from fast neutron induced fission of 235 U and 236 U have been made at the electrostatic accelerator CG-2.5 at IPPE. The preliminary results were obtained and discussed in the frame of the systematics of the average half-life of delayed neutron precursors. It was shown that the average half-life value in both reactions depends on the energy of primary neutrons [ru

Measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 experiment

Energy Technology Data Exchange (ETDEWEB)

Alduino, C.; Avignone, F.T.; Chott, N.; Creswick, R.J.; Rosenfeld, C.; Wilson, J. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); Alfonso, K.; Hickerson, K.P.; Huang, H.Z.; Liu, X.; Trentalange, S.; Zhu, B.X. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Artusa, D.R. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Azzolini, O.; Camacho, A.; Keppel, G.; Palmieri, V.; Pira, C. [INFN-Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy); Banks, T.I.; Drobizhev, A.; Freedman, S.J.; Hennings-Yeomans, R.; O' Donnell, T.; Wagaarachchi, S.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Bari, G.; Deninno, M.M. [INFN-Sezione di Bologna, Bologna (Italy); Beeman, J.W. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); Bellini, F.; Cardani, L.; Casali, N.; Cosmelli, C.; Ferroni, F. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Bersani, A.; Caminata, A. [INFN-Sezione di Genova, Genova (Italy); Biassoni, M.; Carbone, L.; Cremonesi, O.; Ferri, E.; Giachero, A.; Pessina, G.; Previtali, E.; Rusconi, C. [INFN-Sezione di Milano Bicocca, Milan (Italy); Brofferio, C.; Capelli, S.; Carniti, P.; Cassina, L.; Chiesa, D.; Clemenza, M.; Faverzani, M.; Fiorini, E.; Gironi, L.; Gotti, C.; Maino, M.; Nucciotti, A.; Pavan, M.; Pozzi, S.; Sisti, M.; Terranova, F.; Zanotti, L. [Universita di Milano-Bicocca, Dipartimento di Fisica, Milan (Italy); INFN-Sezione di Milano Bicocca, Milan (Italy); Bucci, C.; Cappelli, L.; D' Addabbo, A.; Di Vacri, M.L.; Gorla, P.; Pattavina, L.; Pirro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Canonica, L. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Massachusetts Institute of Technology, Cambridge, MA (United States); Cao, X.G.; Fang, D.Q.; Ma, Y.G.; Wang, H.W.; Zhang, G.Q. [Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai (China); Copello, S.; Di Domizio, S.; Fernandes, G.; Marini, L.; Pallavicini, M. [INFN-Sezione di Genova, Genova (Italy); Universita di Genova, Dipartimento di Fisica, Genova (Italy); Cushman, J.S.; Davis, C.J.; Heeger, K.M.; Lim, K.E.; Maruyama, R.H. [Yale University, Department of Physics, New Haven, CT (United States); Dafinei, I.; Morganti, S.; Mosteiro, P.J.; Orio, F.; Pettinacci, V.; Tomei, C.; Vignati, M. [INFN-Sezione di Roma, Rome (Italy); Dell' Oro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); INFN-Gran Sasso Science Institute, L' Aquila (Italy); Feintzeig, J.; Fujikawa, B.K.; Mei, Y.; Smith, A.R. [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Franceschi, M.A.; Ligi, C.; Napolitano, T.; Piperno, G. [INFN-Laboratori Nazionali di Frascati, Frascati, Rome (Italy); Giuliani, A.; Tenconi, M. [Universite Paris-Saclay, CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Orsay (France); Gladstone, L.; Leder, A.; Winslow, L.A. [Massachusetts Institute of Technology, Cambridge, MA (United States); Gutierrez, T.D. [California Polytechnic State University, Physics Department, San Luis Obispo, CA (United States); Haller, E.E. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); University of California, Department of Materials Science and Engineering, Berkeley, CA (United States); Han, K. [Yale University, Department of Physics, New Haven, CT (United States); Shanghai Jiao Tong University, Department of Physics and Astronomy, Shanghai (China); Hansen, E. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Kadel, R. [Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Kolomensky, Yu.G. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Martinez, M. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Universidad de Zaragoza, Laboratorio de Fisica Nuclear y Astroparticulas, Zaragoza (Spain); Moggi, N. [INFN-Sezione di Bologna, Bologna (Italy); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Scienze per la Qualita della Vita, Bologna (Italy); Nones, C. [Service de Physique des Particules, CEA/Saclay, Gif-sur-Yvette (France); Norman, E.B.; Wang, B.S. [Lawrence Livermore National Laboratory, Livermore, CA (United States); University of California, Department of Nuclear Engineering, Berkeley, CA (United States); Ouellet, J.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Pagliarone, C.E. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita degli Studi di Cassino e del Lazio Meridionale, Dipartimento di Ingegneria Civile e Meccanica, Cassino (Italy); Sangiorgio, S.; Scielzo, N.D. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Santone, D. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita dell' Aquila, Dipartimento di Scienze Fisiche e Chimiche, L' Aquila (Italy); Singh, V. [University of California, Department of Physics, Berkeley, CA (US); Taffarello, L. [INFN-Sezione di Padova, Padova (IT); Wise, T. [Yale University, Department of Physics, New Haven, CT (US); University of Wisconsin, Department of Physics, Madison, WI (US); Woodcraft, A. [University of Edinburgh, SUPA, Institute for Astronomy, Edinburgh (GB); Zimmermann, S. [Lawrence Berkeley National Laboratory, Engineering Division, Berkeley, CA (US); Zucchelli, S. [INFN-Sezione di Bologna, Bologna (IT); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Fisica e Astronomia, Bologna (IT)

2017-01-15

We report on the measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO{sub 2}, the half-life is determined to be T{sub 1/2}{sup 2ν} = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] x 10{sup 20} year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the {sup 130}Te neutrinoless double-beta decay region of interest. (orig.)

Alteration of cell cycle progression by Sindbis virus infection

Energy Technology Data Exchange (ETDEWEB)

Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

2015-07-10

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

Alteration of cell cycle progression by Sindbis virus infection

International Nuclear Information System (INIS)

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

2015-01-01

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G 1 phase preferred to proliferate during S/G 2 phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G 1 phase than in cells infected during S/G 2 phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases

Experiments and Cycling at the LHC Prototype Half-Cell

Science.gov (United States)

Saban, R.; Casas-Cubillos, J.; Coull, L.; Cruikshank, P.; Dahlerup-Petersen, K.; Hilbert, B.; Krainz, G.; Kos, N.; Lebrun, P.; Momal, F.; Misiaen, D.; Parma, V.; Poncet, A.; Riddone, G.; Rijllart, A.; Rodriguez-Mateos, F.; Schmidt, R.; Serio, L.; Wallen, E.; van Weelderen, R.; Williams, L. R.

1997-05-01

The first version of the LHC prototype half-cell has been in operation since February 1995. It consists of one quadrupole and three 10-m twin aperture dipole magnets which operate at 1.8 K. This experimental set-up has been used to observe and study phenomena which appear when the systems are assembled in one unit and influence one another. The 18-month long experimental program has validated the cryogenic system and yielded a number of results on cryogenic instrumentation, magnet protection and vacuum in particular under non-standard operating conditions. The program was recently complemented by the cycling experiment: it consisted in powering the magnets following the ramp rates which will be experienced by the magnets during an LHC injection. In order to simulate 10 years of routine operation of LHC, more than 2000 1-hour cycles were performed interleaved with provoked quenches. The objective of this experiment was to reveal eventual flaws in the design of components. The prototype half-cell performed to expectations showing no sign of failure of fatigue of components for more than 2000 cycles until one of the dipoles started exhibiting an erratic quench behavior.

Measurement of the two neutrino double beta decay half-life of Zr-96 with the NEMO-3 detector

Energy Technology Data Exchange (ETDEWEB)

Argyriades, J. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Arnold, R. [IPHC, Universite de Strasbourg, CNRS/IN2P3, F-67037 Strasbourg (France); Augier, C. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Baker, J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Barabash, A.S. [ITEP, Institute of Theoretical and Experimental Physics, 117259 Moscow (Russian Federation); Basharina-Freshville, A. [University College London, WC1E 6BT London (United Kingdom); Bongrand, M. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Broudin-Bay, G. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Brudanin, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Caffrey, A.J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Chapon, A. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Chauveau, E. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Daraktchieva, Z. [University College London, WC1E 6BT London (United Kingdom); Durand, D. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Egorov, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Fatemi-Ghomi, N. [University of Manchester, M13 9PL Manchester (United Kingdom); Flack, R. [University College London, WC1E 6BT London (United Kingdom); Guillon, B. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Hubert, Ph. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Jullian, S. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France)

2010-12-08

Using 9.4 g of {sup 96}Zr isotope and 1221 days of data from the NEMO-3 detector corresponding to 0.031 kg y, the obtained 2{nu}{beta}{beta} decay half-life measurement is T{sub 1/2}{sup 2{nu}=}[2.35{+-}0.14(stat){+-}0.16(syst)]x10{sup 19} yr. Different characteristics of the final state electrons have been studied, such as the energy sum, individual electron energy, and angular distribution. The 2{nu} nuclear matrix element is extracted using the measured 2{nu}{beta}{beta} half-life and is M{sup 2{nu}=}0.049{+-}0.002. Constraints on 0{nu}{beta}{beta} decay have also been set.

Biological half-life of radiophosphorus in desert locust, Schistocerca gregaria Forskal (orthoptera:acrididae)

International Nuclear Information System (INIS)

Ulagaraj, S.M.; Singh, K.M.; Sethi, G.R.

1975-01-01

Adult desert locust, Schistocerca gregaria Forskal were fed with cabbage leaves, painted with carrier free 32 P 1mCi/ml. Radioactivity of five adults of both sexes and of feces was measured daily for 28 days. The amount of radioactivity appearing in the feces of males was consistently below that found in female locusts. The mean biological half-life of 32 P for males and females were 35.04 and 15.01 days, respectively. (author)

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

Directory of Open Access Journals (Sweden)

Sebastian Hannemann

2017-07-01

Full Text Available Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

Dynamic half-rate connections in GSM

NARCIS (Netherlands)

Winands, E.M.M.; Wieland, J.; Sanders, B.

2006-01-01

Dynamic half-rate is an optional feature that allows a Global System for Mobile communication (GSM) cell to switch new incoming half-rate capable calls to half-rate speech coding, when the cell is nearly congested. Since two half-rate speech calls can be put together in one single-time slot, dynamic

A new value for the half-life of {sup 10}Be by Heavy-Ion Elastic Recoil Detection and liquid scintillation counting

Energy Technology Data Exchange (ETDEWEB)

Korschinek, G., E-mail: Gunther.Korschinek@ph.tum.d [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Bergmaier, A. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Faestermann, T. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Gerstmann, U.C. [Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Radiation Protection, Ingolstaedter Landstr. 1, D-85764 Neuherberg (Germany); Knie, K.; Rugel, G. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Wallner, A. [VERA Laboratory, Faculty of Physics, University of Vienna, Waehringer Strasse 17, A-1090 Wien (Austria); Dillmann, I. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Dollinger, G. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Lierse von Gostomski, Ch. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany); Kossert, K. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Maiti, M.; Poutivtsev, M. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Remmert, A. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany)

2010-01-15

The importance of {sup 10}Be in different applications of accelerator mass spectrometry (AMS) is well-known. In this context the half-life of {sup 10}Be has a crucial impact, and an accurate and precise determination of the half-life is a prerequisite for many of the applications of {sup 10}Be in cosmic-ray and earth science research. Recently, the value of the {sup 10}Be half-life has been the centre of much debate. In order to overcome uncertainties inherent in previous determinations, we introduced a new method of high accuracy and precision. An aliquot of our highly enriched {sup 10}Be master solution was serially diluted with increasing well-known masses of {sup 9}Be. We then determined the initial {sup 10}Be concentration by least square fit to the series of measurements of the resultant {sup 10}Be/{sup 9}Be ratio. In order to minimize uncertainties because of mass bias which plague other low-energy mass spectrometric methods, we used for the first time Heavy-Ion Elastic Recoil Detection (HI-ERD) for the determination of the {sup 10}Be/{sup 9}Be isotopic ratios, a technique which does not suffer from difficult to control mass fractionation. The specific activity of the master solution was measured by means of accurate liquid scintillation counting (LSC). The resultant combination of the {sup 10}Be concentration and activity yields a {sup 10}Be half-life of T{sub 1/2} = 1.388 +- 0.018 (1 s, 1.30%) Ma. In a parallel but independent study (Chmeleff et al. ), found a value of 1.386 +- 0.016 (1.15%) Ma. Our recommended weighted mean and mean standard error for the new value for {sup 10}Be half-life based on these two independent measurements is 1.387 +- 0.012 (0.87%) Ma.

Effect of Leishmania spp infection on the survival, life expectancy, fecundity and fertility of Lutzomyia longipalpiss.l. and Lutzomyia pseudolongipalpis

Directory of Open Access Journals (Sweden)

Irma Fatima Agrela

2015-08-01

Full Text Available We evaluated the effects of Leishmaniaspp infection on several population parameters of Lutzomyia longipalpis sensu lato andLutzomyia pseudolongipalpis, vectors of visceral leishmaniasis in Venezuela, under experimental conditions during the first post-feeding period. Females of both species were allowed to feed and engorge on a suspension of fresh washed human red blood cells in foetal calf serum. These blood cells were either non-infected or infected with one of the fourLeishmaniaspp strains and were offered through a chicken skin membrane. The longevity, life expectancy and the fecundity of uninfected flies were similar in both species, but the fertility was significantly lower in uninfected Lu. longipalpis females. In all cases, the infection of Lu. longipalpis and Lu. pseudolongipalpis by the Leishmaniastrains resulted in significant detrimental effects, which exerted a fitness cost expressed by reduced survival and life expectancy, as well as decreased fertility and fecundity compared with the control groups. Nevertheless, differences in these parameters were observed between these vector species depending on whether they were infected with the autochthonous Venezuelan Leishmania infantum strain (NESA or the Brazilian reference strain (PP75. The experimental data obtained agree with field data on the natural infection of these vector species and the significance of this scenario is discussed.

Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

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W David Wick

Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.

Science.gov (United States)

Zhang, Jie; Liu, Huan; Wei, Bin

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1.

Vitamin E plasma kinetics in swine show low bioavailability and short half-life of -α-tocopheryl acetate.

Science.gov (United States)

van Kempen, T A T G; Reijersen, M H; de Bruijn, C; De Smet, S; Michiels, J; Traber, M G; Lauridsen, C

2016-10-01

Vitamin E is important for animal production because of its effects on health and product quality, but the amount and form required remains controversial. Our objective was to quantify the absolute bioavailability of oral -α-tocopheryl acetate (α-TAc) in swine (22 ± 1 kg and 8 wk old, fitted with jugular catheters) adapted to a diet supplemented with 75 mg/kg -α-TAc; 75 mg/kg was chosen because this level represents the nonweighted average inclusion level in piglet diets across Western key swine-producing countries. For this, a 350-g test meal (6% fat) was supplied at time 0 containing 75 mg deuterated (D9) -α-TAc to 9 animals, and 8 animals received an intravenous () dose containing deuterated (D6) RRR-α-tocopherol (α-T) at one-eighth the oral dose and a test meal without supplemental vitamin E. Plasma samples (12 to 13 per animal) were obtained at incremental intervals over 75 h for analysis of deuterated α-T using liquid chromatography-tandem mass spectrometry. Surprisingly, the i.v. dose rapidly disappeared from plasma and then reappeared. The half-life for this first peak was only 1.7 ± 0.3 min. The second peak had an appearance rate (Ka) of 0.10 ± 0.06 d and a half-life of 5.9 ± 1.2 h. Oral dosing resulted, after a lag of 56 min, in a Ka of 0.91 ± 0.21 d and a half-life of 2.6 ± 0.8 h. The bioavailability for oral α-TAc was 12.5%, whereas the area under the curve was only 5.4%. This low bioavailability, small area under the curve, and short half-life are likely because of various factors, that is, the use of only 6% fat in the diet, the use of the acetate ester and , and the high dose relative to requirements. In conclusion, i.v. dosed vitamin E shows both a rapid and a very slow pool, whereas orally dosed vitamin E shows a single slow pool. The oral material has a very short half-live (44% of i.v. or 2.6 h), low bioavailability (12.5%), and a very small area under the curve (5.4%), bringing into question the efficacy of typical doses of vitamin

Measurement of the half-life of sup 1 sup 7 sup 6 Lu

CERN Document Server

Nir-El, Y

1998-01-01

The half-life of sup 1 sup 7 sup 6 Lu was determined by measuring the disintegration rate of a solution of lutetium oxide, using a calibrated HPGe detector, and found to be (3.69+-0.02)x10 sup 1 sup 0 y. It is recommended that the current adopted value be calculated from the grouping of three published values since 1983, including our value, the weighted mean of which is (3.73+-0.01)x10 sup 1 sup 0 y.

Dendritic cells in dengue virus infection: Targets of virus replication and mediators of immunity

Directory of Open Access Journals (Sweden)

Michael A. Schmid

2014-12-01

Full Text Available Dendritic cells (DCs are sentinels of the immune system and detect pathogens at sites of entry, such as the skin. In addition to the ability of DCs to control infections directly via their innate immune functions, DCs help to prime adaptive B and T cell responses via antigen presentation in lymphoid tissues. Infected Aedes aegypti or Ae. albopictus mosquitoes transmit the four dengue virus (DENV serotypes to humans while probing for small blood vessels in the skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet no vaccine or specific therapeutic is currently approved. Although primary DENV infection confers life-long protective immunity against re-infection with the same DENV serotype, secondary infection with a different DENV serotype can lead to increased disease severity via cross-reactive T cells or enhancing antibodies. This review summarizes recent findings in humans and animal models about DENV infection of DCs, monocytes and macrophages. We discuss the dual role of DCs as both targets of DENV replication and mediators of innate and adaptive immunity, and summarize immune evasion strategies whereby DENV impairs the function of infected DCs. We suggest that DCs play a key role in priming DENV-specific neutralizing or potentially harmful memory B and T cell responses, and that future DC-directed therapies may help induce protective memory responses and reduce dengue pathogenesis.

Biological half-life of iodine in adults with intact thyroid function and in athyreotic persons

Energy Technology Data Exchange (ETDEWEB)

Kramer, G.H.; Hauck, B.M.; Chamberlain, M.J

2002-07-01

A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of {sup 131}I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of {sup 131}I following its medical administration. The average biological half-life of {sup 131}I in 26 euthyroid subjects was found to be 66.1{+-}6.3 days which may be statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2{+-}8.6 days and in three hypothyroid patients the corresponding value was 29.3{+-}8.8 days. Thyroid {sup 131}I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck arteriorly. Measured values were 0.144{+-}0.009, 0.314{+-}0.035 and 0.045{+-}0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06-0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0{+-}0.2 days and 18.4{+-}1.1. days. (author)

Analytical studies by activation. Part A and B: Counting of short half-life radio-nuclides. Part C: Analytical programs for decay curves

International Nuclear Information System (INIS)

Junod, E.

1966-03-01

Part A and B: Since a radio-nuclide of short half-life is characterized essentially by the decrease in its activity even while it is being measured, the report begins by recalling the basic relationships linking the half-life the counting time, the counting rate and the number of particles recorded. The second part is devoted to the problem of corrections for counting losses due to the idle period of multichannel analyzers. Exact correction formulae have been drawn up for the case where the short half-life radionuclide is pure or contains only a long half-life radio-nuclide. By comparison, charts have been drawn up showing the approximations given by the so-called 'active time' counting and by the counting involving the real time associated with a measurement of the overall idle period, this latter method proving to be more valid than the former. A method is given for reducing the case of a complex mixture to that of a two-component mixture. Part C: The problems connected with the qualitative and quantitative analysis of the decay curves of a mixture of radioactive sources of which one at least has a short half-life are presented. A mathematical description is given of six basic processes for which some elements of Fortran programs are proposed. Two supplementary programs are drawn up for giving an overall treatment of problems of dosage in activation analysis: one on the basis of a simultaneous irradiation of the sample and of one or several known samples, the other with separate irradiation of the unknown and known samples, a dosimeter (activation, or external) being used for normalizing the irradiation flux conditions. (author) [fr

Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

LENUS (Irish Health Repository)

Ryan, Ruth CM

2011-10-24

Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3\\/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.

Chemical characterization of solid polymer electrolyte membrane surfaces in LiFePO4 half-cells

Science.gov (United States)

Kyu, Thein; He, Ruixuan; Peng, Fang; Dunn, William E.; Kyu's Group Team, Dr.

High temperature (60 °C) capacity retention of succinonitrile plasticized solid polymer electrolyte membrane (PEM) in a LiFePO4 half-cell was investigated with or without lithium bis(oxalato)borate (LiBOB) modification. Various symmetric cells and half-cells were studied under different thermal and electrochemical conditions. At room temperature cycling, the unmodified PEM in the half-cell appeared stable up to 50 cycles tested. Upon cycling at 60 °C, the capacity decays rapidly and concurrently the cell resistance increased. The chemical compositions of the solid PEM surfaces on both cathode and anode sides were analyzed. New IR bands (including those belonged to amide) were discerned on the unmodified PEM surface of the Li electrode side at 60 °C suggestive of side reaction, but no new bands develop during room temperature cycling. To our astonishment, the side reaction was effectively suppressed upon LiBOB addition (0.4 wt%) into the PEM, contributing to increased high temperature capacity retention at 60°C. Plausible mechanisms of capacity fading and improved cycling performance due to LiBOB modification are discussed.

Mechanisms by Which Interleukin-12 Corrects Defective NK Cell Anticryptococcal Activity in HIV-Infected Patients

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Stephen K. Kyei

2016-08-01

Full Text Available Cryptococcus neoformans is a pathogenic yeast and a leading cause of life-threatening meningitis in AIDS patients. Natural killer (NK cells are important immune effector cells that directly recognize and kill C. neoformans via a perforin-dependent cytotoxic mechanism. We previously showed that NK cells from HIV-infected patients have aberrant anticryptococcal killing and that interleukin-12 (IL-12 restores the activity at least partially through restoration of NKp30. However, the mechanisms causing this defect or how IL-12 restores the function was unknown. By examining the sequential steps in NK cell killing of Cryptococcus, we found that NK cells from HIV-infected patients had defective binding of NK cells to C. neoformans. Moreover, those NK cells that bound to C. neoformans failed to polarize perforin-containing granules to the microbial synapse compared to healthy controls, suggesting that binding was insufficient to restore a defect in perforin polarization. We also identified lower expression of intracellular perforin and defective perforin release from NK cells of HIV-infected patients in response to C. neoformans. Importantly, treatment of NK cells from HIV-infected patients with IL-12 reversed the multiple defects in binding, granule polarization, perforin content, and perforin release and restored anticryptococcal activity. Thus, there are multiple defects in the cytolytic machinery of NK cells from HIV-infected patients, which cumulatively result in defective NK cell anticryptococcal activity, and each of these defects can be reversed with IL-12.

A helium venting model for a SSC half cell

International Nuclear Information System (INIS)

Carcagno, R.H.; McAshan, M.S.; Schiesser, W.E.

1991-01-01

When a Superconducting Super Collider (SSC) dipole magnet quenches, the quench protection system will intentionally quench other magnets in the half cell. The result is that the stored energy of all of these quenched magnets will be absorbed equally among them. These simultaneous quenches produce heat, which diffuses from the magnet coils to the main helium (He) coolant channels and thereby eventually causes an increase in the He pressure. When the quench is detected, vent valves open to minimize the He pressure increase and thus prevent damage to the magnets. The performance of the He venting system has been modeled and simulated to establish whether the venting will take place as required. The model consists of partial differential equation energy balances written radially for the magnet coils, collar, and yoke; and ordinary differential equations of energy and mass balance written for the He in the magnets and relief header. The basic algorithm is the numerical method of lines, with finite difference approximation of the spatial derivatives, and time integration by LSODES. Simulation results are presented for an SSC half cell of the Accelerator Systems String Test (ASST) facility. The results are also compared with recent string quench measurements performed at the Fermilab String Test Facility

Coronavirus infection of polarized epithelial cells

NARCIS (Netherlands)

Rossen, J W; Horzinek, M C; Rottier, P J

1995-01-01

Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

Estimating the biological half-life for radionuclides in homoeothermic vertebrates: a simplified allometric approach

Energy Technology Data Exchange (ETDEWEB)

Beresford, N.A. [Lancaster Environment Centre, NERC Centre for Ecology and Hydrology, Lancaster (United Kingdom); Vives i Batlle, J. [Belgian Nuclear Research Centre, Mol (Belgium)

2013-11-15

The application of allometric, or mass-dependent, relationships within radioecology has increased with the evolution of models to predict the exposure of organisms other than man. Allometry presents a method of addressing the lack of empirical data on radionuclide transfer and metabolism for the many radionuclide-species combinations which may need to be considered. However, sufficient data across a range of species with different masses are required to establish allometric relationships and this is not always available. Here, an alternative allometric approach to predict the biological half-life of radionuclides in homoeothermic vertebrates which does not require such data is derived. Biological half-life values are predicted for four radionuclides and compared to available data for a range of species. All predictions were within a factor of five of the observed values when the model was parameterised appropriate to the feeding strategy of each species. This is an encouraging level of agreement given that the allometric models are intended to provide broad approximations rather than exact values. However, reasons why some radionuclides deviate from what would be anticipated from Kleiber's law need to be determined to allow a more complete exploitation of the potential of allometric extrapolation within radioecological models. (orig.)

Polypeptide synthesis in alphavirus-infected aedes albopictus cells during the establishment of persistent infection

International Nuclear Information System (INIS)

Richardson, M.A.; Boulton, R.W.; Raghow, R.S.; Dalgarno, L.

1980-01-01

Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cells, RRV reached peak titres at 34-48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and <5 per cent of cells assayed as infected. There was not shutdown of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s).The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persistently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK cells host protein synthesis was severely inhibited and by 9-11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity. (author)

Glucagon-like Peptide 1 Conjugated to Recombinant Human Serum Albumin Variants with Modified Neonatal Fc Receptor Binding Properties. Impact on Molecular Structure and Half-Life

DEFF Research Database (Denmark)

Bukrinski, Jens T.; Sønderby, Pernille; Antunes, Filipa

2017-01-01

Glucagon-like peptide 1 (GLP-1) is a small incretin hormone stimulated by food intake, resulting in an amplification of the insulin response. Though interesting as a drug candidate for the treatment of type 2 diabetes mellitus, its short plasma half-life of less than 3 minutes limits its clinical...... use. A strategy to extend the half-life of GLP-1 utilizes the long half-life of human serum albumin (HSA) by combining the two via chemical conjugation or genetic fusion. HSA has a plasma half-life of around 21 days owing to its interaction with the neonatal Fc receptor (FcRn) expressed in endothelial...... with the available structural information on the FcRn and GLP-1 receptor (GLP-1R) obtained from X-ray crystallography, we can explain the observed in-vitro and in-vivo behaviour. We conclude that the conjugation of GLP-1 to rHSA does not affect the interaction between rHSA and FcRn, while the observed decrease...

HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

Directory of Open Access Journals (Sweden)

Mikaël Boullé

2016-11-01

Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

Brucella abortus-infected B cells induce osteoclastogenesis.

Science.gov (United States)

Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

2016-09-01

Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Development of a time-variable nuclear pulser for half life measurements

International Nuclear Information System (INIS)

Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.; Genezini, Frederico A.

2013-01-01

In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decay constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.

Development of a time-variable nuclear pulser for half life measurements

Energy Technology Data Exchange (ETDEWEB)

Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.; Genezini, Frederico A. [Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP. P.O. Box 11049, Sao Paulo, 05422-970 (Brazil)

2013-05-06

In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decay constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.

Comprehensive Evaluation of Streptococcus sanguinis Cell Wall-Anchored Proteins in Early Infective Endocarditis▿ †

OpenAIRE

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L.; Wu, Hui; Kitten, Todd

2009-01-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) a...

Residual stresses and strength of multilayer tape cast solid oxide fuel and electrolysis half-cells

DEFF Research Database (Denmark)

Charlas, Benoit; Frandsen, Henrik Lund; Brodersen, Karen

2015-01-01

those with 3 layers (MTC3: without barrier layer). The bending strength of MTC3 and MTC4 under various loading orientations (electrolyte on the tensile or compressive side of the loading) is compared. The analysis, by taking residual stresses into account, shows that the strength of the half...... coefficient (TEC) mismatch between the layers, cumulated from high temperature, induces significant residual stresses in the half-cells. Furthermore, it has been observed that MTC half-cells with 4 layers (MTC4: support, fuel electrode, electrolyte and barrier layer) are sometimes more fragile to handle than...... stresses, especially in the outer barrier-layer, possible changes to the layer properties are discussed and some optimization guidelines proposed....

Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets

NARCIS (Netherlands)

Ji, Peng; Schachtschneider, Kyle M.; Schook, Lawrence B.; Walker, Frederick R.; Johnson, Rodney W.

2016-01-01

Although poorly understood, early-life infection is predicted to affect brain microglial cells, making them hypersensitive to subsequent stimuli. To investigate this, we assessed gene expression in hippocampal tissue obtained from a previously published study reporting increased microglial cell

Proteomics analysis of BHK-21 cells infected with a fixed strain of rabies virus.

Science.gov (United States)

Zandi, Fatemeh; Eslami, Naser; Soheili, Masoomeh; Fayaz, Ahmad; Gholami, Alireza; Vaziri, Behrouz

2009-05-01

Rabies is a neurotropic virus that causes a life threatening acute viral encephalitis. The complex relationship of rabies virus (RV) with the host leads to its replication and spreading toward the neural network, where viral pathogenic effects appeared as neuronal dysfunction. In order to better understand the molecular basis of this relationship, a proteomics study on baby hamster kidney cells infected with challenge virus standard strain of RV was performed. This cell line is an in vitro model for rabies infection and is commonly used for viral seed preparation. The direct effect of the virus on cellular protein machinery was investigated by 2-DE proteome mapping of infected versus control cells followed by LC-MS/MS identification. This analysis revealed significant changes in expression of 14 proteins, seven of these proteins were viral and the remaining were host proteins with different known functions: cytoskeletal (capping protein, vimentin), anti-oxidative stress (superoxide dismutase), regulatory (Stathmin), and protein synthesis (P0). Despite of limited changes appeared upon rabies infection, they present a set of interesting biochemical pathways for further investigation on viral-host interaction.

Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

Energy Technology Data Exchange (ETDEWEB)

Tilden, A.B.; Cauda, R.; Grossi, C.E.; Balch, C.M.; Lakeman, A.D.; Whitley, R.J.

1986-06-01

Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

Analysis of existing data and specification of an experiment to determine the 252Cf half-life to the required degree of accuracy

International Nuclear Information System (INIS)

Lorenz, A.; Kharitonov, I.A.

1994-02-01

The methods used and the results obtained in measurements of the 252 Cf half-life are analyzed. In calculating the weighted mean value, additional error components as well as those given by the authors are taken into account. In order to reduce the error in the weighted mean value to less than 0.1%, the need and the requirements for an exact measurement are specified. A half-life of 2.6473±0.0028 years is recommended. (author). 16 refs, 3 tabs

Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

International Nuclear Information System (INIS)

Oliveira, P. A.; Santos, J. A. M.

2014-01-01

Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as 99m Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a careful analysis of the methodology, for the case of 99m Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using 99m Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for 99m Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides

Study of the Bs meson and measurement of its half-life with the ALEPH detector

International Nuclear Information System (INIS)

Duarte, H.

1994-01-01

The B s 0 meson is the bound state of a quark anti-quark pair made up of a beauty particle and a strange particle. In the first chapter we review different experimental results leading to the existence of B S 0 meson and we draw the theoretical framework of the concept of beauty particles. The second chapter deals with the probability of the formation of a meson containing a strange quark during the fragmentation. This chapter also contains a re-analysis of the whole data constraining the mixing parameter B s 0 -B s 0 -bar. The relevancy of the analysis relies on the assumption that the B s 0 meson decays only into one D s , one lepton and one neutrino. The ALEPH detector is described in chapter 3, this four-pi, multi-particle detector is installed on the e + e - LEP (Large Electron Positron Collider). The signature selected for the measurement of the half-life is the combination of one D s in the decay modes: φπ, K *0 K with a lepton having opposite charge. This measurement implies the knowledge of the B s 0 momentum and of its flight length. In order to assess the momentum of the neutrino, a technique of measuring missing energy is presented in the chapter 4. The selection of B s 0 events is detailed in the chapter 5. A cutting limit on the energy of B s 0 based on the missing energy is used to deduce the production rate of B s 0 . In the chapter 6 we present the measurement of the half-life of B s 0 , the method used for the reconstruction of decay vertices and of the event main vertex is detailed. The validity of the method has been tested on Monte-Carlo simulations. The final result concerning the measurement of the half-life is: τ(B s )=[1.92(+0.45-0.35)±0.04] ps [fr

Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans.

Science.gov (United States)

Yaginuma-Sakurai, Kozue; Murata, Katsuyuki; Iwai-Shimada, Miyuki; Nakai, Kunihiko; Kurokawa, Naoyuki; Tatsuta, Nozomi; Satoh, Hiroshi

2012-02-01

The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.

Mast cells in viral infections

Directory of Open Access Journals (Sweden)

Piotr Witczak

2012-04-01

Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

Science.gov (United States)

Beckman, D. A.; Evans, J. W.; Oyama, J.

1979-01-01

The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

Preservative Monitoring of a Greek Woman with Hydrops Fetalis due to Parvovirus B19 Infection

Directory of Open Access Journals (Sweden)

Zacharias Fasoulakis

2017-01-01

Full Text Available Primate erythroparvovirus 1 (parvovirus B19 is a member of the Erythrovirus genus of the Parvoviridae family and it is one of the few members of the family known to be pathogenic in human. B19 infection is common and widespread with the virus being associated with numerous rheumatologic and haematologic manifestations. More specifically, maternal infection with parvovirus B19 during pregnancy can cause severe anemia which may lead to nonimmune hydrops or fetal demise, as a result of fetal erythroid progenitor cells infection with shortened half-life of erythrocytes. We present a rare case reported in the Greek population, of subclinical transient reticulocytopenia due to B19 parvovirus infection, in an asymptomatic pregnant woman, without medical history of hemoglobinopathy, and with the presence of hydrops fetalis during the third trimester of her pregnancy.

Goiania radiation accident: 30 years - a half-life for a whole life..

International Nuclear Information System (INIS)

Reis, R.G.; Lucena, E.A.; Arantes, R.R.; Silva, A.A.; Reis, A.A.

2017-01-01

The radiological accident in Goiânia, Brazil, considered the largest urban radiological accident in the world, generated several publications in the technical area that are widely disseminated in the scientific literature, given the importance of the lessons learned. However, in a simple conversation with people who worked on that accident, it is noted that many reports have not been recorded. In this year in which 30 years of the event is completed, it will be of great value to record personal testimonies that are not in technical or scientific books. And what can we tell after a half-life that lasted for a lifetime? The lived stories, the situations, the improvisations, the way to solve, the overcoming, the human side, the emotions, happy or sad, short or long, funny or not. The objective of this work is to preserve, maintain and divulge reports and situations experienced by people who worked on the radiological accident with Cs-137 in Goiânia. Audio or video recordings about experiences lived in Goiânia by people who worked in that emergency situation were carried out. The reports are free and the form of registration is always at the discretion of the narrator. Storing records allows to preserve, maintain, and disclose the accident to other generations

Premenopausal women with recurrent urinary tract infections have lower quality of life.

Science.gov (United States)

Ennis, Siobhan S; Guo, Huifang; Raman, Lata; Tambyah, Paul A; Chen, Swaine L; Tiong, Ho Yee

2018-05-22

To examine the impact on quality of life of recurrent acute uncomplicated urinary tract infection among premenopausal Singaporean women, and to determine the risk factors for lower quality of life among these patients. A total of 85 patients with recurrent acute uncomplicated urinary tract infection who were referred to the Urology Department at the National University Hospital, Singapore, were prospectively recruited over a 3-year period to complete the validated Short Form 36 Health Survey version 1. In addition, demographic and clinical details including symptomology and medical history were analyzed for factors impacting quality of life. Short Form 36 Health Survey version 1 results were compared with published population norms. After adjusting for age, gender and race, recurrent acute uncomplicated urinary tract infection patients had significantly lower quality of life on seven out of eight Short Form 36 Health Survey version 1 domains when compared with age-, gender- and race-adjusted population norms for Singapore. Among those with recurrent acute uncomplicated urinary tract infection, those who also reported caffeine consumption had significantly lower Short Form 36 Health Survey version 1 scores than those who did not. Those who reported chronic constipation also had consistently lower Short Form 36 Health Survey version 1 scores across all domains. Recurrent acute uncomplicated urinary tract infection has a negative impact on the quality of life of premenopausal, otherwise healthy women. Recurrent acute uncomplicated urinary tract infection patients who also have chronic constipation or consume caffeine have lower quality of life than those who do not. More studies are required to understand the relationships between these common problems and risk factors. © 2018 The Japanese Urological Association.

Thirty years after Chernobyl: Long-term determination of 137Cs effective half-life in the lichen Stereocaulon vesuvianum.

Science.gov (United States)

Savino, F; Pugliese, M; Quarto, M; Adamo, P; Loffredo, F; De Cicco, F; Roca, V

2017-06-01

It has been widely shown that nuclear fallout includes substances, which accumulate in organisms such as crustaceans, fish, mushrooms and lichens, helping to evaluate the activity concentration of contaminants accumulated on a long time. In this context, radiocaesium deposited in soil following the Chernobyl accident on 26 April 1986 is known to have remained persistently available for plant uptake in many areas of Europe. Studies on the lichen Stereocaulon vesuvianum show the plant's high capacity to retain radionuclides from the substrate and the air. After the Chernobyl accident, starting from September 1986, at the Radioactivity Laboratory (LaRa) of the University of Naples Federico II, four monitoring campaigns to evaluate the activity concentration of four isotopes of the two elements caesium and ruthenium ( 134 Cs, 137 Cs, 103 Ru and 106 Ru) were carried out until 1999. This study allowed the effective half-life of 134 Cs and 137 Cs to be estimated. Twenty-eight years after the accident, in December 2014, a further sampling was carried out; only 137 Cs was revealed beyond the detection limits, measuring activity concentrations ranging from 20 to 40 Bq/kg, while the other radionuclides were no longer observed due to their shorter half-life. The last sampling allowed more precise determination of the effective half-life of 137 Cs (6.2 ± 0.1 year), due to the larger dataset on a large time period. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

Directory of Open Access Journals (Sweden)

Dina Tsukrov

2016-09-01

Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

Preliminary measurements of the 87Rb half-life by means of the needle counter

International Nuclear Information System (INIS)

Zastawny, A.; Rabsztyn, B.

1989-01-01

In order to test the detector and to obtain the experience before starting the exact measurements, the measurements of 87 Rb half-life have been made. RbNO 3 produced by Merck was used to prepare the samples. The samples were prepared by evaporation of RbNO 3 water solution on an aluminium foil of 2,9 mg/cm 2 . The water solutions were changed in the range from (3286,4±1,8) x 10 -6 to (480,85±0,3) x 10 -6 . The background of the aluminium foil was equal to (0,117±0,007) cpm. In other measurements the back-scattering effect of 87 Rb beta rays on the aluminium foil amounted to 4%, as the measurements were performed in the 2π geometry. The diameters of samples were about 10 mm. The specific radioactivities of samples were measured versus the surface changed in the range (60-320) μg/cm 2 . The extrapolated value of the half-life, corrected for the chemical purity of the compound (as declared by the manufacterer) is equal to (4,86±0,1) x 10 10 years. This value is in good agreement with commonly accepted value of 4,88 x 10 10 years and with another last measurements. 10 refs., 1 fig., 2 tabs. (author)

Mouse model for acute Epstein-Barr virus infection.

Science.gov (United States)

Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

2016-11-29

Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

Fungal cell gigantism during mammalian infection.

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Oscar Zaragoza

2010-06-01

Full Text Available The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

Fungal cell gigantism during mammalian infection.

Science.gov (United States)

Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

2010-06-17

The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

Exogenous cytokines released by spleen and Peyer's patch cells removed from mice infected with Giardia muris.

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Djamiatun, K; Faubert, G M

1998-01-01

The role that T and B lymphocytes play in the clearance of Giardia muris in the mouse model is well known, but the cytokines produced by CD4+ T cells in response to Giardia antigenic stimulation are unknown. In this study, we have determined how Giardia trophozoite antigenic crude extract and T cell mitogens can trigger the production of cytokines by Peyer's patch and spleen cells removed from infected animals. When Giardia trophozoite proteins were used to challenge the cells in vitro, IL-4, IL-5 and IFN-gamma were not detected in the culture supernatant. When the cells were challenged with Con-A, all three cytokines were released in vitro. However, the level of each cytokine released by the spleen or Peyer's patch cells varied with the latent, acute and elimination phases of the infection. The high levels of IL-4 and IL-5 released by Peyer's patch cells confirm the importance of IgA in the control of the infection. However, we propose that the relative success of G. muris in completing its life cycle in a primary infection might be due, in part, to the stimulation of a Th2-type response (IL-4, IL-5). A stronger Th1 response (IFN-gamma) may lead to a better control of the primary infection.

Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER blood-stage infection in mice initiated by the natural route of infection

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Butcher Geoffrey

2007-06-01

Full Text Available Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10 were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the

Accurate γ-ray spectrometry measurements of the half-life of 92Sr

International Nuclear Information System (INIS)

Leconte, P.; Hudelot, J.P.; Antony, M.

2008-01-01

Studies of the nuclear fuel cycle require an accurate knowledge of the energy release from the decay of radioactive nuclides produced in a reactor, including precise half-life data for the short-lived radionuclides. Moreover, short-lived fission products are crucial for fission rate distribution measurements performed in low-power facilities, such as EOLE and MINERVE of CEA Cadarache [Fougeras, P., 2005. EOLE, MINERVE and MASURCA facilities and their associated neutron experimental programs. In: 13th International Conference on Nuclear Engineering, Beijing, China, 16-20 May 2005], and their nuclear decay data need to be known to high precision. For these reasons, the half-life of 92 Sr has been measured to solve a recently observed inconsistency identified with the quoted value in the main nuclear applications libraries (including JEFF3.1): T 1/2 =2.71±0.01 h [Parsa, B., Ashari, A., Goolvard, L., Nobar, Y.M., 1971. Decay scheme of 2.71 h 92 Sr. Nucl. Phys. A 175, 629-640]. An overestimation of 4.5% has been identified in this work, based on two independent methods. Specific γ-ray spectrometry measurements on activated fissile foils have been carried out, using two HPGe detectors. Influencing factors such as net area measurements of photopeaks, pulse pile-up accuracy and dead time corrections in the presence of decaying activity are discussed. A new value has been obtained by combining eight series of measurements: T 1/2 =2.594±0.006 h. The uncertainty has been reduced by a factor of two with respect to previous evaluations. This measured value also shows good agreement with the most recent studies of T 1/2 =2.627±0.009 h [Nir-El, Y., 2003. Private Communications. Soreq Research Centre, Yavne, Israel

Intracellular Events and Cell Fate in Filovirus Infection

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Elena Ryabchikova

2011-08-01

Full Text Available Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.

Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

International Nuclear Information System (INIS)

Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2013-01-01

Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging the intrathyroidal effective half-life of radioiodine. Useful or not?

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Dunkelmann, S.; Kuenstner, H.; Nabavi, E.; Eberlein, U.; Groth, P.; Schuemichen, C. [Rostock Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin, Zentrum fuer Radiologie

2006-07-01

Aim: Evaluation of intrathyroidal kinetics of radioiodine with and without lithium as adjunct with respect to the increase in radiation dose delivered to the thyroid. Patients, methods: 267 patients in three groups were included in the study. Group I with 227 patients served as control group, Group II with 21 patients and Group III with 19 patients were distinguished by an intrathyroidal half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine were defined mathematically as balance of the thyroidal iodine intake and excretion by a two-compartment model. Results: Under therapy the maximum uptake of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective half-life as well as the product of maximum uptake x effective half-life as an equivalent of radiation dose independent of thyroid volume was lowered in the same magnitude. In Group II, the energy-dose equivalent remained constant under therapy. With adjunct lithium in Group III, the effective half-life was prolonged significantly by factor 1.61{+-}0.49 and the volume-independent energy-dose equivalent by factor 1.39{+-}0.37. No severe side effects of lithium were observed. Conclusion: Using lithium as adjunct to radio-iodine therapy increases the radiation dose delivered to the thyroid by 39% on average and nearly 30% of radioiodine activity can be saved in these patients. Lithium is recommended in patients with very short effective half-life in the diagnostic test in order to reduce the activity required and whole-body radiation dose. (orig.)

The Half Life of the 53 keV Level in {sup 197}Pt

Energy Technology Data Exchange (ETDEWEB)

Malmskog, S G

1967-02-15

The half life of the recently proposed 53 keV level in {sup 197}Pt has been measured to 18.5 {+-} 1.5 nsec using the delayed coincidence technique. This level, which is identified with the f{sub 5/2} single particle state, decays directly to the p{sub 1/2} ground state in {sup 197}Pt. The reduced E2 transition probability for this 53 keV transition has been deduced and compared with the results obtained for the corresponding transitions in other Pt, Hg, and Pb isotopes and with the theoretical predictions by Sorensen and by Wahlborn and Martinson.

First 0ν half-life limit from the Gotthard xenon time projection chamber

International Nuclear Information System (INIS)

Wong, H.T.; Boehm, F.; Fisher, P.

1991-01-01

A xenon Time Projection Chamber with an active volume of 207 liters has been built to study 0ν and 2ν double beta decay in 136 Xe. The TPC has been installed in the Gotthard Tunnel Underground Laboratory, and is currently taking data with 5 atm of xenon enriched in 62.5% 136 Xe. The first 166 hours of data are presented. Based on this data set, we deduce a half-life limit of T(0 + → 0 + ) > 6.2 x 10 21 years for the 0ν mode, at a 90% C.L. (author)

A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life

DEFF Research Database (Denmark)

Jensen, Pernille Foged; Schoch, Angela; Larraillet, Vincent

2017-01-01

The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism...... half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct...

NKT cell depletion in humans during early HIV infection.

Science.gov (United States)

Fernandez, Caroline S; Kelleher, Anthony D; Finlayson, Robert; Godfrey, Dale I; Kent, Stephen J

2014-08-01

Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.

A new simplified allometric approach for predicting the biological half-life of radionuclides in reptiles

International Nuclear Information System (INIS)

Beresford, N.A.; Wood, M.D.

2014-01-01

A major source of uncertainty in the estimation of radiation dose to wildlife is the prediction of internal radionuclide activity concentrations. Allometric (mass-dependent) relationships describing biological half-life (T 1/2b ) of radionuclides in organisms can be used to predict organism activity concentrations. The establishment of allometric expressions requires experimental data which are often lacking. An approach to predict the T 1/2b in homeothermic vertebrates has recently been proposed. In this paper we have adapted this to be applicable to reptiles. For Cs, Ra and Sr, over a mass range of 0.02–1.5 kg, resultant predictions were generally within a factor of 6 of reported values demonstrating that the approach can be used when measured T 1/2b data are lacking. However, the effect of mass on reptilian radionuclide T 1/2b is minimal. If sufficient measured data are available for a given radionuclide then it is likely that these would give a reasonable estimate of T 1/2b in any reptile species. - Highlights: • An allometric approach to predict radionuclide T 1/2b values in reptiles is derived. • Predictions are generally within a factor of six of measured values. • Radionuclide biological half-life is in-effect mass independent

In vivo Ebola virus infection leads to a strong innate response in circulating immune cells.

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Caballero, Ignacio S; Honko, Anna N; Gire, Stephen K; Winnicki, Sarah M; Melé, Marta; Gerhardinger, Chiara; Lin, Aaron E; Rinn, John L; Sabeti, Pardis C; Hensley, Lisa E; Connor, John H

2016-09-05

Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. In this study, we analyze RNA sequencing data to determine the host response to Ebola virus infection in circulating immune cells. Approximately half of the 100 genes with the strongest early increases in expression were interferon-stimulated genes, such as ISG15, OAS1, IFIT2, HERC5, MX1 and DHX58. Other highly upregulated genes included cytokines CXCL11, CCL7, IL2RA, IL2R1, IL15RA, and CSF2RB, which have not been previously reported to change during Ebola virus infection. Comparing this response in two different models of exposure (intramuscular and aerosol) revealed a similar signature of infection. The strong innate response in the aerosol model was seen not only in circulating cells, but also in primary and secondary target tissues. Conversely, the innate immune response of vaccinated macaques was almost non-existent. This suggests that the innate response is a major aspect of the cellular response to Ebola virus infection in multiple tissues. Ebola virus causes a severe infection in humans that is associated with high mortality. The host immune response to virus infection is thought to be an important aspect leading to severe pathology, but the components of this overactive response are not well characterized. Here, we analyzed how circulating immune cells respond to the virus and found that there is a strong innate response dependent on active virus replication. This finding is in stark contrast to in vitro evidence showing a suppression of innate immune signaling, and it suggests that the strong innate response we observe in infected animals may be an important contributor to pathogenesis.

Proposal of a new model for dose calculation due to the inhalation of Ru-222, Ru-220 and their sons with brief half-life

International Nuclear Information System (INIS)

Mauricio, C.L.P.

1982-06-01

The consequences of the radiation interactions upon the human body are studied. In order to simulate by computer the radiation interaction of the atoms of radon and thoron atoms and their Sons with a brief half life inhaled with the cells, the compartimental dosimetric model is used. The metabolic pathway of those radionuclides is described by continuous medium dynamic differential equation. The energy transfer processes are seen in details. The individual retention function is determined by bio-analysis. The results of internal dosimetry are consistents with the new international recommendations from ICRP-32. (L.F.S.) [pt

On the way to high-power linear proton accelerator for the long half-life radionuclides transmutation

International Nuclear Information System (INIS)

Batskikh, G.I.; Lupandin, O.S.; Murin, B.P.; Fedotov, A.P.

1991-01-01

The concept of continuous mode high-power linear proton accelerator with 1.5 GeV energy, 0.3 A current for the long half-life nuclides transmutation into the short ones (waste of atomic power plants (APP)) is proposed. The accelerator design main principles, scheme and parameters are presented. The accent is made on the accelerator efficiency, reliability and radiation purity. (author)

Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection

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Adam J. Pelzek

2018-03-01

Full Text Available Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5% of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.

Cyclophilin Inhibitors Remodel the Endoplasmic Reticulum of HCV-Infected Cells in a Unique Pattern Rendering Cells Impervious to a Reinfection.

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Udayan Chatterji

Full Text Available The mechanisms of action by which cyclophilin inhibitors (CypI interfere with the HCV life cycle remain poorly understood. We reported that CypI and NS5A inhibitors (NS5Ai, but not other classes of anti-HCV agents, prevent assembly of double membrane vesicles (DMVs, which protect replication complexes. We demonstrated that both NS5A and the isomerase cyclophilin A (CypA are required for DMV formation. Here, we examined whether CypI mediate an additional antiviral effect that could further explain the high efficacy of CypI. We identified a unique action of CypI. CypI remodel the organization of the endoplasmic reticulum (ER of HCV-infected cells, but not of uninfected cells. This effect is specific since it was not observed for other classes of anti-HCV agents including NS5Ai, and has no effect on the viability of CypI-treated cells. Since ER serves as platform for the establishment of HCV replication complexes, we asked whether the ER reorganization by CypI would prevent cells from being newly infected. Remarkably, CypI-treated HCV-pre-infected cells remain totally impervious to a reinfection, suggesting that the CypI-mediated ER reorganization prevents a reinfection. This block is not due to residual CypI since CypI-resistant HCV variants also fail to infect these cells. The ER reorganization by CypI is rapid and reversible. This study provides the first evidence that CypI trigger a unique ER reorganization of infected cells, rendering cells transiently impervious to a reinfection. This study further suggests that the HCV-induced ER rearrangement represents a key target for the development of new therapies.

Older siblings, pets and early life infections: impact on gut microbiota and allergy prevalence during the first three years of life

DEFF Research Database (Denmark)

Laursen, Martin Frederik; Zachariassen, Gitte; Bahl, Martin Iain

Background: Early life infections and presence of older siblings or pets in the household are factors known to affect the risk of developing allergic diseases, and this effect is suggested to be mediated by interactions between microbes and the immune system. However, very limited research has been...... done on the effect of these factors on the developing gut microbiota in infants. Thus, we aimed to elucidate associations between older siblings, pets and early life infections, the microbial gut communities at 9 and 18 months of age and the prevalence of allergies in three year old children. Methods...... of respiratory allergy, eczema and presence of older siblings, pets and early life infections, previously collected through interviews with parents, were compared to the obtained data on bacterial taxonomy. Results: Early life infections were positively associated with the risk of developing respiratory allergy...

Alemtuzumab-induced elimination of HIV-1-infected immune cells.

Science.gov (United States)

Ruxrungtham, Kiat; Sirivichayakul, Sunee; Buranapraditkun, Supranee; Krause, Werner

2016-01-01

Currently, there is no drug known that is able to eradicate either HIV or HIV-infected host cells. The effectiveness of all available treatments is based on the prevention of viral replication. We investigated whether the monoclonal, CD52 receptor-targeting antibody, alemtuzumab, which is currently approved for the treatment of multiple sclerosis, is able to eliminate HIV-infected immune cells. In blood samples from healthy donors and from HIV-1-infected subjects who were either treatment-naïve or resistant to HAART, we studied whether the CD52 expression on T cells and their subsets (CD3, CD4, CD8), B cells (CD19), dendritic cells (CD123) and monocytes (CD11c) is retained in HIV-1 infection and whether alemtuzumab is able to eradicate infected cells, using four-colour flow cytometry. We found that CD52 expression on immune cells is retained in HIV-1 infection regardless of CD4 cell count, viral load and treatment status, and is amenable to alemtuzumab-induced depletion. For the first time it could be shown in vitro that HIV-1-infected immune cells can be eliminated by using the monoclonal antibody alemtuzumab.

Nipah virus infection and glycoprotein targeting in endothelial cells

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Maisner Andrea

2010-11-01

Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

Science.gov (United States)

Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon

2016-01-01

The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion. Copyright © 2015 Elsevier B.V. All rights reserved.

Stem Cell Transplant Patients and Fungal Infections

Science.gov (United States)

... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

International Nuclear Information System (INIS)

Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

2004-01-01

Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

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Gazzinelli R.T.

1998-01-01

Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Methodology for assessing the probability of corrosion in concrete structures on the basis of half-cell potential and concrete resistivity measurements.

Science.gov (United States)

Sadowski, Lukasz

2013-01-01

In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpose. However, it is generally accepted that it should be supplemented with other techniques. Hence, a methodology for assessing the probability of corrosion in concrete slabs by means of a combination of two methods, that is, the half-cell potential method and the concrete resistivity method, is proposed. An assessment of the probability of corrosion in reinforced concrete structures carried out using the proposed methodology is presented. 200 mm thick 750 mm  ×  750 mm reinforced concrete slab specimens were investigated. Potential E corr and concrete resistivity ρ in each point of the applied grid were measured. The experimental results indicate that the proposed methodology can be successfully used to assess the probability of corrosion in concrete structures.

Methodology for Assessing the Probability of Corrosion in Concrete Structures on the Basis of Half-Cell Potential and Concrete Resistivity Measurements

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Lukasz Sadowski

2013-01-01

Full Text Available In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpose. However, it is generally accepted that it should be supplemented with other techniques. Hence, a methodology for assessing the probability of corrosion in concrete slabs by means of a combination of two methods, that is, the half-cell potential method and the concrete resistivity method, is proposed. An assessment of the probability of corrosion in reinforced concrete structures carried out using the proposed methodology is presented. 200 mm thick 750 mm  ×  750 mm reinforced concrete slab specimens were investigated. Potential Ecorr and concrete resistivity ρ in each point of the applied grid were measured. The experimental results indicate that the proposed methodology can be successfully used to assess the probability of corrosion in concrete structures.

Precision half-life determination of a mirror β transition: The decay of 31S

International Nuclear Information System (INIS)

Bacquias, A.; Kurtukian-Nieto, T.; Ascher, P.; Audirac, L.; Blank, B.; Giovinazzo, J.; Aeystoe, J.; Elomaa, V.V.; Eronen, T.; Hakala, J.; Jokinen, A.; Kankainen, A.; Karvonen, P.; Kolhinen, V.S.; Moore, I.D.; Rahaman, S.; Reponen, M.; Rissanen, J.; Saastamoinen, A.; Souin, J.

2012-01-01

The half-life of the mirror β decay of 31 S has been measured at the IGISOL facility at the University of Jyvaeskylae. The value obtained is T 1/2 ( 31 S)=(2553.4±1.8) ms, in agreement with previous measurements, but with a precision that is better by a factor of ten than the literature value previously adopted. When the new result is combined with the Q EC value measured recently at JYFLTRAP, a precision of better than 10 -3 is obtained for the ft value. (orig.)

Diffusion of single Au, Ag and Cu atoms inside Si(111)-(7 × 7) half unit cells: A comparative study

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Liu, Qin [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Department of Physics, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong (China); Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang, Sichuan 621908 (China); Fu, Qiang [Institut für Physik and IRIS Adlershof, Humboldt-Universität zu Berlin, Zum Großen Windkanal 6, 12489 Berlin (Germany); Shao, Xiji; Ma, Xuhang; Wu, Xuefeng [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Wang, Kedong, E-mail: wangkd@sustc.edu.cn [Department of Physics, Southern University of Science and Technology, Shenzhen, Guangdong 518055 (China); Xiao, Xudong, E-mail: xdxiao@phy.cuhk.edu.hk [Department of Physics, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong (China)

2017-04-15

Highlights: • Diffusions of Au, Ag and Cu atoms in the half unit cells of Si(111)-(7×7) have been studied by using a STM-based I-t method. • Despite their similar absorption sites, the diffusion dynamics show obvious differences between Ag and the other two. • Theoretical calculations suggest that different potential energy profiles are responsible for the observed differences. - Abstract: The diffusion behaviors of single Au, Ag and Cu atoms on Si(111)-(7 × 7) half unit cells have been investigated via combining scanning tunneling microscopy and first-principles calculations. Despite the similar adsorption sites between both half unit cells among these elements, the diffusion dynamics show obvious differences between Ag and the other two. Although obvious asymmetry has been found in the diffusion behaviors of Au and Cu atoms in two half unit cells of Si(111)-(7 × 7), the asymmetry behaves in a way different from that of Ag atoms and no dual-time character has been observed for the diffusions of Au and Cu in both half unit cells. Theoretical calculations suggest a different potential energy profile caused by the stronger hybridization between d states of Au (Cu) and Si states make the concept of basin useless for the diffusion of Au and Cu atoms inside the half unit cells of Si(111)-(7 × 7).

Host responses in life-history traits and tolerance to virus infection in Arabidopsis thaliana.

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Israel Pagán

2008-08-01

Full Text Available Knowing how hosts respond to parasite infection is paramount in understanding the effects of parasites on host populations and hence host-parasite co-evolution. Modification of life-history traits in response to parasitism has received less attention than other defence strategies. Life-history theory predicts that parasitised hosts will increase reproductive effort and accelerate reproduction. However, empirical analyses of these predictions are few and mostly limited to animal-parasite systems. We have analysed life-history trait responses in 18 accessions of Arabidopsis thaliana infected at two different developmental stages with three strains of Cucumber mosaic virus (CMV. Accessions were divided into two groups according to allometric relationships; these groups differed also in their tolerance to CMV infection. Life-history trait modification upon virus infection depended on the host genotype and the stage at infection. While all accessions delayed flowering, only the more tolerant allometric group modified resource allocation to increase the production of reproductive structures and progeny, and reduced the length of reproductive period. Our results are in agreement with modifications of life-history traits reported for parasitised animals and with predictions from life-history theory. Thus, we provide empirical support for the general validity of theoretical predictions. In addition, this experimental approach allowed us to quantitatively estimate the genetic determinism of life-history trait plasticity and to evaluate the role of life-history trait modification in defence against parasites, two largely unexplored issues.

A double labeling technique for performing immunocytochemistry and in situ hybridization in virus infected cell cultures and tissues

International Nuclear Information System (INIS)

Gendelman, H.E.; Moench, T.R.; Narayan, O.; Griffin, D.E.; Clements, J.E.

1985-01-01

This report describes a combined immunocytochemical and in situ hybridization procedure which allows visualization of cellular or viral antigens and viral RNA in the same cell. Cultures infected with visna or measles virus were fixed in periodate-lysine-paraformaldehyde-glutaraldehyde, stained by the avidin-biotin-peroxidase technique using antibodies to viral or cellular proteins and then incubated with radiolabeled specific DNA probes (in situ hybridization). This technique provides a new approach to the study of viral pathogenesis by: (1) identifying the types of cells which are infected in the host and (2) identifying points of blockade in the virus life cycle during persistent infections. (Auth.)

Dependence of radiocaesium biological half-life in freshwater fish on water potassium concentration and temperature

International Nuclear Information System (INIS)

Carreiro, M.C.V.; Corisco, J.A.G.

1998-01-01

Short-term experiments (35-49 days) showed that the rate of cesium elimination from fish increases with increasing potassium concentration in water (the biological half-life decreases); this, however, is only true of the potassium concentration range of 0.35 to 3.5 ppm, whereas higher potassium concentrations do not seem to affect the elimination rate. Decrease in water temperature within the 20 degC to 5 degC range slows down the cesium elimination process. (P.A.)

Relationship between isotope half-life and prostatic edema for optimal prostate dose coverage in permanent seed implants

International Nuclear Information System (INIS)

Villeneuve, Maxime; Leclerc, Ghyslain; Lessard, Etienne; Pouliot, Jean; Beaulieu, Luc

2008-01-01

The robustness of treatment planning to prostatic edema for three different isotopes ( 125 I, 103 Pd, and 131 Cs) is explored using dynamical dose calculations on 25 different clinical prostate cases. The treatment plans were made using the inverse planning by simulated annealing (IPSA) algorithm. The prescription was 144, 127, and 125 Gy for 125 I, 131 Cs, and 103 Pd, respectively. For each isotope, three dose distribution schemes were used to impose different protection levels to the urethra: V 120 =0%, V 150 =0%, and V 150 =30%. Eleven initial edema values were considered ranging from 1.0 (no edema) to 2.0 (100%). The edema was assumed to resolve exponentially with time. The prostate volume, seed positions, and seed activity were dynamically tracked to produce the final dose distribution. Edema decay half-lives of 10, 30, and 50 days were used. A total of 675 dynamical calculations were performed for each initial edema value. For the 125 I isotope, limiting the urethra V 120 to 0% leads to a prostate D 90 under 140 Gy for initial edema values above 1.5. Planning with urethra V 150 at 0% provides a good response to the edema; the prostate D 90 remains higher than 140 Gy for edema values up to 1.8 and a half-life of 30 days or less. For 103 Pd, the prostate D 90 is under 97% of the prescription dose for approximately 66%, 40%, and 30% of edema values for urethra V 120 =0%, V 150 =0%, and V 150 =30%, respectively. Similar behavior is seen for 131 Cs and the center of the prostate becomes 'cold' for almost all edema scenarios. The magnitude of the edema following prostate brachytherapy, as well as the half-life of the isotope used and that of the edema resorption, all have important impacts on the dose distribution. The 125 I isotope with its longer half-life is more robust to prostatic edema. Setting up good planning objectives can provide an adequate compromise between organ doses and robustness. This is even more important since seed misplacements will contribute

Infection of endothelial cells by common human viruses.

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Friedman, H M

1989-01-01

Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

Half-lives for selected actinides and long-lived radionuclides

International Nuclear Information System (INIS)

Holden, N.E.

1988-01-01

Long-lived actinide nuclides are of interest for their use in nuclear reactors, for nuclear reactor burnup studies in waste management, and for safeguard applications, e.g., α counting is used to determine the amount of material present. Some long-lived radionuclides are of interest for their use in determining geological ages using various dating methods, and in calculating the cosmic-ray exposure ages of meteorites. Recommended values are presented for both the total half-life and for the spontaneous fission half-life of /sup 232-236,238/U, of /sup 236,238-242,244/Pu, of /sup 241,242m,243/Am, and of /sup 242-248,250/Cm. Problems with the presentation of uncertainties are discussed. The impact of the revised 14 C half-life on the carbon dating technique and various 14 C ages is discussed. The possible primordial occurrence of 92 Nb is now definitely ruled out. Based on examination of the 26 Al half-life, the calculated value for the cosmic-ray exposure age of meteorites remains too high compared to the age calculated using other radionuclide half-life values. 204 Pb, which was once thought to be radioactive, is shown to be stable. 37 refs., 5 tabs

Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

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Sabyasachi Halder

2009-09-01

Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

Age-related patterns in human myeloid dendritic cell populations in people exposed to Schistosoma haematobium infection.

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Norman Nausch

Full Text Available Urogenital schistosomiasis is caused by the helminth parasite Schistosoma haematobium. In high transmission areas, children acquire schistosome infection early in life with infection levels peaking in early childhood and subsequently declining in late childhood. This age-related infection profile is thought to result from the gradual development of protective acquired immunity. Age-related differences in schistosome-specific humoral and cellular responses have been reported from several field studies. However there has not yet been a systematic study of the age-related changes in human dendritic cells, the drivers of T cell polarisation.Peripheral blood mononuclear cells were obtained from a cohort of 61 Zimbabwean aged 5-45 years with a S. haematobium prevalence of 47.5%. Two subsets of dendritic cells, myeloid and plasmacytoid dendritic cells (mDCs and pDCs, were analyzed by flow cytometry.In this population, schistosome infection levels peaked in the youngest age group (5-9 years, and declined in late childhood and adulthood (10+ years. The proportions of both mDCs and pDCs varied with age. However, for mDCs the age profile depended on host infection status. In the youngest age group infected people had enhanced proportions of mDCs as well as lower levels of HLA-DR on mDCs than un-infected people. In the older age groups (10-13 and 14-45 years infected people had lower proportions of mDCs compared to un-infected individuals, but no infection status-related differences were observed in their levels of HLA-DR. Moreover mDC proportions correlated with levels of schistosome-specific IgG, which can be associated with protective immunity. In contrast proportions of pDCs varied with host age, but not with infection status.Our results show that dendritic cell proportions and activation in a human population living in schistosome-endemic areas vary with host age reflecting differences in cumulative history of exposure to schistosome infection.

Platelet half-life in patients with primary hyperlipoproteinemia type IIa, IIb, and IV according to Fredrickson with and without clinical signs of atherosclerosis

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Jaeger, E; Sinzinger, H; Widhalm, K; Kaliman, J; Hoefer, R [Vienna Univ. (Austria). 2. Medizinische Klinik; Ludwig Boltzmann-Institut fuer Nuklearmedizin, Vienna (Austria); Vienna Univ. (Austria). Kinderklinik; Vienna Univ. (Austria). Kardiologische Klinik)

1982-09-01

It is generally accepted that platelet half-life is shortened in atherosclerotic vascular diseases. Concerning changes due to hyperlipoproteinemia (HLP), however, there exist only few data. Therefore, we examined the platelet-half life in 60 patients with recently discovered HLP type IIa, IIb and IV according to Fredrickson before treatment in comparison to 60 controls. 33 of the HLP-patients had no clinical symptoms of angiopathy. 27 patients suffered from peripheral vascular disease or from coronary heart disease as verified by angiography. The labelling of autologous platelets was performed with 100..mu..Ci of /sup 111/Indium-oxine-sulfate at 37/sup 0/C for 5 minutes. The mean labelling efficiency was 90%, the recovery after 2 hours about 70%. Serum lipoproteins were estimated by means of ultracentrifugation and polyanionprecipitation according to Lipid Research Clinic Methods. In the patients with HLP platelet half-life was significantly shortened in comparison to the control group (p < 0.01). These changes were most pronounced in patients with HLP-type IIa and with atherosclerotic lesions, respectively. In patients with HLP-type IIa a very close correlation could be demonstrated between platelet half-life and LDL-cholesterol (r = -0.72; p < 0.001) as well as total cholesterol (r = -0.73; p < 0.001). These data prove that in HLP in-vivo platelet function as measured by platelet survival is significantly influenced even before the occurrence of clinically relevant symptoms of atherosclerosis.

Human innate lymphoid cells (ILCs) in filarial infections.

Science.gov (United States)

Bonne-Année, S; Nutman, T B

2018-02-01

Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

Science.gov (United States)

Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

2013-01-01

The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

Rodent Plasmodium-infected red blood cells: imaging their fates and interactions within their hosts.

Science.gov (United States)

Claser, Carla; Malleret, Benoit; Peng, Kaitian; Bakocevic, Nadja; Gun, Sin Yee; Russell, Bruce; Ng, Lai Guan; Rénia, Laurent

2014-02-01

Malaria, a disease caused by the Plasmodium parasite, remains one of the most deadly infectious diseases known to mankind. The parasite has a complex life cycle, of which only the erythrocytic stage is responsible for the diverse pathologies induced during infection. To date, the disease mechanisms that underlie these pathologies are still poorly understood. In the case of infections caused by Plasmodium falciparum, the species responsible for most malaria related deaths, pathogenesis is thought to be due to the sequestration of infected red blood cells (IRBCs) in deep tissues. Other human and rodent malaria parasite species are also known to exhibit sequestration. Here, we review the different techniques that allow researchers to study how rodent malaria parasites modify their host cells, the distribution of IRBCs in vivo as well as the interactions between IRBCs and host tissues. © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Infectious mononucleosis accompanied by clonal proliferation of EBV-infected cells and infection of CD8-positive cells.

Science.gov (United States)

Arai, Ayako; Yamaguchi, Takeshi; Komatsu, Honami; Imadome, Ken-Ichi; Kurata, Morito; Nagata, Kaoru; Miura, Osamu

2014-01-01

A 22-year-old male was admitted for a sustained fever of 2 months, lymphadenopathy, and liver dysfunction. Anti-VCA-IgM antibody was positive, with elevated Epstein-Barr virus (EBV)-DNA load in the peripheral blood. Liver biopsy revealed infiltration of CD8-positive and EBV-positive cells. Most peripheral blood mononuclear cells (PBMCs) were also positive for CD8, and showed detectable levels of EBV-DNA. Monoclonal proliferation of EBV-infected cells was detected in the PBMCs by Southern blotting for EBV-terminal repeat (EBV-TR). Although EBV-positive T-cell lymphoproliferative disease (EBV-T-LPD) was suspected, the symptoms spontaneously resolved within 12 months. Anti-VCA-IgM antibody and the clonal band of EBV-TR were negative 1 year after the onset, while anti-EBNA antibody was positive. The final diagnosis was thus confirmed as infectious mononucleosis (IM). Our results indicate that EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells may be temporally detected in IM. EBV-T-LPDs should be carefully excluded in such cases.

Determination of short half-life elements in biological, foodstuff, and environmental samples qualitatively by neutron activation analysis

International Nuclear Information System (INIS)

Syukria Kurniawati; Muhayatun Santoso; Diah Dwiana Lestiani

2010-01-01

NAA applications at routine operation power of 15 MW at Multipurpose Reactor GA Siwabessy (MPR-GAS) for sample matrices analysis have been widely applied. However, the results are not optimum for some matrices especially for short half-live elements. Preliminary study of short half-life elements determination in biological, foodstuff, and environmental samples using 1 MW power have been conducted to solve this problem. The samples were irradiated in rabbit system of MPR-GAS for 5 minutes, counted for 200 seconds by HPGe detector, and the spectrum were analyzed further using software Genie 2000 and Bandung NAA Utility. Analysis under 1 MW power on biological and foodstuff samples were capable to detect eight elements: Al, Br, CI, Ca, I, K, Mg, Ti, and Na for biological samples; Al, Br, CI, Ca, I, K, Mg, Mn, and Na for foodstuff samples, while at 15 MW power only three elements (CI, K, Na) were detected. At 1 MW power the counting process is more optimum due to smaller radiation exposure and dead time. For the environmental samples, the number of elements detected by 1 MW and 15 MW powers did not differ significantly. Generally, the results on the three types of samples showed that the elements of short half-life are better detected at 1 MW than that of 15 MW power. Further research needs to be done to obtain the optimum analytical conditions for irradiation and counting time determination. (author)

Susceptibility of different leukocyte cell types to Vaccinia virus infection

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Sánchez-Puig Juana M

2004-11-01

Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

Dendritic cells during Epstein Barr virus infection

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Christian eMunz

2014-06-01

Full Text Available Epstein Barr virus (EBV causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This -herpesvirus infects primarily human B and epithelial cells, but has been reported to be sensed by dendritic cells (DCs during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV specific vaccine development will be discussed in this review.

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

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Wilke Claus O

2008-01-01

Full Text Available Abstract Background In the setting of highly active antiretroviral therapy (HAART, plasma levels of human immunodeficiency type-1 (HIV-1 rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

Science.gov (United States)

Sedaghat, Ahmad R; Siliciano, Robert F; Wilke, Claus O

2008-01-01

Background In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir. PMID:18171475

Sociodemographic aspects and quality of life of patients with sickle cell anemia

Science.gov (United States)

dos Santos, Juliana Pereira; Gomes Neto, Mansueto

2013-01-01

Background Sickle cell anemia is a chronic inherited disease, widespread in the Brazilian population due to the high degree of miscegenation in the country. Despite the high prevalence, there are few studies describing the characteristics of patients and the impact of the disease on quality of life. Objective To describe the sociodemographic profile and the impact of the disease on the quality of life of sickle cell anemia patients. Methods Over 18-year-old patients with sickle cell anemia who attended meetings held by the Associação Baiana de Portadores de Doenças Falciformes, an association for sickle cell anemia patients in Bahia, were interviewed. Sociodemographic data were collected and the generic the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) questionnaire, which is used to assess quality of life, was applied. The analysis of the descriptive statistics was performed using the Statistics Program for the Social Sciences software. Results Thirty-two mostly female (65.6%) patients were interviewed. The mean age was 31.9 ± 12.67 years, 50.0% considered themselves black, 68.8% did not work and 87.5% had per capita income below the poverty line (up to one and a half minimum wages). The SF-36 scores were: limitation by physical aspects 26.56, functional capacity 28.9, emotional aspects 30.20, social aspects, 50.0, pain 50.31, mental health 54.62, general health status 56.09 and vitality 56.71. This shows that the disease has a huge impact on the patients' quality of life. Conclusion The disease interferes in the working capacity of individuals, who mostly have low incomes and impaired access to healthcare services and significantly impacts on their quality of life. PMID:24106440

A20 (Tnfaip3 deficiency in myeloid cells protects against influenza A virus infection.

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Jonathan Maelfait

Full Text Available The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.

Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.

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Matthew D Martin

2015-10-01

Full Text Available Memory CD8 T cells confer increased protection to immune hosts upon secondary viral, bacterial, and parasitic infections. The level of protection provided depends on the numbers, quality (functional ability, and location of memory CD8 T cells present at the time of infection. While primary memory CD8 T cells can be maintained for the life of the host, the full extent of phenotypic and functional changes that occur over time after initial antigen encounter remains poorly characterized. Here we show that critical properties of circulating primary memory CD8 T cells, including location, phenotype, cytokine production, maintenance, secondary proliferation, secondary memory generation potential, and mitochondrial function change with time after infection. Interestingly, phenotypic and functional alterations in the memory population are not due solely to shifts in the ratio of effector (CD62Llo and central memory (CD62Lhi cells, but also occur within defined CD62Lhi memory CD8 T cell subsets. CD62Lhi memory cells retain the ability to efficiently produce cytokines with time after infection. However, while it is was not formally tested whether changes in CD62Lhi memory CD8 T cells over time occur in a cell intrinsic manner or are due to selective death and/or survival, the gene expression profiles of CD62Lhi memory CD8 T cells change, phenotypic heterogeneity decreases, and mitochondrial function and proliferative capacity in either a lymphopenic environment or in response to antigen re-encounter increase with time. Importantly, and in accordance with their enhanced proliferative and metabolic capabilities, protection provided against chronic LCMV clone-13 infection increases over time for both circulating memory CD8 T cell populations and for CD62Lhi memory cells. Taken together, the data in this study reveal that memory CD8 T cells continue to change with time after infection and suggest that the outcome of vaccination strategies designed to elicit

Immune regulation in Chandipura virus infection: characterization of CD4+ T regulatory cells from infected mice

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Shahir Prajakta

2011-05-01

Full Text Available Abstract Back ground Chandipura virus produces acute infection in mice. During infection drastic reduction of CD4+, CD8+ and CD19 + cell was noticed. Depletion of lymphocytes also noticed in spleen. The reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. There are several mechanisms like generation of regulatory cells, activation induced cell death (ACID etc were indicated to control the activation and maintain cellular homeostasis. Role of regulatory cells in homeostasis has been described in several viral diseases. This study was undertaken to characterize CD4+T regulatory cells from the infected mice. Method In this study we purified the CD4+ T cells from Chandipura virus infected susceptible Balb/c mice. CD4+ T regulatory cells were identified by expression of cell surface markers CD25, CD127 and CTLA-4 and intracellular markers Foxp3, IL-10 and TGF-beta. Antigen specificity and ability to suppress the proliferation of other lymphocytes were studied in vitro by purified CD4+CD25+T regulatory cells from infected mice. The proliferation was calculated by proliferation module of Flow Jo software. Expression of death receptors on regulatory cells were studied by flowcytometer. Results The CD4+ T cells isolated from infected mice expressed characteristic markers of regulatory phenotype at all post infective hours tested. The CD4+ T regulatory cells were proliferated when stimulated with Chandipura virus antigen. The regulatory cells did not suppress the proliferation of splenocytes stimulated with anti CD3 antibody when co cultured with them. Interesting observation was, while purification of CD4+ T cells by negative selection, the population of cells negative for CD4 also co purified along with CD4+ T cell. Flow cytometry analysis and light microscopy revealed that CD4 negative cells were of different size and shape (atypical compared to the normal lymphocytes. Greater percentage of

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

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Dominic Paquin-Proulx

2018-01-01

Full Text Available Dengue virus (DENV and Zika virus (ZIKV are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome. The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

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Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

2017-06-15

Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

Overexpression of Fc receptor-like 1 associated with B-cell activation during hepatitis B virus infection

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Wang, Ke [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Pei, Hao [Wuxi Hospital of Infectious Disease, Wuxi, Jiangsu Province (China); Huang, Biao; Yang, Run-Lin [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Wu, Hang-Yuan [Wuxi Hospital of Infectious Disease, Wuxi, Jiangsu Province (China); Zhu, Xue; Zhu, Lan [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China)

2012-08-17

The role of B cells in the pathogenesis of hepatitis B virus (HBV) infection has not been explored in depth. In the present study, the activation status of B cells from peripheral blood of healthy controls (N = 20) and patients with acute hepatitis B (AHB, N = 15) or chronic hepatitis B (CHB, N = 30) was evaluated by measuring the expression levels of B-cell activation markers CD69 and CD86, using quantitative real-time PCR and flow cytometry. Moreover, the potential mechanism underlying B-cell activation during HBV infection was further investigated by analyzing the expression profile of FCRL1, an intrinsic activation molecule of B cells. An elevation in the levels of B-cell activation markers including CD69 and CD86 was observed in the AHB patients (44.31 ± 9.27, 27.64 ± 9.26%) compared to CHB patients (30.35 ± 11.27, 18.41 ± 6.56%, P < 0.05), which was still higher than healthy controls (12.23 ± 7.84, 8.22 ± 3.43%, P < 0.05). Furthermore, the expression of FCRL1 was found to be similar to B-cell activation markers, which was highest in AHB patients (70.15 ± 17.11%), lowest in healthy donors (36.32 ± 9.98%, P < 0.05) and half-way between these levels in patients with CHB (55.17 ± 12.03%, P < 0.05). The results were positively associated with aberrant B-cell activation. These data suggest that B cells can play a role in HBV infection, and therefore more effort should be devoted to exploring their functions.

Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells.

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Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C; Van Duyne, Rachel; Calvert, Valerie; Petricoin, Emanuel; Saifuddin, Mohammed; Kehn-Hall, Kylene; Kashanchi, Fatah

2015-06-01

Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high-throughput proteomic assays, we have previously identified Bruton's tyrosine kinase (BTK) as a host protein that was uniquely upregulated in the plasma membrane of human immunodeficiency virus (HIV-1)-infected T cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant upregulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells; however, new BTK protein complexes were identified and distributed in both high molecular weight (∼600 kDa) and a small molecular weight complex (∼60-120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1-infected cells using small interfering RNA (siRNA) resulted in selective death of infected, but not uninfected, cells. Using BTK-specific antibody and small-molecule inhibitors including LFM-A13 and a FDA-approved compound, ibrutinib (PCI-32765), we have found that HIV-1-infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1-infected cells are sensitive to treatments targeting BTK expressed in infected cells.

Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

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Stabile, F; Barnett, C R; De Risio, L

2017-02-18

Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

Retroviral infection of non-dividing cells: Old and new perspectives

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Yamashita, Masahiro; Emerman, Michael

2006-01-01

The dependence of retroviral replication on cell proliferation was described as early as 1958, although different classes of retroviruses are able to infect non-dividing cells with different efficiencies. For example, the human immunodeficiency virus (HIV) and other lentiviruses infect most non-dividing cells nearly as well as dividing cells, while the gammaretroviruses such as the murine leukemia virus (MLV) cannot infect non-dividing cells, and other retroviruses have intermediate phenotypes. One exception to the ability of HIV to infect non-dividing cells involves resting CD4+ T cells in vitro where there are multiple restrictions. However, recent data show that there is massive infection of non-activated CD4+ T cell during acute infection which suggests that the situation is different in vivo. Finally, much work trying to explain the difference between HIV and MLV in non-dividing cells has focused on describing the ability of HIV to enter the nucleus during interphase. However, we suggest that events in the viral lifecycle other than nuclear import may be more important in determining the ability of a given retrovirus to infect non-dividing cells

T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

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Pallikkuth, Suresh; de Armas, Lesley; Rinaldi, Stefano; Pahwa, Savita

2017-01-01

T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals.

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Manuela Fogli

2008-07-01

Full Text Available Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research. In vitro studies have shown that natural killer (NK cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cell blasts exogenously infected with several strains of HIV-1. However, it is not known whether the deleterious effects of high HIV-1 viremia interferes with the NK cell-mediated cytolysis of autologous, endogenously HIV-1-infected CD4+ T cells. Here, we stimulate primary CD4+ T cells, purified ex vivo from HIV-1-infected viremic patients, with PHA and rIL2 (with or without rIL-7. This experimental procedure allows for the significant expansion and isolation of endogenously infected CD4+ T cell blasts detected by intracellular staining of p24 HIV-1 core antigen. We show that, subsequent to the selective down-modulation of MHC class-I (MHC-I molecules, HIV-1-infected p24(pos blasts become partially susceptible to lysis by rIL-2-activated NK cells, while uninfected p24(neg blasts are spared from killing. This NK cell-mediated killing occurs mainly through the NKG2D activation pathway. However, the degree of NK cell cytolytic activity against autologous, endogenously HIV-1-infected CD4+ T cell blasts that down-modulate HLA-A and -B alleles and against heterologous MHC-I(neg cell lines is particularly low. This phenomenon is associated with the defective surface expression and engagement of natural cytotoxicity receptors (NCRs and with the high frequency of the anergic CD56(neg/CD16(pos subsets of highly dysfunctional NK cells from HIV-1-infected viremic patients. Collectively, our data demonstrate that the chronic viral replication of HIV-1 in infected individuals results in several phenotypic and functional aberrancies that interfere with the NK cell-mediated killing of autologous p24(pos blasts derived from primary T cells.

Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

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Stephen H-F Macdonald

Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

Mycoplasma agalactiae Induces Cytopathic Effects in Infected Cells Cultured In Vitro.

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Shrilakshmi Hegde

Full Text Available Mycoplasma agalactiae is the etiological agent of the contagious agalactia syndrome in sheep and goats and causes significant economic losses worldwide. Yet the mechanism of pathogenesis is largely unknown. Even whole-genome sequence analysis of its pathogenic type strain did not lead to any conclusions regarding its virulence or pathogenicity factors. Although inflammation and tissue destruction at the local site of M. agalactiae infection are largely considered as effects of the host immune response, the direct effect of the agent on host cells is not completely understood. The aim of this study was to investigate the effect of M. agalactiae infection on the quality and viability of host cells in vitro. Changes in cell morphology including cell elongation, cytoplasm shrinkage and membrane blebbing were observed in infected HeLa cells. Chromatin condensation and increased caspase-3 cleavage in infected HeLa cells 48 h after infection suggests an apoptosis-like phenomenon in M. agalactiae-infected cells. In compliance with these results, decreased viability and cell lysis of M. agalactiae-infected HeLa cells was also observed. Measurement of the amount of LDH released after M. agalactiae infection revealed a time- and dose-dependent increase in HeLa cell lysis. A significant decrease in LDH released after gentamicin treatment of infected cells confirmed the major role of cytadherent M. agalactiae in inducing host cell lysis. This is the first study illustrating M. agalactiae's induction of cytopathic effects in infected HeLa cells. Further detailed investigation of infected host tissue for apoptotic markers might demonstrate the association between M. agalactiae-induced host cell lysis and the tissue destruction observed during M. agalactiae natural infection.

Good quality of life outcomes after treatment of prosthetic joint infection with debridement and prosthesis retention.

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Aboltins, Craig; Dowsey, Michelle; Peel, Trish; Lim, Wen K; Choong, Peter

2016-05-01

Patients treated for early prosthetic joint infection (PJI) with surgical debridement and prosthesis retention have a rate of successful infection eradication that is similar to patients treated with the traditional approach of prosthesis exchange. It is therefore important to consider other outcomes after prosthetic joint infection treatment that may influence management decisions, such as quality of life (QOL). Our aim was to describe infection cure rates and quality of life for patients with prosthetic joint infection treated with debridement and prosthesis retention and to determine if treatment with this approach was a risk factor for poor quality of life outcomes. Prospectively collected pre and post-arthroplasty data were available for 2,134 patients, of which PJI occurred in 41. For patients treated for prosthetic joint infection, the 2-year survival free of treatment failure was 87% (95%CI 84-89). Prosthetic joint infection cases treated with debridement and retention had a similar improvement from pre-arthroplasty to 12-months post-arthroplasty as patients without PJI in QOL according to the SF-12 survey. Prosthetic joint infection treated with debridement and retention was not a risk factor for poor quality of life on univariate or multivariate analysis. Prosthetic joint infection treated with debridement and prosthesis retention results in good cure rates and quality of life. Further studies are required that directly compare quality of life for different surgical approaches for prosthetic joint infection to better inform management decisions. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:898-902, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors.

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Dmitriy Mazurov

2010-02-01

Full Text Available We have developed an efficient method to quantify cell-to-cell infection with single-cycle, replication dependent reporter vectors. This system was used to examine the mechanisms of infection with HTLV-1 and HIV-1 vectors in lymphocyte cell lines. Effector cells transfected with reporter vector, packaging vector, and Env expression plasmid produced virus-like particles that transduced reporter gene activity into cocultured target cells with zero background. Reporter gene expression was detected exclusively in target cells and required an Env-expression plasmid and a viral packaging vector, which provided essential structural and enzymatic proteins for virus replication. Cell-cell fusion did not contribute to infection, as reporter protein was rarely detected in syncytia. Coculture of transfected Jurkat T cells and target Raji/CD4 B cells enhanced HIV-1 infection two fold and HTLV-1 infection ten thousand fold in comparison with cell-free infection of Raji/CD4 cells. Agents that interfere with actin and tubulin polymerization strongly inhibited HTLV-1 and modestly decreased HIV-1 cell-to-cell infection, an indication that cytoskeletal remodeling was more important for HTLV-1 transmission. Time course studies showed that HTLV-1 transmission occurred very rapidly after cell mixing, whereas slower kinetics of HIV-1 coculture infection implies a different mechanism of infectious transmission. HTLV-1 Tax was demonstrated to play an important role in altering cell-cell interactions that enhance virus infection and replication. Interestingly, superantigen-induced synapses between Jurkat cells and Raji/CD4 cells did not enhance infection for either HTLV-1 or HIV-1. In general, the dependence on cell-to-cell infection was determined by the virus, the effector and target cell types, and by the nature of the cell-cell interaction.

Chronic brain damage in sickle cell disease and its relation with quality of life.

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Cela, Elena; Vélez, Ana G; Aguado, Alejandra; Medín, Gabriela; Bellón, José M; Beléndez, Cristina

2016-12-16

Sickle cell anaemia causes progressive organ damage. The objective is to describe school performance of patients with sickle cell anaemia and their clinical parameters and quality of life that may have an influence. The hypothesis is that if school alterations occur without other objective data, additional factors must be present besides the disease itself. Transversal study performed in November 2015 considering analytical variables, complications and neuroradiological images of children with sickle cell anaemia, and family survey on school performance and quality of life. Median age was 6.8 years and 78% were diagnosed at birth. Sixty patients were included. School performance was altered in 51% of cases and was related to nocturnal hypoxemia. Acute stroke incidence was 6.7%. Transcranial ultrasound was abnormal in 4% of cases and magnetic resonance imaging in 16% of cases. Quality of life showed pathological findings in all areas and the low values increased proportionally in older ages. The stroke affected the physical and social sphere, and lung disease affected the physical and emotional spheres. Poor school performance affects half of the patients and it is related to nocturnal hypoxemia, although other socio-cultural factors may have an influence. Quality of life is affected in most of these cases independently of academic results. The absence of alterations in neuroimaging or the apparent lack of severe clinical parameters do not mean that quality of life and schooling are normal. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

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Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

2018-01-01

SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells

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Hansen, Erik C; Ransom, Monica; Hesselberth, Jay R; Hosmane, Nina N; Capoferri, Adam A; Bruner, Katherine M; Pollack, Ross A; Zhang, Hao; Drummond, Michael Bradley; Siliciano, Janet M; Siliciano, Robert; Stivers, James T

2016-01-01

We report that a major subpopulation of monocyte-derived macrophages (MDMs) contains high levels of dUTP, which is incorporated into HIV-1 DNA during reverse transcription (U/A pairs), resulting in pre-integration restriction and post-integration mutagenesis. After entering the nucleus, uracilated viral DNA products are degraded by the uracil base excision repair (UBER) machinery with less than 1% of the uracilated DNA successfully integrating. Although uracilated proviral DNA showed few mutations, the viral genomic RNA was highly mutated, suggesting that errors occur during transcription. Viral DNA isolated from blood monocytes and alveolar macrophages (but not T cells) of drug-suppressed HIV-infected individuals also contained abundant uracils. The presence of viral uracils in short-lived monocytes suggests their recent infection through contact with virus producing cells in a tissue reservoir. These findings reveal new elements of a viral defense mechanism involving host UBER that may be relevant to the establishment and persistence of HIV-1 infection. DOI: http://dx.doi.org/10.7554/eLife.18447.001 PMID:27644592

Life cycle-dependent cytoskeletal modifications in Plasmodium falciparum infected erythrocytes.

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Hui Shi

Full Text Available Plasmodium falciparum infection of human erythrocytes is known to result in the modification of the host cell cytoskeleton by parasite-coded proteins. However, such modifications and corresponding implications in malaria pathogenesis have not been fully explored. Here, we probed the gradual modification of infected erythrocyte cytoskeleton with advancing stages of infection using atomic force microscopy (AFM. We reported a novel strategy to derive accurate and quantitative information on the knob structures and their connections with the spectrin network by performing AFM-based imaging analysis of the cytoplasmic surface of infected erythrocytes. Significant changes on the red cell cytoskeleton were observed from the expansion of spectrin network mesh size, extension of spectrin tetramers and the decrease of spectrin abundance with advancing stages of infection. The spectrin network appeared to aggregate around knobs but also appeared sparser at non-knob areas as the parasite matured. This dramatic modification of the erythrocyte skeleton during the advancing stage of malaria infection could contribute to the loss of deformability of the infected erythrocyte.

Life cycle-dependent cytoskeletal modifications in Plasmodium falciparum infected erythrocytes.

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Shi, Hui; Liu, Zhuo; Li, Ang; Yin, Jing; Chong, Alvin G L; Tan, Kevin S W; Zhang, Yong; Lim, Chwee Teck

2013-01-01

Plasmodium falciparum infection of human erythrocytes is known to result in the modification of the host cell cytoskeleton by parasite-coded proteins. However, such modifications and corresponding implications in malaria pathogenesis have not been fully explored. Here, we probed the gradual modification of infected erythrocyte cytoskeleton with advancing stages of infection using atomic force microscopy (AFM). We reported a novel strategy to derive accurate and quantitative information on the knob structures and their connections with the spectrin network by performing AFM-based imaging analysis of the cytoplasmic surface of infected erythrocytes. Significant changes on the red cell cytoskeleton were observed from the expansion of spectrin network mesh size, extension of spectrin tetramers and the decrease of spectrin abundance with advancing stages of infection. The spectrin network appeared to aggregate around knobs but also appeared sparser at non-knob areas as the parasite matured. This dramatic modification of the erythrocyte skeleton during the advancing stage of malaria infection could contribute to the loss of deformability of the infected erythrocyte.

Direct Deposition Effect on the Distribution of Radiocesium in Persimmon Trees and the Effective Half-life

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Tagami, Keiko; Uchida, Shigeo [National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-7444 (Japan)

2014-07-01

Radiocesium ({sup 137}Cs) concentrations in persimmon tree tissues collected at Chiba, about 220 km south from Fukushima Daiichi nuclear power plant (FDNPP), were measured to obtain half-life of radiocesium in the trees. Persimmon (Diospyros kaki) is a deciduous tree and bears edible fruits in autumn. There were no leaves when the sampling area was received the radioactive fallout in March 2011 due to the FDNPP accident; the amount of {sup 137}Cs radioactivity in this area was ca. 13 kBq/m{sup 3} Both {sup 137}Cs and {sup 134}Cs were found in the newly emerged shoots of the persimmon trees collected at 26 April 2011 mainly due to foliar uptake. The concentrations were 1.1 kBq/kg-dry for {sup 137}Cs and 1.3 kBq/kg-dry for {sup 134}Cs. After that, continuous sampling of leaves, branches and fruits of the persimmon trees had been carried out for two years. Immediately after the collection, samples were transferred to our laboratory and weighed to obtain fresh weight. Leaf samples were usually separated into two portions; one portion was washed with tap water to remove dust from the surface and the other portion was not treated. For fruit samples, if it is possible, fruit flesh, peal and non-edible part were separated. All the samples were oven-dried at 80 deg. C for three days at least. Each dried sample was chopped into fine pieces, mixed well, and then transferred into plastic vessels separately. Radioactivity concentration was measured by a Ge-detecting system (Seiko EG and G Ortec) using 3000-40000 s counting intervals. By August 14, 2013, about 140 samples were collected from the trees; about 60 samples were leaves (both washed and untreated). Radiocesium concentrations in tree leaves decreased with time, and the effective half-life was about 190 d; the value was similar to those in branches (160 d for new branches, and 250 d for 1-2 y.o. branches) and fruits (250 d for fruit flesh and 230 d for peals). Thus we concluded that the half-life of radiocesium in

Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses.

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Punyadarsaniya, Darsaniya; Winter, Christine; Mork, Ann-Kathrin; Amiri, Mahdi; Naim, Hassan Y; Rautenschlein, Silke; Herrler, Georg

2015-02-01

Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl. To analyze infection of enterocytes is a challenging task as culture systems for differentiated intestinal epithelial cells are not readily available and often have a life span that is too short for infection studies. Precision-cut intestinal slices (PCIS) from chicken embryos were prepared and shown that the epithelial cells lining the lumen of the intestine are viable for up to 4 days. Using lectin staining, it was demonstrated that α2,3-linked sialic acids, the preferred receptor determinants of avian influenza viruses, are present on the apical side of the epithelial cells. Furthermore, the epithelial cells (at the tips) of the villi were shown to be susceptible to infection by an avian influenza virus of the H9N2 subtype. This culture system will be useful to analyze virus infection of intestinal epithelial cells and it should be applicable also to the intestine of other species. Copyright © 2014 Elsevier B.V. All rights reserved.

Measuring radioactive half-lives via statistical sampling in practice

Science.gov (United States)

Lorusso, G.; Collins, S. M.; Jagan, K.; Hitt, G. W.; Sadek, A. M.; Aitken-Smith, P. M.; Bridi, D.; Keightley, J. D.

2017-10-01

The statistical sampling method for the measurement of radioactive decay half-lives exhibits intriguing features such as that the half-life is approximately the median of a distribution closely resembling a Cauchy distribution. Whilst initial theoretical considerations suggested that in certain cases the method could have significant advantages, accurate measurements by statistical sampling have proven difficult, for they require an exercise in non-standard statistical analysis. As a consequence, no half-life measurement using this method has yet been reported and no comparison with traditional methods has ever been made. We used a Monte Carlo approach to address these analysis difficulties, and present the first experimental measurement of a radioisotope half-life (211Pb) by statistical sampling in good agreement with the literature recommended value. Our work also focused on the comparison between statistical sampling and exponential regression analysis, and concluded that exponential regression achieves generally the highest accuracy.

Regulation of NKT Cell Localization in Homeostasis and Infection

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Slauenwhite, Drew; Johnston, Brent

2015-01-01

Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection. PMID:26074921

Regulation of NKT Cell Localization in Homeostasis and Infection.

Science.gov (United States)

Slauenwhite, Drew; Johnston, Brent

2015-01-01

Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection.

Determination of the half-life of sup 1 sup 0 sup 5 sup m Rh

CERN Document Server

Kronenberg, A K; Weber, R; Esterlund, R A; Patzelt, P

1998-01-01

Following a fast chemical separation of Ru isotopes from a fission-product mixture, sup 1 sup 0 sup 5 sup m Rh was periodically extracted from its precursor (4.44-h sup 1 sup 0 sup 5 Ru) for measurements of its half-life. The new value for the T sub 1 sub / sub 2 of sup 1 sup 0 sup 5 sup m Rh of (43.0+-0.3) s resolves the long-standing conflict in the literature between the two earlier measured values of 45 and 30 s.

Health-related quality of life of HIV infected adults with and without Visceral Leishmaniasis in Northwest Ethiopia

OpenAIRE

Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu; Tamiru, Aschalew; Gebayehu, Abebaw

2017-01-01

Background Health-related quality of life (HRQoL) is an important outcome measure among HIV infected patients receiving antiretroviral therapy (ART). When HIV infected patients coinfected with Visceral Leishmaniasis (VL) the problem become severe because VL accelerates HIV replication and disease progression. The impact of VL on the quality of life of HIV infected patients has not been studied. In this study in Ethiopia, we compared the quality of life of HIV infected patients with and withou...

Differential pulmonic NK and NKT cell responses in Schistosoma japonicum-infected mice.

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Cha, Hefei; Qin, Wenjuan; Yang, Quan; Xie, Hongyan; Qu, Jiale; Wang, Mei; Chen, Daixiong; Wang, Fang; Dong, Nuo; Chen, Longhua; Huang, Jun

2017-02-01

Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas. Moreover, flow cytometry revealed that the percentage and number of pulmonic NK cells in S. japonicum-infected mice were significantly increased (P cell number of NKT cells were decreased compared to those of normal mice (P NKT cells was increased after infection (P NKT cells (P cells (P NKT cells significantly increased (P NKT cells (P NKT cell activation during S. japonicum infection.

NK cell-like behavior of Valpha14i NK T cells during MCMV infection.

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Johnna D Wesley

2008-07-01

Full Text Available Immunity to the murine cytomegalovirus (MCMV is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Valpha14 invariant natural killer T cell response to MCMV has not been examined. We found that Valpha14i NK T cells become activated and produce significant levels of IFN-gamma, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Valpha14i NK T cells into MCMV-infected CD1d(-/- mice demonstrate that CD1d is dispensable for Valpha14i NK T cell activation. In contrast, both IFN-alpha/beta and IL-12 are required for optimal activation. Valpha14i NK T cell-derived IFN-gamma is partially dependent on IFN-alpha/beta but highly dependent on IL-12. Valpha14i NK T cells contribute to the immune response to MCMV and amplify NK cell-derived IFN-gamma. Importantly, mortality is increased in CD1d(-/- mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Valpha14i NK T cells that act as effector T cells during bacterial infection, but have NK cell-like behavior during the innate immune response to MCMV infection.

Effects of interferon on cultured cells persistently infected with viruses

Energy Technology Data Exchange (ETDEWEB)

Crespi, M

1986-01-01

The role of interferon (IFN) in viral persistence at the cellular level was investigated. Two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, C11 cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. The aim of this work was to determine what effect IFN had in these infections in terms of its antiviral and antiproliferative effects; which of the two major IFN-induced pathways, E enzyme or protein kinase were induced; whether there were any differences in sensitivity to IFN between the DNA and RNA virus persistent infections. The anti-viral effect of IFN was examined by its ability to inhibit Sindbis virus replication using a radioimmunoassay system. The antiproliferative effect of IFN was determined by cell counting and /sup 3/H-thymidine incorporation. The activation of the ribonuclease F, determined by the inhibition of /sup 3/H-leucine incorporation after introduction of 2-5 actin into the cells, was variable, being activated in all cell lines with the exception of the PLC/PRF/5, Hep 3B and Hep G2 cells. Major differences between the two DNA persistent infections and the two RNA persistent infections were found. No correlation was found between the presence of HBV or SV40 persistent infections and the sensitivity of the cell lines to IFN. Both the SSPE and Sendai virus persistent infections were resistant to the antiviral and antiproliferative effect of IFN.

Defective Natural Killer cell antiviral capacity in paediatric HBV infection

DEFF Research Database (Denmark)

Heiberg, Ida Louise; Laura J., Pallett; Winther, Thilde Nordmann

2015-01-01

Natural Killer (NK) cells exhibit dysregulated effector function in adult chronic HBV infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK...... cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell IFN-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells...

Invariant NKT cells: regulation and function during viral infection.

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Jennifer A Juno

Full Text Available Natural killer T cells (NKT cells represent a subset of T lymphocytes that express natural killer (NK cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT, express a highly restricted T cell receptor (TCR and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

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Leonardo D'Aiuto

Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

Least square method of estimation of ecological half-lives of radionuclides in sediments

International Nuclear Information System (INIS)

Ranade, A.K.; Pandey, M.; Datta, D.; Ravi, P.M.

2012-01-01

Long term behavior of radionuclides in the environment is an important issue for estimating probable radiological consequences and associated risks. It is also useful for evaluating potential use of contaminated areas and the possible effectiveness of remediation activities. The long term behavior is quantified by means of ecological half life, a parameter that aggregates all processes except radioactive decay which causes a decrease of activity in a specific medium. The process involved in ecological half life depends upon the environmental condition of the medium involved. A fitting model based on least square regression approach was used to evaluate the ecological half life. This least square method has to run several times to evaluate the number of ecological half lives present in the medium for the radionuclide. The case study data considered here is for 137 Cs in Mumbai Harbour Bay. The study shows the trend of 137 Cs over the years at a location in Mumbai Harbour Bay. First iteration model illustrate the ecological half life as 4.94 y and subsequently it passes through a number of runs for more number of ecological half-life present by goodness of fit test. The paper presents a methodology for evaluating ecological half life and exemplifies it with a case study of 137 Cs. (author)

Biological half-life and distribution of radiocesium in a contaminated population of green treefrogs Hyla cinerea

International Nuclear Information System (INIS)

Dapson, R.W.; Kaplan, L.

1975-01-01

Radiocesium content of adult male green treefrogs Hyla cinerea from a contaminated habitat is adequately described by a log normal distribution with mean 2.277 log 10 pCi g -1 dry wt (189.2 pCi g -1 ) and variance of 0.031. There was significant negative correlation of body burden with body length and weight (p 2 = 0.10). Biological half-life of radiocesium in unfed, captive frogs held at 20 deg - 30 deg C averaged 30.1 d. (author)

Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

Science.gov (United States)

Katri, Patricia; Ruan, Shigui

2004-11-01

Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

Detection of bacteriophage-infected cells of Lactococcus lactis using flow cytometry

DEFF Research Database (Denmark)

Michelsen, Ole; Cuesta-Dominguez, Álvaro; Albrektsen, Bjarne

2007-01-01

Bacteriophage infection in dairy fermentation constitutes a serious problem worldwide. We have studied bacteriophage infection in Lactococcus lactis by using the flow cytometer. The first effect of the infection of the bacterium is a change from cells in chains toward single cells. We interpret...... describe a new method for detection of phage infection in Lactococcus lactis dairy cultures. The method is based on flow cytometric detection of cells with low-density cell walls. The method allows fast and early detection of phage-infected bacteria, independently of which phage has infected the culture...

Role of Bruton’s Tyrosine Kinase inhibitors in HIV-1 infected cells

Science.gov (United States)

Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C; Van Duyne, Rachel; Calvert, Valerie; Petricoin, Emanuel; Saifuddin, Mohammed; Kehn-Hall, Kylene; Kashanchi, Fatah

2015-01-01

Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high throughput proteomic assays, we have previously identified Bruton’s tyrosine kinase (BTK) as a host protein that was uniquely up-regulated in the plasma membrane of HIV-1 infected T-cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant up-regulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells, however new BTK protein complexes were identified and distributed in both high molecular weight (~600 kDa) and a small molecular weight complex (~60–120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1 infected cells using siRNA resulted in selective death of infected, but not uninfected, cells. Using BTK specific antibody and small molecule inhibitors including LFM-A13 and a FDA approved compound, Ibrutinib (PCI – 32765), we have found that HIV-1 infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1 infected cells are sensitive to treatments targeting BTK expressed in infected cells. PMID:25672887

The homeostasis of Plasmodium falciparum-infected red blood cells.

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Jakob M A Mauritz

2009-04-01

Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

Uranium half-lives: a critical review

International Nuclear Information System (INIS)

Holden, N.E.

1981-01-01

The experimental data are evaluated and values for the spontaneous fission half-life of 238 U and the total half-lives for 232 U, 233 U, 234 U, 235 U, 236 U, and 238 U are recommended. Also the variation of the isotopic abundance of 234 U in nature and the error involved in the assumption of secular equilibrium between 234 U and 238 U in the determination of the specific activity of natural uranium samples are discussed. The recommended half-life values and 95% confidence limits are: 238 U spontaneous fission: 8.09 +- 0.26 x 10 15 years; 232 U total: 69.8 +- 1.0 years; 233 U total: 1.592 +- 0.002 x 10 5 years; 234 U total: 2.454 +- 0.006 x 10 5 years; 235 U total: 7.037 +- 0.011 x 10 8 years; 236 U total: 2.342 +- 0.003 x 10 7 years 238 U total: 4.468 +- 0.005 x 10 9 years

T-cell-dependent control of acute Giardia lamblia infections in mice.

Science.gov (United States)

Singer, S M; Nash, T E

2000-01-01

We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.

Natural Killer Cell Function and Dysfunction in Hepatitis C Virus Infection

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Kayla A. Holder

2014-01-01

Full Text Available Viruses must continually adapt against dynamic innate and adaptive responses of the host immune system to establish chronic infection. Only a small minority (~20% of those exposed to hepatitis C virus (HCV spontaneously clear infection, leaving approximately 200 million people worldwide chronically infected with HCV. A number of recent research studies suggest that establishment and maintenance of chronic HCV infection involve natural killer (NK cell dysfunction. This relationship is illustrated in vitro by disruption of typical NK cell responses including both cell-mediated cytotoxicity and cytokine production. Expression of a number of activating NK cell receptors in vivo is also affected in chronic HCV infection. Thus, direct in vivo and in vitro evidence of compromised NK function in chronic HCV infection in conjunction with significant epidemiological associations between the outcome of HCV infection and certain combinations of NK cell regulatory receptor and class I human histocompatibility linked antigen (HLA genotypes indicate that NK cells are important in the immune response against HCV infection. In this review, we highlight evidence suggesting that selective impairment of NK cell activity is related to establishment of chronic HCV infection.

Past Life and Future Effects—How Heterologous Infections Alter Immunity to Influenza Viruses

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Aisha Souquette

2018-05-01

Full Text Available Influenza virus frequently mutates due to its error-prone polymerase. This feature contributes to influenza virus’s ability to evade pre-existing immunity, leading to annual epidemics and periodic pandemics. T cell memory plays a key protective role in the face of an antigenically distinct influenza virus strain because T cell targets are often derived from conserved internal proteins, whereas humoral immunity targets are often sites of increased mutation rates that are tolerated by the virus. Most studies of influenza T cell memory are conducted in naive, specific pathogen free mice and do not account for repetitive influenza infection throughout a lifetime, sequential acute heterologous infections between influenza infections, or heterologous chronic co-infections. By contrast to these mouse models, humans often experience numerous influenza infections, encounter heterologous acute infections between influenza infections, and are infected with at least one chronic virus. In this review, we discuss recent advances in understanding the effects of heterologous infections on the establishment and maintenance of CD8+ T cell immunological memory. Understanding the various factors that affect immune memory can provide insights into the development of more effective vaccines and increase reproducibility of translational studies between animal models and clinical results.

Electron Microscopy of Ebola Virus-Infected Cells.

Science.gov (United States)

Noda, Takeshi

2017-01-01

Ebola virus (EBOV) replicates in host cells, where both viral and cellular components show morphological changes during the process of viral replication from entry to budding. These steps in the replication cycle can be studied using electron microscopy (EM), including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), which is one of the most useful methods for visualizing EBOV particles and EBOV-infected cells at the ultrastructural level. This chapter describes conventional methods for EM sample preparation of cultured cells infected with EBOV.

Human neuronal cell protein responses to Nipah virus infection

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Hassan Sharifah

2007-06-01

Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

Adrenaline-induced mobilization of T cells in HIV-infected patients

DEFF Research Database (Denmark)

Søndergaard, S R; Cozzi-Lepri, A; Ullum, H

2000-01-01

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline...... infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45......RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect...

High-precision measurement of the 19Ne half-life and implications for right-handed weak currents.

Science.gov (United States)

Triambak, S; Finlay, P; Sumithrarachchi, C S; Hackman, G; Ball, G C; Garrett, P E; Svensson, C E; Cross, D S; Garnsworthy, A B; Kshetri, R; Orce, J N; Pearson, M R; Tardiff, E R; Al-Falou, H; Austin, R A E; Churchman, R; Djongolov, M K; D'Entremont, R; Kierans, C; Milovanovic, L; O'Hagan, S; Reeve, S; Sjue, S K L; Williams, S J

2012-07-27

We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

High-Precision Measurement of the Ne19 Half-Life and Implications for Right-Handed Weak Currents

Science.gov (United States)

Triambak, S.; Finlay, P.; Sumithrarachchi, C. S.; Hackman, G.; Ball, G. C.; Garrett, P. E.; Svensson, C. E.; Cross, D. S.; Garnsworthy, A. B.; Kshetri, R.; Orce, J. N.; Pearson, M. R.; Tardiff, E. R.; Al-Falou, H.; Austin, R. A. E.; Churchman, R.; Djongolov, M. K.; D'Entremont, R.; Kierans, C.; Milovanovic, L.; O'Hagan, S.; Reeve, S.; Sjue, S. K. L.; Williams, S. J.

2012-07-01

We report a precise determination of the Ne19 half-life to be T1/2=17.262±0.007s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

Genetic parameters of resistance to Vibrio aestuarianus, and OsHV-1 infections in the Pacific oyster, Crassostrea gigas, at three different life stages.

Science.gov (United States)

Azéma, Patrick; Lamy, Jean-Baptiste; Boudry, Pierre; Renault, Tristan; Travers, Marie-Agnès; Dégremont, Lionel

2017-02-15

In France, two main diseases threaten Pacific oyster production. Since 2008, Crassostrea gigas spat have suffered massive losses due to the ostreid herpesvirus OsHV-1, and since 2012, significant mortalities in commercial-size adults have been related to infection by the bacterium Vibrio aestuarianus. The genetic basis for resistance to V. aestuarianus and OsHV-1 and the nature of the genetic correlation between these two traits were investigated by using 20 half-sib sire families, each containing two full-sib families. For each disease, controlled infectious challenges were conducted using naïve oysters that were 3 to 26 months old. In addition, siblings were tested under field, pond and raceway conditions to determine whether laboratory trials reflected mortality events that occur in the oyster industry. First, we estimated the genetic basis of resistance to V. aestuarianus in C. gigas. Susceptibility to the infection was low for oysters in spat stage but increased with later life stages. Second, we confirmed a strong genetic basis of resistance to OsHV-1 infection at early stages and demonstrated that it was also strong at later stages. Most families had increased resistance to OsHV-1 infection from the spat to adult stages, while others consistently showed low or high mortality rates related to OsHV-1 infection, regardless of the life stage. Our third main finding was the absence of genetic correlations between resistance to OsHV-1 infection and resistance to V. aestuarianus infection. Selective breeding to enhance resistance to OsHV-1 infection could be achieved through selective breeding at early stages and would not affect resistance to V. aestuarianus infection. However, our results suggest that the potential to select for improved resistance to V. aestuarianus is lower. Selection for dual resistance to OsHV-1 and V. aestuarianus infection in C. gigas might reduce the impact of these two major diseases by selecting families that have the highest

The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1.

Science.gov (United States)

Lee, Jihun; Blaber, Michael

2009-10-16

Protein biopharmaceuticals are an important and growing area of human therapeutics; however, the intrinsic property of proteins to adopt alternative conformations (such as during protein unfolding and aggregation) presents numerous challenges, limiting their effective application as biopharmaceuticals. Using fibroblast growth factor-1 as model system, we describe a cooperative interaction between the intrinsic property of thermostability and the reactivity of buried free-cysteine residues that can substantially modulate protein functional half-life. A mutational strategy that combines elimination of buried free cysteines and secondary mutations that enhance thermostability to achieve a substantial gain in functional half-life is described. Furthermore, the implementation of this design strategy utilizing stabilizing mutations within the core region resulted in a mutant protein that is essentially indistinguishable from wild type as regard protein surface and solvent structure, thus minimizing the immunogenic potential of the mutations. This design strategy should be generally applicable to soluble globular proteins containing buried free-cysteine residues.

The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions.

Science.gov (United States)

Glick, Matthew; Biddle, Perry; Jantzi, Josh; Weaver, Samantha; Schirch, Doug

2014-09-12

Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported. Copyright © 2014 Elsevier Inc. All rights reserved.

Early life vaccination

DEFF Research Database (Denmark)

Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

2016-01-01

Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

Infections and endothelial cells

NARCIS (Netherlands)

Keller, Tymen T.; Mairuhu, Albert T. A.; de Kruif, Martijn D.; Klein, Saskia K.; Gerdes, Victor E. A.; ten Cate, Hugo; Brandjes, Dees P. M.; Levi, Marcel; van Gorp, Eric C. M.

2003-01-01

Systemic infection by various pathogens interacts with the endothelium and may result in altered coagulation, vasculitis and atherosclerosis. Endothelium plays a role in the initiation and regulation of both coagulation and fibrinolysis. Exposure of endothelial cells may lead to rapid activation of

Half-Life Measurements in {sup 134}l

Energy Technology Data Exchange (ETDEWEB)

Berg, V; Hoeglund, Aa

1970-07-01

Properties of levels in I following the decay of {sup 13T}e have been investigated using a Ge(Li) detector and a double lens coincidence spectrometer. 4 new transitions were found. Half-lives of the lowest excited levels were measured with the following results: T{sub 1/2} (79.5 keV) = 1.62 {+-} 10 ns; T{sub 1/2} (181.1 keV) < 100 ps; T{sub 1/2} (210.8 keV) < 150 ps.

Identification of a Monocyte Receptor on Herpesvirus-Infected Endothelial Cells

Science.gov (United States)

Etingin, Orli R.; Silverstein, Roy L.; Hajjar, David P.

1991-08-01

The adhesion of circulating blood cells to vascular endothelium may be an initial step in atherosclerosis, inflammation, and wound healing. One mechanism for promoting cell-cell adhesion involves the expression of adhesion molecules on the surface of the target cell. Herpes simplex virus infection of endothelium induces arterial injury and has been implicated in the development of human atherosclerosis. We now demonstrate that HSV-infected endothelial cells express the adhesion molecule GMP140 and that this requires cell surface expression of HSV glycoprotein C and local thrombin generation. Monocyte adhesion to HSV-infected endothelial cells was completely inhibited by anti-GMP140 antibodies but not by antibodies to other adhesion molecules such as VCAM and ELAM-1. The induction of GMP140 expression on HSV-infected endothelium may be an important pathophysiological mechanism in virus-induced cell injury and inflammation.

On the statistical evaluation of inconsistent measurement results illustrated on the example of the 90Sr half-life

International Nuclear Information System (INIS)

Zijp, W.L.

1985-12-01

The problem how to make an objective evaluation of inconsistent numerical observations made by different authors or laboratories on the same physical quantity is dealt with. The problem is treated in a practical way in the light of the example on the half-life of 90 Sr, and it is to some extent a response to a document by Gray (1985) on the same topic

Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

Directory of Open Access Journals (Sweden)

Elena Ufimtseva

2016-01-01

Full Text Available The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells.

Infection and Proliferation of Giant Viruses in Amoeba Cells.

Science.gov (United States)

Takemura, Masaharu

2016-01-01

Acanthamoeba polyphaga mimivirus, the first discovered giant virus with genome size and particle size much larger than previously discovered viruses, possesses several genes for translation and CRISPER Cas system-like defense mechanism against virophages, which co-infect amoeba cells with the giant virus and which inhibit giant virus proliferation. Mimiviruses infect amoeba cells by phagocytosis and release their DNA into amoeba cytoplasm through their stargate structure. After infection, giant virion factories (VFs) form in amoeba cytoplasm, followed by DNA replication and particle formation at peripheral regions of VF. Marseilleviruses, the smallest giant viruses, infect amoeba cells by phagocytosis or endocytosis, form larger VF than Mimivirus's VF in amoeba cytoplasm, and replicate their particles. Pandoraviruses found in 2013 have the largest genome size and particle size among all viruses ever found. Pandoraviruses infect amoeba cells by phagocytosis and release their DNA into amoeba cytoplasm through their mouth-like apical pores. The proliferation of Pandoraviruses occurs along with nucleus disruption. New virions form at the periphery of the region formerly occupied by the amoeba cell nucleus.

Potential Cellular Signatures of Viral Infections in Human Hematopoietic Cells

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J. Mikovits

2001-01-01

Full Text Available Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kapsosi’s Sarcoma -associated Virus (KSHV also known as Human Herpesvirus 8 (HHV8 and Human T cell leukemia virus-1 (HTLV-1. We performed cell-free {\\it in vitro} infection of primary bone marrow derived CD34+ cells using semi-purified HHV8 and a mature IL-2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV-1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two-fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4, cyclin B2, TBP-associated factor, eukaryotic elongation factor and pim 2 were up-regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than two-fold following chronic infection of a mature T cell line with HTLV-1. Of these, only cdc7 was up-regulated more than 3.5 fold. These data may provide insight into cellular signatures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention.

Alterations in the nuclear proteome of HIV-1 infected T-cells

International Nuclear Information System (INIS)

DeBoer, Jason; Jagadish, Teena; Haverland, Nicole A.; Madson, Christian J.; Ciborowski, Pawel; Belshan, Michael

2014-01-01

Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines

Alterations in the nuclear proteome of HIV-1 infected T-cells

Energy Technology Data Exchange (ETDEWEB)

DeBoer, Jason [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Jagadish, Teena; Haverland, Nicole A. [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Ciborowski, Pawel [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States)

2014-11-15

Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.

6K2-induced vesicles can move cell to cell during turnip mosaic virus infection

Directory of Open Access Journals (Sweden)

Romain eGrangeon

2013-12-01

Full Text Available To successfully infect plants, viruses replicate in an initially infected cell and then move to neighboring cells through plasmodesmata (PDs. However, the nature of the viral entity that crosses over the cell barrier into non-infected ones is not clear. The membrane-associated 6K2 protein of turnip mosaic virus (TuMV induces the formation of vesicles involved in the replication and intracellular movement of viral RNA. This study shows that 6K2-induced vesicles trafficked towards the plasma membrane and were associated with plasmodesmata (PD. We demonstrated also that 6K2 moved cell-to-cell into adjoining cells when plants were infected with TuMV. 6K2 was then fused to photo-activable GFP (6K2:PAGFP to visualize how 6K2 move intercellularly during TuMV infection. After activation, 6K2:PAGFP-tagged vesicles moved to the cell periphery and across the cell wall into adjacent cells. These vesicles were shown to contain the viral RNA-dependent RNA polymerase and viral RNA. Symplasmic movement of TuMV may thus be achieved in the form of a membrane-associated viral RNA complex induced by 6K2.

Microsporidia infection impacts the host cell's cycle and reduces host cell apoptosis

Science.gov (United States)

Higes, Mariano; Sagastume, Soledad; Juarranz, Ángeles; Dias-Almeida, Joyce; Budge, Giles E.; Meana, Aránzazu; Boonham, Neil

2017-01-01

Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host’s cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite’s survival within the cell. PMID:28152065

Safe extension of red blood cell storage life at 4{degree}C

Energy Technology Data Exchange (ETDEWEB)

Bitensky, M.; Yoshida, Tatsuro

1996-04-01

The project sought to develop methods to extend the storage life of red blood cells. Extended storage would allow donor to self or autologous transfusion, expand and stabilize the blood supply, reduce the cost of medical care and eliminate the risk of transfusion related infections, including a spectrum of hepatitides (A, B and C) and HIV. The putative cause of red blood cell spoilage at 4 C has been identified as oxidative membrane damage resulting from deoxyhemoglobin and its denaturation products including hemichrome, hemin and Fe{sup 3+}. Trials with carbon monoxide, which is a stabilizer of hemoglobin, have produced striking improvement of red blood cell diagnostics for cells stored at 4 C. Carbonmonoxy hemoglobin is readily converted to oxyhemoglobin by light in the presence of oxygen. These findings have generated a working model and an approach to identify the best protocols for optimal red cell storage and hemoglobin regeneration.

Ureaplasma parvum infection alters filamin a dynamics in host cells

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Brown Mary B

2011-04-01

Full Text Available Abstract Background Ureaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasmas can produce asymptomatic infections or disease characterized by an exaggerated inflammatory response. Most investigations have focused on elucidating the pathogenic potential of Ureaplasma species, but little attention has been paid to understanding the mechanisms by which these organisms are capable of establishing asymptomatic infection. Methods We employed differential proteome profiling of bladder tissues from rats experimentally infected with U. parvum in order to identify host cell processes perturbed by colonization with the microbe. Tissues were grouped into four categories: sham inoculated controls, animals that spontaneously cleared infection, asymptomatic urinary tract infection (UTI, and complicated UTI. One protein that was perturbed by infection (filamin A was used to further elucidate the mechanism of U. parvum-induced disruption in human benign prostate cells (BPH-1. BPH-1 cells were evaluated by confocal microscopy, immunoblotting and ELISA. Results Bladder tissue from animals actively colonized with U. parvum displayed significant alterations in actin binding proteins (profilin 1, vinculin, α actinin, and filamin A that regulate both actin polymerization and cell cytoskeletal function pertaining to focal adhesion formation and signal transduction (Fisher's exact test, P U. parvum perturbed the regulation of filamin A. Specifically, infected BPH-1 cells exhibited a significant increase in filamin A phosphorylated at serine2152 (P ≤ 0.01, which correlated with impaired proteolysis of the protein and its normal intracellular distribution. Conclusion Filamin A dynamics were perturbed in both models of infection. Phosphorylation of filamin A occurs in response to various cell signaling cascades that regulate cell motility, differentiation, apoptosis and inflammation. Thus, this phenomenon may be a useful

Long life nickel electrodes for a nickel-hydrogen cell: Cycle life tests

Science.gov (United States)

Lim, H. S.; Verzwyvelt, S. A.

1985-01-01

In order to develop a long life nickel electrode for a Ni/H2 cell, the cycle life of nickel electrodes was tested in Ni/H2 boiler plate cells. A 19 test cell matrix was made of various nickel electrode designs including three levels each of plaque mechanical strength, median pore size of the plaque, and active material loading. Test cells were cycled to the end of their life (0.5v) in a 45 minute low Earth orbit cycle regime at 80% depth-of-discharge. It is shown that the active material loading level affects the cycle life the most with the optimum loading at 1.6 g/cc void. Mechanical strength does not affect the cycle life noticeably in the bend strength range of 400 to 700 psi. It is found that the best plaque is made of INCO nickel powder type 287 and has median pore size of 13 micron.

Measurement of the half-life of 60Fe using the Argonne FN tandem-superconducting Linac system as an accelerator mass spectrometer

International Nuclear Information System (INIS)

Kutschera, W.; Billquist, P.J.; Frekers, D.

1983-01-01

An experiment to improve the accuracy in the half-life value of 60 Fe by measuring both the amount of 60 Fe nuclei and the decay-rate of a spallation produced sample using the relation dN/dt = -lambda N is briefly discussed

The effective and environmental half-life of 137Cs at Coral Islands at the former US nuclear test site

International Nuclear Information System (INIS)

Robison, William L.; Conrado, Cynthia L.; Bogen, Kenneth T.; Stoker, A. Carol

2003-01-01

The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 ( 137 Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of 137 Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of 137 Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of 137 Cs and 90 Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of 137 Cs and 90 Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of 137 Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the 137 Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the 137 Cs/ 90 Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the 137 Cs/ 90 Sr ratios in soil in 1987 relative to the 137 Cs/ 90 Sr ratios at the time of deposition in 1954 is less than 17 years. The magnitude of the decrease below 17 years depends on

The effective and environmental half-life of 137Cs at Coral Islands at the former US nuclear test site.

Science.gov (United States)

Robison, William L; Conrado, Cynthia L; Bogen, Kenneth T; Stoker, A Carol

2003-01-01

The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 (137Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of 137Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of 137Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of 137Cs and 90Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of 137Cs and 90Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of 137Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the 137Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the 137Cs/90Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the 137Cs/90Sr ratios in soil in 1987 relative to the 137Cs/90Sr ratios at the time of deposition in 1954 is less than 17 years. The magnitude of the decrease below 17 years depends on the ELH for 90Sr

A three-dimensional model for negative half cell of the vanadium redox flow battery

International Nuclear Information System (INIS)

Ma Xiangkun; Zhang Huamin; Xing Feng

2011-01-01

A stationary, isothermal, three-dimensional model for negative half cell of the vanadium redox flow battery is developed, which is based on the comprehensive conservation laws, such as charge, mass and momentum, together with a kinetic model for reaction involving vanadium species. The model is validated against the results calculated by the available two-dimensional model. With the given geometry of the negative half cell, the distributions of velocity, concentration, overpotential and transfer current density in the sections that are perpendicular and parallel to the applied current are studied. It is shown that the distribution of the electrolyte velocity in the electrode has significant impact on the distribution of concentration, overpotential and transfer current density. The lower velocity in the electrode will cause the higher overpotential, further result in the side reaction and corrosion of key materials locally. The development of the design of the vanadium redox flow battery is discussed, and the further research is proposed.

IL-15 STIMULATED NATURAL KILLER CELLS CLEAR HIV-1 INFECTED CELLS FOLLOWING LATENCY REVERSAL EX VIVO.

Science.gov (United States)

Garrido, Carolina; Abad-Fernandez, Maria; Tuyishime, Marina; Pollara, Justin J; Ferrari, Guido; Soriano-Sarabia, Natalia; Margolis, David M

2018-03-28

Current efforts towards HIV eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8 + T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of IL-15 treatment on NK cell function and the potential of stimulated NK cells to clear the HIV reservoir. We measured NK cell receptor expression, antibody-dependent cell-dependent cytotoxicity (ADCC), cytotoxicity, IFN-γ production and antiviral activity in autologous HIV replication systems. All NK cell functions were uniformly improved by IL-15, and more importantly, IL-15-treated NK cells were able to clear latently HIV infected cells after exposure to vorinostat, a clinically relevant latency reversing agent. We also demonstrate that NK cells from HIV infected individuals aviremic on antiretroviral therapy can be efficiently stimulated with IL-15. Our work opens a promising line of investigation towards future immunotherapies to clear persistent HIV infection using NK cells. IMPORTANCE In the search for an HIV cure, strategies to enhance immune function to allow recognition and clearance of HIV infected cells following latency reversal are being evaluated. Natural killer (NK) cells possess characteristics that can be exploited for immunotherapy against persistent HIV infection. We demonstrate that NK cells from HIV-positive donors can be strongly stimulated with IL-15, improving their antiviral and cytotoxic potential, and more importantly, clearing HIV infected cells after latency reversal with a clinically relevant drug. Our results encourage further investigation to design NK cell-based immunotherapies to achieve HIV eradication. Copyright © 2018 American Society for Microbiology.

Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

International Nuclear Information System (INIS)

Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

2005-01-01

In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

Science.gov (United States)

Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

2014-01-01

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives

International Nuclear Information System (INIS)

Chen Zhe; Nath, Ravinder

2003-01-01

Purpose: To develop a tool for evaluating interstitial seed implants that contain a mixture of radionuclides with different half-lives and to demonstrate its utility by examining the clinical implications of prescribing to an isodose surface for such an implant. Methods and Materials: A linear-quadratic model for continuous low dose rate irradiation was developed for permanent implants containing a mixture of radionuclides. Using a generalized equation for the biologically effective dose (BED), the effects of cell proliferation and sublethal damage repair were examined systematically for implants containing a mixture of radionuclides. A head-and-neck permanent seed implant that contained a mixture of 125 I and 103 Pd seeds was used to demonstrate the utility of the generalized BED. Results: An equation of BED for implants containing a mixture of radionuclides with different half-lives was obtained. In such an implant, the effective cell kill was shown to depend strongly on the relative dose contributions from each radionuclide type; dose delivered by radionuclides with shorter half-life always resulted in more cell kill for any given sublethal damage repair and cell proliferation rates. Application of the BED formula to an implant containing a mixture of 125 I and 103 Pd seeds demonstrates that the conventional dose prescription to an isodose surface is not unique for such an implant. When the prescription dose was based on existing clinical experience of using 125 I seeds alone, mixing 103 Pd seeds with 125 I seeds would increase the cell kill. On the other hand, if the prescription dose were based on existing clinical experience of using 103 Pd seeds alone, mixing 125 I seeds with 103 Pd seeds in the same implant would create radiobiologically 'cold' spots (i.e., an increase in cell survival) at locations where a major portion of the prescription dose is contributed by the 125 I seeds. For fast-growing tumors, these 'cold' spots can become significant

Molecular and clinical evaluation of the acute human parvovirus B19 infection: comparison of two cases in children with sickle cell disease and discussion of the literature

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Svetoslav Nanev Slavov

2013-02-01

Full Text Available Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.

Molecular and clinical evaluation of the acute human parvovirus B19 infection: comparison of two cases in children with sickle cell disease and discussion of the literature

Directory of Open Access Journals (Sweden)

Svetoslav Nanev Slavov

Full Text Available Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.

[Trends in participation in nonformal education in the second half of life : Increasing educational participation in retirement].

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Wiest, Maja; Hoffmann, Madlain; Widany, Sarah; Kaufmann, Katrin

2017-05-22

Research on nonformal education often focuses on participation within employment. Participation of workers decreases with age; however, recent studies show an increase in participation in nonformal education of older workers. It remains, however, unclear if this trend spills over to retirement. In the context of social change processes, trends in nonformal educational participation are analyzed. The study addresses employment and retirement as opportunity structures and investigates their impact on educational participation in the second half of life. Predictors of educational participation are modeled in logistic regression, including interaction effects. Analyses are based on cross-sectional data of the German Ageing Survey and covers 20,129 respondents aged 40-85 years (T 1 : 1996 n = 4838; T 2 : 2002 n = 3084; T 3 : 2008 n = 6205; T 4 : 2014 n = 6002). Educational level, age, gender, employment status, region, social integration, and subjective health predict participation in nonformal education for people aged 40 to 85 years. Employment as an opportunity structure has a constant impact on participation, whereas retirees' participation increases over the course of time. The increase of retirees' participation in nonformal education is discussed in the context of social change processes and connected to theoretical und empirical research gaps with regard to educational participation in the second half of life.

Clinical risk factors for life-threatening lower respiratory tract infections in children: a retrospective study in an urban city in Malaysia.

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Nathan, Anna Marie; Rani, Fairuz; Lee, Rachel Jiun Yi; Zaki, Rafdzah; Westerhout, Caroline; Sam, I-Ching; Lum, Lucy Chai See; de Bruyne, Jessie

2014-01-01

Lower respiratory tract infections (LRTIs) are an important cause of morbidity and mortality, especially in low income countries. The aim of this study was to determine risk factors of life-threatening LRTIs in hospitalised children in Malaysia. This retrospective study included children aged less than 18 years admitted for LRTIs over 13 months in a tertiary referral centre in Kuala Lumpur, Malaysia. Neonates, children with asthma and those with either no or a normal chest radiograph were excluded. Life-threatening infection was defined as that needing non-invasive ventilation or admission to the paediatric intensive care unit. Routine blood investigations and nasopharyngeal secretion results (bacterial and viral) were obtained. Chest radiographs were reviewed by a designated radiologist. Environmental data (rainfall, particulate matter ≤ 10 µm [PM10] and air pollution index [API]) was obtained from the respective government departments. Three hundred and ninety-one episodes of LRTIs were included. Viruses were implicated in 48.5% of LRTIs, with respiratory syncytial virus (RSV) being detected in 44% of viral LRTIs. Forty-six (11.8%) children had life-threatening disease and the overall mortality rate was 1.3% (5 children). RSV was detected in 26% of children with life-threatening LRTIs. In multivariate logistic regression, chronic lung disease, presenting history of apnoea and signs of hypoxia, was associated with life threatening LRTIs. Increased LRTI admissions were associated with low rainfall but not PM10 nor API. Of those on follow-up, 39% had persistent respiratory symptoms. One in nine children admitted with LRTI had a life-threatening LRTI. The aetiology was viral in almost half of admitted children. RSV was detected in a quarter of children with life-threatening LRTIs. Children who present with LRTIs and either have chronic lung disease, presenting history of apnoea or signs of hypoxia, should be observed carefully as the risk of deterioration to life

Role of Bunyamwera Orthobunyavirus NSs protein in infection of mosquito cells.

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Szemiel, Agnieszka M; Failloux, Anna-Bella; Elliott, Richard M

2012-01-01

Bunyamwera orthobunyavirus is both the prototype and study model of the Bunyaviridae family. The viral NSs protein seems to contribute to the different outcomes of infection in mammalian and mosquito cell lines. However, only limited information is available on the growth of Bunyamwera virus in cultured mosquito cells other than the Aedes albopictus C6/36 line. To determine potential functions of the NSs protein in mosquito cells, replication of wild-type virus and a recombinant NSs deletion mutant was compared in Ae. albopictus C6/36, C7-10 and U4.4 cells, and in Ae. aegypti Ae cells by monitoring N protein production and virus yields at various times post infection. Both viruses established persistent infections, with the exception of NSs deletion mutant in U4.4 cells. The NSs protein was nonessential for growth in C6/36 and C7-10 cells, but was important for productive replication in U4.4 and Ae cells. Fluorescence microscopy studies using recombinant viruses expressing green fluorescent protein allowed observation of three stages of infection, early, acute and late, during which infected cells underwent morphological changes. In the absence of NSs, these changes were less pronounced. An RNAi response efficiently reduced virus replication in U4.4 cells transfected with virus specific dsRNA, but not in C6/36 or C7/10 cells. Lastly, Ae. aegypti mosquitoes were exposed to blood-meal containing either wild-type or NSs deletion virus, and at various times post-feeding, infection and disseminated infection rates were measured. Compared to wild-type virus, infection rates by the mutant virus were lower and more variable. If the NSs deletion virus was able to establish infection, it was detected in salivary glands at 6 days post-infection, 3 days later than wild-type virus. Bunyamwera virus NSs is required for efficient replication in certain mosquito cell lines and in Ae. aegypti mosquitoes.

Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells.

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Shuid, Ahmad Naqib; Safi, Nikoo; Haghani, Amin; Mehrbod, Parvaneh; Haron, Mohd Syamsul Reza; Tan, Sheau Wei; Omar, Abdul Rahman

2015-11-01

Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p apoptosis at 12 hpi (p apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells.

Is social stress in the first half of life detrimental to later physical and mental health in both men and women?

NARCIS (Netherlands)

Steverink, N.; Veenstra, R.; Oldehinkel, A.J.; Gans, R.O.B.; Rosmalen, J.G.M.

This study examined gender differences in the associations between affection-and status-related stressors encountered in the first half of life and physical and mental health problems later on. Based on the theory of Social Production Functions (SPF) two hypotheses have been formulated, which were

TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

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Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

2017-01-15

Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope. TIM family proteins were recently found to enhance infections by many different viruses, including several members of the Flaviviridae family. However, their importance in HCV infection has not previously been examined experimentally. The TIM family proteins include three members in humans: TIM-1, TIM-3, and TIM-4. The findings derived from our studies demonstrate that TIM-1, but not TIM-3 or TIM-4, promotes HCV infection by functioning as an HCV attachment factor. Knockout of the TIM-1 gene resulted in a remarkable reduction of HCV cell attachment and infection. PS-containing liposomes blocked HCV cell attachment and subsequent HCV infection. HCV particles could also be precipitated with a PS-specific monoclonal antibody. These findings suggest that TIM-1

In vivo infection of IgG-containing cells by Jembrana disease virus during acute infection

International Nuclear Information System (INIS)

Desport, Moira; Tenaya, I.W. Masa; McLachlan, Alexander; McNab, Tegan J.; Rachmat, Judhi; Hartaningsih, Nining; Wilcox, Graham E.

2009-01-01

Jembrana disease virus (JDV) is an unusual bovine lentivirus which causes a non-follicular proliferation of lymphocytes, a transient immunosuppression and a delayed humoral response in infected Bali cattle in Indonesia. A double-immunofluorescent labeling method was developed to identify the subset of mononuclear cells in which the viral capsid protein could be detected. Viral antigen was present in pleomorphic centroblast-like cells which were identified as IgG-containing cells, including plasma cells, in lymphoid tissues. There was no evidence of infection of CD3 + T-cells or MAC387 + monocytes in tissues but large vacuolated cells with a macrophage-like morphology in the lung were found to contain viral antigen although they could not be shown conclusively to be infected. The tropism of JDV for mature IgG-containing cells may be relevant to understanding the pathogenesis of Jembrana disease, the delayed antibody responses and the genetic composition of this atypical lentivirus.

Determination of half-life of Ks0

International Nuclear Information System (INIS)

Urrutia, Z.; Felix, J.

1999-01-01

In a K s 0 high statistics sample, created in pp reactions at 27.5 GeV, we determined K s 0 mean life to be (0.893 ± 0.006) x 10 -10 s. This result agrees, inside experimental errors, with the world wide accepted value. In this paper we describe the experimental details and the used technique to measure K s 0 mean life. (Author)

Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis

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Mamo Gezahagne

2011-07-01

Full Text Available Abstract Background Dendritic cells (DCs can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.

Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

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Melisa Gorosito Serrán

2017-11-01

Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able

c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

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Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

2018-01-15

Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

Targeted sorting of single virus-infected cells of the coccolithophore Emiliania huxleyi.

Science.gov (United States)

Martínez Martínez, Joaquín; Poulton, Nicole J; Stepanauskas, Ramunas; Sieracki, Michael E; Wilson, William H

2011-01-01

Discriminating infected from healthy cells is the first step to understanding the mechanisms and ecological implications of viral infection. We have developed a method for detecting, sorting, and performing molecular analysis of individual, infected cells of the important microalga Emiliania huxleyi, based on known physiological responses to viral infection. Of three fluorescent dyes tested, FM 1-43 (for detecting membrane blebbing) gave the most unequivocal and earliest separation of cells. Furthermore, we were able to amplify the genomes of single infected cells using Multiple Displacement Amplification. This novel method to reliably discriminate infected from healthy cells in cultures will allow researchers to answer numerous questions regarding the mechanisms and implications of viral infection of E. huxleyi. The method may be transferable to other virus-host systems.

Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

Science.gov (United States)

Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

2013-08-01

Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection

NARCIS (Netherlands)

Geldmacher, Christof; Ngwenyama, Njabulo; Schuetz, Alexandra; Petrovas, Constantinos; Reither, Klaus; Heeregrave, Edwin J.; Casazza, Joseph P.; Ambrozak, David R.; Louder, Mark; Ampofo, William; Pollakis, Georgios; Hill, Brenna; Sanga, Erica; Saathoff, Elmar; Maboko, Leonard; Roederer, Mario; Paxton, William A.; Hoelscher, Michael; Koup, Richard A.

2010-01-01

HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common

Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability

International Nuclear Information System (INIS)

Rivera, Julie A.; McGuire, Travis C.

2005-01-01

To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV WSU5 infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected macrophages and DC stimulated similar levels of memory CTL responses in mixtures of CD8+ and CD4+ cells as detected with 51 Cr-release assays indicating that EIAV infection of DC did not alter antigen presentation. However, EIAV-infected DC were more effective than infected macrophages when used to stimulate memory CTL in isolated CD8+ cells. The maintenance of antigen processing and presenting function by EIAV-infected DC in vitro suggests that this function is maintained during in vivo infection

Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells

Science.gov (United States)

Rac, Jürgen; Haas, Florian; Schumacher, Andrina; Middeldorp, Jaap M.; Delecluse, Henri-Jacques; Speck, Roberto F.

2015-01-01

The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is associated with epithelial malignancies including nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform epithelial cells in vitro where it is rapidly lost from infected primary epithelial cells or epithelial tumor cells. Long-term infection by EBV, however, can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here, we hypothesized that increased telomerase activity in epithelial cells enhances their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we generated epithelial model cell lines with increased or suppressed telomerase activity by stable ectopic expression of hTERT or of a catalytically inactive, dominant negative hTERT mutant. Infection experiments with recombinant prototypic EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able to undergo lytic replication, revealed that infection frequencies positively correlate with telomerase activity in AGS cells but also partly depend on the cellular background. AGS cells with increased telomerase activity showed increased expression mainly of latent EBV genes, suggesting that increased telomerase activity directly acts on the EBV infection of epithelial cells by facilitating latent EBV gene expression early upon virus inoculation. Thus, our results indicate that infection of epithelial cells by EBV is a very selective process involving, among others, telomerase activity and cellular background to allow for optimized host-to-host transmission via saliva. PMID:25856387

Cell migration is another player of the minute virus of mice infection

Energy Technology Data Exchange (ETDEWEB)

Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

2014-11-15

The parvovirus minute virus of mice, prototype strain (MVMp), preferentially infects and kills cancer cells. This intrinsic MVMp oncotropism may depend in part on the early stages of MVMp infection. To test this hypothesis, we investigated the early events of MVMp infection in mouse LA9 fibroblasts and a highly invasive mouse mammary tumor cell line derived from polyomavirus middle T antigen-mediated transformation. Using a combination of fluorescence and electron microscopy, we found that various parameters of the cell migration process affect MVMp infection. We show that, after binding to the plasma membrane, MVMp particles rapidly cluster at the leading edge of migrating cells, which exhibit higher levels of MVMp uptake than non-motile cells. Moreover, promoting cell migration on a fibronectin matrix increased MVMp infection, and induction of epithelial–mesenchymal transition allowed MVMp replication in non-permissive epithelial cells. Hence, we propose that cell migration influences the early stages of MVMp infection. - Highlights: • We document early steps of MVMp infection. • We report that a fibronectin matrix promotes MVMp infection. • We show that cellular migration plays a role in MVMp uptake. • We show that epithelial–mesenchymal transition allows MVMp replication.

Cell migration is another player of the minute virus of mice infection

International Nuclear Information System (INIS)

Garcin, Pierre O.; Panté, Nelly