| 1. |
- Bethge, WA, et al.
(författare)
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Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients
- 2022
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 57:3, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.
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| 2. |
- Kazaks, A, et al.
(författare)
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Stop codon insertion restores the particle formation ability of hepatitis B virus core-hantavirus nucleocapsid protein fusions
- 2002
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Ingår i: Intervirology. - : S. Karger AG. - 0300-5526 .- 1423-0100. ; 45:4-6, s. 340-349
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, epitopes of various origin have been inserted into the core protein of hepatitis B virus (HBc), allowing the formation of chimeric HBc particles. Although the C-terminus of a C-terminally truncated HBc (HBcΔ) tolerates the insertion of extended foreign sequences, the insertion capacity is still a limiting factor for the construction of multivalent vaccines. Previously, we described a new system to generate HBcΔ mosaic particles based on a read-through mechanism in an <i>Escherichia coli</i> suppressor strain [J Gen Virol 1997;78:2049–2053]. Those mosaic particles allowed the insertion of a 114-amino acid (aa)-long segment of a Puumala hantavirus (PUUV) nucleocapsid (N) protein. To study the value and the potential limitations of the mosaic approach in more detail, we investigated the assembly capacity of ‘non-mosaic’ HBcΔ fusion proteins and the corresponding mosaic constructs carrying 94, 213 and 433 aa of the hantaviral N protein. Whereas the fusion proteins carrying 94, 114, 213 or 433 aa were not assembled into HBcΔ particles, or only at a low yield, the insertion of a stop codon-bearing linker restored the ability to form particles with 94, 114 and 213 foreign aa. The mosaic particles formed exhibited PUUV-N protein antigenicity. Immunization of BALB/c mice with these mosaic particles carrying PUUV-N protein aa 1–114, aa 1–213 and aa 340–433, respectively, induced HBc-specific antibodies, whereas PUUV-N protein-specific antibodies were detected only in mice immunized with particles carrying N-terminal aa 1–114 or aa 1–213 of the N protein. Both the anti-HBc and anti-PUUV antibody responses were IgG1 dominated. In conclusion, stop codon suppression allows the formation of mosaic core particles carrying large-sized and ‘problematic’, e.g. hydrophobic, hantavirus sequences.
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| 3. |
- Kero, J., et al.
(författare)
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The 2009-2010 MU radar head echo observation programme for sporadic and shower meteors : radiant densities and diurnal rates
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - Hoboken, NJ : Wiley-Blackwell. - 0035-8711 .- 1365-2966. ; 425:1, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to give an overview of the monthly meteor head echo observations (528.8?h) conducted between 2009 June and 2010 December using the Shigaraki Middle and Upper atmosphere radar in Japan (34 degrees.85 N, 136 degrees.10 E). We present diurnal detection rates and radiant density plots from 18 separate observational campaigns, each lasting for at least one diurnal cycle. Our data comprise more than 106?000 meteors. All six recognized apparent sporadic meteor sources are discernable and their average orbital distributions are presented in terms of geocentric velocity, semimajor axis, inclination and eccentricity. The north and south apex have radiant densities an order of magnitude higher than other apparent source regions. The diurnal detection rates show clear seasonal dependence. The main cause of the seasonal variation is the tilt of the Earth's axis, causing the elevation of the Earth's apex above the local horizon to change as the Earth revolves around the Sun. Yet, the meteor rate variation is not symmetric with respect to the equinoxes. When comparing the radiant density at different times of the year, and thus at different solar longitudes along the Earth's orbit, we have found that the north and south apex source regions fluctuate in strength.
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| 4. |
- Capela, J P, et al.
(författare)
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Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia
- 2006
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 139:3, s. 1069-1081
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Tidskriftsartikel (refereegranskat)abstract
- Studies on 3,4-methylenedioxymethamphetamine ("ecstasy")-induced neurotoxicity mainly focus on damage of serotonergic terminals. Less attention has been given to neuronal cell death produced by 3,4-methylenedioxymethamphetamine and other amphetamines in areas including the cortex, striatum and thalamus. In the present study we investigated 3,4-methylenedioxymethamphetamine-induced neurotoxicity in neuronal serum free cultures from rat cortex. Since 3,4-methylenedioxymethamphetamine intake induces hyperthermia in both animals and humans, the experiments were performed under normal (36.5 degrees C) and hyperthermic conditions (40 degrees C). Our findings showed a dose-, time- and temperature-dependent apoptotic cell death induced by 3,4-methylenedioxymethamphetamine in cortical neurons. 3,4-Methylenedioxymethamphetamine-induced damage was potentiated under hyperthermia. The neurotoxicity was reduced by the serotonin 2A-receptor antagonists, ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride, in both normothermic and hyperthermic conditions. (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride, a model agonist for the serotonin 2A-receptor, also induced a dose- and time-dependent apoptotic cell death. Again, protection was provided by ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride against (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-induced neurotoxicity, thereby indicating that the 3,4-methylenedioxymethamphetamine stimulation of the serotonin 2A-receptor leads to neurotoxicity. This study provides for the first time evidence that direct 3,4-methylenedioxymethamphetamine serotonin 2A-receptor stimulation leads to neuronal cortical death. alpha-Phenyl-N-tert-butyl nitrone a free radical scavenger and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine as well as the NMDA-receptor antagonist MK-801 provided protection under normothermia and hyperthermia, thereby suggesting the participation of free radicals in 3,4-methylenedioxymethamphetamine-induced cell death. Since 3,4-methylenedioxymethamphetamine serotonin 2A-receptor agonistic properties lead to neuronal death, clinically available atypical antipsychotic drugs with serotonin 2A-antagonistic properties could be a valuable therapeutic tool against 3,4-methylenedioxymethamphetamine-induced neurodegeneration.
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| 9. |
- Meisel, David D., et al.
(författare)
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Physical Characteristics of Kazan Minor Showers as Determined by Correlations with the Arecibo UHF radar
- 2008
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Ingår i: Advances in Meteoroid and Meteor Science. - New York, NY : Springer. - 9780387784182
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Bokkapitel (refereegranskat)abstract
- In the northern hemisphere, the month of February is characterized by a lack of major meteor shower activity yet a number of weak minor showers are present as seen bythe Kazan radar. Using the Feller transformation to obtain the distribution of true meteor velocities from the distribution of radial velocities enables the angle of incidence to be obtained for the single beam AO (Arecibo Observatory) data. Thus the loci of AO radiants become beam-centered circles on the sky and one can, with simple search routines, find where these circles intersect on radiants determined by other means. Including geocentric velocity as an additional search criterion, we have examined a set of February radiants obtained at Kazan for coincidence in position and velocity. Although some may be chance associations, only those events with probabilities of association[0.5 have been kept. Roughly 90 of the Kazan showers have been verified in this way with mass, radius anddensity histograms derived from the AO results. By comparing these histograms with those of the ‘‘background’’ in which the minor showers are found, a qualitative scale of dynamical minor shower age can be formulated. Most of the showers are found outside the usual ‘‘apex’’ sporadic source areas where it is easiest to detect discrete showers with less confusion from the background.
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| 10. |
- Meisel, David D., et al.
(författare)
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Physical Characteristics of Kazan Minor Showers as Determined by Correlations with the Arecibo UHF Radar
- 2008
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Ingår i: Earth, moon, and planets. - : Springer Netherlands. - 0167-9295 .- 1573-0794. ; 102:1-4, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- In the northern hemisphere, the month of February is characterized by a lack of major meteor shower activity yet a number of weak minor showers are present as seen by the Kazan radar. Using the Feller transformation to obtain the distribution of true meteor velocities from the distribution of radial velocities enables the angle of incidence to be obtained for the single beam AO (Arecibo Observatory) data. Thus the loci of AO radiants become beam-centered circles on the sky and one can, with simple search routines, find where these circles intersect on radiants determined by other means. Including geocentric velocity as an additional search criterion, we have examined a set of February radiants obtained at Kazan for coincidence in position and velocity. Although some may be chance associations, only those events with probabilities of association[0.5 have been kept. Roughly 90 of the Kazan showers have been verified in this way with mass, radius and density histograms derived from the AO results. By comparing these histograms with those of the ‘‘background’’ in which the minor showers are found, a qualitative scale of dynamical minor shower age can be formulated. Most of the showers are found outside the usual ‘‘apex’’ sporadic source areas where it is easiest to detect discrete showers with less confusion from the background.
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