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1.
  • Villa, Luisa L., et al. (author)
  • Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
  • 2007
  • In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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3.
  • Björkholm, P., et al. (author)
  • Navigation in vehicle crash test using MEMS-based IMU
  • 2010
  • In: IEEE PLANS, Position Location and Navigation Symposium. - 9781424450367 ; , s. 27-31
  • Conference paper (other academic/artistic)abstract
    • Results from our experiments on inertial navigation in crash testing of vehicles are presented. A custom designed inertial measurement unit (IMU) has been developed, and several tests in dummy calibration rigs including full-scale Euro NCAP collisions have been performed at our partners' crash test laboratories. For reference, the IMU data is compared to camera data and traditional single-axis inertial sensors. ©2010 IEEE.
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  • Lindholm, L, et al. (author)
  • Genetic re-targeting of adenovirus using a hyperstable scFv domain and an affibody (R) molecule against Her2/neu
  • 2004
  • In: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 9, s. S250-S250
  • Journal article (peer-reviewed)abstract
    • One important goal in gene therapy is to develop adenovirus (Ad) vectors that are genetically de-targeted as well as re-targeted. Genetic re-targeting of Ad using complex cell-binding ligands has previously not been possible. We have previously demonstrated that ligands for genetic re-targeting of adenoviruses must be able to fold correctly in the cytoplasm of virus producing cells, a milieu that is not conducive to the formation of disulphide bonds. Here, we describe functional Ad5 viruses with fibers and pIX capsid proteins genetically modified to contain two types of complex ligands. One is affibody® molecules, corresponding to small (6 kDa) binding proteins developed by combinatorial protein engineering using a single three-helix bundle staphylococcal protein A domain. The other type is hyperstable antibody scFv domains. The affibody molecule used here (ZH2N) is directed against Her2/neu. Recombinant viruses were constructed with ZH2N in three different positions: (i) at the C-terminus of shaft repeat 7 of de-knobbed fibers; (ii) at the C-terminus of pIX; and (iii) in the HI-loop of the fiber knob. Each of the viruses exhibited a characteristic phenotype regarding fiber content, growth and ability to infect Her2/neu expressing cells. In order to test the potentials of scFv liganded Ad vectors, a hyperstable antibody scFv against b-galactosidase was genetically incorporated into knobless fibers, in tandem with a mutated protein A domain reactive with IgG1 Fc that targeted the virus to Fc-expressing 293 cells. These fibers could be rescued into viable virions that retained the original antigen binding specificity of the scFv, demonstrating the basic potential of hyperstable scFvs for genetic re-targeting of Ad. Quite unexpectedly, the fiber content of Ad with knobless, scFv containing fibers was close to normal in contrast to other Ad with knobless fibers that generally has a much reduced fiber content. The hyperstable scFv was further fused to the C-terminus of the capsid protein pIX. The recombinant molecules could be rescued into viable viruses with wt fibers. The scFv retained its binding-specificity on the recombinant virions. The results demonstrate that, contrary to current beliefs, it is possible to construct Ad that genetically incorporates functional scFvs and other complex ligands into the virus fiber and pIX. The feasibility is demonstrated by the creation of different viruses that are re-targeted to Her2/neu. These viruses are currently in pre-clinical development.
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6.
  • Anderson, D., et al. (author)
  • Collapse of optical vacuum pulses due to QED nonlinearities
  • 2002
  • In: Nonlinear Guided Waves and Their Applications, 1–4 September 2002, Stresa, Italy. - : Optics Info Base, Optical Society of America. - 1557527237
  • Conference paper (other academic/artistic)abstract
    • Due to quantum electrodynamical (QED) effects there are nonlinear corrections to Maxwell's equations in vacuum. We show that stationary two-dimensional light bullets can form, which are unstable and exhibit, the possibility of self-focusing collapse.
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7.
  • Björnelius, E, et al. (author)
  • Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial.
  • 2008
  • In: Sexually transmitted infections. - : BMJ. - 1472-3263 .- 1368-4973. ; 84:1, s. 72-6
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To evaluate the microbiological cure rate after treatment with tetracyclines or azithromycin in patients infected with M genitalium. METHODS: One hundred and fifty-two men and 60 women positive for M genitalium were recruited. Patients treated either with doxycyline for 9 days or with azithromycin 1 g stat. were compared. Those still positive for M genitalium after primary doxycycline treatment received an extended course of azithromycin 500 mg on day 1 followed by 250 mg daily for the following 4 days, whereas those with treatment failure after azithromycin received doxycycline 100 mg twice daily for 15 days. RESULTS: The eradication rate after azithromycin 1 g stat. was 85% (95% CI 69 to 94) in men (n = 39) and 88% (95% CI 64 to 99) in women (n = 17) and after doxycycline 17% (95% CI 9 to 27) in men (n = 76) and 37% (95% CI 19 to 58) in women (n = 27). Extended azithromycin eradicated M genitalium from 96% (95% CI 85 to 99) of the men (n = 47) and from all six women who failed on doxycycline. Extended doxycycline treatment was insufficient. Persistent urethral inflammation was seen in a substantial portion of the men after eradication of M genitalium regardless of the antibiotic drug, indicating a poor predictive value of urethral smears in evaluation of persistent or recurrent infection. CONCLUSIONS: Azithromycin was more effective than doxycycline in treating patients infected with M genitalium. The extended course of azithromycin was highly effective but was given after the initial treatment with doxycycline. Randomised clinical trials are needed to compare the different dosages of azithromycin.
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  • Hagberg, Johan, 1988-, et al. (author)
  • Lithium iron phosphate coated carbon fiber electrodes for structural lithium ion batteries
  • 2018
  • In: Composites Science And Technology. - : Elsevier. - 0266-3538 .- 1879-1050. ; 162, s. 235-243
  • Journal article (peer-reviewed)abstract
    • A structural lithium ion battery is a material that can carry load and simultaneously be used to store electrical energy. We describe a path to manufacture structural positive electrodes via electrophoretic deposition (EPD) of LiFePO4 (LFP), carbon black and polyvinylidene fluoride (PVDF) onto carbon fibers. The carbon fibers act as load-bearers as well as current collectors. The quality of the coating was studied using scanning electron microscopy and energy dispersive X-ray spectroscopy. The active electrode material (LFP particles), conductive additive (carbon black) and binder (PVDF) were found to be well dispersed on the surface of the carbon fibers. Electrochemical characterization revealed a specific capacity of around 60–110 mAh g−1 with good rate performance and high coulombic efficiency. The cell was stable during cycling, with a capacity retention of around 0.5 after 1000 cycles, which indicates that the coating remained well adhered to the fibers. To investigate the adhesion of the coating, the carbon fibers were made into composite laminae in epoxy resin, and then tested using 3-point bending and double cantilever beam (DCB) tests. The former showed a small difference between coated and uncoated carbon fibers, suggesting good adhesion. The latter showed a critical strain energy release rate of ∼200–600 J m−2 for coated carbon fibers and ∼500 J m−2 for uncoated fibers, which also indicates good adhesion. This study shows that EPD can be used to produce viable structural positive electrodes.
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11.
  • Harrison, P. J., et al. (author)
  • Shared reflex pathways of group I afferents of different cat hind‐limb muscles.
  • 1983
  • In: The Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 338, s. 113-128
  • Journal article (peer-reviewed)abstract
    • The convergence of group I muscle afferents of different muscle origin onto interneurones in spinal reflex pathways has been investigated using the technique of spatial facilitation of the transmission from afferents to motoneurones. The investigated pathways are those of non‐reciprocal inhibition and of oligosynaptic excitation of motoneurones. Extensive convergence has been found of group I afferents from muscles operating at the same and different joints onto the interneurones interposed in both excitatory and inhibitory, disynaptic and trisynaptic pathways to motoneurones. Convergence has been found between muscle spindle Ia and/or tendon organ Ib afferents from different muscles, thereby extending observations on convergence of these subgroups of group I afferents from the same muscles. The results show that group I afferents of different muscles influence motoneurones via shared neuronal pathways and that transmission from these afferents is influenced by afferents originating in other muscles. The afferent information forwarded to individual motoneurones is therefore the ensemble picture of the length and tension of many muscles. © 1983 The Physiological Society
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12.
  • Koonjaenak, S., et al. (author)
  • Seasonal variation in nuclear DNA integrity of frozen-thawed spermatozoa from Thai AI swamp buffaloes (Bubalus bubalis)
  • 2007
  • In: Journal of Veterinary Medicine A. - : Wiley-Blackwell. - 0931-184X .- 1439-0442. ; 54:7, s. 377-383
  • Journal article (peer-reviewed)abstract
    • In this study, we investigated the susceptibility of frozen-thawed swamp buffalo sperm nuclear DNA to undergo controlled acid-induced denaturation in situ, as analysed by flow cytometry, and aimed to correlate the results with sperm head morphology over three seasons in tropical Thailand. Artificial insemination (AI) doses (n = 218) from 18 AI buffalo sires, prepared between 1980 and 1989 and 2003 and 2005, were tested and compared among three seasons, the rainy season, July-October; winter, November-February; and summer , March-June. The overall mean of DNA fragmentation index (DFI) (+/- SD) was 1.84 +/- 1.68%, range from 0.19 to 7.92%, with 0.221 +/- 0.021 of the x-DFI ranging from 0.190 to 0.350 and 0.023 +/- 0.009 of the SD-DFI ranging from 0.010 to 0.070. The DFI was consistently low (range 1.40 +/- 0.21% to 2.16 +/- 0.21%; LSM +/- SEM), with x-DFI ranging from 0.216 +/- 0.003 to 0.225 +/- 0.003 and SD-DFI ranging from 0.022 +/- 0.001 to 0.024 +/- 0.001 across the seasons. The DFI was low enough to be related to high fertility potential. However, DFI values varied statistically among seasons, being lower in the rainy season (1.40 +/- 0.21%, P less than 0.05) than in winter (2.16 +/- 0.21%) or summer (2.00 +/- 0.20%), and were also affected by the year of semen collection and processing (P less than 0.001). The proportion of morphologically abnormal sperm head shapes was low, with no significant differences between seasons. However, DFI was significantly related to the proportion of loose abnormal sperm heads (r = 0.27, P less than 0.01). In conclusion, frozen-thawed swamp buffalo sperm chromatin integrity is not seriously damaged by cryo-preservation or affected by the seasonal variations in temperature and humidity seen in tropical Thailand.
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  • Koonjaenak, S., et al. (author)
  • Seasonality affects post-thaw plasma membrane intactness and sperm velocities in spermatozoa from Thai AI swamp buffaloes (Bubalus bubalis)
  • 2007
  • In: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 67:9, s. 1424-1435
  • Journal article (peer-reviewed)abstract
    • Altogether 218 frozen semen Al doses, prepared between 1980 and 1989 and also between 2003 and 2005 from 18 Al Thai swamp buffalo sires, were examined to determine whether seasonality affects post-thaw viability, as plasma membrane integrity (PMI, using SYBR-14/PI), plasma membrane stability (PMS, using Annexin-V/PI), or motility (Mot, using CASA). A thermoresistance test (38 degrees C for 60 min) was used to further analyze sperm survivability in vitro. All variables were compared over 3 seasons of the year (rainy: July-October; winter: November-February; and summer: March-June), with distinct ambient temperature and humidity. PMI (% of alive spermatozoa) was higher in winter (54.6%, P less than 0.001) than in the rainy (43.5%) or summer (46.7%) seasons. Outcomes of PMS (Annexin-V/PI assay) confirmed those of PMI, the highest PMS in spermatozoa processed in winter (55.7%, P less than 0.001). Spermatozoa depicting linear Mot post-thaw ranged from 48.2% to 48.8% across seasons (ns), proportions that decreased during incubation (33.5-37.9%), albeit without seasonal differences. The mean percentages of straight linear velocity (VSL), average path velocity (VAP), or curvilinear velocity (VCL) were higher (P less than 0.05-0.001) in the rainy season than in winter or summer, while average lateral head displacement (ALH) was higher (P less than 0.05) in summer, differences maintained after incubation. In conclusion, post-thaw PMS and PMI, assessed by flow cytometry, were significantly better in sperm samples processed during winter than in samples processed during the other seasons of the year, a seasonal difference not picked up by CASA, probably due to the larger number of spermatozoa assessed. (C) 2007 Elsevier Inc. All rights reserved.
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14.
  • Kumaresan, A., et al. (author)
  • Quantification of kinetic changes in protein tyrosine phosphorylation and cytosolic Ca2+ concentration in boar spermatozoa during cryopreservation
  • 2012
  • In: Reproduction, Fertility and Development. - 1031-3613 .- 1448-5990. ; 24:4, s. 531-542
  • Journal article (peer-reviewed)abstract
    • Protein tyrosine phosphorylation in sperm is associated with capacitation in several mammalian species. Although tyrosine phosphorylated proteins have been demonstrated in cryopreserved sperm, indicating capacitation-like changes during cryopreservation, these changes have not yet been quantified objectively. We monitored tyrosine phosphorylation, intracellular calcium and sperm kinematics throughout the cryopreservation process, and studied the relationships among them in boar spermatozoa. Sperm kinetics changed significantly during cryopreservation: curvilinear velocity, average path velocity and straight line velocity all decreased significantly (P < 0.05). While the percentage of sperm with high intracellular calcium declined (P < 0.05), global phosphorylation increased significantly (P < 0.01). Specifically, cooling to 5 degrees C induced phosphorylation in the spermatozoa. After cooling, a 32-kDa protein not observed in fresh semen appeared and was consistently present throughout the cryopreservation process. While the level of expression of this phosphoprotein decreased after addition of the second extender, frozen-thawed spermatozoa showed an increased expression. The proportion of sperm cells with phosphorylation in the acrosomal area also increased significantly (P < 0.05) during cryopreservation, indicating that phosphorylation might be associated with capacitation-like changes. These results provide the first quantitative evidence of dynamic changes in the subpopulation of boar spermatozoa undergoing tyrosine phosphorylation during cryopreservation.
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15.
  • Köhler, Elof, 1980, et al. (author)
  • MEMS meander harvester with tungsten proof-mass
  • 2019
  • In: Journal of Physics. - : Institute of Physics Publishing.
  • Conference paper (peer-reviewed)abstract
    • Using current battery technology the life-time of a leadless pacemaker is approximately 6-10 years, with a large portion of the pacemaker occupied by the battery. This paper investigates the possibility to use a MEMS piezoelectric harvester as a complementary energy source in leadless pacemakers. The challenge is to combine the low resonance frequency required to harvest energy from a heartbeat with the small volume of 20×4×3 mm3 available, with the corresponding harvester displacement restricted to 2 mm. Due to the displacement restriction the selected structure was a double clamped bridge in order to reduce the mass displacement, with various meander-type designs simulated to reduce resonance frequency. To further reduce resonance frequency large proof-masses of tungsten were attached by gluing. Two types of tungsten proof-masses were added to four different harvesters, 16.4 mg and 16.6 mg on sample 1 and 2 and 502 mg and 492 mg proof-mass on sample 3 and 4. The structures have 2 μm patterned PZT (deposited by sol-gel technique) and Pt metal electrodes for d31 mode harvesting. The power output measured from one of the two PZT/electrodes was 0.13 nW with 50 μm deflection at 100 k Ω optimal load resistance and 9.1 mVpp at 232 Hz.
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  • Quist, E, et al. (author)
  • Responses of a nitrogen-saturated forest to a sharp decrease in nitrogen input
  • 1999
  • In: Journal of Environmental Quality. - 0047-2425 .- 1537-2537. ; 28, s. 1970-1977
  • Journal article (peer-reviewed)abstract
    • The reversibility of induced N saturation was investigated in a 46- yr-old pine (Pinus sylvestris L.) forest in northern Sweden Ammonium nitrate has been applied annually since 1971 to plots (30 by 30 m) at average dosages of 36 (N1), 72 (N2), and 108 (N3) kg N ha(-1) yr(-1): with or without P and K addition (background N deposition is <4 kg ha(-1) yr(-1)). In 1990, after two decades of treatment, the largest N application (N3) was suspended, while N1 and N2 still received ammonium nitrate applications. Seven gears after the last application in N3, the N availability measured as N concentration in plants spine roots and needles and in leaves of the grass Deschampsia flexuosa (L.) Trin.] and activity of the enzyme nitrate reductase in leaves of D. flexuosa, and N-15 uptake by excised pine roots, was at the same levels as in N1, although more than twice the amount of N has been applied in total to N3. The arginine concentrations in pine needles, concentrations of exchangeable mineral N in the organic layer and the uppermost 20 cm of the mineral soil were at the same levels as in the control plots. Thus, an experimentally induced N excess was, according to these measurements, to a high degree reversed 7 yr after the last N application. However, the composition of the understory vegetation still differed markedly from the untreated control 8 yr after the last N3 application.
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  • Rodriguez-Martinez, Heriberto, et al. (author)
  • Boar spermatozoa in the oviduct
  • 2005
  • In: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 63:2, s. 514-535
  • Journal article (peer-reviewed)abstract
    • In the pig, a functional tubal sperm reservoir (SR) is established before ovulation to ensure availability of suitable numbers of viable spermatozoa for fertilization. The boars large ejaculate is split: most spermatozoa are delivered in a sperm-rich fraction (SRF) followed by a post-SRF fraction containing increasing amounts of the spermadhesin PSP-I/PSP-II-rich seminal vesicle secretion. This heterodimer acts as leukocyte chemoattractant both in vitro and in vivo, contributing to the phagocytosis of those spermatozoa not reaching the SR. Sequential ejaculate deposition of marked spermatozoa and SR screening showed that most spermatozoa in the SR arose from the fortuitous PSP-poor, first portion of the SRF fraction, escaping phagocytosis and replenishing the SR within 23 h. The SR-sperm numbers diminish gradually in relation to ovulation, spermatozoa. being continuously redistributed toward the upper isthmus. In vitro, only uncapacitated spermatozoa bind to epithelial explants, suggesting that the SR influences sperm capacitation. In vivo, most viable spermatozoa - usually harbored in the deep furrows in the pre- or peri-ovulatory SR during spontaneous standing estrus - are uncapacitated, but capacitation significantly increases after ovulation. Pre-/peri-ovulatory SR spermatozoa promptly capacitate in vitro when exposed to the effector bicarbonate, an influence that can be reversed by co-incubation with SR fluid or its component hyaluronan. Fluid collected from the ampullar segment (rich in bicarbonate) induces capacitation in vitro. In conclusion, the lack of massive sperm capacitation in the SR and the diverse individual response to capacitation shown by tubal spermatozoa would relate both to the insurance of full sperm viability before ovulation and the presence of spermatozoa at different stages of capacitation in the upper oviduct, thus maximizing the chances of normal fertilization. (C) 2004 Elsevier Inc. All rights reserved.
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20.
  • Siqueira, A P, et al. (author)
  • Quality of boar spermatozoa from the sperm-peak portion of the ejaculate after simplified freezing in MiniFlatpacks compared to the remaining spermatozoa of the sperm-rich fraction
  • 2011
  • In: THERIOGENOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0093-691X .- 1879-3231. ; 75:7, s. 1175-1184
  • Journal article (peer-reviewed)abstract
    • Boar sperm viability post-thaw differs depending on the ejaculate fraction used, with spermatozoa present in the first 10 mL of the sperm-rich fraction (SRF) (portion 1, P1, sperm-peak portion) displaying the best cryosurvival in vitro compared with that of spermatozoa from the rest of the ejaculate (portion 2 of the SRF plus the post-spermatic fraction), even when using simplified freezing routines. This viability apparently relates to the specific profile of seminal plasma in P1 (i.e., glycoprotein and bicarbonate concentrations, and pH). However, spermatozoa from PI have not been compared with spermatozoa from the rest of the SRF (SRF P1, usually 30-40 mL of the SRF), which is routinely used for freezing. We compared P1 with SRF P I in terms of sperm kinematics (using the QualiSperm (TM) system), while membrane integrity (SYBR-14/PI), acrosome integrity (FITC PNA/PI), and sperm membrane stability (Annexin-V) were explored using flow cytomety. As well, total protein concentration and the proteomics of the seminal plasma (SP) of both portions of the SRF were studied using two-dimensional electrophoresis (2DE), mass fingerprinting (MALDI-TOF), and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) on selected peptides. The SRF portions were collected weekly from four mature boars (4-5 replicates per boar, sperm concentration: P1, 1.86 +/- 0.20; SRF P1, 1.25 +/- 0.14 x 10(9) spz/mL) and processed using a quick freezing method in MiniFlatPacks. Post-thaw sperm motility reached 50%, without differences between SRF portions, but with clear inter-boar variation. Neither plasma membrane nor acrosome integrity differed (ns) between fractions. These results indicate that there are no differences in cryosurvival after quick freezing of boar spermatozoa derived from either of the two SRF portions. While P1 and SRF-P1 clearly differed in relative total protein contents, as expected, they displayed very similar protein profiles as assessed using 2DE and mass spectrometry (tryptic peptide mass fingerprint analysis and CID-MS/MS), indicating a similar emission of epididymal protein content.
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