IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.
Many quasi-simultaneous optical observations of 17 blazars are obtained from previous papers published over the last 19 years in order to investigate the spectral slope variability and understand the radiation mechanism of blazars. The long-period dereddened optical spectral slopes are calculated. We analyse the average spectral slope distribution, which suggests that the spectra of flat spectrum radio quasars (FSRQs) and high energy peaked BL Lac objects (HBLs) are probably deformed by other emission components. The average spectral slopes of low energy peaked BL Lac objects(LBLs), which scatter around 1.5, show a good accordance with the synchrotron self-Compton (SSC) loss-dominated model. We present and discuss the variability between the spectral slope and optical luminosity. The spectra of all HBLs and LBLs get flatter when they turn brighter, while for FSRQs this trend does not exist or may even be reversed. This phenomenon may imply that there is a thermal contribution to the optical spectrum for FSRQs. For the FSRQ 1156+295, there is a hint that the slope gets flatter at both the brightest and faintest states. Our result shows that three subclasses locate in different regions in the pattern of slope variability indicator versus average spectral slope. The relativistic jet mechanism is supported by the significant correlation between the optical Doppler factor and the average spectral slope.Comment: 17 pages, 7 figures, Accepted by MNRA
We present the results of optical photometric (BVRI ) monitoring of three gamma-ray-loud BL Lac objects (3C 66A, PKS 0735+178, and BL Lacertae) in 1999-2002. During our observations, these objects showed significant rapid variations: 3C 66A and PKS 0735+178 exhibit short-timescale ($1 hr) variability in the B band, and BL Lac exhibits intraday variability in B and V. We find that there is a strong correlation between brightness and color for 3C 66A and BL Lac. We have analyzed the relationship between optical variability and gamma-ray variability and discuss theoretical models for gamma-ray-loud BL Lac emission. We have found shorter time variability for 3C 66A and PKS 0735+178 compared with previous reports.
BackgroundThe objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (−)-(1-((2R,3R)-8-(2-[18F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([18F]VAT) based on PET imaging in nonhuman primates. [18F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia.MethodsThree macaque fascicularis (two males, one female) received 185.4–198.3 MBq [18F]VAT prior to whole-body imaging in a MicroPET-F220 scanner. Time activity curves (TACs) were created from regions of interest (ROIs) that encompassed the entire small organs or samples with the highest activity within large organs. Organ residence times were calculated based on the TACs. We then used OLINDA/EXM 1.1 to calculate human radiation dose estimates based on scaled organ residence times.ResultsMeasurements from directly sampled arterial blood yielded a residence time of 0.30 h in agreement with the residence time of 0.39 h calculated from a PET-generated time activity curve measured in the left ventricle. Organ dosimetry revealed the liver as the critical organ (51.1 and 65.4 μGy/MBq) and an effective dose of 16 and 19 μSv/MBq for male and female, respectively.ConclusionsThe macaque biodistribution data showed high retention of [18F]VAT in the liver consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [18F]VAT can be administered to obtain imaging in humans.
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