Browsing by Author "Chen, Xi"
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Item Analysis of Ion Motion and Diffusion Confinement in Inverted Drift Tubes and Trapped Ion Mobility Spectrometry Devices(ACS, 2019) Larriba-Andaluz, Carlos; Chen, Xi; Nahin, Minal; Wu, Tianyang; Fukushima, Nobuhiko; Mechanical and Energy Engineering, School of Engineering and TechnologyIon motion in trapped ion mobility spectrometers (TIMS) and inverted drift tubes (IDT) has been investigated. The two-dimensional (2D) axisymmetric analytical solution to the Nernst–Planck equation for constant gas flows and opposed linearly increasing fields is presented for the first time and is used to study the dynamics of ion distributions in the ramp region. It is shown that axial diffusion confinement is possible and that broad packets of ions injected initially into the system can be contracted. This comes at the expense of the generation of a residual radial field that pushes the ions outward. This residual electric field is of significant importance as it hampers sensitivity and resolution when parabolic velocity profiles form. When radio frequency (RF) is employed at low pressures, this radial field affects the stability of ions inside the mobility cell. Trajectories and frequencies for stable motion are determined through the study of Mathieu’s equation. Finally, effective resolutions for the ramp and plateau regions of the TIMS instrument are provided. While resolution depends on the inverse of the square root of mobility, when proper parameters are used, resolutions in the thousands can be achieved theoretically for modest distances and large mobilities.Item ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis(American Association for the Advancement of Science, 2017-01-20) Li, Zhaomin; Zhang, Peng; Yan, Aimin; Guo, Zhengyu; Ban, Yuguang; Li, Jin; Chen, Shi; Yang, Hui; He, Yongzheng; Li, Jianping; Guo, Ying; Zhang, Wen; Hajiramezanali, Ehsan; An, Huangda; Fajardo, Darlene; Harbour, J. William; Ruan, Yijun; Nimer, Stephen D.; Yu, Peng; Chen, Xi; Xu, Mingjiang; Yang, Feng-Chun; Department of Pediatrics, IU School of MedicineASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin-cKit+ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A and alters the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and regulate gene expression in hematopoietic cells.Item Autophagy induced by calcium phosphate precipitates targets damaged endosomes(ASBMB, 2014-04-18) Chen, Xi; Khambu, Bilon; Zhang, Hao; Gao, Wentao; Li, Min; Chen, Xiaoyun; Yoshimori, Tamotsu; Yin, Xiao-Ming; Department of Pathology & Laboratory Medicine, IU School of MedicineCalcium phosphate precipitates (CPPs) form complexes with DNA, which enter cells via endocytosis. Under this condition CPPs induce autophagy via the canonic autophagy machinery. Here we showed that CPP-induced autophagy was also dependent on endocytosis as the process was significantly inhibited by methyl-β-cyclodextrin and dynasore, which suppress clathrin-dependent endocytosis. Consistently, CPP treatment triggered the formation of filipin-positive intracellular vesicles whose membranes are rich in cholesterol. Unexpectedly, these vesicles were also positive for galectin 3, suggesting that they were damaged and the membrane glycans became accessible to galectins to bind. Endosome damage was caused by endocytosis of CPPs and was reversed by calcium chelators or by endocytosis inhibitors. Notably, CPP-induced LC3-positive autophagosomes were colocalized with galectin 3, ubiquitin, and p62/SQSTM1. Inhibition of galectin 3 reduced p62 puncta and autophagosome formation. Knockdown of p62 additionally inhibited the colocalization of autophagosomes with galectins. Furthermore, most of the galectin 3-positive vesicles were colocalized with Rab7 or LAMP1. Agents that affect endosome/lysosome maturation and function, such as bafilomycin A1, also significantly affected CPP-induced tubulovesicular autophagosome formation. These findings thus indicate that endocytosed CPPs caused endosome damage and recruitment of galectins, particularly at the later endosome stage, which led to the interaction of the autophagosomal membranes with the damaged endosome in the presence of p62.Item Enhancing Separation and Constriction of Ion Mobility Distributions in Drift Tubes at Atmospheric Pressure Using Varying Fields(American Chemical Society, 2022-03-31) Chen, Xi; Latif, Mohsen; Gandhi, Viraj D.; Chen, Xuemeng; Hua, Leyan; Fukushima, Nobuhiko; Larriba-Andaluz, Carlos; Mechanical and Energy Engineering, School of Engineering and TechnologyA linearly decreasing electric field has been previously proven to be effective for diffusional correction of ions in a varying field drift tube (VFDT) system, leading to higher resolving powers compared to a conventional drift tube due to its capacity to narrow distributions midflight. However, the theoretical predictions in resolving power of the VFDT were much higher than what was observed experimentally. The reason behind this discrepancy has been identified as the difference between the theoretically calculated resolving power (spatial) and the experimental one (time). To match the high spatial resolving power experimentally, a secondary high voltage pulse (HVP) at a properly adjusted time is used to provide the ions with enough momentum to increase their drift velocity and hence their time-resolving power. A series of systematic numerical simulations and experimental tests have been designed to corroborate our theoretical findings. The HVP-VFDT atmospheric pressure portable system improves the resolving power from the maximum expected of 60–80 for a regular drift tube to 250 in just 21 cm in length and 7kV, an unprecedent accomplishment.Item Field-Switching Repeller Flowing Atmospheric-Pressure Afterglow Drift Tube Ion Mobility Spectrometry(American Chemical Society, 2022-03-02) Latif, Mohsen; Chen, Xi; Gandhi, Viraj D.; Larriba-Andaluz, Carlos; Gamez, Gerardo; Mechanical and Energy Engineering, School of Engineering and TechnologyIn this work, a field-switching (FS) technique is employed with a flowing atmospheric pressure afterglow (FAPA) source in drift tube ion mobility spectrometry (DTIMS). The premise is to incorporate a tip-repeller electrode as a substitute for the Bradbury–Nielsen gate (BNG) so as to overcome corresponding disadvantages of the BNG, including the gate depletion effect (GDE). The DTIMS spectra were optimized in terms of peak shape and full width by inserting an aperture at the DTIMS inlet that was used to control the neutral molecules’ penetration into the separation region, thus preventing neutral-ion reactions inside. The FAPA and repeller’s experimental operating conditions including drift and plasma gas flow rates, pulse injection times, repeller positioning and voltage, FAPA current, and effluent angle were optimized. Ion mobility spectra of selected compounds were captured, and the corresponding reduced mobility values were calculated and compared with the literature. The 6-fold improvements in limit of detection (LOD) compared with previous work were obtained for 2,6-DTBP and acetaminophen. The enhanced performance of the FS-FAPA-DTIMS was also investigated as a function of the GDE when compared with FAPA-DTIMS containing BNG.Item Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older(Elsevier, 2021-02) Liu, Hang; Su, Liqin; Chen, Xi; Wang, Sisi; Cheng, Yibin; Lin, Shaobin; Ding, Liang; Liu, Jingyi; Chen, Chen; Unverzagt, Frederick W.; Hake, Ann M.; Jin, Yinlong; Gao, Sujuan; Psychiatry, School of MedicineCadmium (Cd) exposure has been reported to have neurotoxic effects in animal studies and associated with increased Alzheimer's Disease mortality and lower cognitive function in cross-sectional and case-control studies. However, no results from longitudinal studies on Cd and cognitive decline are available. In this prospective cohort study, we recruited 1867 participants aged 65 years or older from rural areas in China, blood Cd and cognitive function were measured at baseline (2010−2012), and 1554 participants completed cognitive function tests during a 3-year follow-up (2013–2015). Cognitive function was evaluated using nine standardized cognitive tests: The Community Screening Instrument for Dementia, the CERAD Word List Learning, Word list recall, IU Story Recall, Animal Fluency Test, Boston Naming Test, Stick Design, Delayed Stick Design and the IU Token Test. Analysis of covariance models and logistic regression models were used to determine the association between Cd and standardized cognitive decline adjusting for covariates. The median blood Cd concentration of this study population was 2.12 μg/L, and the interquartile range was 1.42–4.64 μg/L. Significant association of higher Cd levels with lower cognitive scores were observed in five individual cognitive tests (Delayed Stick Design Test, Boston Naming Test, CERAD Word List Learning Test, Word List Recall Test and IU Story Recall Test) and the composite cognitive score adjusting for multi-covariates at baseline. Higher Cd levels were significantly associated with greater 3-year cognitive decline in Delayed Stick Design Test, Boston Naming Test, IU Token Test, Word List Recall Test and Composite cognitive score. For these cognitive tests, participants in the top two Cd quartile groups had significantly greater decline than those in the lowest Cd quartile group, while the two lowest Cd quartile groups were not significantly different. Our findings suggest that higher Cd exposure is associated with greater cognitive decline in older Chinese adults.Item Higher blood selenium level is associated with lower risk of hyperhomocysteinemia in the elderly(Elsevier, 2023-01) Wang, Ting; Su, Liqin; Chen, Xi; Wang, Sisi; Han, Xu; Cheng, Yibin; Lin, Shaobin; Ding, Liang; Liu, Jingyi; Chen, Chen; Unverzagt, Frederick W.; Hake, Ann M.; Jin, Yinlong; Gao, Sujuan; Biostatistics and Health Data Science, School of MedicineBackground and aims Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. Methods A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. Results For this sample, the mean blood Se concentration was 156.34 (74.65) μg/L and the mean serum Hcy concentration was 17.25 (8.42) μmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 μg/L and greater than 156.919 μg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. Conclusions Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderlyItem Measurement and Theory of Gas-Phase Ion Mobility Shifts Resulting from Isotopomer Mass Distribution Changes(American Chemical Society, 2021) Harrilal, Christopher P.; Gandhi, Viraj D.; Nagy, Gabe; Chen, Xi; Buchanan, Michael G.; Wojcik, Roza; Conant, Christopher R.; Donor, Micah T.; Ibrahim, Yehia M.; Garimella, Sandilya V.B.; Smith, Richard D.; Larriba-Andaluz, Carlos; Mechanical and Energy Engineering, School of Engineering and TechnologyThe unanticipated discovery of recent ultra-high-resolution ion mobility spectrometry (IMS) measurements revealing that isotopomers─compounds that differ only in the isotopic substitution sites─can be separated has raised questions as to the physical basis for their separation. A study comparing IMS separations for two isotopomer sets in conjunction with theory and simulations accounting for ion rotational effects provides the first-ever prediction of rotation-mediated shifts. The simulations produce observable mobility shifts due to differences in gas-ion collision frequency and translational-to-rotational energy transfer. These differences can be attributed to distinct changes in the moment of inertia and center of mass between isotopomers. The simulations are in broad agreement with the observed experiments and consistent with relative mobility differences between isotopomers. These results provide a basis for refining IMS theory and a new foundation to obtain additional structural insights through IMS.Item Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study(Springer Nature, 2021-01-29) Lin, Andrew; Wong, Nathan D.; Razipour, Aryabod; McElhinney, Priscilla A.; Commandeur, Frederic; Cadet, Sebastien J.; Gransar, Heidi; Chen, Xi; Cantu, Stephanie; Miller, Robert J. H.; Nerlekar, Nitesh; Wong, Dennis T. L.; Slomka, Piotr J.; Rozanski, Alan; Tamarappoo, Balaji K.; Berman, Daniel S.; Dey, Damini; Medicine, School of MedicineBackground: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. Methods: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU. Results: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score). Conclusions: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification.Item Optimization of long range potential interaction parameters in ion mobility spectrometry(AIP, 2018) Wu, Tianyang; Derrick, Joseph; Nahin, Minal; Chen, Xi; Larriba-Andaluz, Carlos; Mechanical Engineering, School of Engineering and TechnologyThe problem of optimizing Lennard-Jones (L-J) potential parameters to perform collision cross section (CCS) calculations in ion mobility spectrometry has been undertaken. The experimental CCS of 16 small organic molecules containing carbon, hydrogen, oxygen, nitrogen, and fluoride in N2 was compared to numerical calculations using Density Functional Theory (DFT). CCS calculations were performed using the momentum transfer algorithm IMoS and a 4-6-12 potential without incorporating the ion-quadrupole potential. A ceteris paribus optimization method was used to optimize the intercept σ and potential well-depth ϵ for the given atoms. This method yields important information that otherwise would remain concealed. Results show that the optimized L-J parameters are not necessarily unique with intercept and well-depth following an exponential relation at an existing line of minimums. Similarly, the method shows that some molecules containing atoms of interest may be ill-conditioned candidates to perform optimizations of the L-J parameters. The final calculated CCSs for the chosen parameters differ 1% on average from their experimental counterparts. This result conveys the notion that DFT calculations can indeed be used as potential candidates for CCS calculations and that effects, such as the ion-quadrupole potential or diffuse scattering, can be embedded into the L-J parameters without loss of accuracy but with a large increase in computational efficiency.