Browsing by Author "Li, Jing"
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Item Open Access Development of a Novel c-MET-Based CTC Detection Platform.(Mol Cancer Res, 2016-06) Zhang, Tian; Boominathan, Rengasamy; Foulk, Brad; Rao, Chandra; Kemeny, Gabor; Strickler, John H; Abbruzzese, James L; Harrison, Michael R; Hsu, David S; Healy, Patrick; Li, Jing; Pi, Cinthia; Prendergast, Katherine M; Hobbs, Carey; Gemberling, Sarah; George, Daniel J; Hurwitz, Herbert I; Connelly, Mark; Garcia-Blanco, Mariano A; Armstrong, Andrew JUNLABELLED: Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45(+) leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers. IMPLICATIONS: This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability. Mol Cancer Res; 14(6); 539-47. ©2016 AACR.Item Open Access Increased proteasomal activity supports photoreceptor survival in inherited retinal degeneration.(Nature communications, 2018-04-30) Lobanova, Ekaterina S; Finkelstein, Stella; Li, Jing; Travis, Amanda M; Hao, Ying; Klingeborn, Mikael; Skiba, Nikolai P; Deshaies, Raymond J; Arshavsky, Vadim YInherited retinal degenerations, affecting more than 2 million people worldwide, are caused by mutations in over 200 genes. This suggests that the most efficient therapeutic strategies would be mutation independent, i.e., targeting common pathological conditions arising from many disease-causing mutations. Previous studies revealed that one such condition is an insufficiency of the ubiquitin-proteasome system to process misfolded or mistargeted proteins in affected photoreceptor cells. We now report that retinal degeneration in mice can be significantly delayed by increasing photoreceptor proteasomal activity. The largest effect is observed upon overexpression of the 11S proteasome cap subunit, PA28α, which enhanced ubiquitin-independent protein degradation in photoreceptors. Applying this strategy to mice bearing one copy of the P23H rhodopsin mutant, a mutation frequently encountered in human patients, quadruples the number of surviving photoreceptors in the inferior retina of 6-month-old mice. This striking therapeutic effect demonstrates that proteasomes are an attractive target for fighting inherited blindness.Item Open Access Multi-Row Aerodynamic Interactions and Mistuned Forced Response of an Embedded Compressor Rotor(2016) Li, JingThis research investigates the forced response of mistuned rotor blades that can lead to excessive vibration, noise, and high cycle fatigue failure in a turbomachine. In particular, an embedded rotor in the Purdue Three-Stage Axial Compressor Research Facility is considered. The prediction of the rotor forced response contains three key elements: the prediction of forcing function, damping, and the effect of frequency mistuning. These computational results are compared with experimental aerodynamic and vibratory response measurements to understand the accuracy of each prediction.
A state-of-the-art time-marching computational fluid dynamic (CFD) code is used to predict the rotor forcing function. A highly-efficient nonlinear frequency-domain Harmonic Balance CFD code is employed for the prediction of aerodynamic damping. These allow the compressor aerodynamics to be depicted and the tuned rotor response amplitude to be predicted. Frequency mistuning is considered by using two reduced-order models of different levels of fidelity, namely the Fundamental Mistuning Model (FMM) and the Component Mode Mistuning (CMM) methods. This allows a cost-effective method to be identified for mistuning analysis, especially for probabilistic mistuning analysis.
The first topic of this work concerns the prediction of the forcing function of the embedded rotor due to the periodic passing of the neighboring stators that have the same vane counts. Superposition and decomposition methods are introduced under a linearity assumption, which states that the rotor forcing function comprises of two components that are induced by each neighboring stator, and that these components stay unchanged with only a phase shift with respect to a change in the stator-stator clocking position. It is found that this assumption captures the first-order linear relation, but neglects the secondary nonlinear effect which alters each stator-induced forcing functions with respect to a change in the clocking position.
The second part of this work presents a comprehensive mistuned forced response prediction of the embedded rotor at a high-frequency (higher-order) mode. Three steady loading conditions are considered. The predicted aerodynamics are in good agreement with experimental measurements in terms of the compressor performance, rotor tip leakage flow, and circumferential distributions of the stator wake and potential fields. Mistuning analyses using FMM and CMM models show that the extremely low-cost FMM model produces very similar predictions to those of CMM. The predicted response is in good agreement with the measured response, especially after taking the uncertainty in the experimentally-determined frequency mistuning into consideration. Experimentally, the characteristics of the mistuned response change considerably with respect to loading. This is not very well predicted, and is attributed to un-identified and un-modeled effects. A significant amplification factor over 1.5 is observed both experimentally and computationally for this higher-order mode.
Item Open Access Sampling Migrants from their Social Networks: The Demography and Social Organization of Chinese Migrants in Dar es Salaam, Tanzania.(Migr Stud, 2016-07) Merli, M Giovanna; Verdery, Ashton; Mouw, Ted; Li, JingThe streams of Chinese migration to Africa are growing in tandem with rising Chinese investments and trade flows in and to the African continent. In spite of the high profile of this phenomenon in the media, there are few rich and broad descriptions of Chinese communities in Africa. Reasons for this include the rarity of official statistics on foreign-born populations in African censuses, the absence of predefined sampling frames required to draw representative samples with conventional survey methods and difficulties to reach certain segments of this population. Here, we use a novel network-based approach, Network Sampling with Memory, which overcomes the challenges of sampling 'hidden' populations in the absence of a sampling frame, to recruit a sample of recent Chinese immigrants in Dar es Salaam, Tanzania and collect information on the demographic characteristics, migration histories and social ties of members of this sample. These data reveal a heterogeneous Chinese community composed of "state-led" migrants who come to Africa to work on projects undertaken by large Chinese state-owned enterprises and "independent" migrants who come on their own accord to engage in various types of business ventures. They offer a rich description of the demographic profile and social organization of this community, highlight key differences between the two categories of migrants and map the structure of the social ties linking them. We highlight needs for future research on inter-group differences in individual motivations for migration, economic activities, migration outcomes, expectations about future residence in Africa, social integration and relations with local communities.Item Open Access Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.(Oncotarget, 2016-08-02) Ware, Kathryn E; Somarelli, Jason A; Schaeffer, Daneen; Li, Jing; Zhang, Tian; Park, Sally; Patierno, Steven R; Freedman, Jennifer; Foo, Wen-Chi; Garcia-Blanco, Mariano A; Armstrong, Andrew JTreatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment-resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail-mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer.