Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “progress”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

LSINCT5 activates Wnt/β-catenin signaling by interacting with NCYM to promote bladder cancer progression

Highlights: • LSINCT5 promotes bladder cancer. • LSINCT5 interacts with NCYM. • LSINCT5 activates Wnt/β-catenin signaling by NCYM. Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression. Mechanistic investigations showed that LSINCT5 could physically interact with NCYM, a de novo gene product from the MYCN cis-antisense RNA and inhibit GSK3β activity leading to enhanced Wnt/β-catenin signaling activation and epithelial mesenchymal transition (EMT). Taken together, our findings have created a novel LSINCT5 mediated process which facilitates bladder cancer progression and may provide a potential target for therapeutic intervention.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Overexpressing circular RNA hsa{sub c}irc{sub 0}002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, whose importance in cancer has been gradually acknowledged. However, the functions of circRNAs in tumorigenesis have not been fully understood. In the present study, we identified a novel circRNA hsa{sub c}irc{sub 0}002052 significantly downregulated in osteosarcoma (OS) tissues and cell lines. Moreover, we found that hsa{sub c}irc{sub 0}002052 could act as a biomarker to indicate the prognosis of OS patients. Functionally, we showed that hsa{sub c}irc{sub 0}002052 overexpression significantly suppressed OS cell proliferation, migration and invasion while promoting apoptosis in vitro. Similarly, in vivo assay indicated that ectopic expression of hsa{sub c}irc{sub 0}002052 impaired OS cell growth. In terms of mechanism, we found that hsa{sub c}irc{sub 0}002052 inhibited miR-1205 while miR1205 targeted APC2, a negative regulator of Wnt/β-catenin signaling pathway. By releasing the inhibition of miR-1205 on APC2 expression, hsa{sub c}irc{sub 0}002052 suppressed the activation of Wnt/β-catenin signaling pathway, leading to attenuated OS progression. Taken together, our study for the first time revealed a suppressive circRNA hsa{sub c}irc{sub 0}002052 involved in OS progression. Our study suggested hsa{sub c}irc{sub 0}002052/miR-1205/APC2/Wnt/β-catenin axis might be a potential target for OS therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2

Highlights: • We first confirmed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. • We further clarified that Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. • Finally, we demonstrated that FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1. Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circ{sub 0}026344 as a prognostic biomarker suppresses colorectal cancer progression via microRNA-21 and microRNA-31

Recently, circular RNA (circRNA) is identified as a novel class of noncoding RNA with important roles in human diseases, such as cancer. However, how circRNA participates in colorectal cancer (CRC) remains unclear. In this study, we aimed to illustrate the role of circ{sub 0}026344 in CRC progression. We showed that circ{sub 0}026344 expression was downregulated in CRC tissues compared to adjacent normal tissues. Moreover, the level of circ{sub 0}026344 was inversely correlated with CRC advance and lymphoid node metastasis. Additionally, circ{sub 0}026344 low expression predicted poor prognosis in CRC patients. We identified circ{sub 0}026344 as a miRNA sponge for microRNA-21 (miR-21) and microRNA-31 (miR-31) whose expression levels were elevated in CRC tissues. And the level of circ{sub 0}026344 was reversely correlated with both miR-21 and miR-31 levels in CRC tissues. Functionally, we found that ectopic expression of circ{sub 0}026344 decreased the growth and invasion of CRC cells while promoting apoptosis in vitro. The xenograft experiment indicated that circ{sub 0}026344 overexpress led to CRC growth inhibition in vivo. Rescue assays further demonstrated that circ{sub 0}026344 exerted biological functions by sponging miR-21 and miR-31 in CRC. In conclusion, this study revealed that circ{sub 0}026344/miR-21/miR-31 regulatory signaling was implicated in CRC progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-410–3p promotes prostate cancer progression via regulating PTEN/AKT/mTOR signaling pathway

Prostate cancer has become one of commonest urologic tumors in male. In recent years, miRNAs are continually attracting attentions of researchers for their special regulatory function in human cancers. Previous study has revealed that miR-410 acts as a biomarker for the diagnosis of prostate cancer. Whereas, the specific biological function of miR-410–3p in prostate cancer remains unknown. The aim of this study is to explore the function and molecular mechanism of miR-410–3p in prostate cancer. The high expression of miR-410–3p was examined in prostate cancer tissues and cell lines by qRT-PCR. Next, the prognostic value was identified by Kaplan Meier method. High expression of miR-410–3p indicated poor prognosis of prostate cancer patients. To investigate the biological function of miR-410–3p in prostate cancer, loss-of function assays were designed and performed in two prostate cancer cell lines (PC3 and DU145). As a result, downregulated miR-410–3p suppressed cell proliferation, migration and EMT progress. Moreover, flow cytometry analysis was performed to determine that the acceleration effects of miR-410–3p on cell apoptosis. Mechanistically, further analysis demonstrated that the effects of miR-410–3p exert oncogenic functions through downregulating PTEN. All findings in this study revealed that miR-410–3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ketohexokinase is involved in fructose utilization and promotes tumor progression in glioma

Highlights: • KHK was overexpressed in glioma and correlated with glioma malignancy and patients' poor survival. • Silencing KHK could significantly inhibit glioma cell proliferation and migration in fructose medium. • Culturing glioma cells in fructose medium could promote the expression of KHK and increase cells malignancy progression. Many studies have pinpointed that fructose could be utilized as a carbon source in some cancers, and we also defined that glioma cells could utilize fructose to maintain themselves survival and proliferation depending on GLUT5 expression recently. However, ketohexokinase (KHK), as a key enzyme involved in fructose catabolism, drew less attention in cancers, especially in glioma. In the present study, we first analyzed the expression levels of KHK in glioma tissues and the correlations of KHK expression with clinicopathological variables of patients with glioma. Meanwhile, we detected the effect of silencing KHK on the biological functions of glioma cells in fructose medium. From the results, we found that KHK was expressed at significantly higher level in glioma tissues than in non-tumor brain, and KHK expression was significantly correlated with tumor malignancy and poor survival of glioma patients (p < 0.01). Functionally, knockdown of KHK could significantly inhibit cell proliferation and migration of glioma cells in fructose medium. Furthermore, we investigated the KHK expression level after long-time treatment with fructose, and detected the change of cell biological behaviour, then we found that the expression level of KHK was significantly increased and these cells showed more malignant properties. Taken together, our results suggest that high fructose diet and KHK overexpression are correlated with glioma malignant progression and patients' poor survival, and we believe this hypothesis would open the door for novel therapeutic agents and mentalities for glioma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Lysophosphatidic acid receptor-2 (LPA2) and LPA5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells

Highlights: • LPAR2 and LPAR5 expressions were elevated by long-term anticancer drug treatment in HT1080 cells. • Highly invasion HT1080-M6 cells were generated from HT1080 cells using Matrigel-coated filters. • HT1080-M6 cell invasion was shown to be 4.5 times higher than that of HT1080 cells. • The cell motile and invasive activities of HT1080-M6 cells were reduced by LPA{sub 2} inhibition. • LPA signaling via LPA{sub 2} is a potent target for the regulation of tumor progression in HT1080 cells. Lysophosphatidic acid (LPA) receptors (LPA{sub 1} to LPA{sub 6}) regulate a variety of malignant properties in cancer cells. In the present study, we investigated the roles of LPA receptors in the promotion of cellular functions during tumor progression in fibrosarcoma cells. To obtain long-term anticancer drug treated cells, human fibrosarcoma HT1080 cells were treated with methotrexate (MTX) and cisplatin (CDDP) for 6 months. LPAR2 and LPAR5 expressions were significantly higher in MTX-treated (HT-MTX) cells than in HT1080 cells. The cell motile and invasive activities of HT-MTX cells were significantly elevated compared with HT1080 cells. Although LPAR5 expression was increased in MTX and CDDP treated (HT-M-C) cells, no change of LPAR2 expression was observed. The cell motile and invasive activities of HT-M-C cells were lower than those of HT1080 cells. Moreover, to evaluate whether LPA receptors promote cell invasive activity, highly invasion (HT1080-M6) cells were established from HT1080 cells. The cell invasive activity of HT1080-M6 cells was approximately 4.5 times higher than HT1080 cell invasion. LPAR2 expression was markedly elevated in HT1080-M6 cells compared with HT1080 cells. The high cell invasion activity of HT1080-M6 cells was significantly suppressed by an antagonist of LPA{sub 2}, H2L5186303. These results suggest that LPA{sub 2} acts as a key regulator of malignant properties in HT1080 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulation of LINC00963 facilitates melanoma progression through miR-608/NACC1 pathway and predicts poor prognosis

Long noncoding RNAs (lncRNAs) are acknowledged as crucial regulators involved in multiple pathological processes, including cancer. Although some lncRNAs are studied in melanoma, the association between lncRNA and melanoma progression still remains vague. And the function of LINC00963 in melanoma is waiting for investigation. In this study, upregulated level of LINC00963 in melanoma tissues was observed. Notably, we found DNA copy-number-gain of LINC00963 contributes to its high expression. And high expression of LINC00963 predicts poor prognosis in patients with melanoma. Functional investigation indicated that LINC00963 knockdown dramatically suppressed melanoma cell proliferation, migration and invasion. Mechanistically, we found that LINC00963 could interact with miR-608 while miR-608 could target NACC1. Upregulated LINC00963 led to elevated expression of NACC1 through inhibiting miR-608, which consequently promoted melanoma malignant progression. Taken together, our results illustrated that LINC00963-miR-608-NACC1 pathway might be a potential target for melanoma therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway

While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The circular RNA circ-ITCH suppresses ovarian carcinoma progression through targeting miR-145/RASA1 signaling

Highlights: • A broad down-regulation of circ-ITCH and a worse prognosis were found in OC patients. • Circ-ITCH inhibits the cell viability and motility by CCK8, cell cycle, wound healing and invasion assay. • Circ-ITCH inhibits the tumorigenesis ability in xenograft NOD mice in vivo. • Circ-TCH acts as a ceRNA role of circ-ITCH through sponging miR-145 and up-regulation of RASA1 expression. As the leading cause of death for gynecological cancers, ovarian cancer (OC) ranks fifth overall for cancer-related death among women. Emerging evidence has indicated that circular RNA (circRNA), recognized as functional non-coding transcripts in eukaryotic cells, may be involved in many physiological or pathological processes. It was reported that circ-ITCH is downregulated in multi cancers and serves as a powerful tumor suppressor among through a competing endogenous RNA (ceRNA) pathway. However, the existence and the role of circ-ITCH in OC was not reported. Here, we found a broad down-regulation of circ-ITCH in OC tissues and cells, which correlates with a worse prognosis in OC patients. Functional studies suggest that circ-ITCH overexpression inhibits the cell viability and motility by CCK8, cell cycle, wound healing assay and invasion assay. It also inhibits the tumorigenesis ability in xenograft NOD mice in vivo. Mechanically, we demonstrated that circ-TCH acts as a ceRNA to sponge miR-145, increases the level of RASA1, and inhibits the malignant progression of OC cells via the circ-ITCH-miR-145-RASA1 axis in vitro and in vivo. Taken together, our findings provide a novel tumor suppressive role regarding circ-ITCH function in the malignant progression of OC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA OGFRP1 regulates LYPD3 expression by sponging miR-124-3p and promotes non-small cell lung cancer progression

Highlights: • The expression levels of lncRNA OGFRP1 was up-regulated in NSCLC tissues and cell lines. • Overexpression of lncRNA OGFRP1 was associated with advanced clinical features and poor prognosis in NSCLC patients. • LncRNA OGFRP1 promoted NSCLC cells proliferation, migration and invasion by regulation of miR-124-3p-LYPD3 pathway. Long noncoding RNA (OGFRP1) has been reported to be involved in the progression of non-small cell lung cancer (NSCLC). However, the expression pattern, functions and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present study, we found that OGFRP1 expression was significantly up-regulated in both NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a powerful predictor of advanced clinical stage, lymph nodes metastasis and poor prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the expression of the target gene LYPD3. Taken together, OGFRP1 contributed to progression of NSCLC at least partly through upregulating LYPD3 expression by sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker and therapeutic target in NSCLC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Upregulation of circ-UBAP2 predicts poor prognosis and promotes triple-negative breast cancer progression through the miR-661/MTA1 pathway

Highlights: • circ-UBAP2 is significantly up-regulated in TNBC and predicts poor prognosis. • Knockdown of circ-UBAP2 remarkably inhibits TNBC progression both in vitro and in vivo. • circ-UBAP2 exerts its oncogenic effect via miR-661/MTA1 axis in TNBC. Recently, a large number of studies have shown that circular RNA (circRNA) is involved in the development and progression of human cancer. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, a novel circRNA, circ-UBAP2 (hsa{sub c}irc{sub 0}001846), was shown to be markedly upregulated in TNBC. Moreover, high circ-UBAP2 expression was closely associated with larger tumour size (p = 0.003), advanced TNM stage (p = 0.005), lymph node metastasis (p = 0.002), and unfavourable prognosis (p = 0.0256). Functionally, lentivirus-mediated stable knockdown of circ-UBAP2 dramatically weakened the ability of TNBC cells to proliferate and migrate and induced apoptosis in vitro and in vivo. Regarding the mechanism, we found that circ-UBAP2 was mainly observed in the cytoplasm and was capable of sponging miRNA-661 to increase the expression of the oncogene MTA1. Additionally, silencing of miRNA-661 or overexpression of MTA1 could partially rescue the attenuated malignant phenotype caused by circ-UBAP2 knockdown. Taken together, our data reveal that circ-UBAP2 plays a vital regulatory role in TNBC via the miR-661/MTA1 axis and may serve as a promising therapeutic target for TNBC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

AURKA contributes to the progression of oral squamous cell carcinoma (OSCC) through modulating epithelial-to-mesenchymal transition (EMT) and apoptosis via the regulation of ROS

Highlights: • AURKA knockdown inhibited the proliferation and ETM in OSCC cell lines. • Silencing AURKA induced apoptosis and ROS in OSCC cell lines. • AURKA knockdown inhibited tumor growth in vivo. Oral squamous cell carcinoma (OSCC) is known as one of the most common cancer influencing the head and neck region. However, the molecular mechanisms revealing OSCC progression is largely unclear. Aurora kinase A (AURKA) is a serine-threonine kinase that functions in mitotic spindle formation and chromosome segregation, and is associated with the progression of human cancers. But its role in regulating OSCC development has not yet been investigated. In the study, we found that AURKA expression was up-regulated in OSCC cell lines and tumor specimens from patients. OSCC patients with high expression of AURKA exhibited a significant decreased overall survival rate. In vitro, AURKA knockdown markedly reduced the proliferation, migration and invasion of OSCC cells using cell counting kit-8 (CCK-8), EdU, colony formation and transwell analysis. EMT was suppressed by AURKA silence, as evidenced by the up-regulated expression of E-cadherin and down-regulated Vimentin in OSCC cells. In addition, apoptosis was markedly induced by AURKA inhibition through promoting the expression of cleaved Caspase-3 and poly (ADP)-ribose polymerase (PARP). Reactive oxygen species (ROS) production was also markedly enhanced in AURKA-knockdown OSCC cells. Importantly, we found that repressing ROS generation using its scavenger of n-acetylcysteine (NAC) significantly abolished AURKA silence-induced apoptosis, accompanied with restored proliferation and EMT. In vivo, AURKA knockdown notably inhibited tumor growth. Therefore, knockdown of AURKA suppressed cell proliferation, migration and invasion, and also induced apoptosis and ROS generation in OSCC possibly via the production of ROS, demonstrating that AURKA inhibition might represent a novel therapeutic target for the prevention of OSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA MAGI2-AS3 regulates CCDC19 expression by sponging miR-15b-5p and suppresses bladder cancer progression

Highlights: • Expression of MAGI2-AS3, miR-15b-5p and CCDC19 in BCa. • MAGI2-AS3 regulates miR-15b-5p/CCDC19 cascade expression in BCa. • CCDC19 knockdown partly reverses the effects caused by MAGI2-AS3 overexpression in vitro. • MAGI2-AS3 suppresses BCa growth in vivo. Bladder cancer (BCa) belongs to a popular urological malignancy and leads to large numbers of deaths worldwide. Recently, emerging evidences indicate that long noncoding RNAs (lncRNAs) are closely related with BC occurrence and progression. However, the function of lncRNA MAGI2-AS3 remains poorly understood in BC. In this present study, we screened out a novel lncRNA MAGI2-AS3 whose expression was downregulated in BCa tissues. We showed that MAGI2-AS3 downregulation in BCa patients indicated a poor prognosis. Functionally, we showed that MAGI2-AS3 overexpression inhibits proliferation, migration and invasion of BCa cells. Moreover, ectopic expression of MAGI2-AS3 suppresses BCa growth in vivo. Bioinformatics analysis revealed that MAGI2-AS3 could serve as a competing endogenous RNA (ceRNA) for miR-15b-5p. In the meantime, miR-15b-5p directly targeted CCDC19, a tumor suppressor in BCa. Rescue assays demonstrated that knockdown of CCDC19 restored the proliferation, migration and invasion of BCa cells suppressed by MAGI2-AS3 overexpression. In conclusion, this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates BCa progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a {sup 137}Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Neutron imaging the spatial progression of chemical oxidation of lithium-ion cathode material in a packed bed reactor

Emerging electrochemical systems relevant to energy applications including redox targeted flow batteries rely on chemical redox of solid electroactive materials using dissolved redox couples. One configuration to facilitate contact between the redox shuttles and solid material which is volume efficient is a packed bed reactor. While methods have been reported to assess the overall progression by analysis of the packed bed reactor effluent, herein analysis of the spatial progression of the chemical redox will be reported. Combination of neutron and x-ray tomography enabled assessing the pore and particle structure in the packed bed reactor and the spatial homogeneity of the reaction at different overall extents of conversion of the reactor bed. Finally, these characterization tools provide methods to probe the chemical redox processes occurring within the reactor environment.

25 ENERGY STORAGE↗