Search NASA⌕ Search

SEARCH · Search NASA

Results for “Cells”

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 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Hydrogen peroxide stimulates cell motile activity through LPA receptor-3 in liver epithelial WB-F344 cells

Highlights: •Hydrogen peroxide stimulates cell motility of WB-F344 cells. •LPA{sub 3} is induced by hydrogen peroxide in WB-F344 cells. •Cell motility by hydrogen peroxide is inhibited in LPA{sub 3} knockdown cells. •LPA signaling is involved in cell migration by hydrogen peroxide. -- Abstract: Hydrogen peroxide which is one of reactive oxygen species (ROS) mediates a variety of biological responses, including cell proliferation and migration. In the present study, we investigated whether lysophosphatidic acid (LPA) signaling is involved in cell motile activity stimulated by hydrogen peroxide. The rat liver epithelial WB-F344 cells were treated with hydrogen peroxide at 0.1 or 1 μM for 48 h. In cell motility assays, hydrogen peroxide treated cells showed significantly high cell motile activity, compared with untreated cells. To measure the expression levels of LPA receptor genes, quantitative real time RT-PCR analysis was performed. The expressions of LPA receptor-3 (Lpar3) in hydrogen peroxide treated cells were significantly higher than those in control cells, but not Lpar1 and Lpar2 genes. Next, to assess the effect of LPA{sub 3} on cell motile activity, the Lpar3 knockdown cells from WB-F344 cells were also treated with hydrogen peroxide. The cell motile activity of the knockdown cells was not stimulated by hydrogen peroxide. Moreover, in liver cancer cells, hydrogen peroxide significantly activated cell motility of Lpar3-expressing cells, but not Lpar3-unexpressing cells. These results suggest that LPA signaling via LPA{sub 3} may be mainly involved in cell motile activity of WB-F344 cells stimulated by hydrogen peroxide.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Luteoloside induces G0/G1 arrest and pro-death autophagy through the ROS-mediated AKT/mTOR/p70S6K signalling pathway in human non-small cell lung cancer cell lines

Highlights: • Luteoloside has the promising anticancer effects on non-small cell lung cancer (NSCLC) cells, which displayed lower cytotoxic activity toward normal lung cells. • Luteoloside contributes to growth inhibition by inducing G{sub 0}/G{sub 1} phase arrest associated with reduced expression of cell cycle proteins in NSCLC cells. • Luteoloside induces autophagy in NSCLC cells. However, luteoloside does not strongly result in apoptotic cell death in NSCLC cells. • Luteoloside induces autophagy through ROS-mediated specifically the inhibition of AKT/mTOR/p70S6K signalling pathway in NSCLC cells. Autophagy has attracted a great deal of interest in tumour therapy research in recent years. However, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on autophagy remains poorly understood in human lung cells. In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation, inducing G{sub 0}/G{sub 1} phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells. Interestingly, luteoloside induced autophagy in lung cancer cells, which was correlated with the formation of autophagic vacuoles, breakdown of p62, and the overexpression of Beclin-1 and LC3-II, but not in a human bronchial epithelial cell line (BEAS-2B). Notably, pretreatment of cancer cells with 3-MA, an autophagy inhibitor, protected against autophagy and promoted cell viability but not apoptosis. To further clarify whether luteoloside-induced autophagy depended on the PI3K/AKT/mTOR/p70S6K signalling pathway, a major autophagy-suppressive cascade, cells were treated with a combination of AKT inhibitor (LY294002) and mTOR inhibitor (Rap). These results demonstrated that luteoloside induced autophagy in lung cancer cell lines by inhibiting the pathway at p-Akt (Ser473), p-mTOR and p-p70S6K (Thr389). Moreover, we observed that luteoloside-induced cell autophagy was correlated with production of reactive oxygen species (ROS). NAC-mediated protection against ROS clearly implicated ROS in the activation of autophagy and cell death. In addition, the results showed that ROS served as an upstream effector of the PI3K/AKT/mTOR/p70S6K pathway. Taken together, the present study provides new insights into the molecular mechanisms underlying luteoloside-mediated cell death in NSCLC cells and supports luteoloside as a potential anti-cancer agent for targeting NSCLC through the induction of autophagy, inhibition of proliferation and PI3K/AKT/mTOR/p70S6K signalling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Synthesis and electrochemical characterization of Ti{sub x}Ta{sub y}Al{sub z}N{sub 1-δ}O{sub γ} for fuel cell catalyst supports

Quinary Ti{sub x}Ta{sub y}Al{sub z}N{sub 1-δ}O{sub γ} of various compositions have been prepared by a co-precipitation method followed by ammonolysis. The nitride samples were examined as potential catalyst supports in polymer electrolyte membrane fuel cells. The nitride products crystallized in the rock salt (NaCl) structure over a wide range of compositions. The addition of Ta and Al was highly beneficial towards improving the chemical and electrochemical stability of TiN, without a significant loss of electrical conductivity. Platinum particles were successfully deposited on the (oxy)nitride samples, and the composite samples at some compositions were found to be comparable to Pt/carbon in their stability and catalytic activity even without optimizing the Pt deposition and dispersion processes. - Graphical abstract: The effect of additions of Ta and Al into TiN structure. Shifts the lattice constant, and increases its chemical stability in acidic environment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

In vitro-induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells

Highlights: • THP-1CM treatment decreased the susceptibility of CRPC cells to NK cell action. • THP-1 CM treatment increased PD-L1 while decreasing NKG2D ligands in CRPC cells. • IL-6 may be the key cytokine to exert the THP-1 CM effect. • JAK/Stat3 is the critical IL-6 downstream signaling that triggers the THP-1 CM effect. • Targeting the JAK/Stat3 signaling may enhance the NK cell action to CRPC tumors. Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells. Meanwhile, the decreased susceptibility of tumor cells was also detected when NK cells were treated with THP-1 CM and used in NK cell cytotoxicity tests. Therefore, we observed higher resistance of CRPC cells when both tumor and NK cells were treated with THP-1 CM than when tumor cells or NK cells were individually treated. We further discovered that the PMA/IL-4 treated THP-1 cells secrete a high level of IL-6, so blocking the IL-6 action significantly decreased the PD-L1 level while recovering the NKG2D ligands, thus increasing the susceptibility of CRPC cells to NK cell action. Moreover, we discovered that JAK-Stat3 is the most critical IL-6 downstream signaling in triggering the THP-1 CM effect. Consequently, we found the susceptibility of CRPC cells to NK cells was increased when either JAK or Stat 3 inhibitor was added when tumor cells were treated with THP-1 CM, and that the best effect was observed when the JAK inhibitor and PD-L1 Ab were added together.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Fuel Cell Backup Power System for Grid-Service and Micro-Grid in Telecommunication Applications

This paper presents the feasibility and economics of using fuel cell backup power systems in telecommunication cell towers to provide grid services (e.g., ancillary services, demand response). The fuel cells are able to provide power for the cell tower during emergency conditions. This study evaluates the strategic integration of clean, efficient, and reliable fuel cell systems with the grid for improved economic benefits. The backup systems have potential as enhanced capability through information exchanges with the power grid to add value as grid services that depend on location and time. The economic analysis has been focused on the potential revenue for distributed telecommunications fuel cell backup units to provide value-added power supply. This paper shows case studies on current fuel cell backup power locations and regional grid service programs. The grid service benefits and system configurations for different operation modes provide opportunities for expanding backup fuel cell applications responsive to grid needs. The objective of this work primarily focuses on how fuel cells can become a significant part of the telecom backup power to reduce system costs, environmental impact, and dependence on fossil fuels, while ensuring continuity of indispensable service for mobile users. The study identifies the approaches on the fuel cell application through nano/microgrids for an extensive network of fuel cells as distributed energy resources. The possibilities of various application scenarios extend the fuel cell technologies and microgrid for reliable power supply.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2018

Change of cell growth and mitochondrial membrane polarization in the progeny of cells surviving low-dose high-LET irradiation from Ra-226

Highlights: • Chronic low-dose high-LET α-radiation from Ra-226 is effective in inducing lethal mutations. • Decreased clonogenic survival did not occur in descendants of irradiated HaCaT survivors, and hormesis may be induced. • Mitochondrial membrane depolarization may be involved in the induction of lethal mutation. In order to test the delayed effect of radiation on the progeny of irradiated survivors, the human keratinocyte cell line HaCaT and the fish common bluegill embryonic cell line CHSE/F were exposed to low-dose high-LET α-radiation from Ra-226 or γ-rays. The clonogenic survival fraction, mitochondrial membrane polarization (MMP) and reproductive ability of the descendants of the surviving cells were measured. For progeny of irradiated HaCaT survivors, no delayed cell death occurred. On the contrary, progeny at about 47 cell doublings after Ra-226 irradiation and progeny at about 14 cell doublings after γ-irradiation showed increased clonogenic survival. However the total cell number was reduced for progeny of Ra-226-treated cells up to about 47 cell doublings after irradiation and for progeny of γ-irradiated cells up to about 28 doublings after irradiation, which means low reproductive ability had appeared. In addition, α-radiation from Ra-226 had greater impact on the MMP of the HaCaT progeny than γ-rays. MMP of progeny of Ra-226-treated cells decreased at 5 cell doublings after irradiation and increased dose-dependently at 19 cell doublings after treatment, and then decreased dose-dependently at 47 cell doublings, while there was no significant effect on MMP in progeny of γ irradiated cells. The progeny of Ra-226-irradiated CHSE/F survivors showed more serious damage than the offspring of γ-irradiated CHSE/F cells. Significant, dose-dependent delayed cell death occurred in progeny of surviving cells up to about 61 cell doublings after Ra-226 treatment, and the reproductive ability was also significantly reduced. But the MMP increased, which might be because of the increased removal of dead cells. For progeny of CHSE/F cells surviving γ-rays radiation, no significant change in clonogenic survival occurred, except for offspring of cells surviving low dose (0.1 Gy and 0.5 Gy) irradiation, which had higher survival than control up to about 28 cell doublings after irradiation. But the number of cells which were the progeny of γ-irradiated survivors decreased dose-dependently up to about 28 cell doublings after γ-irradiation.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation

Highlights: •Parg{sup −/−} ES cells were more sensitive to γ-irradiation than Parp-1{sup −/−} ES cells. •Parg{sup −/−} cells were more sensitive to carbon-ion irradiation than Parp-1{sup −/−} cells. •Parg{sup −/−} cells showed defects in DSB repair after carbon-ion irradiation. •PAR accumulation was enhanced after carbon-ion irradiation compared to γ-irradiation. -- Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg{sup −/−} and poly(ADP-ribose) polymerase-1 deficient (Parp-1{sup −/−}) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg{sup −/−} cells were more sensitive to γ-irradiation than Parp-1{sup −/−} cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg{sup −/−} cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg{sup −/−} ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1{sup −/−} cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg{sup −/−} ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg{sup −/−} cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1{sup −/−} cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg{sup −/−} cells. The augmented level of poly(ADP-ribose) accumulation was noted after carbon-ion irradiation compared to γ-irradiation even in the wild-type cells. An enhanced poly(ADP-ribose) accumulation was further observed in Parg{sup −/−} cells. Both Parg{sup −/−} cells and Parp-1{sup −/−} cells did not show sensitization to Fe-ion irradiation. Parg deficiency sensitizes mouse ES cells to a wide therapeutic range of LET radiation through the effects on DNA double strand break repair responses and enhanced cell death.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2018

Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction

Highlights: • Lipofectamine 2000 inhibits entotic cell-in-cell formation. • Lipofectamine 2000 inhibits actomyosin contraction. • Cholesterol and phospholipids inhibits entotic cell-in-cell formation. • Cholesterol inhibits the phosphorylation of myosin light chain. Cell-in-cell structure is prevalent in human cancer, and associated with several specific pathophysiological phenomena. Although cell membrane adhesion molecules were found critical for cell-in-cell formation, the roles of other membrane components, such as lipids, remain to be explored. In this study, we attempted to investigate the effects of cholesterol and phospholipids on the formation of cell-in-cell structures by utilizing liposome as a vector. We found that Lipofectamine-2000, the reagent commonly used for routine transfection, could significantly reduce entotic cell-in-cell formation in a cell-specific manner, which is correlated with suppressed actomyosin contraction as indicated by reduced β-actin expression and myosin light chain phosphorylation. The influence on cell-in-cell formation was likely dictated by specific liposome components as some liposomes affected cell-in-cell formation while some others didn't. Screening on a limited number of lipids, the major components of liposome, identified phosphatidylethanolamine (PE), stearamide (SA), lysophosphatidic acid (LPA) and cholesterol (CHOL) as the inhibitors of cell-in-cell formation. Importantly, cholesterol treatment significantly inhibited myosin light chain phosphorylation, which resembles the effect of Lipofectamine-2000, suggesting cholesterol might be partially responsible for liposomes' effects on cell-in-cell formation. Together, our findings supporting a role of membrane lipids and cholesterol in cell-in-cell formation probably via regulating actomyosin contraction.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2005

Traction in smooth muscle cells varies with cell spreading

Changes in cell shape regulate cell growth, differentiation, and apoptosis. It has been suggested that the regulation of cell function by the cell shape is a result of the tension in the cytoskeleton and the distortion of the cell. Here we explore the association between cell-generated mechanical forces and the cell morphology. We hypothesized that the cell contractile force is associated with the degree of cell spreading, in particular with the cell length. We measured traction fields of single human airway smooth muscle cells plated on a polyacrylamide gel, in which fluorescent microbeads were embedded to serve as markers of gel deformation. The traction exerted by the cells at the cell-substrate interface was determined from the measured deformation of the gel. The traction was measured before and after treatment with the contractile agonist histamine, or the relaxing agonist isoproterenol. The relative increase in traction induced by histamine was negatively correlated with the baseline traction. On the contrary, the relative decrease in traction due to isoproterenol was independent of the baseline traction, but it was associated with cell shape: traction decreased more in elongated than in round cells. Maximum cell width, mean cell width, and projected area of the cell were the parameters most tightly coupled to both baseline and histamine-induced traction in this study. Wide and well-spread cells exerted larger traction than slim cells. These results suggest that cell contractility is controlled by cell spreading.

Non-NASA Center↗
DOE OSTI2021

Antitumor CD8 T cell responses in glioma patients are effectively suppressed by T follicular regulatory cells

Regulatory T (Treg) cells are thought to contribute to tumor pathogenesis by suppressing tumor immunosurveillance and antitumor immunity. T follicular regulatory (Tfr) cells are a recently characterized Treg subset that expresses both the Treg transcription factor (TF) Foxp3 and the T follicular helper (Tfh) TF Bcl-6. The role of Tfr cells in glioma patients remains unclear. In this study, we found that the level of Tfr cells, identified as Foxp3{sup +}Bcl-6{sup +} CD4 T cells, was significantly elevated in tumor-infiltrating CD4 T cells from resected glioma tumors. Both Tfr cells and Treg cells significantly suppressed the proliferation and the cytotoxic capacity of CD8 T cells toward glioma tumor cells, and the suppression was positively associated with the proportion of Tfr cells and Treg cells, respectively. Tfr and Treg cells from glioma tumor samples demonstrated higher suppression potency than those from healthy blood samples and glioma blood samples. Interestingly, canonical CXCR5{sup -} Treg cells could suppress both CXCR5{sup +} and CXCR5{sup -} CD8 T cells, albeit with stronger potency toward CXCR5{sup -} CD8 T cells. However, Tfr cells presented much higher suppression potency toward CXCR5{sup +} CD8 T cells, whereas CXCR5{sup +} CD8 T cells are a potent CD8 T cell subset previously described to have antiviral and antitumor roles. Overall, these data indicate that Tfr cells are enriched in glioma tumors and have suppressive capacity toward CD8 T cell-mediated effector functions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells

Background: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expression of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance. Methods: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analyzed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72 h on expression and cisplatin cytotoxicity was tested. Results: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. Conclusions: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin resistance of NSCLC and MPM cells. Tumour cell resistance to MDR1 inhibitors of cell surface MDR1 and Gb3 could explain the aggressiveness of NSCLC and MPM. Therapy with GCS activity inhibitors or toxin targeting of the Gb3 receptor may substantially reduce acquired cisplatin drug resistance of NSCLC and MPM cells. - Highlights: • The cisplatin-resistant cells had increased cell surface Gb3 and MDR1. • PPMP decreased extracellular Gb3 in the resistant cell lines. • Cyclosporin A decreased extracellular Gb3 and MDR1 in H1299 cells. • PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. • Resistance to inhibitors of MDR1 and Gb3 could explain aggressiveness of NSCLC and MPM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Follicular helper T cells promote the effector functions of CD8+ T cells via the provision of IL-21, which is downregulated due to PD-1/PD-L1-mediated suppression in colorectal cancer

Highlights: • The frequency of Tfh cells was progressively reduced with CRC severity. • Tfh cells in CRC patients presented increasing PD-1 expression with CRC severity. • PD-1 + Tfh presented reduced capacity to stimulate CD8 + T cells than PD-1- Tfh. • Tfh presented progressive loss of IL-21 which controlled CD8 + T cell functions. • Presence of PD-L1-expressing tumor cells further inhibited PD-1 + Tfh cells. Recent studies have demonstrated that higher expression of follicular helper T cell (Tfh)-associated genes is associated with better prognosis in breast cancer and colorectal cancer (CRC), but the underlying mechanisms remain unclear. In this study, we compared the function of Tfh cells in non-cancer (NC) controls and in CRC patients between stages II and IV. Data showed that the level of CD4{sup +}CXCR5{sup +} Tfh cells were significantly upregulated in stage II CRC patients but was progressively reduced in stage III and stage IV patients. The frequency of PD-1{sup +} cells in CD4{sup +}CXCR5{sup +} Tfh cells, on the other hand, was progressively increased from NC patients to CRC patients with increasing severity. Interestingly, the CD4{sup +}CXCR5{sup +}PD-1{sup -} Tfh cells, but not the CD4{sup +}CXCR5{sup +}PD-1{sup +} Tfh cells, promoted the CD107a expression and IFN-γ expression by CD8{sup +} T cells. This CD8{sup +} T cell-promoting capacity was dependent on the expression of IL-21, as this capacity was significantly impaired by IL-21 neutralization. Tfh cells from CRC patients with advanced stages presented gradual reduction in the capacity to stimulate CD8{sup +} T cells and the capacity to produce IL-21. In addition, treatment with autologous PD-L1-expressing tumor cells further suppressed the IL-21 expression by PD-1{sup +} Tfh cells. Together, these data demonstrated that Tfh cells potently enhanced the effector functions of CD8{sup +} T cells in an IL-21-dependent pathway; however, this role of Tfh cells was limited in CRC patients due to PD-1/PD-L1-mediated suppression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Comparison of single junction AlGaInP and GaInP solar cells grown by molecular beam epitaxy

We have investigated ∼2.0 eV (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P and ∼1.9 eV Ga{sub 0.51}In{sub 0.49}P single junction solar cells grown on both on-axis and misoriented GaAs substrates by molecular beam epitaxy (MBE). Although lattice-matched (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P solar cells are highly attractive for space and concentrator photovoltaics, there have been few reports on the MBE growth of such cells. In this work, we demonstrate open circuit voltages (V{sub oc}) ranging from 1.29 to 1.30 V for Ga{sub 0.51}In{sub 0.49}P cells, and 1.35–1.37 V for (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P cells. Growth on misoriented substrates enabled the bandgap-voltage offset (W{sub oc} = E{sub g}/q − V{sub oc}) of Ga{sub 0.51}In{sub 0.49}P cells to decrease from ∼575 mV to ∼565 mV, while that of (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P cells remained nearly constant at 620 mV. The constant W{sub oc} as a function of substrate offcut for (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P implies greater losses from non-radiative recombination compared with the Ga{sub 0.51}In{sub 0.49}P devices. In addition to larger W{sub oc} values, the (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P cells exhibited significantly lower internal quantum efficiency (IQE) values than Ga{sub 0.51}In{sub 0.49}P cells due to recombination at the emitter/window layer interface. A thin emitter design is experimentally shown to be highly effective in improving IQE, particularly at short wavelengths. Our work shows that with further optimization of both cell structure and growth conditions, MBE-grown (Al{sub x}Ga{sub 1−x}){sub 0.51}In{sub 0.49}P will be a promising wide-bandgap candidate material for high-efficiency, lattice-matched multi-junction solar cells.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2017

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture

Background: Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. Methods: The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. Results: TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. Conclusions: SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell populations that had been selected for TRAIL-resistance from initially TRAIL-sensitive populations. SAHA may increase TRAIL sensitivity in insensitive cells, but not in cells that have specifically been selected for acquired TRAIL-resistance. - Highlights: • The HDAC inhibitor SAHA sensitised Myeloma cells to TRAIL-induced apoptosis. • TRAIL, SAHA and combination apoptotic responses are potentiated in 3D cell culture. • TRAIL-resistant cells are not further sensitised to TRAIL-induced apoptosis by SAHA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Snail modulates cell metabolism in MDCK cells

Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of key enzymes. This results in enhanced glucose dependency and leads to cell death under low-glucose conditions. On the other hand, the reduced requirements for oxygen and nutrients from the surrounding environment, might confer the resistance to cell death induced by hypoxia and malnutrition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells

Highlights: •Nanosecond pulsed electric field (nsPEF) is a new and unique means for life sciences. •Apoptosis was induced by nsPEF exposure in Jurkat cells. •No signs of apoptosis were detected in HeLa S3 cells exposed to nsPEFs. •Formation of poly(ADP-ribose) was induced in nsPEF-exposed HeLa S3 cells. •Two distinct modes of cell death were activated by nsPEF in a cell-dependent manner. -- Abstract: Nanosecond pulsed electric fields (nsPEFs) have recently gained attention as effective cancer therapy owing to their potency for cell death induction. Previous studies have shown that apoptosis is a predominant mode of nsPEF-induced cell death in several cell lines, such as Jurkat cells. In this study, we analyzed molecular mechanisms for cell death induced by nsPEFs. When nsPEFs were applied to Jurkat cells, apoptosis was readily induced. Next, we used HeLa S3 cells and analyzed apoptotic events. Contrary to our expectation, nsPEF-exposed HeLa S3 cells exhibited no molecular signs of apoptosis execution. Instead, nsPEFs induced the formation of poly(ADP-ribose) (PAR), a hallmark of necrosis. PAR formation occurred concurrently with a decrease in cell viability, supporting implications of nsPEF-induced PAR formation for cell death. Necrotic PAR formation is known to be catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), and PARP-1 in apoptotic cells is inactivated by caspase-mediated proteolysis. Consistently, we observed intact and cleaved forms of PARP-1 in nsPEF-exposed and UV-irradiated cells, respectively. Taken together, nsPEFs induce two distinct modes of cell death in a cell type-specific manner, and HeLa S3 cells show PAR-associated non-apoptotic cell death in response to nsPEFs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Function and regulation of LAG3 on CD4{sup +}CD25{sup -} T cells in non-small cell lung cancer

LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4{sup +}CD25{sup -} T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4{sup +} T cells directly ex vivo and primarily in the CD4{sup +}CD25{sup -} fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27. TCR stimulation also increased CD25 expression, but not Foxp3 expression, in LAG3-expressing CD4{sup +}CD25{sup -} cells Compared to LAG3-nonexpressing CD4{sup +}CD25{sup -} cells, LAG3-expressing CD4{sup +}CD25{sup -} cells presented significantly higher levels of PD1 and TIM3, two inhibitory receptors best described in exhausted CD8{sup +} T effector cells. LAG3-expressing CD4{sup +}CD25{sup -} cells also presented impaired proliferation compared with LAG3-nonexpressing CD4{sup +}CD25{sup -} cells but could be partially rescued by inhibiting both PD1 and TIM3. Interestingly, CD8{sup +} T cells co-incubated with LAG3-expressing CD4{sup +}CD25{sup -} cells at equal cell numbers demonstrated significantly lower proliferation than CD8{sup +} T cells incubated alone. Co-culture with CD8{sup +} T cell and LAG3-expressing CD4{sup +}CD25{sup -} T cell also upregulated soluble IL-10 level in the supernatant, of which the concentration was positively correlated with the number of LAG3-expressing CD4{sup +}CD25{sup -} T cells. In addition, we found that LAG3-expressing CD4{sup +}CD25{sup -} T cells infiltrated the resected tumors and were present at higher frequencies of in metastases than in primary tumors. Taken together, these data suggest that LAG3-expressing CD4{sup +}CD25{sup -} T cells represent another regulatory immune cell type with potential to interfere with anti-tumor immunity.

60 APPLIED LIFE SCIENCES↗