Antimutagenic and antioxidant properties of the aqueous extracts of organic and conventional grapevine Vitis labrusca cv. Isabella leaves in V79 cells.

PubMed

Trindade, Cristiano; Bortolini, Giovana Vera; Costa, Bárbara Segalotto; Anghinoni, Joanna Carra; Guecheva, Temenouga Nikolova; Arias, Ximena; Césio, Maria Verónica; Heinzen, Horácio; Moura, Dinara Jaqueline; Saffi, Jenifer; Salvador, Mirian; Henriques, João Antonio Pêgas

2016-01-01

Grapes are one of the most commonly consumed fruit, in both fresh and processed forms; however, a significant amount is disposed of in the environment. Searching for a use of this waste, the antigenotoxic, antimutagenic, and antioxidant activities of aqueous extracts from organic and conventional Vitis labrusca leaves were determined using V79 cells as model. The antigenotoxic activity was analyzed by the alkaline comet assay using endonuclease III and formamidopyrimidine DNA glycosylase enzymes. The antimutagenic property was assessed through the micronucleus (MN) formation, and antioxidant activities were assessed using 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA) assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH(●)) radical scavenging, as well as with superoxide dismutase (SOD) and catalase (CAT) activity assays. In addition, phenolic content and ascorbic acid levels of both extracts were determined. Data showed that both organic and conventional grapevine leaves extracts possessed antigenotoxic and antimutagenic properties. The extract of organic leaves significantly reduced intracellular reactive oxygen species (ROS) levels in V79 cells, and displayed greater ability for DPPH(●) scavenging and higher SOD and CAT activities than extract from conventional leaves. Further, the extract from organic leaves contained higher phenolic and ascorbic acid concentrations. In summary, extracts from organic and conventional grape leaves induced important in vitro biological effects.

Enhanced conversion efficiency in wide-bandgap GaNP solar cells

DOE PAGES

Sukrittanon, Supanee; Liu, Ren; Ro, Yun Goo; ...

2015-10-12

In this study, we demonstrate –2.05 eV dilute nitride GaNP solar cells on GaP substrates for potential use as the top junction in dual-junction integrated cells on Si. By adding a small amount of N into indirect-bandgap GaP, GaNP has several extremely important attributes: a direct-bandgap that is also tunable, and easily attained lattice-match with Si. Our best GaNP solar cell ([N] –1.8%, E g –2.05 eV) achieves an efficiency of 7.9%, even in the absence of a window layer. This GaNP solar cell's efficiency is 3× higher than the most efficient GaP solar cell to date and higher thanmore » other solar cells with similar direct bandgap (InGaP, GaAsP). Through a systematic study of the structural, electrical, and optical properties of the device, efficient broadband optical absorption and enhanced solar cell performance are demonstrated.« less

Enhanced microbial reduction of vanadium (V) in groundwater with bioelectricity from microbial fuel cells

NASA Astrophysics Data System (ADS)

Hao, Liting; Zhang, Baogang; Tian, Caixing; Liu, Ye; Shi, Chunhong; Cheng, Ming; Feng, Chuanping

2015-08-01

Bioelectricity generated from the microbial fuel cell (MFC) is applied to the bioelectrical reactor (BER) directly to enhance microbial reduction of vanadium (V) (V(V)) in groundwater. With the maximum power density of 543.4 mW m-2 from the MFC, V(V) removal is accelerated with efficiency of 93.6% during 12 h operation. Higher applied voltage can facilitate this process. V(V) removals decrease with the increase of initial V(V) concentration, while extra addition of chemical oxygen demand (COD) has little effect on performance improvement. Microbial V(V) reduction is enhanced and then suppressed with the increase of conductivity. High-throughput 16S rRNA gene pyrosequencing analysis implies the accumulated Enterobacter and Lactococcus reduce V(V) with products from fermentative microorganisms such as Macellibacteroides. The presentation of electrochemically active bacteria as Enterobacter promotes electron transfers. This study indicates that application of bioelectricity from MFCs is a promising strategy to improve the efficiency of in-situ bioremediation of V(V) polluted groundwater.

The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity.

PubMed

Kersten, B; Zhang, J; Brendler-Schwaab, S Y; Kasper, P; Müller, L

1999-09-15

Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation. Among the phenothiazines tested, chlorpromazine and 2-chlorophenothiazine, were positive for both endpoints, whereas triflupromazine was only slightly photoclastogenic in the presence of strong phototoxicity. Among the other potential human photosensitizers tested (oxytetracycline, doxycycline, metronidazole, emodin, hypericin, griseofulvin), only hypericin was slightly photogenotoxic. Photochemical toxicity in the absence of photochemical genotoxicity was noted for doxycycline and emodin. With the assay system described, it is possible to determine photochemical toxicity and photochemical genotoxicity concomitantly with sufficient reliability.

76 FR 11847 - Thirteenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision...

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2011-03-03

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76 FR 20437 - Fourteenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision...

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2011-04-12

... Special Committee 213: EUROCAE WG- 79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS... Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems... Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS...

Identification of a Secondary Promoter within the Human B Cell Receptor Component Gene hCD79b*

PubMed Central

Yoo, Eung Jae; Cooke, Nancy E.; Liebhaber, Stephen A.

2013-01-01

The human B cell-specific protein, CD79b (also known as Igβ and B29) constitutes an essential signal transduction component of the B cell receptor. Although its function is central to the triggering of B cell terminal differentiation in response to antigen stimulation, the transcriptional determinants that control CD79b gene expression remain poorly defined. In the present study, we explored these determinants using a series of hCD79b transgenic mouse models. Remarkably, we observed that the previously described hCD79b promoter along with its associated enhancer elements and first exon could be deleted without appreciable loss of hCD79b transcriptional activity or tissue specificity. In this deletion setting, a secondary promoter located within exon 2 maintained full levels and specificity of hCD79b transcription. Of note, this secondary promoter was also active, albeit at lower levels, in the wild-type hCD79b locus. The activity of the secondary promoter was dependent on the action(s) of a conserved sequence element mapping to a chromatin DNase I hypersensitive site located within intron 1. mRNA generated from this secondary promoter is predicted to encode an Igβ protein lacking a signal sequence and thus unable to serve normal B cell receptor function. Although the physiologic role of the hCD79b secondary promoter and its encoded protein remain unclear, the current data suggest that it has the capacity to play a role in normal as well as pathologic states in B cell proliferation and function. PMID:23649625

Enhancing the effect of 4MeV electron beam using gold nanoparticles in breast cancer cells.

PubMed

Mehrnia, Somayeh Sadat; Hashemi, Bijan; Mowla, Seyed Javad; Arbabi, Azim

2017-03-01

Gold nanoparticles (GNPs) have been applied as radiosensitizer in radiotherapy. Limited reports have shown that GNPs may be effective as a dose enhancer agent for electron radiation therapy. Some Monte Carlo Simulation studies have shown that selecting suitable size of GNPs and electron energies are critical for effective dose enhancement. The aim of this study was to assess possible radiosensitization effect of GNPs on cancer cell treated with 4MeV electron beams. Approximately 10nm GNPs were synthesized and characterized by electron microscope and dynamic light scattering. MCF-7 and MDA-MB-231 breast cancer cells were used and their viability was measured by MTT assay. Radiosensitization effect of GNPs under 4MeV electron beams was measured by clonogenic assay. The result showed a concentration dependent uptake of GNPs without reducing cell viability at concentrations ≤50mg/L. Incubation of cancer cells with GNPs caused a significant decrease in their viability following exposure to electron beams as well as a decrease in their survival fraction when compared to control. The sensitizer enhancement ratio (SER) by electron beams in MCF-7 cells was 1.43 and 1.40 in presence of 25 and 50mg/L GNPs, respectively. For MDA-MB-231 cells, it was 1.62 in presence of 25mg/L GNPs. Our data demonstrated the significant dose enhancement of the GNPs in combination with 4MeV electron beams that could be applicable for the treatment of superficial tumors and intra operative radiation therapy. Copyright © 2017. Published by Elsevier Ltd.

75 FR 44306 - Eleventh Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-07-28

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75 FR 71183 - Twelfth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-11-22

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Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma

PubMed Central

Nagel, Daniel; Bognar, Miriam; Eitelhuber, Andrea C.; Kutzner, Kerstin; Vincendeau, Michelle; Krappmann, Daniel

2015-01-01

Survival of activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL) is driven by chronic B cell receptor (BCR) signaling that activates the canonical NF-κB pathway. Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79. However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant. Therefore, we assessed here the simultaneous inhibition of BTK and the protease MALT1 that acts downstream of CARMA1 and is essential for ABC DLBCL tumor growth. We show that in CD79 mutant cells BTK is a crucial upstream regulator of MALT1, but dispensable in CARMA1 mutant ABC DLBCL. Combined inhibition of BTK by Ibrutinib and MALT1 by S-Mepazine additively impaired MALT1 cleavage activity and expression of NF-κB pro-survival factors. Thereby, combinatorial Ibrutinib and S-Mepazine treatment enhanced killing of CD79 mutant ABC DLBCL cells. Moreover, while expression of oncogenic CARMA1 in CD79 mutant cells conferred Ibrutinib resistance, double mutant cells were still sensitive to MALT1 inhibition by S-Mepazine. Thus, based on the genetic background combinatorial BTK and MALT1 inhibition may improve effectiveness of therapeutic treatment and reduce the chances for the development of drug resistances. PMID:26540570

Ultraviolet-induced sister chromatid exchanges in V-79 cells with normal and BrdUrd-substituted DNA and the influence of intercalating substances and cysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Speit, G.; Mehnert, K.; Wolf, M.

1982-06-01

The influence of intercalating substances (proflavine, ethidium bromide) and of an SH compound (L-cysteine) on uv-induced sister chromatid exchanges (SCEs) was investigated in V-79 cells with normal and BrdUrd-substituted DNA. The results are discussed in relation to the primary damages leading to SCE induction produced by uv irradiation. The data indicate that neither the pyrimidine dimers nor DNA single-strand breaks are the primary cause of SCE induction, and that the damages leading to SCEs by uv irradiation differ from those which cause chromosome aberrations.

Enhanced vanadium (V) reduction and bioelectricity generation in microbial fuel cells with biocathode

NASA Astrophysics Data System (ADS)

Qiu, Rui; Zhang, Baogang; Li, Jiaxin; Lv, Qing; Wang, Song; Gu, Qian

2017-08-01

Microbial fuel cells (MFCs) represent a promising approach for remediation of toxic vanadium (V) contaminated environment. Herein, enhanced V(V) reduction and bioelectricity generation are realized in MFCs with biocathode. Synergistically electrochemical and microbial reductions result in the nearly complete removals of V(V) within 7 d operation with initial concentration of 200 mg L-1. Maximum power density of 529 ± 12 mW m-2 is obtained. Electrochemical tests reveal that biocathode promotes electron transfers and reduces charge transfer resistance. XPS analysis confirms that V(IV) is the main reduction product, which precipitates naturally under neutral conditions. High-throughput 16S rRNA gene sequencing analysis indicates that the newly appeared Dysgonomonas is responsible for V(V) reduction and Klebsiella contributes mainly to bioelectricity generation in MFCs with biocathode. This study further improves the performance of remediating V(V) contaminated environment based on MFC technology.

Interleukin-4 production by Follicular Helper T cells requires the conserved Il4 enhancer HS V

PubMed Central

Vijayanand, Pandurangan; Seumois, Grégory; Simpson, Laura J.; Abdul-Wajid, Sarah; Baumjohann, Dirk; Panduro, Marisella; Huang, Xiaozhu; Interlandi, Jeneen; Djuretic, Ivana M.; Brown, Daniel R.; Sharpe, Arlene H.; Rao, Anjana; Ansel, K. Mark

2012-01-01

SUMMARY Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that HS V (also known as CNS2), a 3’ enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in Th2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation, and increased accessibility of the Il4 promoter. Thus Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of Th2 mediated allergic diseases. PMID:22326582

75 FR 38863 - Tenth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-07-06

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY...-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing...: Enhanced Flight [[Page 38864

The attachment of V79 and human periodontal ligament fibroblasts on periodontally involved root surfaces following treatment with EDTA, citric acid, or tetracycline HCL: an SEM in vitro study.

PubMed

Chandra, R Viswa; Jagetia, Ganesh Chandra; Bhat, K Mahalinga

2006-02-15

The present in vitro study has been designed to establish and compare the effects of citric acid, EDTA, and tetracycline HCl on human periodontally diseased roots on the structure, attachment, and orientation of V79 (primary Chinese hamster lung fibroblasts) cells and human periodontal ligament fibroblasts (HPDL). Commercially available V79 cells and HPDL derived from healthy human third molars were used in this study. These fibroblasts were left in solution for seven days in order to attain confluence. Forty single-rooted teeth were obtained from patients diagnosed with periodontitis. The crown part was removed under constant irrigation and the root was split vertically into two equal halves, thus, yielding 80 specimens. Following scaling and root planing, the specimens were washed with phosphate buffered saline (PBS) and kept in 50 microg/ml gentamycin sulphate solution for 24 hours. The root pieces were then treated as follows: citric acid at pH 1, 24% EDTA, or with a 10% solution of tetracycline HCl and were then placed in V79 fibroblast cultures and HPDL cultures. The specimens were harvested after four weeks and were fixed in 2.5% glutaraldehyde in PBS before preparation for scanning electron microscopy (SEM). The behavior of V79 cells was similar to that of human periodontal ligament cells on root conditioned surfaces. V79 and HPDL showed a healthy morphology on root surfaces treated with citric acid and EDTA and a relatively unhealthy appearance on root surfaces treated with tetracycline HCl and distilled water (control group). The results suggest the use of citric acid and EDTA as root conditioning agents favorably affects the migration, attachment, and morphology of fibroblasts on human root surfaces, which may play a significant role in periodontal healing and regeneration.

Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

PubMed Central

Burgett, Monica E.; Lathia, Justin D.; Roth, Patrick; Nowacki, Amy S.; Galileo, Deni S.; Pugacheva, Elena; Huang, Ping; Vasanji, Amit; Li, Meizhang; Byzova, Tatiana; Mikkelsen, Tom; Bao, Shideng; Rich, Jeremy N.; Weller, Michael; Gladson, Candece L.

2016-01-01

The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin αvβ3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs. It promotes both EC network formation and enhances directed migration toward basic fibroblast growth factor. Activation of αvβ3 and bone marrow tyrosine kinase on chromosome X (BMX) is required for migration stimulated by direct binding but not for migration stimulated by soluble factors. RGD-peptide treatment of mice with established intracerebral GBM xenografts significantly reduced the percentage of Sox2-positive tumor cells and CSCs in close proximity to ECs, decreased integrin αvβ3 and BMX activation and p130CAS phosphorylation in the ECs, and reduced the vessel surface area. These results reveal a previously unrecognized aspect of the regulation of angiogenesis in GBM that can impact therapeutic anti-angiogenic targeting. PMID:27270311

Preventive efficacy of hydroalcoholic extract of Cymbopogon citratus against radiation-induced DNA damage on V79 cells and free radical scavenging ability against radicals generated in vitro.

PubMed

Rao, B S S; Shanbhoge, R; Rao, B N; Adiga, S K; Upadhya, D; Aithal, B K; Kumar, M R S

2009-04-01

This study presents the findings of free radical scavenging and antigenotoxic effect of hydroalcoholic extract of Cymbopogon citratus (CCE). The CCE at a concentration of 60 microg/mL resulted in a significant scavenging ability of 2,2-diphenyl-2-picryl hydrazyl (DPPH; (85%), 2,2-azinobis (3-ethyl benzothiazoline-6-sulphonic acid) (ABTS; 77%), hydroxyl (70%), superoxide (76%), nitric oxide (78%) free radicals generated using in vitro and also a moderate anti-lipid peroxidative effect (57%). Further, the radiation-induced antigenotoxic potential of CCE was assessed in Chinese hamster lung fibroblast cells (V79) using micronucleus assay. The CCE resulted in a dose-dependent decrease in the yield of radiation-induced micronuclei, with a maximum effect at 125 microg/mL CCE for 1 h before 2 Gy of radiation. Similarly, there was a significant (P < 0.05-0.0001) decrease in percentage of micronuclei when V79 cells were treated with optimal dose of CCE (125 microg/mL) before exposure to different doses of gamma radiation, that is, 0.5-4 Gy, compared with radiation alone groups. The results of the micronucleus study indicated antigenotoxic effect demonstrating the radioprotective potential of CCE and, which may partly due to its and antioxidant capacity as it presented its ability to scavenge various free radicals in vitro and anti-lipid peroxidative potential.

75 FR 17202 - Eighth Meeting: Joint RTCA Special Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems...

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2010-04-05

... Committee 213: EUROCAE WG-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS) AGENCY...-79: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). SUMMARY: The FAA is issuing...: Enhanced Flight Vision Systems/Synthetic Vision Systems (EFVS/SVS). DATES: The meeting will be held April...

X-ray-induced bystander responses reduce spontaneous mutations in V79 cells

PubMed Central

Maeda, Munetoshi; Kobayashi, Katsumi; Matsumoto, Hideki; Usami, Noriko; Tomita, Masanori

2013-01-01

The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10–5 (background level), and the frequency decreased to 5.3 × 10–6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. PMID:23660275

Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies

PubMed Central

Peifang, S.; Pira, G. L.; Fenoglio, D.; Harris, S.; Costa, M. G.; Venturino, V.; Dessì, V.; Layton, G.; Laman, J.; Huisman, J. G.; Manca, F.

1994-01-01

Recombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP p1-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fc receptor-positive antigen-presenting cells. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-specific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP p1 moiety. This suggests that T helper cells specific for the carrier VLP p1 protein can be activated to provide help to V3-specific B cells in the presence of the appropriate antigen construct. PMID:7915974

Enhanced mutagenesis parallels enhanced reactivation of herpes virus in a human cell line.

PubMed Central

Lytle, C D; Knott, D C

1982-01-01

U.v. irradiation of human NB-E cells results in enhanced mutagenesis and enhanced reactivation of u.v.-irradiated H-1 virus grown in those cells ( Cornelis et al., 1982). This paper reports a similar study using herpes simplex virus (HSV) in NB-E cells. The mutation frequency of HSV (resistance of virus plaque formation to 40 micrograms/ml iododeoxycytidine ) increased approximately linearly with exposure of the virus to u.v. radiation. HSV grown in unirradiated cells gave a slope of 1.8 X 10(-5)m2/J, with 3.2 X 10(-5)m2/J for HSV grown in cells irradiated (3 J/m2) 24 h before infection. There was no evidence for mutagenesis of unirradiated virus by irradiated cells, as seen with H-1 virus. Enhanced reactivation of irradiated HSV in parallel cultures increased virus survival, manifested as a change in slope of the final component of the two-component survival curve from a D0 of 27 J/m2 in unirradiated cells to 45 J/m2 in irradiated cells. Thus, enhanced mutagenesis and enhanced reactivation occurred for irradiated HSV in NB-E cells. The difference in the enhanced mutagenesis of HSV (dependent on damaged DNA sites) and of H-1 virus (primarily independent of damaged DNA sites) is discussed in terms of differences in DNA polymerases. PMID:6329698

Melatonin and its precursors in Y79 human retinoblastoma cells - Effect of sodium butyrate

NASA Technical Reports Server (NTRS)

Deng, Mei H.; Lopez G.-Coviella, Ignacio; Lynch, Harry J.; Wurtman, Richard J.

1991-01-01

We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for three days. This protocol dramatically increased the release of melatonin, and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine or L-DOPA markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 ceils.

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

PubMed Central

Cao, Guo-fan; Cao, Cong; Jiang, Qin

2016-01-01

Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. Akt inhibition, via an Akt specific inhibitor (MK-2206) or Akt1 shRNA silence, almost abolished SC79-induced RPE cytoprotection. Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited UV-induced oxidative stress in RPE cells. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. PMID:27517753

Evaluation of the genotoxic and antigenotoxic potential of Baccharis dracunculifolia extract on V79 cells by the comet assay.

PubMed

Munari, Carla Carolina; Alves, Jacqueline Morais; Bastos, Jairo Kenupp; Tavares, Denise Crispim

2010-01-01

Baccharis dracunculifolia (Asteraceae), the main botanical source of green propolis, is a shrub of the Brazilian 'cerrado'. In folk medicine it is used as an anti-inflammatory agent, mainly for the treatment of gastrointestinal diseases. The aim of the present study was to evaluate the genotoxic and antigenotoxic effects of B. dracunculifolia ethyl acetate extract (Bd-EAE) on Chinese hamster lung fibroblasts (V79 cells) by the comet assay. Methyl methanesulfonate (MMS; 200 microM) was used as an inducer of DNA damage. Genotoxicity was evaluated using four different concentrations of Bd-EAE: 12.5, 25.0, 50.0 and 100.0 microg ml(-1). Antigenotoxicity was assessed before, simultaneously, and after treatment with the mutagen. The results showed a significant increase in the frequency of DNA damage in cultures treated with 50.0 and 100.0 microg ml(-1) Bd-EAE. Regarding its antigenotoxic potential, Bd-EAE reduced the frequency of DNA damage induced by MMS. However, this chemopreventive activity depended on the concentrations and treatment regimens used. The antioxidant activity of phenolic components present in Bd-EAE may contribute to reduce the alkylation damage induced by MMS. In conclusion, our findings confirmed the chemopreventive activity of Bd-EAE and showed that this effect occurs under different mechanism.

Mutation of Chinese Hamster V79 cells and transformation and mutation of mouse fibroblast C3H/10T1/2 clone 8 cells by aflatoxin B1 and four other furocoumarins isolated from two Nigerian medicinal plants.

PubMed

Uwaifo, A O; Billings, P C; Heidelberger, C

1983-03-01

Mutation by aflatoxin B1 (AFB1), imperatorin, marmesin, chalepin, and 8-methoxypsoralen (MOP), with and without black light (BL; long-wavelength ultraviolet light) activation, was determined at the hypoxanthine-guanine phosphoribosyltransferase locus (8-azaguanine resistance) in Chinese hamster V79 cells and at the ouabain locus in mouse C3H/1OT1/2 cells. Transformation by these furocoumarins under the same activation conditions was also investigated in C3H/1OT1/2 cells. In V79 cells, AFB1 induced a 4-fold maximum mutation frequency over controls under BL activation at a concentration of 5 micrograms/ml; marmesin induced a 2-fold increased mutation frequency at 1.5 micrograms/ml; MOP induced a 19-fold increase at 10 micrograms/ml; chalepin induced a 3-fold increase at 5 micrograms/ml; and imperatorin induced a 20-fold increase at 10 micrograms/ml. Essentially no mutation was observed at the ouabain-resistant (Ouar) locus in C3H/1OT1/2 cells with any of these compounds. In the transformation assays, type II and type III foci were observed at a 1-microgram/ml addition of AFB1 with or without BL activation; while with MOP and imperatorin, these types of foci were observed only with BL activation. Marmesin, although relatively more cytotoxic than the other furocoumarins studied, with a 50% lethal dose of less than 0.5 micrograms/ml, was not as mutagenic or potentially carcinogenic as were AFB1, imperatorin, or MOP with BL activation. These furocoumarins are considered to be involved in the etiology of the high incidence of skin cancer in Nigeria. Our experiments reinforce that concept and suggest that exposure to these furocoumarins may constitute a real carcinogenic hazard.

Melatonin and its precursors in Y79 human retinoblastoma cells: Effect of sodium butyrate

NASA Technical Reports Server (NTRS)

Deng, Mei Hua; Coviella, Ignacio Lopez G.; Lynch, Harry J.; Wurtman, Richard J.

1991-01-01

The release of melatonin and the production of its precursors, S-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells were studied. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for 3 days. This protocol dramatically increased the release of melatonin, and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine (10 micro-M) or L-DOPA (100 micro-M) markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation (e.g. treatment with sodium butyrate) can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 cells. The inhibition of melatonin release by dopamine supports the hypothesis that in these cells, melatonin and dopamine are components of a retinal feedback loop.

Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells

PubMed Central

Mutschlechner, Sonja; Ferreira, Fatima; Lackner, Peter; Bohle, Barbara; Fischer, Gottfried F.; Vogt, Anne B.; Duschl, Albert

2012-01-01

Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins. PMID:22348091

Enhanced Charge Extraction of Li-Doped TiO₂ for Efficient Thermal-Evaporated Sb₂S₃ Thin Film Solar Cells.

PubMed

Lan, Chunfeng; Luo, Jingting; Lan, Huabin; Fan, Bo; Peng, Huanxin; Zhao, Jun; Sun, Huibin; Zheng, Zhuanghao; Liang, Guangxing; Fan, Ping

2018-02-28

We provided a new method to improve the efficiency of Sb₂S₃ thin film solar cells. The TiO₂ electron transport layers were doped by lithium to improve their charge extraction properties for the thermal-evaporated Sb₂S₃ solar cells. The Mott-Schottky curves suggested a change of energy band and faster charge transport in the Li-doped TiO₂ films. Compared with the undoped TiO₂, Li-doped mesoporous TiO₂ dramatically improved the photo-voltaic performance of the thermal-evaporated Sb₂S₃ thin film solar cells, with the average power conversion efficiency ( PCE ) increasing from 1.79% to 4.03%, as well as the improved open-voltage ( V oc ), short-circuit current ( J sc ) and fill factors. The best device based on Li-doped TiO₂ achieved a power conversion efficiency up to 4.42% as well as a V oc of 0.645 V, which are the highest values among the reported thermal-evaporated Sb₂S₃ solar cells. This study showed that Li-doping on TiO₂ can effectively enhance the charge extraction properties of electron transport layers, offering a new strategy to improve the efficiency of Sb₂S₃-based solar cells.

In vitro characterization of CD133lo cancer stem cells in Retinoblastoma Y79 cell line.

PubMed

Nair, Rohini M; Balla, Murali Ms; Khan, Imran; Kalathur, Ravi Kiran Reddy; Kondaiah, Paturu; Vemuganti, Geeta K

2017-11-21

Retinoblastoma (Rb), the most common childhood intraocular malignant tumor, is reported to have cancer stem cells (CSCs) similar to other tumors. Our previous investigation in primary tumors identified the small sized cells with low CD133 (Prominin-1) and high CD44 (Hyaluronic acid receptor) expression to be putative Rb CSCs using flow cytometry (FSC lo /SSC lo /CD133 lo /CD44 hi ). With this preliminary data, we have now utilized a comprehensive approach of in vitro characterization of Y79 Rb cell line following CSC enrichment using CD133 surface marker and subsequent validation to confirm the functional properties of CSCs. The cultured Rb Y79 cells were evaluated for surface markers by flow cytometry and CD133 sorted cells (CD133 lo /CD133 hi ) were compared for CSC characteristics by size/percentage, cell cycle assay, colony formation assay, differentiation, Matrigel transwell invasion assay, cytotoxicity assay, gene expression using microarray and validation by semi-quantitative PCR. Rb Y79 cell line shared the profile (CD133, CD90, CXCR4 and ABCB1) of primary tumors except for CD44 expression. The CD133 lo cells (16.1 ± 0.2%) were FSC lo /SSC lo , predominantly within the G0/G1 phase, formed larger and higher number of colonies with ability to differentiate to CD133 hi cells, exhibited increased invasive potential in a matrigel transwell assay (p < 0.05) and were resistant to Carboplatin treatment (p < 0.001) as compared to CD133 hi cells. The CD133 lo cells showed higher expression of several embryonic stem cell genes (HOXB2, HOXA9, SALL1, NANOG, OCT4, LEFTY), stem cells/progenitor genes (MSI2, BMI1, PROX1, ABCB1, ABCB5, ABCG2), and metastasis related gene- MACC1, when compared to the CD133 hi cells. This study validates the observation from our earlier primary tumor study that CSC properties in Rb Y79 cell line are endowed within the CD133 lo population, evident by their characteristics- i.e. small sized, dormant in nature, increased colony forming

Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced radiosensitivity of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations.

PubMed

Huang, Xiaomin; Liu, Ting; Wang, Qiongyao; Zhu, Weiliang; Meng, Hui; Guo, Linlang; Wei, Ting; Zhang, Jian

2017-05-23

N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyses the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR. GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. Subsequently, we further explored the signalling downstream of EGF, particularly the PI3K/Akt signalling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumour growth. In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC radiosensitivity, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Hyeon-Ok; Hong, Sung-Eun; Kim, Chang Soon

2015-08-15

Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drugmore » alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.« less

Enhancement of Photovoltaic Performance by Utilizing Readily Accessible Hole Transporting Layer of Vanadium(V) Oxide Hydrate in a Polymer-Fullerene Blend Solar Cell.

PubMed

Jiang, Youyu; Xiao, Shengqiang; Xu, Biao; Zhan, Chun; Mai, Liqiang; Lu, Xinhui; You, Wei

2016-05-11

Herein, a successful application of V2O5·nH2O film as hole transporting layer (HTL) instead of PSS in polymer solar cells is demonstrated. The V2O5·nH2O layer was spin-coated from V2O5·nH2O sol made from melting-quenching sol-gel method by directly using vanadium oxide powder, which is readily accessible and cost-effective. V2O5·nH2O (n ≈ 1) HTL is found to have comparable work function and smooth surface to that of PSS. For the solar cell containing V2O5·nH2O HTL and the active layer of the blend of a novel polymer donor (PBDSe-DT2PyT) and the acceptor of PC71BM, the PCE was significantly improved to 5.87% with a 30% increase over 4.55% attained with PSS HTL. Incorporation of V2O5·nH2O as HTL in the polymer solar cell was found to enhance the crystallinity of the active layer, electron-blocking at the anode and the light-harvest in the wavelength range of 400-550 nm in the cell. V2O5·nH2O HTL improves the charge generation and collection and suppress the charge recombination within the PBDSe-DT2PyT:PC71BM solar cell, leading to a simultaneous enhancement in Voc, Jsc, and FF. The V2O5·nH2O HTL proposed in this work is envisioned to be of great potential to fabricate highly efficient PSCs with low-cost and massive production.

5-Fluorouracil, colchicine, benzo[a]pyrene and cytosine arabinoside tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster V79 cells at Covance Laboratories, Harrogate, UK in support of OECD draft Test Guideline 487.

PubMed

Whitwell, James; Fowler, Paul; Allars, Sarah; Jenner, Karen; Lloyd, Melvyn; Wood, Debbie; Smith, Katie; Young, Jamie; Jeffrey, Laura; Kirkland, David

2010-10-29

The reference genotoxic agents 5-fluorouracil (a nucleoside analogue, characterised by a steep dose response profile), colchicine (an aneugen that inhibits tubulin polymerisation), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation) and cytosine arabinoside (a nucleoside analogue that inhibits the gap-filling step of excision repair) were tested in the in vitro micronucleus assay using the Chinese hamster V79 cell line at Covance Laboratories, Harrogate, UK. All chemicals were treated in the absence and presence of cytokinesis block (via addition of cytochalasin B) with this work forming part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 on the In Vitro Mammalian Cell Micronucleus Test (MNvit). The toxicity measures used, detecting a possible combination of both cytostasis and cell death (though not cell death directly), were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index in the presence of cytokinesis block. All of the chemicals tested either gave marked increases in the percentage of micronucleated cells with and without cytokinesis block, or did not induce micronuclei at concentrations giving approximately 50-60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcome from this series of tests supports the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells.

PubMed

Thust, R; Mendel, J; Bach, B; Schwarz, H

1985-06-01

The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid.

EZH2 and CD79B mutational status over time in B-cell non-Hodgkin lymphomas detected by high-throughput sequencing using minimal samples

PubMed Central

Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Bailey, Denis; Crump, Michael; da Cunha Santos, Gilda

2013-01-01

BACKGROUND: Numerous genomic abnormalities in B-cell non-Hodgkin lymphomas (NHLs) have been revealed by novel high-throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B-cell NHLs, through use of a customized multiplex mutation assay. METHODS: DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin-fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing. RESULTS: All 121 samples from 80 B-cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B-cell lymphomas. In one-third of the positive cases, a wild type was detected in a different sample from the same patient during follow-up. CONCLUSIONS: Testing multiple minimal tissue samples using a high-throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B-cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013;121:377–386. © 2013 American Cancer Society. PMID:23361872

Enhanced current collection in 1.7 eV GaInAsP solar cells grown on GaAs by metalorganic vapor phase epitaxy

DOE PAGES

Jain, Nikhil; Geisz, John F.; France, Ryan M.; ...

2017-02-08

Quaternary GaInAsP solar cells with a bandgap of ~1.7 eV offer an attractive Al-free alternative to AlGaAs solar cells for integration in next generation of III-V multijunction solar cells with five or more junctions. Development of a high quality 1.7 eV solar cell is also highly sought for III-V/Si tandem solar cells. In this work, we systematically investigate the impact of varying base thicknesses and doping concentrations on the carrier collection and performance of 1.7 eV GaInAsP solar cells. The photoresponse of these cells is found to be very sensitive to p-type zinc doping concentration in the base layer. Prototypemore » 1.7 eV GaInAsP n-i-p solar cell designs are demonstrated that leverage enhanced depletion width as an effective method to achieve peak quantum efficiency exceeding 90%. We also show the importance of optimal i-layer thickness as a critical parameter to reduce the drop in fill-factor (FF) due to field-aided collection. Furthermore, we demonstrate substantial improvement in the cell performance when the GaInAsP base layer is grown at 650 degrees C instead of 600 degrees C. The best GaInAsP solar cell (Eg ~ 1.65 eV) in this study achieved JSC of 21.1 mA/cm 2, VOC of 1.18 V, FF of 83.8%, and an efficiency of 20.8 +/- 1% under AM1.5D spectrum (21.5 +/- 1% under AM1.5G spectrum). Finally, these results highlight the potential of Al-free GaInAsP solar cells for integration in the next generation of III-V multijunction solar cells.« less

Enhanced current collection in 1.7 eV GaInAsP solar cells grown on GaAs by metalorganic vapor phase epitaxy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Nikhil; Geisz, John F.; France, Ryan M.

Quaternary GaInAsP solar cells with a bandgap of ~1.7 eV offer an attractive Al-free alternative to AlGaAs solar cells for integration in next generation of III-V multijunction solar cells with five or more junctions. Development of a high quality 1.7 eV solar cell is also highly sought for III-V/Si tandem solar cells. In this work, we systematically investigate the impact of varying base thicknesses and doping concentrations on the carrier collection and performance of 1.7 eV GaInAsP solar cells. The photoresponse of these cells is found to be very sensitive to p-type zinc doping concentration in the base layer. Prototypemore » 1.7 eV GaInAsP n-i-p solar cell designs are demonstrated that leverage enhanced depletion width as an effective method to achieve peak quantum efficiency exceeding 90%. We also show the importance of optimal i-layer thickness as a critical parameter to reduce the drop in fill-factor (FF) due to field-aided collection. Furthermore, we demonstrate substantial improvement in the cell performance when the GaInAsP base layer is grown at 650 degrees C instead of 600 degrees C. The best GaInAsP solar cell (Eg ~ 1.65 eV) in this study achieved JSC of 21.1 mA/cm 2, VOC of 1.18 V, FF of 83.8%, and an efficiency of 20.8 +/- 1% under AM1.5D spectrum (21.5 +/- 1% under AM1.5G spectrum). Finally, these results highlight the potential of Al-free GaInAsP solar cells for integration in the next generation of III-V multijunction solar cells.« less

Alkylarylnitrosoureas--stability in aqueous solution, partition coefficient, alkylating activity and its relationship to SCE induction in Chinese hamster V 79-E cells.

PubMed

Mendel, J; Thust, R; Schwarz, H

1982-01-01

The alkylating activity, chemical stability in aqueous solution (pH 7.0; 37 degrees C), and partition coefficient (octanol/water) of the following compounds were determined: 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1-isopropyl-3-phenyl-1-nitrosourea (i-PrPNU), 1-methyl-3-(p-fluorophenyl)-1-nitrosourea (F-MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (Cl-MPNU), 1-methyl-3-(p-bromophenyl)-1-nitrosourea (Br-MPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU), and 1-methyl-3-naphthyl-1-nitrosocarbamate (NCA). 1-Methyl-1-nitrosourea (MNU) and 1-ethyl-1-nitrosourea (ENU) were used for the comparison. THe rate of decomposition in aqueous solution is discussed concerning the influences of the substituents at the 1- and 3-N-atom. The mono- and disubstituted N-nitrosoureas showed a coarse correlation between alkylating activity and SCE induction in Chinese hamster V 79-E cells. On the other hand, this correlation is missing in the case of NCA, which is a potent SCE inducer despite relatively low alkylating activity. DMPNU is the strongest SCE inducer, but this compound shows a high stability in aqueous solution and, consequently, we were not able to detect an alkylating activity.

Toward an Objective Enhanced-V Detection Algorithm

NASA Technical Reports Server (NTRS)

Brunner, Jason; Feltz, Wayne; Moses, John; Rabin, Robert; Ackerman, Steven

2007-01-01

The area of coldest cloud tops above thunderstorms sometimes has a distinct V or U shape. This pattern, often referred to as an "enhanced-V' signature, has been observed to occur during and preceding severe weather in previous studies. This study describes an algorithmic approach to objectively detect enhanced-V features with observations from the Geostationary Operational Environmental Satellite and Low Earth Orbit data. The methodology consists of cross correlation statistics of pixels and thresholds of enhanced-V quantitative parameters. The effectiveness of the enhanced-V detection method will be examined using Geostationary Operational Environmental Satellite, MODerate-resolution Imaging Spectroradiometer, and Advanced Very High Resolution Radiometer image data from case studies in the 2003-2006 seasons. The main goal of this study is to develop an objective enhanced-V detection algorithm for future implementation into operations with future sensors, such as GOES-R.

Different sensitivities of cultured mammalian cells towards aphidicolin-enhanced DNA effects in the comet assay.

PubMed

Speit, Günter; Schütz, Petra; Bausinger, Julia

2016-06-01

The comet assay in combination with the polymerase inhibitor aphidicolin (APC) has been used to measure DNA excision repair activity, DNA repair kinetics and individual DNA repair capacity. Since APC can enhance genotoxic effects of mutagens measured by the comet assay, this approach has been proposed for increasing the sensitivity of the comet assay in human biomonitoring. The APC-modified comet assay has mainly been performed with human blood and it was shown that it not only enhances the detection of DNA damage repaired by nucleotide excision repair (NER) but also damage typically repaired by base excision repair (BER). Recently, we reported that in contrast to blood leukocytes, A549 cells (a human lung adenocarcinoma cell line) seem to be insensitive towards the repair-inhibiting action of APC. To further elucidate the general usefulness of the APC-modified comet assay for studying repair in cultured mammalian cells, we comparatively investigated further cell lines (HeLa, TK6, V79). DNA damage was induced by BPDE (benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide) and MMS (methyl methanesulfonate) in the absence and presence of APC (3 or 15μM). APC was either added for 2h together with the mutagen or cells were pre-incubated for 30min with APC before the mutagen was added. The results indicate that the cell lines tested differ fundamentally with regard to their sensitivity and specificity towards the repair-inhibiting effect of APC. The actual cause for these differences is still unclear but potential molecular explanations are discussed. Irrespective of the underlying mechanism(s), our study revealed practical limitations of the use of the APC-modified comet assay. Copyright © 2016 Elsevier B.V. All rights reserved.

Bombyx mori nucleopolyhedrovirus ORF79 is a per os infectivity factor associated with the PIF complex.

PubMed

Dong, Zhan-Qi; Zhang, Jun; Chen, Xue-Mei; He, Qian; Cao, Ming-Ya; Wang, La; Li, Hai-Qing; Xiao, Wen-Fu; Pan, Cai-Xia; Lu, Cheng; Pan, Min-Hui

2014-05-12

Bombyx mori nucleopolyhedrovirus (BmNPV) ORF79 (Bm79) encodes an occlusion-derived virus (ODV)-specific envelope protein, which is a homologue of the per os infectivity factor 4 (PIF4) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). To investigate the role of ORF79 in the BmNPV life cycle, a Bm79 knockout virus (vBm(Bm79KO)) was constructed through homologous recombination in Escherichia coli. Viral DNA replication, budded virus (BV) production and polyhedra formation were unaffected by the absence of BM79. However, results of the larval bioassay demonstrated that the Bm79 deletion resulted in a complete loss of per os infection. Immunofluorescence analysis showed that BM79 localized at the innernuclear membrane of infected cells through its N-terminal sorting motif (SM). Further bimolecular fluorescence protein complementation and co-immunoprecipitation assays demonstrated the interaction of BM79 with PIF1, PIF2, PIF3 and ODV-E66. Thus, BM79 plays an important role in per os infection and is associated with the viral PIF complex of BmNPV. Copyright © 2014 Elsevier B.V. All rights reserved.

B cell receptor accessory molecule CD79α: Characterisation and expression analysis in a cartilaginous fish, the spiny dogfish (Squalus acanthias)

PubMed Central

Li, Ronggai; Wang, Tiehui; Bird, Steve; Zou, Jun; Dooley, Helen; Secombes, Christopher J.

2013-01-01

CD79α (also known as Igα) is a component of the B cell antigen receptor complex and plays an important role in B cell signalling. The CD79α protein is present on the surface of B cells throughout their life cycle, and is absent on all other healthy cells, making it a highly reliable marker for B cells in mammals. In this study the spiny dogfish (Squalus acanthias) CD79α (SaCD79α) is described and its expression studied under constitutive and stimulated conditions. The spiny dogfish CD79α cDNA contains an open reading frame of 618 bp, encoding a protein of 205 amino acids. Comparison of the SaCD79α gene with that of other species shows that the gross structure (number of exons, exon/intron boundaries, etc.) is highly conserved across phylogeny. Additionally, analysis of the 5′ flanking region shows SaCD79α lacks a TATA box and possesses binding sites for multiple transcription factors implicated in its B cell-specific gene transcription in other species. Spiny dogfish CD79α is most highly expressed in immune tissues, such as spleen, epigonal and Leydig organ, and its transcript level significantly correlates with those of spiny dogfish immunoglobulin heavy chains. Additionally, CD79α transcription is up-regulated, to a small but significant degree, in peripheral blood cells following stimulation with pokeweed mitogen. These results strongly indicate that, as in mammals, spiny dogfish CD79α is expressed by shark B cells where it associates with surface-bound immunoglobulin to form a fully functional BCR, and thus may serve as a pan-B cell marker in future shark immunological studies. PMID:23454429

B cell receptor accessory molecule CD79α: characterisation and expression analysis in a cartilaginous fish, the spiny dogfish (Squalus acanthias).

PubMed

Li, Ronggai; Wang, Tiehui; Bird, Steve; Zou, Jun; Dooley, Helen; Secombes, Christopher J

2013-06-01

CD79α (also known as Igα) is a component of the B cell antigen receptor complex and plays an important role in B cell signalling. The CD79α protein is present on the surface of B cells throughout their life cycle, and is absent on all other healthy cells, making it a highly reliable marker for B cells in mammals. In this study the spiny dogfish (Squalus acanthias) CD79α (SaCD79α) is described and its expression studied under constitutive and stimulated conditions. The spiny dogfish CD79α cDNA contains an open reading frame of 618 bp, encoding a protein of 205 amino acids. Comparison of the SaCD79α gene with that of other species shows that the gross structure (number of exons, exon/intron boundaries, etc.) is highly conserved across phylogeny. Additionally, analysis of the 5' flanking region shows SaCD79α lacks a TATA box and possesses binding sites for multiple transcription factors implicated in its B cell-specific gene transcription in other species. Spiny dogfish CD79α is most highly expressed in immune tissues, such as spleen, epigonal and Leydig organ, and its transcript level significantly correlates with those of spiny dogfish immunoglobulin heavy chains. Additionally, CD79α transcription is up-regulated, to a small but significant degree, in peripheral blood cells following stimulation with pokeweed mitogen. These results strongly indicate that, as in mammals, spiny dogfish CD79α is expressed by shark B cells where it associates with surface-bound immunoglobulin to form a fully functional BCR, and thus may serve as a pan-B cell marker in future shark immunological studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Membrane penetrating peptides greatly enhance baculovirus transduction efficiency into mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Hong-Zhang; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, ROC; Wu, Carol P.

2011-02-11

Research highlights: {yields} Ligation of CTP with GP64 enhances baculovirus transduction into mammalian cells. {yields} Fusion of PTD with VP39 enhances baculovirus transduction into mammalian cells. {yields} CTP and PTD-carrying viruses improve the transduction of co-transduced baculoviruses. {yields} Virus entry and gene expression can be separate events in different cell types. -- Abstract: The baculovirus group of insect viruses is widely used for foreign gene introduction into mammalian cells for gene expression and protein production; however, the efficiency of baculovirus entry into mammalian cells is in general still low. In this study, two recombinant baculoviruses were engineered and their abilitymore » to improve viral entry was examined: (1) cytoplasmic transduction peptide (CTP) was fused with baculovirus envelope protein, GP64, to produce a cytoplasmic membrane penetrating baculovirus (vE-CTP); and (2) the protein transduction domain (PTD) of HIV TAT protein was fused with the baculovirus capsid protein VP39 to form a nuclear membrane penetrating baculovirus (vE-PTD). Transduction experiments showed that both viruses had better transduction efficiency than vE, a control virus that only expresses EGFP in mammalian cells. Interestingly, vE-CTP and vE-PTD were also able to improve the transduction efficiency of a co-transduced baculovirus, resulting in higher levels of gene expression. Our results have described new routes to further enhance the development of baculovirus as a tool for gene delivery into mammalian cells.« less

Silencing of secretory clusterin sensitizes NSCLC cells to V-ATPase inhibitors by downregulating survivin.

PubMed

Kim, Young-Sun; Jin, Hyeon-Ok; Hong, Sung-Eun; Song, Jie-Young; Hwang, Chang-Sun; Park, In-Chul

2018-01-08

Secretory clusterin (sCLU) is a stress-associated protein that confers resistance to therapy when overexpressed. In this study, we observed that the V-ATPase inhibitors bafilomycin A1 and concanamycin A significantly stimulated sCLU protein expression. Knockdown of sCLU with siRNA sensitized non-small cell lung cancer (NSCLC) cells to bafilomycin A1, suggesting that sCLU expression renders cells resistant to V-ATPase inhibitors. The dual PI3K/AKT and mTOR inhibitor BEZ235 suppressed sCLU expression and enhanced cell sensitivity induced by bafilomycin A1. Notably, sCLU knockdown further decreased the expression of the survivin protein by bafilomycin A1, and the ectopic expression of survivin alleviated the cell sensitivity by bafilomycin A1 and sCLU depletion, suggesting that increased sensitivity to sCLU depletion in the cells with V-ATPase inhibitors is due, at least in part, to the down-regulation of survivin. Taken together, we demonstrated that the depletion of sCLU expression enhances the sensitivity of NSCLC cells to V-ATPase inhibitors by decreasing survivin expression. Inhibition of the PI3K/AKT/mTOR pathway enhances the sensitivity of NSCLC cells to V-ATPase inhibitors, leading to decreased sCLU and survivin expression. Thus, we suggest that a combination of PI3K/AKT/mTOR inhibitors with V-ATPase inhibitors might be an effective approach for NSCLC treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-CD22 and anti-CD79b antibody-drug conjugates preferentially target proliferating B cells.

PubMed

Fuh, Franklin K; Looney, Caroline; Li, Dongwei; Poon, Kirsten A; Dere, Randall C; Danilenko, Dimitry M; McBride, Jacqueline; Reed, Chae; Chung, Shan; Zheng, Bing; Mathews, William Rodney; Polson, Andrew; Prabhu, Saileta; Williams, Marna

2017-04-01

CD22 and CD79b are cell-surface receptors expressed on B-cell-derived malignancies such as non-Hodgkin's lymphoma (NHL). An anti-mitotic agent, monomethyl auristatin E, was conjugated to anti-CD22 and anti-CD79b antibodies to develop target-specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody-drug conjugates (ADCs) were investigated in cynomolgus monkeys. Animals were administered anti-CD22 or anti-CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of the ADCs were evaluated in vitro. Depletion of B cells was observed after administration of either ADC or the respective unconjugated antibodies. An extended duration of depletion was observed in animals administered ADCs. Similarly, preferential depletion of proliferating B cells in blood and germinal centre B cells in spleen were only observed in animals administered ADCs. Serum PK profiles of ADCs and respective unconjugated antibodies were comparable. In vitro, anti-human CD22 and anti-human CD79b antibodies showed no or only moderate ADCC activity, respectively; neither antibody had CDC activity. The findings support the proposed MOA: initial depletion of total B cells by antibody-mediated opsonization, followed by preferential, sustained depletion of proliferating B cells by the auristatin conjugate due to its anti-mitotic action. Delivering potent anti-mitotic agents to B cells via the specificity of monoclonal antibodies provides a means to eliminate pathogenic B cells in NHL with improved risk-benefit profiles over traditional chemotherapeutics. © 2016 Genentech. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Enhanced Conversion Efficiency of III–V Triple-junction Solar Cells with Graphene Quantum Dots

PubMed Central

Lin, Tzu-Neng; Santiago, Svette Reina Merden S.; Zheng, Jie-An; Chao, Yu-Chiang; Yuan, Chi-Tsu; Shen, Ji-Lin; Wu, Chih-Hung; Lin, Cheng- An J.; Liu, Wei-Ren; Cheng, Ming-Chiang; Chou, Wu-Ching

2016-01-01

Graphene has been used to synthesize graphene quantum dots (GQDs) via pulsed laser ablation. By depositing the synthesized GQDs on the surface of InGaP/InGaAs/Ge triple-junction solar cells, the short-circuit current, fill factor, and conversion efficiency were enhanced remarkably. As the GQD concentration is increased, the conversion efficiency in the solar cell increases accordingly. A conversion efficiency of 33.2% for InGaP/InGaAs/Ge triple-junction solar cells has been achieved at the GQD concentration of 1.2 mg/ml, corresponding to a 35% enhancement compared to the cell without GQDs. On the basis of time-resolved photoluminescence, external quantum efficiency, and work-function measurements, we suggest that the efficiency enhancement in the InGaP/InGaAs/Ge triple-junction solar cells is primarily caused by the carrier injection from GQDs to the InGaP top subcell. PMID:27982073

Anti‐CD22 and anti‐CD79b antibody‐drug conjugates preferentially target proliferating B cells

PubMed Central

Fuh, Franklin K; Looney, Caroline; Li, Dongwei; Poon, Kirsten A; Dere, Randall C; Danilenko, Dimitry M; McBride, Jacqueline; Reed, Chae; Chung, Shan; Zheng, Bing; Mathews, William Rodney; Polson, Andrew; Williams, Marna

2017-01-01

Background and Purpose CD22 and CD79b are cell‐surface receptors expressed on B‐cell‐derived malignancies such as non‐Hodgkin's lymphoma (NHL). An anti‐mitotic agent, monomethyl auristatin E, was conjugated to anti‐CD22 and anti‐CD79b antibodies to develop target‐specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody‐drug conjugates (ADCs) were investigated in cynomolgus monkeys. Experimental Approach Animals were administered anti‐CD22 or anti‐CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) of the ADCs were evaluated in vitro. Key Results Depletion of B cells was observed after administration of either ADC or the respective unconjugated antibodies. An extended duration of depletion was observed in animals administered ADCs. Similarly, preferential depletion of proliferating B cells in blood and germinal centre B cells in spleen were only observed in animals administered ADCs. Serum PK profiles of ADCs and respective unconjugated antibodies were comparable. In vitro, anti‐human CD22 and anti‐human CD79b antibodies showed no or only moderate ADCC activity, respectively; neither antibody had CDC activity. Conclusions and Implications The findings support the proposed MOA: initial depletion of total B cells by antibody‐mediated opsonization, followed by preferential, sustained depletion of proliferating B cells by the auristatin conjugate due to its anti‐mitotic action. Delivering potent anti‐mitotic agents to B cells via the specificity of monoclonal antibodies provides a means to eliminate pathogenic B cells in NHL with improved risk–benefit profiles over traditional chemotherapeutics. PMID:28009435

Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells.

PubMed

Molnár, Eszter; Rittler, Dominika; Baranyi, Marcell; Grusch, Michael; Berger, Walter; Döme, Balázs; Tóvári, József; Aigner, Clemens; Tímár, József; Garay, Tamás; Hegedűs, Balázs

2018-05-08

Currently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines. Six BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model. All cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment. Our data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors.

Hybrid silicon honeycomb/organic solar cells with enhanced efficiency using surface etching.

PubMed

Liu, Ruiyuan; Sun, Teng; Liu, Jiawei; Wu, Shan; Sun, Baoquan

2016-06-24

Silicon (Si) nanostructure-based photovoltaic devices are attractive for their excellent optical and electrical performance, but show lower efficiency than their planar counterparts due to the increased surface recombination associated with the high surface area and roughness. Here, we demonstrate an efficiency enhancement for hybrid nanostructured Si/polymer solar cells based on a novel Si honeycomb (SiHC) structure using a simple etching method. SiHC structures are fabricated using a combination of nanosphere lithography and plasma treatment followed by a wet chemical post-etching. SiHC has shown superior light-trapping ability in comparison with the other Si nanostructures, along with a robust structure. Anisotropic tetramethylammonium hydroxide etching not only tunes the final surface morphologies of the nanostructures, but also reduces the surface roughness leading to a lower recombination rate in the hybrid solar cells. The suppressed recombination loss, benefiting from the reduced surface-to-volume ratio and roughness, has resulted in a high open-circuit voltage of 600 mV, a short-circuit current of 31.46 mA cm(-2) due to the light-trapping ability of the SiHCs, and yields a power conversion efficiency of 12.79% without any other device structure optimization.

Back reflectors based on buried Al{sub 2}O{sub 3} for enhancement of photon recycling in monolithic, on-substrate III-V solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

García, I.; Instituto de Energía Solar, Universidad Politécnica de Madrid, Avda Complutense s/n, 28040 Madrid; Kearns-McCoy, C. F.

Photon management has been shown to be a fruitful way to boost the open circuit voltage and efficiency of high quality solar cells. Metal or low-index dielectric-based back reflectors can be used to confine the reemitted photons and enhance photon recycling. Gaining access to the back of the solar cell for placing these reflectors implies having to remove the substrate, with the associated added complexity to the solar cell manufacturing. In this work, we analyze the effectiveness of a single-layer reflector placed at the back of on-substrate solar cells, and assess the photon recycling improvement as a function of themore » refractive index of this layer. Al{sub 2}O{sub 3}-based reflectors, created by lateral oxidation of an AlAs layer, are identified as a feasible choice for on-substrate solar cells, which can produce a V{sub oc} increase of around 65% of the maximum increase attainable with an ideal reflector. The experimental results obtained using prototype GaAs cell structures show a greater than two-fold increase in the external radiative efficiency and a V{sub oc} increase of ∼2% (∼18 mV), consistent with theoretical calculations. For GaAs cells with higher internal luminescence, this V{sub oc} boost is calculated to be up to 4% relative (36 mV), which directly translates into at least 4% higher relative efficiency.« less

Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.

PubMed

Wu, Youbin; Wu, Shipo; Hou, Lihua; Wei, Wei; Zhou, Meng; Su, Zhiguo; Wu, Jie; Chen, Wei; Ma, Guanghui

2012-08-01

A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Economic Analysis. Volume V. Course Segments 65-79.

ERIC Educational Resources Information Center

Sterling Inst., Washington, DC. Educational Technology Center.

The fifth volume of the multimedia, individualized course in economic analysis produced for the United States Naval Academy covers segments 65-79 of the course. Included in the volume are discussions of monopoly markets, monopolistic competition, oligopoly markets, and the theory of factor demand and supply. Other segments of the course, the…

Enhancing Efficiency of Perovskite Solar Cells via Surface Passivation with Graphene Oxide Interlayer.

PubMed

Li, Hao; Tao, Leiming; Huang, Feihong; Sun, Qiang; Zhao, Xiaojuan; Han, Junbo; Shen, Yan; Wang, Mingkui

2017-11-08

Perovskite solar cells have been demonstrated as promising low-cost and highly efficient next-generation solar cells. Enhancing V OC by minimization the interfacial recombination kinetics can further improve device performance. In this work, we for the first time reported on surface passivation of perovskite layers with chemical modified graphene oxides, which act as efficient interlayer to reduce interfacial recombination and enhance hole extraction as well. Our modeling points out that the passivation effect mainly comes from the interaction between functional group (4-fluorophenyl) and under-coordinated Pb ions. The resulting perovskite solar cells achieved high efficient power conversion efficiency of 18.75% with enhanced high open circuit V OC of 1.11 V. Ultrafast spectroscopy, photovoltage/photocurrent transient decay, and electronic impedance spectroscopy characterizations reveal the effective passivation effect and the energy loss mechanism. This work sheds light on the importance of interfacial engineering on the surface of perovskite layers and provides possible ways to improve device efficiency.

Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization.

PubMed

Driffort, Virginie; Gillet, Ludovic; Bon, Emeline; Marionneau-Lambot, Séverine; Oullier, Thibauld; Joulin, Virginie; Collin, Christine; Pagès, Jean-Christophe; Jourdan, Marie-Lise; Chevalier, Stéphan; Bougnoux, Philippe; Le Guennec, Jean-Yves; Besson, Pierre; Roger, Sébastien

2014-12-11

Na(V)1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expression level is associated with metastatic occurrence and patients' death. In breast cancer cells, Na(V)1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness. In this study, we showed that the extinction of Na(V)1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 μM) inhibited Na(V)1.5 currents in breast cancer cells and reduced Na(V)1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by Na(V)1.5-expressing human breast cancer cells. Taken together, our results demonstrate the importance of Na(V)1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with Na(V) activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.

Metamorphic III–V Solar Cells: Recent Progress and Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, Ivan; France, Ryan M.; Geisz, John F.

Inverted metamorphic multijunction solar cells have been demonstrated to be a pathway to achieve the highest photovoltaic (PV) conversion efficiencies. Attaining high-quality lattice-mismatched (metamorphic) semiconductor devices is challenging. However, recent improvements to compositionally graded buffer epitaxy and junction structures have led to the achievement of high-quality metamorphic solar cells exhibiting internal luminescence efficiencies over 90%. For this high material quality, photon recycling is significant, and therefore, the optical environment of the solar cell becomes important. In this paper, we first present recent progress and performance results for 1- and 0.7-eV GaInAs solar cells grown on GaAs substrates. Then, an electroopticalmore » model is used to assess the potential performance improvements in current metamorphic solar cells under different realizable design scenarios. The results show that the quality of 1-eV subcells is such that further improving its electronic quality does not produce significant Voc increases in the four-junction inverted metamorphic subcells, unless a back reflector is used to enhance photon recycling, which would significantly complicate the structure. Conversely, improving the electronic quality of the 0.7-eV subcell would lead to significant Voc boosts, driving the progress of four-junction inverted metamorphic solar cells.« less

Toward an Objective Enhanced-V Detection Algorithm

NASA Technical Reports Server (NTRS)

Moses, John F.; Brunner,Jason C.; Feltz, Wayne F.; Ackerman, Steven A.; Moses, John F.; Rabin, Robert M.

2007-01-01

The area of coldest cloud tops above thunderstorms sometimes has a distinct V or U shape. This pattern, often referred to as an "enhanced-V signature, has been observed to occur during and preceding severe weather. This study describes an algorithmic approach to objectively detect overshooting tops, temperature couplets, and enhanced-V features with observations from the Geostationary Operational Environmental Satellite and Low Earth Orbit data. The methodology consists of temperature, temperature difference, and distance thresholds for the overshooting top and temperature couplet detection parts of the algorithm and consists of cross correlation statistics of pixels for the enhanced-V detection part of the algorithm. The effectiveness of the overshooting top and temperature couplet detection components of the algorithm is examined using GOES and MODIS image data for case studies in the 2003-2006 seasons. The main goal is for the algorithm to be useful for operations with future sensors, such as GOES-R.

Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes

PubMed Central

Balasubramaniyan, Natarajan; Ananthanarayanan, Meena

2012-01-01

The farnesoid X receptor (FXR) is a ligand (bile acid)-dependent nuclear receptor that regulates target genes involved in every aspect of bile acid homeostasis. Upon binding of ligand, FXR recruits an array of coactivators and associated proteins, some of which have intrinsic enzymatic activity that modify histones or even components of the transcriptional complex. In this study, we show chromatin occupancy by the Set7/9 methyltransferase at the FXR response element (FXRE) and direct methylation of FXR in vivo and in vitro at lysine 206. siRNA depletion of Set7/9 in the Huh-7 liver cell line decreased endogenous mRNAs of the FXR target genes, the short heterodimer partner (SHP) and bile salt export pump (BSEP). Mutation of the methylation site at K206 of FXR to an arginine prevented methylation by Set7/9. A pan-methyllysine antibody recognized the wild-type FXR but not the K206R mutant form. An electromobility shift assay showed that methylation by Set7/9 enhanced binding of FXR/retinoic X receptor-α to the FXRE. Interaction between hinge domain of FXR (containing K206) and Set7/9 was confirmed by coimmunoprecipitation, GST pull down, and mammalian two-hybrid experiments. Set7/9 overexpression in Huh-7 cells significantly enhanced transactivation of the SHP and BSEP promoters in a ligand-dependent fashion by wild-type FXR but not the K206R mutant FXR. A Set7/9 mutant deficient in methyltransferase activity was also not effective in increasing transactivation of the BSEP promoter. These studies demonstrate that posttranslational methylation of FXR by Set7/9 contributes to the transcriptional activation of FXR-target genes. PMID:22345554

Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes.

PubMed

Pfeifer, M; Zheng, B; Erdmann, T; Koeppen, H; McCord, R; Grau, M; Staiger, A; Chai, A; Sandmann, T; Madle, H; Dörken, B; Chu, Y-W; Chen, A I; Lebovic, D; Salles, G A; Czuczman, M S; Palanca-Wessels, M C; Press, O W; Advani, R; Morschhauser, F; Cheson, B D; Lenz, P; Ott, G; Polson, A G; Mundt, K E; Lenz, G

2015-07-01

Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment because of low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.

Chronic lithium treatment up-regulates cell surface Na(V)1.7 sodium channels via inhibition of glycogen synthase kinase-3 in adrenal chromaffin cells: enhancement of Na(+) influx, Ca(2+) influx and catecholamine secretion after lithium withdrawal.

PubMed

Yanagita, Toshihiko; Maruta, Toyoaki; Nemoto, Takayuki; Uezono, Yasuhito; Matsuo, Kiyotaka; Satoh, Shinya; Yoshikawa, Norie; Kanai, Tasuku; Kobayashi, Hideyuki; Wada, Akihiko

2009-09-01

In cultured bovine adrenal chromaffin cells expressing Na(V)1.7 isoform of voltage-dependent Na(+) channels, we have previously reported that lithium chloride (LiCl) inhibits function of Na(+) channels independent of glycogen synthase kinase-3 (GSK-3) (Yanagita et al., 2007). Here, we further examined the effects of chronic lithium treatment on Na(+) channels. LiCl treatment (1-30 mM, > or = 12 h) increased cell surface [(3)H]saxitoxin ([(3)H]STX) binding by approximately 32% without altering the affinity of [(3)H]STX binding. This increase was prevented by cycloheximide and actinomycin D. SB216763 and SB415286 (GSK-3 inhibitors) also increased cell surface [(3)H]STX binding by approximately 31%. Simultaneous treatment with LiCl and SB216763 or SB415286 did not produce an increased effect on [(3)H]STX binding compared with either treatment alone. LiCl increased Na(+) channel alpha-subunit mRNA level by 32% at 24 h. LiCl accelerated alpha-subunit gene transcription by 35% without altering alpha-subunit mRNA stability. In LiCl-treated cells, LiCl inhibited veratridine-induced (22)Na(+) influx as in untreated cells. However, washout of LiCl after chronic treatment enhanced veratridine-induced (22)Na(+) influx, (45)Ca(2+) influx and catecholamine secretion by approximately 30%. Washout of LiCl after 24 h treatment shifted concentration-response curve of veratridine upon (22)Na(+) influx upward, without altering its EC(50) value. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced (22)Na(+) influx by two-fold in untreated and LiCl-treated cells. Whole-cell patch-clamp analysis indicated that I-V curve and steady-state inactivation/activation curves were comparable between untreated and LiCl-treated cells. Thus, GSK-3 inhibition by LiCl up-regulated cell surface Na(V)1.7 via acceleration of alpha-subunit gene transcription, enhancing veratridine-induced Na(+) influx, Ca(2+) influx and catecholamine secretion.

PDGF Suppresses the Sulfation of CD44v and Potentiates CD44v-Mediated Binding of Colon Carcinoma Cells to Fibrin under Flow

PubMed Central

Alves, Christina S.; Konstantopoulos, Konstantinos

2012-01-01

Fibrin(ogen) mediates sustained tumor cell adhesion and survival in the pulmonary vasculature, thereby facilitating the metastatic dissemination of tumor cells. CD44 is the major functional fibrin receptor on colon carcinoma cells. Growth factors, such as platelet-derived growth factor (PDGF), induce post-translational protein modifications, which modulate ligand binding activity. In view of the roles of PDGF, fibrin(ogen) and CD44 in cancer metastasis, we aimed to delineate the effect of PDGF on CD44-fibrin recognition. By immunoprecipitating CD44 from PDGF-treated and untreated LS174T colon carcinoma cells, which express primarily CD44v, we demonstrate that PDGF enhances the adhesion of CD44v-coated beads to immobilized fibrin. Enzymatic inhibition studies coupled with flow-based adhesion assays and autoradiography reveal that PDGF augments the binding of CD44v to fibrin by significantly attenuating the extent of CD44 sulfation primarily on chondroitin and dermatan sulfate chains. Surface plasmon resonance assays confirm that PDGF enhances the affinity of CD44v-fibrin binding by markedly reducing its dissociation rate while modestly increasing the association rate. PDGF mildly reduces the affinity of CD44v-hyaluronan binding without affecting selectin-CD44v recognition. The latter is attributed to the fact that CD44v binds to selectins via sialofucosylated O-linked residues independent of heparan, dermatan and chondroitin sulfates. Interestingly, PDGF moderately reduces the sulfation of CD44s and CD44s-fibrin recognition. Collectively, these data offer a novel perspective into the mechanism by which PGDF regulates CD44-dependent binding of metastatic colon carcinoma cells to fibrin(ogen). PMID:23056168

Knockdown of peroxiredoxin V increases glutamate‑induced apoptosis in HT22 hippocampal neuron cells.

PubMed

Shen, Gui-Nan; Liu, Lei; Feng, Li; Jin, Yu; Jin, Mei-Hua; Han, Ying-Hao; Jin, Cheng-Hao; Jin, Yong-Zhe; Lee, Dong-Soek; Kwon, Tae Ho; Cui, Yu-Dong; Sun, Hu-Nan

2018-06-01

High concentrations of glutamate may mediate neuronal cell apoptosis by increasing intracellular reactive oxygen species (ROS) levels. Peroxiredoxin V (Prx V), a member of the Prx family, serves crucial roles in protecting cells from oxidative stress. The present study investigated the regulatory effect of Prx V on glutamate‑induced effects on viability and apoptosis in HT22 cells. Western blotting was used for protein expression analysis and Annexin V/PI staining and flow cytometry for determination of apoptosis. The results demonstrated that glutamate may ROS‑dependently increase HT22 cell apoptosis and upregulate Prx V protein levels. Furthermore, knockdown of Prx V protein expression with a lentivirus significantly enhanced HT22 cell apoptosis mediated by glutamate, which was reversed by inhibition of ROS with N‑acetyl‑L‑cysteine. Inhibiting the extracellular signal‑regulated kinase (ERK) signaling pathway with PD98059, a specific inhibitor for ERK phosphorylation, markedly decreased glutamate‑induced HT22 cell apoptosis in Prx V knockdown cells, indicating the potential involvement of ERK signaling in glutamate‑induced HT22 cell apoptosis. In addition, an increase in nuclear apoptosis‑inducing factor was observed in Prx V knockdown HT22 cells following glutamate treatment, compared with mock cells, whereas no differences in B‑cell lymphoma‑2 and cleaved‑caspase‑3 protein expression levels were observed between mock and Prx V knockdown cells. The results of the present study indicated that Prx V may have potential as a therapeutic molecular target for glutamate‑induced neuronal cell death and provide novel insight into the role of Prx V in oxidative‑stress induced neuronal cell death.

Protection by beverages, fruits, vegetables, herbs, and flavonoids against genotoxicity of 2-acetylaminofluorene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in metabolically competent V79 cells.

PubMed

Edenharder, R; Sager, J W; Glatt, H; Muckel, E; Platt, K L

2002-11-26

Chinese hamster lung fibroblasts, genetically engineered for the expression of rat cytochrome P450 dependent monooxygenase 1A2 and rat sulfotransferase 1C1 (V79-rCYP1A2-rSULT1C1 cells), were utilized to check for possible protective effects of beverages of plant origin, fruits, vegetables, and spices against genotoxicity induced by 2-acetylaminofluorene (AAF) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Antigenotoxic activities of juices from spinach and red beets against AAF could be monitored with similar effectivity by the HPRT-mutagenicity test (IC(50)=0.64%; 2.57%) and alkaline single cell gel electrophoresis (comet assay; IC(50)=0.12%; 0.89%) which detects DNA strand breaks and abasic sites. Applying the comet assay, genotoxicity of PhIP could, however, be demonstrated only in the presence of hydroxyurea and 1-[beta-D-arabinofuranosyl]cytosine, known inhibitors of DNA repair synthesis. As expected, AAF and PhIP were unable to induce any genotoxic effects in the parent V79 cells. Genotoxic activity of PhIP was strongly reduced in a dose-related manner by green tea and red wine, by blueberries, blackberries, red grapes, kiwi, watermelon, parsley, and spinach, while two brands of beer, coffee, black tea, rooibos tea, morellos, black-currants, plums, red beets, broccoli (raw and cooked), and chives were somewhat less active. One brand of beer was only moderately active while white wine, bananas, white grapes, and strawberries were inactive. Similarly, genotoxicity of AAF was strongly reduced by green, black, and rooibos tea, red wine, morellos, black-currants, kiwi, watermelon, and spinach while plums, red beets, and broccoli (raw) were less potent. Broccoli cooked exerted only moderate and white wine weak antigenotoxic activity. With respect to the possible mechanism(s) of inhibition of genotoxicity, benzo[a]pyrene-7,8-dihydrodiol (BaP-7,8-OH) and N-OH-PhIP were applied as substrates for the CYP1A family and for rSULT 1C1, respectively. Morellos

B29 Gene Silencing in Pituitary Cells is Regulated by Its 3′ Enhancer

PubMed Central

Malone, Cindy S.; Kuraishy, Ali I.; Fike, Francesca M.; Loya, Ruchika G.; Mikkili, Minil R.; Teitell, Michael A.; Wall, Randolph

2007-01-01

Summary B cell-specific B29 (Igβ, CD79b) genes in rat, mouse, and human are situated between the 5′ growth hormone (GH) locus control region (LCR) and the 3′ GH gene cluster. The entire GH genomic region is DNase1 hypersensitive in GH-expressing pituitary cells, which predicts an “open” chromatin configuration, and yet B29 is not expressed. The B29 promoter and enhancers exhibit histone deacetylation in pituitary cells, but histone deacetylase inhibition failed to activate B29 expression. The B29 promoter and a 3′ enhancer showed local dense DNA methylation in both pituitary and non-lymphoid cells consistent with gene silencing. However, DNA methyltransferase inhibition did not activate B29 expression either. B29 promoter constructs were minimally activated in transfected pituitary cells. Co-transfection of the B cell-specific octamer transcriptional co-activator Bob1 with the B29 promoter construct resulted in high level promoter activity in pituitary cells comparable to B29 promoter activity in transfected B cells. Unexpectedly, inclusion of the B29 3′ enhancer in B29 promoter constructs strongly inhibited B29 transcriptional activity even when pituitary cells were co-transfected with Bob1. Both Oct-1 and Pit-1 bind the B29 3′ enhancer in in vitro EMSA and in in vivo chromatin immunoprecipitation analyses. These data indicate that the GH locus-embedded, tissue-specific B29 gene is silenced in GH-expressing pituitary cells by epigenetic mechanisms, the lack of a B cell-specific transcription factor, and likely by the B29 3′ enhancer acting as a powerful silencer in a context and tissue-specific manner. PMID:16920149

Annexin V-induced rat Leydig cell proliferation involves Ect2 via RhoA/ROCK signaling pathway.

PubMed

Jing, Jun; Chen, Li; Fu, Hai-Yan; Fan, Kai; Yao, Qi; Ge, Yi-Feng; Lu, Jin-Chun; Yao, Bing

2015-03-24

This study investigated the effect of annexin V on the proliferation of primary rat Leydig cells and the potential mechanism. Our results showed that annexin V promoted rat Leydig cell proliferation and cell cycle progression in a dose- and time-dependent manner. Increased level of annexin V also enhanced Ect2 protein expression. However, siRNA knockdown of Ect2 attenuated annexin V-induced proliferation of rat Leydig cells. Taken together, these data suggest that increased level of annexin V induced rat Leydig cell proliferation and cell cycle progression via Ect2. Since RhoA activity was increased following Ect2 activation, we further investigated whether Ect2 was involved in annexin V-induced proliferation via the RhoA/ROCK pathway, and the results showed that annexin V increased RhoA activity too, and this effect was abolished by the knockdown of Ect2. Moreover, inhibition of the RhoA/ROCK pathway by a ROCK inhibitor, Y27632, also attenuated annexin V-induced proliferation and cell cycle progression. We thus conclude that Ect2 is involved in annexin V-induced rat Leydig cell proliferation through the RhoA/ROCK pathway.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirai, Hidenori; Fujimori, Hiroaki; Gunji, Akemi

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 responsesmore » 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

Synthesis and characterization of two crystallographic forms of Ag{sub 0.79}VS{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Mazhar N., E-mail: maz@berkeley.edu; Ji, Huiwen; Hirai, Daigorou

2013-06-15

A previously unreported compound, Ag{sub 0.79}VS{sub 2}, has been synthesized; its structure and elementary properties are reported. Ag{sub 0.79}VS{sub 2} crystallizes in two forms, designated as the α and β, related to the 1s-InTaS{sub 2} structure. Single crystal x-ray diffraction shows the α form to have a single layer hexagonal structure with a unit cell of 3.213(3) Å×7.809(6) Å, consisting of layers of edge-shared VS{sub 6} triangular prisms separated by layers of Ag. The β form is similar but has an a{sub o}√((3)) supercell in the basal plane, yielding a unit cell of 5.573(5) Å×7.822(6) Å. Both forms have disorderedmore » and displaced silver in the basal plane, but the β form has partial ordering of its silver sublattice and in-plane vanadium trimers. Resistivity measurements show metallic temperature dependence with an unusual hysteresis between 210 K and 130 K. Magnetic susceptibility measurements show Pauli Paramagnetic behavior. The Seebeck coefficient at 300 K is 42 µV/K. - Graphical abstract: Red=Vanadium, Gray=Silver, Yellow=Sulfur. Top left is α-Ag{sub 0.79}VS{sub 2} in the 1s-InTaS{sub 2} structure type. Top right: 2a×2b projection down the c-axis with displacement ellipsoids (50% probability) of atoms drawn to illustrate the split silver model. Bottom left is β-Ag{sub 0.79}VS{sub 2} having the a{sub o}√((3)) supercell. Bottom right: projection along the c-axis, displacement ellipsoids of atoms drawn. - Highlights: • Two crystallographic forms of Ag{sub 0.79}VS{sub 2}, designated α and β, are reported. • They are found to crystallize in the 1s-InTaS{sub 2} structure type. • β-Ag{sub 0.79}VS{sub 2} has partial ordering of the Ag sublattice and vanadium trimers. • Ag{sub 0.79}VS{sub 2} shows Pauli Paramagnetic behavior, a Seebeck coefficient of 42 µV/K at 300 K. • Ag{sub 0.79}VS{sub 2} shows metallic resistivity with an unusual hysteresis between 210 K and 130 K.« less

Extracellular matrix protein laminin enhances mesenchymal stem cell (MSC) paracrine function through αvβ3/CD61 integrin to reduce cardiomyocyte apoptosis.

PubMed

Peng, Kai-Yen; Liu, Yuan-Hung; Li, Yu-Wei; Yen, Betty Linju; Yen, Men-Luh

2017-08-01

Myocardial ischaemia (MI) results in extensive cardiomyocyte death and reactive oxygen species (ROS)-induced damage in an organ with little or no regenerative capacity. Although the use of adult bone marrow mesenchymal stem cells (BMMSCs) has been proposed as a treatment option, the high cell numbers required for clinical use are difficult to achieve with this source of MSCs, and animal studies have produced inconsistent data. We recently demonstrated in small and large animal models of acute MI that the application of human term placenta-derived multipotent cells (PDMCs), a foetal-stage MSC, resulted in reversal of cardiac injury with therapeutic efficacy. However, the mechanisms involved are unclear, making it difficult to strategize for therapeutic improvements. We found that PDMCs significantly reduced cardiomyocyte apoptosis and ROS production through the paracrine factors GRO-α, HGF and IL-8. Moreover, culturing PDMCs on plates coated with laminin, an extracellular matrix (ECM) protein, resulted in significantly enhanced secretion of all three paracrine factors, which further reduced cardiomyocyte apoptosis. The enhancement of PDMC paracrine function by laminin was mediated through αvβ3 integrin, with involvement of the signalling pathways of JNK, for GRO-α and IL-8 secretion, and PI3K/AKT, for HGF secretion. Our results demonstrated the utility of PDMC therapy to reduce cardiomyocyte apoptosis through modulation of ECM proteins in in vitro culture systems as a strategy to enhance the therapeutic functions of stem cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Clostridium beijerinckii mutant obtained atmospheric pressure glow discharge generates enhanced electricity in a microbial fuel cell.

PubMed

Liu, Jun; Guo, Ting; Wang, Dong; Ying, Hanjie

2015-01-01

A Clostridium beijerinckii mutant M13 was derived from C. beijerinckii NCIMB 8052 by atmospheric pressure glow discharge. C. beijerinckii M13 generated a maximum output power density of 79.2 mW m(-2) and a maximum output voltage of 230 mV in a microbial fuel cell containing 1 g glucose l(-1) as carbon source and 0.15 g methyl viologen l(-1) as an electron carrier.

Enhanced Charge Extraction of Li-Doped TiO2 for Efficient Thermal-Evaporated Sb2S3 Thin Film Solar Cells

PubMed Central

Lan, Chunfeng; Luo, Jingting; Lan, Huabin; Fan, Bo; Peng, Huanxin; Zhao, Jun; Sun, Huibin; Zheng, Zhuanghao; Liang, Guangxing; Fan, Ping

2018-01-01

We provided a new method to improve the efficiency of Sb2S3 thin film solar cells. The TiO2 electron transport layers were doped by lithium to improve their charge extraction properties for the thermal-evaporated Sb2S3 solar cells. The Mott-Schottky curves suggested a change of energy band and faster charge transport in the Li-doped TiO2 films. Compared with the undoped TiO2, Li-doped mesoporous TiO2 dramatically improved the photo-voltaic performance of the thermal-evaporated Sb2S3 thin film solar cells, with the average power conversion efficiency (PCE) increasing from 1.79% to 4.03%, as well as the improved open-voltage (Voc), short-circuit current (Jsc) and fill factors. The best device based on Li-doped TiO2 achieved a power conversion efficiency up to 4.42% as well as a Voc of 0.645 V, which are the highest values among the reported thermal-evaporated Sb2S3 solar cells. This study showed that Li-doping on TiO2 can effectively enhance the charge extraction properties of electron transport layers, offering a new strategy to improve the efficiency of Sb2S3-based solar cells. PMID:29495612

A silencing suppressor protein (NSs) of a tospovirus enhances baculovirus replication in permissive and semipermissive insect cell lines.

PubMed

Oliveira, Virgínia Carla; Bartasson, Lorrainy; de Castro, Maria Elita Batista; Corrêa, José Raimundo; Ribeiro, Bergmann Morais; Resende, Renato Oliveira

2011-01-01

The nonstructural protein (NSs) of the Tomato spotted wilt virus (TSWV) has been identified as an RNAi suppressor in plant cells. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) designated vAcNSs, containing the NSs gene under the control of the viral polyhedrin (polh) gene promoter, was constructed and the effects of NSs in permissive, semipermissive and nonpermissive insect cells to vAcNSs infection were evaluated. vAcNSs produced more budded virus when compared to wild type in semipermissive cells. Co-infection of vAcNSs with wild type baculoviruses clearly enhanced polyhedra production in all host cells. Confocal microscopy analysis showed that NSs accumulated in abundance in the cytoplasm of permissive and semipermissive cells. In contrast, high amounts of NSs were detected in the nuclei of nonpermissive cells. Co-infection of vAcNSs with a recombinant AcMNPV containing the enhanced green fluorescent protein (egfp) gene, significantly increased EGFP expression in semipermissive cells and in Anticarsia gemmatalis-hemocytes. Absence of small RNA molecules of egfp transcripts in this cell line and in a permissive cell line indicates the suppression of gene silencing activity. On the other hand, vAcNSs was not able to suppress RNAi in a nonpermissive cell line. Our data showed that NSs protein of TSWV facilitates baculovirus replication in different lepidopteran cell lines, and these results indicate that NSs could play a similar role during TSWV-infection in its thrips vector. Copyright © 2010 Elsevier B.V. All rights reserved.

Mitotic accumulation of dimethylated lysine 79 of histone H3 is important for maintaining genome integrity during mitosis in human cells.

PubMed

Guppy, Brent J; McManus, Kirk J

2015-02-01

The loss of genome stability is an early event that drives the development and progression of virtually all tumor types. Recent studies have revealed that certain histone post-translational modifications exhibit dynamic and global increases in abundance that coincide with mitosis and exhibit essential roles in maintaining genomic stability. Histone H2B ubiquitination at lysine 120 (H2Bub1) is regulated by RNF20, an E3 ubiquitin ligase that is altered in many tumor types. Through an evolutionarily conserved trans-histone pathway, H2Bub1 is an essential prerequisite for subsequent downstream dimethylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Although the role that RNF20 plays in tumorigenesis has garnered much attention, the downstream components of the trans-histone pathway, H3K4me2 and H3K79me2, and their potential contributions to genome stability remain largely overlooked. In this study, we employ single-cell imaging and biochemical approaches to investigate the spatial and temporal patterning of RNF20, H2Bub1, H3K4me2, and H3K79me2 throughout the cell cycle, with a particular focus on mitosis. We show that H2Bub1, H3K4me2, and H3K79me2 exhibit distinct temporal progression patterns throughout the cell cycle. Most notably, we demonstrate that H3K79me2 is a highly dynamic histone post-translational modification that reaches maximal abundance during mitosis in an H2Bub1-independent manner. Using RNAi and chemical genetic approaches, we identify DOT1L as a histone methyltransferase required for the mitotic-associated increases in H3K79me2. We also demonstrate that the loss of mitotic H3K79me2 levels correlates with increases in chromosome numbers and increases in mitotic defects. Collectively, these data suggest that H3K79me2 dynamics during mitosis are normally required to maintain genome stability and further implicate the loss of H3K79me2 during mitosis as a pathogenic event that contributes to the development and progression of tumors

Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity.

PubMed

Kitzmüller, Claudia; Kalser, Julia; Mutschlechner, Sonja; Hauser, Michael; Zlabinger, Gerhard J; Ferreira, Fatima; Bohle, Barbara

2018-01-01

Recombinant fusion proteins of flagellin and antigens have been demonstrated to induce strong innate and adaptive immune responses. Such fusion proteins can enhance the efficacy of allergen-specific immunotherapy. We sought to characterize different fusion proteins of flagellin and the major birch pollen allergen Bet v 1 for suitability as allergy vaccines. A truncated version of flagellin (NtCFlg) was genetically fused to the N- or C-terminus of Bet v 1. Toll-like receptor (TLR) 5 binding was assessed with HEK293 cells expressing TLR5. Upregulation of CD40, CD80, CD83, and CD86 on monocyte-derived dendritic cells from allergic patients was analyzed by using flow cytometry. The T cell-stimulatory capacity of the fusion proteins was assessed with naive and Bet v 1-specific T cells. IgE binding was tested in inhibition ELISAs and basophil activation tests. Mice were immunized with the fusion proteins in the absence and presence of aluminum hydroxide. Cellular and antibody responses were monitored. Murine antibodies were tested for blocking capacity in basophil activation tests. Both fusion proteins matured monocyte-derived dendritic cells through TLR5. Compared with Bet v 1, the fusion proteins showed stronger T cell-stimulatory and reduced IgE-binding capacity and induced murine Bet v 1-specific antibodies in the absence of aluminum hydroxide. However, only antibodies induced by means of immunization with NtCFlg fused to the C-terminus of Bet v 1 inhibited binding of patients' IgE antibodies to Bet v 1. Bet v 1-flagellin fusion proteins show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity and thus represent promising vaccines for birch pollen allergen-specific immunotherapy. However, the sequential order of allergen and adjuvant within a fusion protein determines its immunologic characteristics. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Osteoblast Cell Response on the Ti6Al4V Alloy Heat-Treated

PubMed Central

Chávez-Díaz, Mercedes Paulina; Escudero-Rincón, María Lorenza; Arce-Estrada, Elsa Miriam; Cabrera-Sierra, Román

2017-01-01

In an effort to examine the effect of the microstructural changes of the Ti6Al4V alloy, two heat treatments were carried out below (Ti6Al4V800) and above (Ti6Al4V1050) its β-phase transformation temperature. After each treatment, globular and lamellar microstructures were obtained. Saos-2 pre-osteoblast human osteosarcoma cells were seeded onto Ti6Al4V alloy disks and immersed in cell culture for 7 days. Electrochemical assays in situ were performed using OCP and EIS measurements. Impedance data show a passive behavior for the three Ti6Al4V alloys; additionally, enhanced impedance values were recorded for Ti6Al4V800 and Ti6Al4V1050 alloys. This passive behavior in culture medium is mostly due to the formation of TiO2 during their sterilization. Biocompatibility and cell adhesion were characterized using the SEM technique; Ti6Al4V as received and Ti6Al4V800 alloys exhibited polygonal and elongated morphology, whereas Ti6Al4V1050 alloy displayed a spherical morphology. Ti and O elements were identified by EDX analysis due to the TiO2 and signals of C, N and O, related to the formation of organic compounds from extracellular matrix. These results suggest that cell adhesion is more likely to occur on TiO2 formed in discrete α-phase regions (hcp) depending on its microstructure (grains). PMID:28772804

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

40 CFR 86.328-79 - Leak checks.

Code of Federal Regulations, 2011 CFR

2011-07-01

... flows may be used to estimate the in-use flow rates. (3) The sample probe and the connection between the sample probe and valve V2 (Figure D79-1) may be excluded from the leak check. (b) Pressure side leak...

Regulation of Glutathione in a Rat Diploid Hepatic Epithelial Cell Line

DTIC Science & Technology

1990-06-01

supporting the contention that they are not pre-neoplastic (60). Metabolic cooperation by gap- junctional intercellular communication has been demonstrated...counted. The resulting population statistics allowed calculation and display of cycle-specific cell characteristics and compartment transit times (see...was repeated in chinese hamster V79 cells to see if the effect is idiosyncratic. It is not - V79 cells respond to CYC in the same fashion as WB344(s) if

Two Herbivore-Induced Cytochrome P450 Enzymes CYP79D6 and CYP79D7 Catalyze the Formation of Volatile Aldoximes Involved in Poplar Defense[C][W

PubMed Central

Irmisch, Sandra; Clavijo McCormick, Andrea; Boeckler, G. Andreas; Schmidt, Axel; Reichelt, Michael; Schneider, Bernd; Block, Katja; Schnitzler, Jörg-Peter; Gershenzon, Jonathan; Unsicker, Sybille B.; Köllner, Tobias G.

2013-01-01

Aldoximes are known as floral and vegetative plant volatiles but also as biosynthetic intermediates for other plant defense compounds. While the cytochrome P450 monooxygenases (CYP) from the CYP79 family forming aldoximes as biosynthetic intermediates have been intensively studied, little is known about the enzymology of volatile aldoxime formation. We characterized two P450 enzymes, CYP79D6v3 and CYP79D7v2, which are involved in herbivore-induced aldoxime formation in western balsam poplar (Populus trichocarpa). Heterologous expression in Saccharomyces cerevisiae revealed that both enzymes produce a mixture of different aldoximes. Knockdown lines of CYP79D6/7 in gray poplar (Populus × canescens) exhibited a decreased emission of aldoximes, nitriles, and alcohols, emphasizing that the CYP79s catalyze the first step in the formation of a complex volatile blend. Aldoxime emission was found to be restricted to herbivore-damaged leaves and is closely correlated with CYP79D6 and CYP79D7 gene expression. The semi-volatile phenylacetaldoxime decreased survival and weight gain of gypsy moth (Lymantria dispar) caterpillars, suggesting that aldoximes may be involved in direct defense. The wide distribution of volatile aldoximes throughout the plant kingdom and the presence of CYP79 genes in all sequenced genomes of angiosperms suggest that volatile formation mediated by CYP79s is a general phenomenon in the plant kingdom. PMID:24220631

EQUILUMINANCE CELLS IN VISUAL CORTICAL AREA V4

PubMed Central

Bushnell, Brittany N.; Harding, Philip J.; Kosai, Yoshito; Bair, Wyeth; Pasupathy, Anitha

2011-01-01

We report a novel class of V4 neuron in the macaque monkey that responds selectively to equiluminant colored form. These "equiluminance" cells stand apart because they violate the well established trend throughout the visual system that responses are minimal at low luminance contrast and grow and saturate as contrast increases. Equiluminance cells, which compose about 22% of V4, exhibit the opposite behavior: responses are greatest near zero contrast and decrease as contrast increases. While equilumiance cells respond preferentially to equiluminant colored stimuli, strong hue tuning is not their distinguishing feature—some equilumiance cells do exhibit strong unimodal hue tuning but many show little or no tuning for hue. We find that equiluminance cells are color and shape selective to a degree comparable to other classes of V4 cells with more conventional contrast response functions. Those more conventional cells respond equally well to achromatic luminance and equiluminant color stimuli, analogous to color-luminance cells described in V1. The existence of equiluminance cells, which have not been reported in V1 or V2, suggests that chromatically-defined boundaries and shapes are given special status in V4 and raises the possibility that form at equiluminance and form at higher contrasts are processed in separate channels in V4. PMID:21880901

Effects of various organic carbon sources on simultaneous V(V) reduction and bioelectricity generation in single chamber microbial fuel cells.

PubMed

Hao, Liting; Zhang, Baogang; Cheng, Ming; Feng, Chuanping

2016-02-01

Four ordinary carbon sources affecting V(V) reduction and bioelectricity generation in single chamber microbial fuel cells (MFCs) were investigated. Acetate supported highest maximum power density of 589.1mW/m(2), with highest V(V) removal efficiency of 77.6% during 12h operation, compared with glucose, citrate and soluble starch. Exorbitant initial V(V) concentration led to lower V(V) removal efficiencies and power outputs. Extra addition of organics had little effect on the improvement of MFCs performance. V(V) reduction and bioelectricity generation were enhanced and then suppressed by the increase of conductivity. The larger the external resistance, the higher the V(V) removal efficiencies and voltage outputs. High-throughput 16S rRNA gene pyrosequencing analysis implied the accumulation of Enterobacter which had the capabilities of V(V) reduction, electrochemical activity and fermentation, accompanied with other functional species as Pseudomonas, Spirochaeta, Sedimentibacter and Dysgonomonas. This study steps forward to remediate V(V) contaminated environment based on MFC technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reliability Improvement in III-V Concentrator Solar Cells by Means of Perimeter Protection

NASA Astrophysics Data System (ADS)

González, José R.; Vázquez, Manuel; Núñez, Neftalí; Algora, Carlos; Espinet, Pilar

2010-10-01

This paper presents the evolution in the strategy to assess the reliability of III-V solar cells and a new thermal ageing test carried out over GaAs single junction solar cells at three different temperatures (130, 150 and 170° C). The perimeter of the solar cells has been protected with silicone, which seems to be an effective way of enhancing the reliability of the solar cells. A preliminary analysis of the results indicates a mean time to failure (MTTF) one order of magnitude larger than the one obtained in a previous thermal test with the perimeter uncoated.

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

PubMed Central

Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

2014-01-01

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.

PubMed

Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

2014-01-01

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects

Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamada, Shin; Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp; Takikawa, Tetsuya

2012-05-04

Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression ofmore » pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.« less

Modification of uptake and antiproliferative effect of methylglyoxal bis(guanylhydrazone) by treatment with alpha-difluoromethylornithine in rodent cell lines with different sensitivities to methylglyoxal bis(guanylhydrazone).

PubMed

Alhonen-Hongisto, L; Levin, V A; Marton, L J

1985-02-01

Uptake characteristics and growth-inhibitory effects of methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were investigated in 9L rat brain tumor cells and in V79 hamster lung cells. Proliferation of 9L cells was only slightly inhibited by treatment with 40 microM MGBG alone, but when used in combination with 0.5 mM alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, proliferation was much more effectively inhibited. The intracellular concentration of MGBG was approximately 2-fold higher 4 days after cells were treated with both DFMO and MGBG, either simultaneously or when MGBG was added after a 48-hr DFMO pretreatment, than that in cells treated with MGBG alone. Polyamine levels in DFMO- and MGBG-treated cells correlated with the antiproliferative effects of the drugs. Used either alone or in combination with 1 mM DFMO, 0.5 microM MGBG inhibited the growth of and eventually killed V79 cells. Simultaneous or sequential treatment with DFMO and MGBG increased intracellular concentrations of MGBG at 4 days by 2- and 3-fold, respectively, compared to treatment with MGBG alone. Intracellular polyamine levels did not correlate with the antiproliferative effect of the two drugs in V79 cells. In both cell lines, polyamines and MGBG share a common transport system. The net transport of polyamines and MGBG was more temperature dependent and up to 10-fold more active in V79 cells than in 9L cells. The Km and Vmax values for spermidine and MGBG measured 10 sec after addition (initial permeation) were not affected by DFMO pretreatment in either cell line. However, 1 hr after administration, the Vmax values for spermidine and MGBG uptake were doubled in V79 cells pretreated for 48 hr with DFMO; no significant change occurred in 9L cells. Mitochondrial function, assessed by pyruvate oxidation, was substantially impaired by MGBG in V79 cells but not in 9L cells when the intracellular

Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

PubMed

Motegi, Tomoki; Katayama, Masaaki; Uzuka, Yuji; Okamura, Yasuhiko

2013-10-01

Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pure Single-Crystalline Na1.1V3O7.9 Nanobelts as Superior Cathode Materials for Rechargeable Sodium-Ion Batteries.

PubMed

Yuan, Shuang; Liu, Yong-Bing; Xu, Dan; Ma, De-Long; Wang, Sai; Yang, Xiao-Hong; Cao, Zhan-Yi; Zhang, Xin-Bo

2015-03-01

Pure single-crystalline Na 1.1 V 3 O 7.9 nanobelts are successfully synthesized for the first time via a facile yet effective strategy. When used as cathode materials for Na-ion batteries, the novel nanobelts exhibit excellent electrochemical performance. Given the ease and effectiveness of the synthesis route as well as the very promising electrochemical performance, the results obtained may be extended to other next-generation cathode materials for Na-ion batteries.

Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels.

PubMed

Wang, Tian; Yang, Yu-Qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S; Jiang, Zhi-Gen

2013-04-01

Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby canine kidney (MDCK) cells. We found that bumetanide and furosemide dose-dependently enhanced cytoplasmic GTTR fluorescence by ~60 %. This enhancement was suppressed by La(3+), a non-selective cation channel (NSCC) blocker, and by K(+) channel blockers Ba(2+) and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl(-) channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (V r) ~-80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba(2+) or clotrimazole, and absent in elevated [Ca(2+)]i, but was not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA, or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca(2+). Ba(2+) and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current V r near -85 mV, and reduced GTTR uptake by ~20 %. La(3+) alone hyperpolarized the cells by ~-14 mV, reduced the I/V slope with a net current V r near -10 mV, and inhibited GTTR uptake by ~50 %. In the presence of La(3+), bumetanide-caused negligible change in potential or I/V. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases the cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating intracellular Ca(2+) and thus facilitating

Hypoxic cell sensitizers and heavy charged-particle radiations.

PubMed Central

Chapman, J. D.; Urtasun, R. C.; Blakely, E. A.; Smith, K. C.; Tobias, C. A.

1978-01-01

Stationary-phase populations of Chinese hamster V-79 cells were irradiated with 250 kV X-rays and the Bragg peaks (spread to a width of 4 cm) of energetic He-, C-, Ne-, and A-ion beams produced at the 184-inch cyclotron and BEVALAC at Lawrence Berkeley Laboratory. Survival curves were generated with each radiation for cells suspended in air-saturated and nitrogen-saturated medium with and without sensitizer present. The oxygen enhancement ratios (OERs) measured for X-rays with 1mM metronidazole and 0.5 mM misonidazole were 2.0 and 1.6 respectively. The OERs without sensitizer for He-, C-, Ne-, and A-ion Bragg peaks were 2.4, 1.7, 1.6 and 1.4 respectively. For each type of radiation tested the presence of hypoxic-cell sensitizers resulted in an additional reduction in the measured OERs, indicating that these drugs should be of benefit in the radiotherapy planned with these and other high LET radiations. PMID:277223

High local carcinogenic activity of 1,3-dimethyl-3-phenyl-1-nitrosourea and its inactivation by intravenous application in rats: comparison of in vivo findings with the in vitro direct and a combined in vivo/in vitro sister chromatid exchange assay in V79-E cells.

PubMed

Thust, R; Martin, J; Mendel, J; Schreiber, D

1987-02-01

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) is a very potent local carcinogen in rats and induces a 100% frequency of forestomach carcinomas when applied i.g. in two different dosages (10 applications of 0.3 or 0.03 mmol/kg body wt, respectively, at 14-day intervals), but it is inactive upon i.v. administration (10 applications of 0.03 mmol/kg body wt at 14-day intervals). By means of the direct sister chromatid exchange (SCE) assay in V79-E cells in the presence of rat blood, serum or plasma, respectively, as well as by a 'host-mediated' SCE assay (in which the agent was given i.v. to rats, and blood taken from the animal was checked for the recovery of genotoxic activity in cell cultures), we tried to elucidate the unexpected lack of carcinogenic activity of i.v. DMPNU. The direct SCE assay revealed a drastic reduction of DMPNU genotoxicity by rat blood, serum or plasma, respectively, which is abolished by the esterase inhibitor diisopropylfluorophosphate. In the 'host-mediated' SCE assay a genotoxic activity of DMPNU was only recoverable after a very high i.v. dose and when the blood added to the cell cultures had been taken from the rat heart within 1 min after DMPNU administration in vivo. 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-phenyl-1-nitrosourea (MPNU) were used as positive controls in these experiments and also gave a lower response than theoretically expected, but the relative loss of activity with the latter compounds was much lower than with DMPNU. It is assumed that an esterase in rat blood effectively decomposes this trisubstituted nitrosourea. Problems of the novel 'host-mediated' SCE assay are discussed.

Differential KrasV12 protein levels control a switch regulating lung cancer cell morphology and motility

PubMed Central

Schäfer, C.; Mohan, A.; Burford, W.; Driscoll, M. K.; Ludlow, A. T.; Wright, W. E.; Shay, J. W.; Danuser, G.

2016-01-01

Introduction Oncogenic Kras mutations are important drivers of lung cancer development and metastasis. They are known to activate numerous cellular signaling pathways implicated in enhanced proliferation, survival, tumorigenicity and motility during malignant progression. Objectives Most previous studies of Kras in cancer have focused on the comparison of cell states in the absence or presence of oncogenic Kras mutations. Here we show that differential expression of the constitutively active mutation KrasV12 has profound effects on cell morphology and motility that drive metastatic processes. Methods The study relies on lung cancer cell transformation models, patient-derived lung cancer cell lines, and human lung tumor sections combined with molecular biology techniques, live-cell imaging and staining methods. Results Our analysis shows two cell functional states driven by KrasV12 protein levels: a non-motile state associated with high KrasV12 levels and tumorigenicity, and a motile state associated with low KrasV12 levels and cell dissemination. Conversion between the states is conferred by differential activation of a mechano-sensitive double-negative feedback between KrasV12/ERK/Myosin II and matrix-adhesion signaling. KrasV12 expression levels change upon cues such as hypoxia and integrin-mediated cell-matrix adhesion, rendering KrasV12 levels an integrator of micro-environmental signals that translate into cellular function. By live cell imaging of tumor models we observe shedding of mixed high and low KrasV12 expressers forming multi-functional collectives with potentially optimal metastatic properties composed of a highly mobile and a highly tumorigenic unit. Discussion Together these data highlight previously unappreciated roles for the quantitative effects of expression level variation of oncogenic signaling molecules in conferring fundamental alterations in cell function regulation required for cancer progression. PMID:29057096

Primary Central Nervous System T-Cell Lymphoma With Aberrant Expression of CD20 and CD79a: A Diagnostic Pitfall.

PubMed

Gupta, Neha; Nasim, Mansoor; Spitzer, Silvia G; Zhang, Xinmin

2017-10-01

Primary central nervous system T-cell lymphoma (PCNSTCL) is rare, accounting for 2% of CNS lymphomas. We report the first case of PCNSTCL with aberrant expression of CD20 and CD79a in an 81-year-old man with a left periventricular brain mass. A biopsy revealed dense lymphoid infiltrate consisting of medium-sized cells in a background of gliosis and many histiocytes. The lymphoid cells were positive for CD2, CD3, CD7, CD8, T-cell intracellular antigen-1, granzyme B, CD20, and CD79a and negative for CD4, CD5, PAX-5, OCT-2, BOB-1, human herpes virus-8, and Epstein-Barr virus-encoded small RNAs. Molecular studies revealed clonal TCR-β and TCR-γ gene rearrangements and negative immunoglobulin gene rearrangements. The patient was treated with chemotherapy (vincristine and methotrexate) and rituximab, but he died 1 month after the diagnosis. This is a unique case that emphasizes the use of a multimodal approach, including a broad immunohistochemical panel and molecular studies in lineage determination for lymphomas with ambiguous phenotype.

A Mutant Connexin50 with Enhanced Hemichannel Function Leads to Cell Death

PubMed Central

Minogue, Peter J.; Tong, Jun-Jie; Arora, Anita; Russell-Eggitt, Isabelle; Hunt, David M.; Moore, Anthony T.; Ebihara, Lisa; Beyer, Eric C.; Berthoud, Viviana M.

2009-01-01

PURPOSE To determine the consequences of expression of a novel connexin50 (CX50) mutant identified in a child with congenital total cataracts. METHODS The GJA8 gene was directly sequenced. Formation of functional channels was assessed by two-microelectrode voltage-clamp. Connexin protein levels and distribution were assessed by immunoblotting and immunofluorescence. The proportion of apoptotic cells was determined by flow cytometry. RESULTS Direct sequencing of the GJA8 gene identified a 137 G>T transition that resulted in the replacement of glycine by valine at position 46 of the coding region of CX50 (CX50G46V). Both CX50 and CX50G46V induced gap junctional currents in pairs of Xenopus oocytes. In single Xenopus oocytes, CX50G46V induced connexin hemichannel currents that were activated by removal of external calcium; their magnitudes were much higher than those in oocytes injected with similar amounts of CX50 cRNA. When expressed in HeLa cells under the control of an inducible promoter, both CX50 and CX50G46V formed gap junctional plaques. Induction of CX50G46V expression led to a decrease in cell number and an increase in the proportion of apoptotic cells. CX50G46V-induced cell death was prevented by high concentrations of extracellular calcium ions. CONCLUSIONS Unlike previously characterized CX50 mutants that exhibit impaired trafficking and/or lack of function, CX50G46V traffics properly to the plasma membrane and forms functional hemichannels and gap junction channels; however, it causes cell death even when expressed at minute levels. The biochemical results indirectly suggest a potential novel mechanism by which connexin mutants could lead to cataracts: cytotoxicity due to enhanced hemichannel function. PMID:19684000

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics.

PubMed

Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda; Venugopal, Balu; Vinay, M B; Pillai, Malini S; Kassem, Moustapha; Dhawan, Jyotsna

2018-05-17

Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on soft polyacrylamide substrate; and examined their molecular and functional phenotype. Induction of G0 was confirmed by bromo-deoxyuridine (BrdU) labelling and analysis of cell cycle gene expression. Upon reactivation and re-entry into cell cycle, G0 state-BMSC exhibited enhanced clonogenic self-renewal, preferential differentiation into osteoblastic rather than adipocytic cells and increased ectopic bone formation when implanted subcutaneously in vivo in immune-deficient mice, compared to asynchronous proliferating (pre-G0) BMSC. Global gene expression profiling revealed reprogramming of the transcriptome during G0 state including significant alterations in relevant pathways and expression of secreted factors, suggesting altered autocrine and paracrine signaling by G0 state-BMSC and a possible mechanism for enhanced bone formation. G0 state-BMSC might provide a clinically relevant model for understanding the in vivo biology of BMSC. Copyright © 2018. Published by Elsevier B.V.

Self-assembled monolayers of alendronate on Ti6Al4V alloy surfaces enhance osteogenesis in mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Rojo, Luis; Gharibi, Borzo; McLister, Robert; Meenan, Brian J.; Deb, Sanjukta

2016-07-01

Phosphonates have emerged as an alternative for functionalization of titanium surfaces by the formation of homogeneous self-assembled monolayers (SAMs) via Ti-O-P linkages. This study presents results from an investigation of the modification of Ti6Al4V alloy by chemisorption of osseoinductive alendronate using a simple, effective and clean methodology. The modified surfaces showed a tailored topography and surface chemistry as determined by SEM microscopy and RAMAN spectroscopy. X-ray photoelectron spectroscopy revealed that an effective mode of bonding is created between the metal oxide surface and the phosphate residue of alendronate, leading to formation of homogenous drug distribution along the surface. In-vitro studies showed that alendronate SAMs induce differentiation of hMSC to a bone cell phenotype and promote bone formation on modified surfaces. Here we show that this novel method for the preparation of functional coatings on titanium-based medical devices provides osseoinductive bioactive molecules to promote enhanced integration at the site of implantation.

Self-assembled monolayers of alendronate on Ti6Al4V alloy surfaces enhance osteogenesis in mesenchymal stem cells

PubMed Central

Rojo, Luis; Gharibi, Borzo; McLister, Robert; Meenan, Brian J.; Deb, Sanjukta

2016-01-01

Phosphonates have emerged as an alternative for functionalization of titanium surfaces by the formation of homogeneous self-assembled monolayers (SAMs) via Ti-O-P linkages. This study presents results from an investigation of the modification of Ti6Al4V alloy by chemisorption of osseoinductive alendronate using a simple, effective and clean methodology. The modified surfaces showed a tailored topography and surface chemistry as determined by SEM microscopy and RAMAN spectroscopy. X-ray photoelectron spectroscopy revealed that an effective mode of bonding is created between the metal oxide surface and the phosphate residue of alendronate, leading to formation of homogenous drug distribution along the surface. In-vitro studies showed that alendronate SAMs induce differentiation of hMSC to a bone cell phenotype and promote bone formation on modified surfaces. Here we show that this novel method for the preparation of functional coatings on titanium-based medical devices provides osseoinductive bioactive molecules to promote enhanced integration at the site of implantation. PMID:27468811

Bumetanide hyperpolarizes Madin-Darby canine kidney cells and enhances cellular gentamicin uptake via elevating cytosolic Ca2+ thus facilitating intermediate conductance Ca2+-activated potassium channels

PubMed Central

Wang, Tian; Yang, Yu-qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S.; Jiang, Zhi-Gen

2012-01-01

Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby Canine kidney (MDCK) cells. We found that bumetanide and furosemide concentration-dependently enhanced cytoplasmic GTTR fluorescence by ~60%. This enhancement was suppressed by La3+, a non-selective cation channel (NSCC) blocker, and by K+ channel blockers Ba2+ and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl− channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (Vr) ~−80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba2+ or clotrimazole, and absent in elevated [Ca2+]i, but not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca2+. Ba2+ and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current Vr near −85 mV, and reduced GTTR uptake by ~20%. La3+ alone hyperpolarized the cells by ~−14 mV, reduced the I/V slope with a net current Vr near −10 mV, and inhibited GTTR uptake by ~50%. In the presence of La3+, bumetanide caused negligible potential or I/V change. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating the intracellular Ca2+ and thus a facilitation of the

Fermi-LAT Observations of Supernova Remnants Kesteven 79

NASA Astrophysics Data System (ADS)

Auchettl, Katie; Slane, Patrick; Castro, Daniel

2014-03-01

In this paper, we report on the detection of γ-ray emission coincident with the Galactic supernova remnant (SNR) Kesteven 79 (Kes 79). We analyzed approximately 52 months of data obtained with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. Kes 79 is thought to be interacting with adjacent molecular clouds, based on the presence of strong 12CO J = 1 → 0 and HCO+ J = 1 → 0 emission and the detection of 1720 MHz line emission toward the east of the remnant. Acceleration of cosmic rays is expected to occur at SNR shocks, and SNRs interacting with dense molecular clouds provide a good testing ground for detecting and analyzing the production of γ-rays from the decay of π0 into two γ-ray photons. This analysis investigates γ-ray emission coincident with Kes 79, which has a detection significance of ~7σ. Additionally, we present an investigation of the spatial and spectral characteristics of Kes 79 using multiple archival XMM-Newton observations of this remnant. We determine the global X-ray properties of Kes 79 and estimate the ambient density across the remnant. We also performed a similar analysis for Galactic SNR Kesteven 78 (Kes 78), but due to large uncertainties in the γ-ray background model, no conclusion can be made about an excess of GeV γ-ray associated with the remnant.

Inhibition of SET Domain–Containing Lysine Methyltransferase 7/9 Ameliorates Renal Fibrosis

PubMed Central

Sasaki, Kensuke; Nakashima, Ayumu; Irifuku, Taisuke; Yamada, Kyoko; Kokoroishi, Keiko; Ueno, Toshinori; Doi, Toshiki; Hida, Eisuke; Arihiro, Koji; Kohno, Nobuoki

2016-01-01

TGF-β1 activity results in methylation of lysine 4 of histone H3 (H3K4) through SET domain–containing lysine methyltransferase 7/9 (SET7/9) induction, which is important for the transcriptional activation of fibrotic genes in vitro. However, in vivo studies utilizing an experimental model of renal fibrosis are required to develop therapeutic interventions that target SET7/9. In this study, we investigated the signaling pathway of TGF-β1-induced SET7/9 expression and whether inhibition of SET7/9 suppresses renal fibrosis in unilateral ureteral obstruction (UUO) mice and kidney cell lines. Among the SET family, SET7/9 was upregulated on days 3 and 7 in UUO mice, and the upregulation was suppressed by TGF-β1 neutralizing antibody. TGF-β1 induced SET7/9 expression via Smad3 in normal rat kidney (NRK)-52E cells. In human kidney biopsy specimens from patients diagnosed with IgA nephropathy and membranous nephropathy, SET7/9 expression was positively correlated with the degree of interstitial fibrosis (r=0.59, P=0.001 in patients with IgA nephropathy; and r=0.58, P<0.05 in patients with membranous nephropathy). In addition, small interfering RNA-mediated knockdown of SET7/9 expression significantly attenuated renal fibrosis in UUO mice. Sinefungin, an inhibitor of SET7/9, also suppressed the expression of mesenchymal markers and extracellular matrix proteins and inhibited H3K4 mono-methylation (H3K4me1) in kidneys of UUO mice. Moreover, sinefungin had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and H3K4me1 in both NRK-52E and NRK-49F cells. In conclusion, sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4me1 and may be a candidate therapeutic agent. PMID:26045091

Enhancement of therapeutic drug and DNA delivery into cells by electroporation* Enhancement of therapeutic drug and DNA delivery into cells by electroporation

NASA Astrophysics Data System (ADS)

Rabussay, Dietmar; Dev, Nagendu B.; Fewell, Jason; Smith, Louis C.; Widera, Georg; Zhang, Lei

2003-02-01

The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as `electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing `pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm-1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco

Voc enhancement of a solar cell with doped Li+-PbS as the active layer

NASA Astrophysics Data System (ADS)

Chávez Portillo, M.; Alvarado Pulido, J.; Gallardo Hernández, S.; Soto Cruz, B. S.; Alcántara Iniesta, S.; Gutiérrez Pérez, R.; Portillo Moreno, O.

2018-06-01

In this report, we investigate the fabrication of solar cells obtained by chemical bath technique, based on CdS as window layer and PbS and PbS-Li+-doped as the active layer. We report open-circuit-voltage Voc values of ∼392 meV for PbS and ∼630 meV for PbSLi+-doped, a remarkable enhanced in the open circuit voltage is shown for solar cells with doped active layer. Li+ ion passivate the dangling bonds in PbS-metal layer interface in consequence reducing the recombination centers.

Differences in temporal aspects of mutagenesis and cytotoxicity in Chinese hamster cells treated with methylating agents and thymidine.

PubMed Central

Peterson, A R; Peterson, H

1982-01-01

Equitoxic concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methanesulfonate (MeMes) produced different frequencies of 8-azaguanine-resistant mutants and different amounts of N7-methylguanine, O6-methylguanine (m6G), and N3-methyladenine in the DNA of V79 Chinese hamster cells. Thus, neither the cytotoxicities nor the mutagenicities of these methylating agents could be attributed solely to nitrogen or to oxygen methylations in the DNA. However, MNNG produced 12-fold more m6G and 5-fold more mutants than did MeMes, indicating that a substantial part of the MNNG-induced mutations resulted from m6G--thymine mispairing during DNA replication. The expression as mutants of mutagenic oxygen methylations in the DNA of cells treated with MNNG was enhanced by thymidine (dThd) and deoxycytidine (dCyd), but these nucleosides did not significantly enhance MeMes-induced mutagenesis. The cytotoxicities of MNNG and MeMes were also increased by 10 microM dThd in proportion to the amount of m6G in the DNA. These increases in cytotoxicity were abolished by dCyd, which did not greatly reduce the dThd-induced enhancements of mutagenesis. Moreover, when dThd was present only during the 2-hr treatment with MNNG, maximal cytotoxicity occurred, but MNNG-induced mutagenesis was not increased. Maximal mutagenesis occurred when the dThd was present throughout the first doubling time of the MNNG-treated cells. Thus, the expression of the cytotoxicity and the mutagenicity associated with m6G in the DNA of V79 cells occurred by quite different mechanisms. PMID:6951203

Differences in temporal aspects of mutagenesis and cytotoxicity in Chinese hamster cells treated with methylating agents and thymidine.

PubMed

Peterson, A R; Peterson, H

1982-03-01

Equitoxic concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methanesulfonate (MeMes) produced different frequencies of 8-azaguanine-resistant mutants and different amounts of N7-methylguanine, O6-methylguanine (m6G), and N3-methyladenine in the DNA of V79 Chinese hamster cells. Thus, neither the cytotoxicities nor the mutagenicities of these methylating agents could be attributed solely to nitrogen or to oxygen methylations in the DNA. However, MNNG produced 12-fold more m6G and 5-fold more mutants than did MeMes, indicating that a substantial part of the MNNG-induced mutations resulted from m6G--thymine mispairing during DNA replication. The expression as mutants of mutagenic oxygen methylations in the DNA of cells treated with MNNG was enhanced by thymidine (dThd) and deoxycytidine (dCyd), but these nucleosides did not significantly enhance MeMes-induced mutagenesis. The cytotoxicities of MNNG and MeMes were also increased by 10 microM dThd in proportion to the amount of m6G in the DNA. These increases in cytotoxicity were abolished by dCyd, which did not greatly reduce the dThd-induced enhancements of mutagenesis. Moreover, when dThd was present only during the 2-hr treatment with MNNG, maximal cytotoxicity occurred, but MNNG-induced mutagenesis was not increased. Maximal mutagenesis occurred when the dThd was present throughout the first doubling time of the MNNG-treated cells. Thus, the expression of the cytotoxicity and the mutagenicity associated with m6G in the DNA of V79 cells occurred by quite different mechanisms.

Using high haze (> 90%) light-trapping film to enhance the efficiency of a-Si:H solar cells

NASA Astrophysics Data System (ADS)

Chu, Wei-Ping; Lin, Jian-Shian; Lin, Tien-Chai; Tsai, Yu-Sheng; Kuo, Chen-Wei; Chung, Ming-Hua; Hsieh, Tsung-Eong; Liu, Lung-Chang; Juang, Fuh-Shyang; Chen, Nien-Po

2012-07-01

The high haze light-trapping (LT) film offers enhanced scattering of light and is applied to a-Si:H solar cells. UV glue was spin coated on glass, and then the LT pattern was imprinted. Finally, a UV lamp was used to cure the UV glue on the glass. The LT film effectively increased the Haze ratio of glass and decreased the reflectance of a-Si:H solar cells. Therefore, the photon path length was increased to obtain maximum absorption by the absorber layer. High Haze LT film is able to enhance short circuit current density and efficiency of the device, as partial composite film generates broader scattering light, thereby causing shorter wave length light to be absorbed by the P layer so that the short circuit current density decreases. In case of lab-made a-Si:H thin film solar cells with v-shaped LT films, superior optoelectronic performances have been found (Voc = 0.74 V, Jsc = 15.62 mA/cm2, F.F. = 70%, and η = 8.09%). We observed ~ 35% enhancement of the short-circuit current density and ~ 31% enhancement of the conversion efficiency.

Light-induced V{sub oc} increase and decrease in high-efficiency amorphous silicon solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuckelberger, M., E-mail: michael.stuckelberger@epfl.ch; Riesen, Y.; Despeisse, M.

High-efficiency amorphous silicon (a-Si:H) solar cells were deposited with different thicknesses of the p-type amorphous silicon carbide layer on substrates of varying roughness. We observed a light-induced open-circuit voltage (V{sub oc}) increase upon light soaking for thin p-layers, but a decrease for thick p-layers. Further, the V{sub oc} increase is enhanced with increasing substrate roughness. After correction of the p-layer thickness for the increased surface area of rough substrates, we can exclude varying the effective p-layer thickness as the cause of the substrate roughness dependence. Instead, we explain the observations by an increase of the dangling-bond density in both themore » p-layer—causing a V{sub oc} increase—and in the intrinsic absorber layer, causing a V{sub oc} decrease. We present a mechanism for the light-induced increase and decrease, justified by the investigation of light-induced changes of the p-layer and supported by Advanced Semiconductor Analysis simulation. We conclude that a shift of the electron quasi-Fermi level towards the conduction band is the reason for the observed V{sub oc} enhancements, and poor amorphous silicon quality on rough substrates enhances this effect.« less

Predominant expansion of V gamma 9/V delta 2 T cells in a tularemia patient.

PubMed Central

Sumida, T; Maeda, T; Takahashi, H; Yoshida, S; Yonaha, F; Sakamoto, A; Tomioka, H; Koike, T; Yoshida, S

1992-01-01

We describe a 58-year-old man with tularemia and expanding gamma delta T cells in his peripheral blood lymphocytes (PBL) (32.7% of total PBL). In the present work, we analyzed the T-cell receptor V gamma/V delta repertoire of these cells by making use of the polymerase chain reaction and flow cytometry and found that they were mostly CD4- CD8- CD3+ V gamma 9/V delta 2+. The sequence analysis of 16 cDNA clones encoding the V gamma 9-J region revealed that the V gamma 9-Jp combination was strikingly overrepresented but that the junctional (N) region was heterogeneous. This suggested that the gamma delta T cells in PBL from a patient with tularemia were polyclonally expanded. Images PMID:1534075

Mast cells enhance T cell activation: Importance of mast cell-derived TNF

NASA Astrophysics Data System (ADS)

Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

2005-05-01

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

Evidence that pulsed electric field treatment enhances the cell wall porosity of yeast cells.

PubMed

Ganeva, Valentina; Galutzov, Bojidar; Teissie, Justin

2014-02-01

The application of rectangular electric pulses, with 0.1-2 ms duration and field intensity of 2.5-4.5 kV/cm, to yeast suspension mediates liberation of cytoplasmic proteins without cell lysis. The aim of this study was to evaluate the effect of pulsed electric field with similar parameters on cell wall porosity of different yeast species. We found that electrically treated cells become more susceptible to lyticase digestion. In dependence on the strain and the electrical conditions, cell lysis was obtained at 2-8 times lower enzyme concentration in comparison with control untreated cells. The increase of the maximal lysis rate was between two and nine times. Furthermore, when applied at low concentration (1 U/ml), the lyticase enhanced the rate of protein liberation from electropermeabilized cells without provoking cell lysis. Significant differences in the cell surface of control and electrically treated cells were revealed by scanning electron microscopy. Data presented in this study allow us to conclude that electric field pulses provoke not only plasma membrane permeabilization, but also changes in the cell wall structure, leading to increased wall porosity.

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

PubMed Central

Matnani, Rahul G.; Stewart, Rachel L.; Pulliam, Joseph; Jennings, Chester D.; Kesler, Melissa

2013-01-01

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones. PMID:24066244

Low-Cost III-V Solar Cells | Photovoltaic Research | NREL

Science.gov Websites

Low-Cost III-V Solar Cells Low-Cost III-V Solar Cells At present, the cost of III-V solar cells is to drastically lower the cost of these devices, while maintaining their conversion efficiency, thus costs in the production of high-efficiency III-V devices: the cost of the epitaxy and the single-crystal

Drug depot-anchoring hydrogel: A self-assembling scaffold for localized drug release and enhanced stem cell differentiation.

PubMed

Li, Ruixiang; Pang, Zhiqing; He, Huining; Lee, Seungjin; Qin, Jing; Wu, Jian; Pang, Liang; Wang, Jianxin; Yang, Victor C

2017-09-10

Localized and long-term delivery of growth factors has been a long-standing challenge for stem cell-based tissue engineering. In the current study, a polymeric drug depot-anchoring hydrogel scaffold was developed for the sustained release of macromolecules to enhance the differentiation of stem cells. Self-assembling peptide (RADA16)-modified drug depots (RDDs) were prepared and anchored to a RADA16 hydrogel. The anchoring effect of RADA16 modification on the RDDs was tested both in vitro and in vivo. It was shown that the in vitro leakage of RDDs from the RADA16 hydrogel was significantly less than that of the unmodified drug depots (DDs). In addition, the in vivo retention of injected hydrogel-incorporated RDDs was significantly longer than that of hydrogel-incorporated unmodified DDs. A model drug, vascular endothelial growth factor (VEGF), was encapsulated in RDDs (V-RDDs) as drug depot that was then anchored to the hydrogel. The release of VEGF could be sustained for 4weeks. Endothelial progenitor cells (EPCs) were cultured on the V-RDDs-anchoring scaffold and enhanced cell proliferation and differentiation were observed, compared with a VEGF-loaded scaffold. Furthermore, this scaffold laden with EPCs promoted neovascularization in an animal model of hind limb ischemia. These results demonstrate that self-assembling hydrogel-anchored drug-loaded RDDs are promising for localized and sustained drug release, and can effectively enhance the proliferation and differentiation of resident stem cells, thus lead to successful tissue regeneration. Copyright © 2017. Published by Elsevier B.V.

Cell Growth Enhancement

NASA Technical Reports Server (NTRS)

1992-01-01

Exogene Corporation uses advanced technologies to enhance production of bio-processed substances like proteins, antibiotics and amino acids. Among them are genetic modification and a genetic switch. They originated in research for Jet Propulsion Laboratory. Extensive experiments in cell growth through production of hemoglobin to improve oxygen supply to cells were performed. By improving efficiency of oxygen use by cells, major operational expenses can be reduced. Greater product yields result in decreased raw material costs and more efficient use of equipment. A broad range of applications is cited.

Mechanisms for Flow-Enhanced Cell Adhesion

PubMed Central

Zhu, Cheng; Yago, Tadayuki; Lou, Jizhong; Zarnitsyna, Veronika I.; McEver, Rodger P.

2009-01-01

Cell adhesion is mediated by specific receptor—ligand bonds. In several biological systems, increasing flow has been observed to enhance cell adhesion despite the increasing dislodging fluid shear forces. Flow-enhanced cell adhesion includes several aspects: flow augments the initial tethering of flowing cells to a stationary surface, slows the velocity and increases the regularity of rolling cells, and increases the number of rollingly adherent cells. Mechanisms for this intriguing phenomenon may include transport-dependent acceleration of bond formation and force-dependent deceleration of bond dissociation. The former includes three distinct transport modes: sliding of cell bottom on the surface, Brownian motion of the cell, and rotational diffusion of the interacting molecules. The latter involves a recently demonstrated counterintuitive behavior called catch bonds where force prolongs rather than shortens the lifetimes of receptor—ligand bonds. In this article, we summarize our recently published data that used dimensional analysis and mutational analysis to elucidate the above mechanisms for flow-enhanced leukocyte adhesion mediated by L-selectinligand interactions. PMID:18299992

A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes.

PubMed

Liu, Wei; Jing, Zhen-Tang; Wu, Shu-Xiang; He, Yun; Lin, Yan-Ting; Chen, Wan-Nan; Lin, Xin-Jian; Lin, Xu

2018-05-01

Acute liver failure is a serious clinical problem of which the underlying pathogenesis remains unclear and for which effective therapies are lacking. The Fas receptor/ligand system, which is negatively regulated by AKT, is known to play a prominent role in hepatocytic cell death. We hypothesized that AKT activation may represent a strategy to alleviate Fas-induced fulminant liver failure. We report here that a novel AKT activator, SC79, protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2. Under Fas-signaling stimulation, SC79 inhibited Fas aggregation, prevented the recruitment of the adaptor molecule Fas-associated death domain (FADD) and procaspase-8 [or FADD-like IL-1β-converting enzyme (FLICE)] into the death-inducing signaling complex (DISC), but SC79 enhanced the recruitment of the long and short isoforms of cellular FLICE-inhibitory protein at the DISC. All of the SC79-induced hepatoprotective and DISC-interruptive effects were confirmed to have been reversed by the Akt inhibitor LY294002. These results strongly indicate that SC79 protects hepatocytes from Fas-induced fatal hepatic apoptosis. The potent alleviation of Fas-mediated hepatotoxicity by the relatively safe drug SC79 highlights the potential of our findings for immediate hepatoprotective translation. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Preparation of well-distributed titania nanopillar arrays on Ti6Al4V surface by induction heating for enhancing osteogenic differentiation of stem cells

NASA Astrophysics Data System (ADS)

Li, Ning-Bo; Sun, Sheng-Jun; Bai, Han-Ying; Xiao, Gui-Yong; Xu, Wen-Hua; Zhao, Jun-Han; Chen, Xin; Lu, Yu-Peng; Zhang, Yi-Lin

2018-01-01

Great effort has recently been devoted to the preparation of nanoscale surfaces on titanium-based implants to achieve clinically fast osteoinduction and osseointegration, which relies on the unique characteristics of the nanostructure. In this work, we used induction heating treatment (IHT) as a rapid oxidation method to fabricate a porous nanoscale oxide layer on the Ti6Al4V surface for better medical application. Well-distributed vertical nanopillars were yielded by IHT for 20-35 s on the alloy surface. The composition of the oxides contained rutile/anatase TiO2 and a small amount of Al2O3 between the TiO2 grain boundaries (GBs). This technology resulted in a reduction and subsequent increase of surface roughness of 26-32 nm when upregulating the heating time, followed by the successive enhancement of the thickness, wettability and adhesion strength of the oxidation layer to the matrix. The surface hardness also distinctly rose to 554 HV in the IHT-35 s group compared with the 350 HV of bare Ti6Al4V. The massive small-angle GBs in the bare alloy promoted the formation of nanosized oxide crystallites. The grain refinement and deformation texture reduction further improved the mechanical properties of the matrix after IHT. Moreover, in vitro experiments on a mesenchymal stem cell (BMSC) culture derived from human bone marrow for 1-7 days indicated that the nanoscale layers did not cause cytotoxicity, and facilitated cell differentiation in osteoblasts by enhancing the gene and osteogenesis-related protein expressions after 1-3 weeks of culturing. The increase of the IHT time slightly advanced the BMSC proliferation and differentiation, especially during long-term culture. Our findings provide strong evidence that IHT oxidation technology is a novel nanosurface modification technology, which is potentially promising for further clinical development.

In vitro biocorrosion of Ti-6Al-4V implant alloy by a mouse macrophage cell line.

PubMed

Lin, Hsin-Yi; Bumgardner, Joel D

2004-03-15

Corrosion of implant alloys releasing metal ions has the potential to cause adverse tissue reactions and implant failure. We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect the alloy's corrosion properties. A custom cell culture corrosion box was used to evaluate how cell culture medium, macrophage cells and RCS altered the Ti-6Al-4V corrosion behaviors in 72 h and how corrosion products affected the cells. There was no difference in the charge transfer in the presence (75.2 +/- 17.7 mC) and absence (62.3 +/- 18.8 mC) of cells. The alloy had the lowest charge transfer (28.2 +/- 4.1 mC) and metal ion release (Ti < 10 ppb, V < 2 ppb) with activated cells (releasing RCS) compared with the other two conditions. This was attributed to an enhancement of the surface oxides by RCS. Metal ion release was very low (Ti < 20 ppb, V < 10 ppb) with nonactivated cells and did not change cell morphology, viability, and NO and ATP release compared with controls. However, IL-1beta released from the activated cells and the proliferation of nonactivated cells were greater on the alloy than the controls. In summary, macrophage cells and RCS reduced the corrosion of Ti-6Al-4V alloys as hypothesized. These data are important in understanding host tissue-material interactions. Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 717-724, 2004

Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells

PubMed Central

Jin, Fangming; Su, Zisheng; Chu, Bei; Cheng, Pengfei; Wang, Junbo; Zhao, Haifeng; Gao, Yuan; Yan, Xingwu; Li, Wenlian

2016-01-01

In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm2, an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm2. Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification. PMID:27185635

Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells

NASA Astrophysics Data System (ADS)

Jin, Fangming; Su, Zisheng; Chu, Bei; Cheng, Pengfei; Wang, Junbo; Zhao, Haifeng; Gao, Yuan; Yan, Xingwu; Li, Wenlian

2016-05-01

In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm2, an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm2. Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification.

Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells.

PubMed

Jin, Fangming; Su, Zisheng; Chu, Bei; Cheng, Pengfei; Wang, Junbo; Zhao, Haifeng; Gao, Yuan; Yan, Xingwu; Li, Wenlian

2016-05-17

In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm(2), an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm(2). Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification.

In vitro studies on human periodontal ligament stem cell sheets enhanced by enamel matrix derivative.

PubMed

Wang, Zhongshan; Feng, Zhihong; Wu, Guofeng; Bai, Shizhu; Dong, Yan; Zhao, Yimin

2016-05-01

Numerous preclinical and clinical studies have focused on the periodontal regenerative functions of enamel matrix derivative (EMD), a heat-treated preparation derived from enamel matrix proteins (EMPs) of developing porcine teeth. In this study, periodontal ligament (PDL) stem cells (PDLSCs) were isolated, and the effects of EMD on the extracorporeal induction process and the characteristics of PDLSC sheets were investigated for their potential as a more effective stem-cell therapy. EMD-enhanced cell sheets could be induced by complete medium supplemented with 50 μg/mL vitamin C and 100 μg/mL EMD. The EMD-enhanced cell sheets appeared thicker and more compact than the normal PDLSC sheets, demonstrated more layers of cells (3-7 layers), secreted richer extracellular matrix (ECM), showed varying degrees of increases in mRNA expression of periodontal tissue-specific genes (COL I, POSTN), calcification-related genes (RUNX2, OPN, OCN) and a cementum tissue-specific gene (CAP), and possessed a better mineralization ability in terms of osteogenic differentiation in vitro. These EMD-enhanced cell sheets may represent a potential option for stem-cell therapy for PDL regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Versatile graphene biosensors for enhancing human cell therapy.

PubMed

Vlăsceanu, George M; Amărandi, Roxana-Maria; Ioniță, Mariana; Tite, Teddy; Iovu, Horia; Pilan, Luisa; Burns, Jorge S

2018-05-01

Technological advances in engineering and cell biology stimulate novel approaches for medical treatment, in particular cell-based therapy. The first cell-based gene therapy against cancer was recently approved by the US Food and Drug Administration. Progress in cancer diagnosis includes a blood test detecting five cancer types. Numerous stem cell phase I/II clinical trials showing safety and efficacy will soon pursue qualifying criteria for advanced therapy medicinal products (ATMP), aspiring to join the first stem-cell therapy approved by the European Medicines Agency. Cell based therapy requires extensive preclinical characterisation of biomarkers indicating mechanisms of action crucial to the desired therapeutic effect. Quantitative analyses monitoring critical functions for the manufacture of optimal cell and tissue-based clinical products include successful potency assays for implementation. The challenge to achieve high quality measurement is increasingly met by progress in biosensor design. We adopt a cell therapy perspective to highlight recent examples of graphene-enhanced biointerfaces for measurement of biomarkers relevant to cancer treatment, diagnosis and tissue regeneration. Graphene based biosensor design problems can thwart their use for health care transformative point of care testing and real-time applications. We discuss concerns to be addressed and emerging solutions for establishing clinical grade biosensors to accelerate human cell therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Methods for fabricating thin film III-V compound solar cell

DOEpatents

Pan, Noren; Hillier, Glen; Vu, Duy Phach; Tatavarti, Rao; Youtsey, Christopher; McCallum, David; Martin, Genevieve

2011-08-09

The present invention utilizes epitaxial lift-off in which a sacrificial layer is included in the epitaxial growth between the substrate and a thin film III-V compound solar cell. To provide support for the thin film III-V compound solar cell in absence of the substrate, a backing layer is applied to a surface of the thin film III-V compound solar cell before it is separated from the substrate. To separate the thin film III-V compound solar cell from the substrate, the sacrificial layer is removed as part of the epitaxial lift-off. Once the substrate is separated from the thin film III-V compound solar cell, the substrate may then be reused in the formation of another thin film III-V compound solar cell.

Hyperfine-resolved 3.4-{mu}m spectroscopy of CH{sub 3}I with a widely tunable difference frequency generation source and a cavity-enhanced cell: A case study of a local Coriolis interaction between the v{sub 1}=1 and (v{sub 2},v{sub 6}{sup l})=(1,2{sup 2}) states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okubo, Sho; Nakayama, Hirotaka; Sasada, Hiroyuki

Saturated absorption spectra of the {nu}{sub 1} fundamental band of CH{sub 3}I are recorded with a cavity-enhanced cell and a tunable difference frequency generation source having an 86-cm{sup -1} range. The recorded spectral lines are 250 kHz wide, and most of them are resolved into the individual hyperfine components. The Coriolis interaction between the v{sub 1}=1 and (v{sub 2},v{sub 6}{sup l})=(1,2{sup 2}) states locally perturbing the hyperfine structures is analyzed to yield the Coriolis and hyperfine coupling constants with uncertainties similar to those in typical microwave spectroscopy. The spectrometer has demonstrated the potential for precisely determining the energy structure inmore » the vibrational excited states.« less

Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1

PubMed Central

2017-01-01

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are thought to be initiated by projections from the mesencephalic locomotor region, the latter through a disinhibitory circuit in V1. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a threefold to fivefold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving. SIGNIFICANCE STATEMENT This paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of 3 the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.

PubMed

Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha

2018-05-01

Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

PubMed

Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

2007-01-01

Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

Evaluation of differential representative values between Chinese hamster cells and human lymphocytes in mitomycin C-induced cytogenetic assays and caspase-3 activity.

PubMed

Liao, Pei-Hu; Lin, Ruey-Hseng; Yang, Ming-Ling; Li, Yi-Ching; Kuan, Yu-Hsiang

2012-03-01

Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting

2013-02-15

In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells.more » Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.« less

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage.

PubMed

Hao, Shuangying; Song, Chuanhui; Shang, Longcheng; Yu, Jiang; Qiao, Tong; Li, Kuanyu

2016-03-10

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague-Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Enhanced electrochemical sensing of leukemia cells using drug/lipid co-immobilized on the conducting polymer layer.

PubMed

Gurudatt, N G; Naveen, M Halappa; Ban, Changill; Shim, Yoon-Bo

2016-12-15

Electrochemical biosensors using five anticancer drug and lipid molecules attached on the conducting polymer layer to obtain the orientation of drug molecules toward cancer cells, were evaluated as sensing materials and their performances were compared. Conjugation of the drug molecules with a lipid, phosphatidylcholine (PC) has enhanced the sensitivity towards leukemia cells and differentiates cancer cells from normal cells. The composition of each layer of sensor probe was confirmed by electrochemical and surface characterization experiments. Both impedance spectroscopy and voltammetry show the enhanced interaction of leukemia cells using the drug/lipid modified sensor probe. As the number of leukemia cells increased, the charge transfer resistance (Rct) in impedance spectra increased and the amine oxidation peak current of drug molecules in voltammograms decreased at around 0.7-1.0V. Of test drug molecules, raltitrexed (Rtx) showed the best performance for the cancer cells detection. Cancer and normal cell lines from different origins were examined to evaluate the degree of expression of folate receptors (FR) on cells surface, where cervical HeLa cell line was found to be shown the highest expression of the receptor. Impedance and chronoamperometric experiments for leukemia cell line (Jurkat E6-1) showed linear dynamic ranges of 1.0×10(3)-2.5×10(5) cells/mL and 1.0×10(3)-8.0×10(3) cells/mL with detection limits of 68±5 cells/mL and 21±3 cells/mL, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Band engineering in core/shell ZnTe/CdSe for photovoltage and efficiency enhancement in exciplex quantum dot sensitized solar cells.

PubMed

Jiao, Shuang; Shen, Qing; Mora-Seró, Iván; Wang, Jin; Pan, Zhenxiao; Zhao, Ke; Kuga, Yuki; Zhong, Xinhua; Bisquert, Juan

2015-01-27

Even though previously reported CdTe/CdSe type-II core/shell QD sensitizers possess intrinsic superior optoelectronic properties (such as wide absorption range, fast charge separation, and slow charge recombination) in serving as light absorbers, the efficiency of the resultant solar cell is still limited by the relatively low photovoltage. To further enhance photovoltage and cell efficiency accordingly, ZnTe/CdSe type-II core/shell QDs with much larger conduction band (CB) offset in comparison with that of CdTe/CdSe (1.22 eV vs 0.27 eV) are adopted as sensitizers in the construction of quantum dot sensitized solar cells (QDSCs). The augment of band offset produces an increase of the charge accumulation across the QD/TiO2 interface under illumination and induces stronger dipole effects, therefore bringing forward an upward shift of the TiO2 CB edge after sensitization and resulting in enhancement of the photovoltage of the resultant cell devices. The variation of relative chemical capacitance, Cμ, between ZnTe/CdSe and reference CdTe/CdSe cells extracted from impedance spectroscopy (IS) characterization under dark and illumination conditions clearly demonstrates that, under light irradiation conditions, the sensitization of ZnTe/CdSe QDs upshifts the CB edge of TiO2 by the level of ∼ 50 mV related to that in the reference cell and results in the enhancement of V(oc) of the corresponding cell devices. In addition, charge extraction measurements have also confirmed the photovoltage enhancement in the ZnTe/CdSe cell related to reference CdTe/CdSe cell. Furthermore, transient grating (TG) measurements have revealed a faster electron injection rate for the ZnTe/CdSe-based QDSCs in comparison with the CdSe cells. The resultant ZnTe/CdSe QD-based QDSCs exhibit a champion power conversion efficiency of 7.17% and a certified efficiency of 6.82% under AM 1.5 G full one sun illumination, which is, as far as we know, one of the highest efficiencies for liquid-junction QDSCs.

Wiring microbial biofilms to the electrode by osmium redox polymer for the performance enhancement of microbial fuel cells.

PubMed

Yuan, Yong; Shin, Hyosul; Kang, Chan; Kim, Sunghyun

2016-04-01

An osmium redox polymer, PAA-PVI-[Os(4,4'-dimethyl-2,2'-bipyridine)2Cl]+/2+ that has been used in enzymatic fuel cells and microbial sensors, was applied for the first time to the anode of single-chamber microbial fuel cells with the mixed culture inoculum aiming at enhancing performance. Functioning as a molecular wire connecting the biofilm to the anode, power density increased from 1479 mW m(-2) without modification to 2355 mW m(-2) after modification of the anode. Evidence from cyclic voltammetry showed that the catalytic activity of an anodic biofilm was greatly enhanced in the presence of an osmium redox polymer, indicating that electrons were more efficiently transferred to the anode via co-immobilized osmium complex tethered to wiring polymer chains at the potential range of -0.3 V-+0.1 V (vs. SCE). The optimum amount of the redox polymer was determined to be 0.163 mg cm(-2). Copyright © 2015 Elsevier B.V. All rights reserved.

Myeloid derived suppressor cells enhance IgE-mediated mast cell responses

USDA-ARS?s Scientific Manuscript database

We previously demonstrated that enhanced development of myeloid derived suppressor cells (MDSC) in ADAM10 transgenic mice yielded resistance to infection with Nippostrongylus brasiliensis infection, and that co-culturing MDSC with IgE-activated mast cells enhanced cytokine production. In the current...

Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes.

PubMed

Moreno-Viedma, Veronica; Tardelli, Matteo; Zeyda, Maximilian; Sibilia, Maria; Burks, J Deborah; Stulnig, Thomas M

2018-03-06

Osteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation. OPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1 -/- female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1 -/- mice (n=15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR. We show that Spp1 -/- maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1 -/- mice. Strikingly, APC from Spp1 -/- were diminished but differentiated more efficiently to adipocytes than those from control mice. APC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance. Copyright © 2018. Published by Elsevier Ltd.

[Short-term screening of anticarcinogenic ingredients of tea by cell biology assays].

PubMed

Liu, L; Han, C; Chen, J

1998-01-01

By using a panel of short term cell biology assays, several ingredients of tea (tea pigments, caffeine, tea polysaccharide, tea polyphenols tablet and mixed tea) were screened in order to investigate their anticarcinogenic effects. The cytokinesis block micronuclei test in V79 cells induced by mitomycin, the test of metabolic cooperation between V79 and M cells and the test of growth ability of Hela cells in soft agar were used in the screening. The results showed that the six kinds of tea ingredients tested were effective in the test involved in different stages of carcinogenesis, i.e. initiation, promotion and progression. The effects of mixed tea and tea pigments were the strongest among the ingredients tested.

High-Concentration III-V Multijunction Solar Cells | Photovoltaic Research

Science.gov Websites

| NREL High-Concentration III-V Multijunction Solar Cells High-Concentration III-V transfer to the high-efficiency cell industry, and the invention and development of the inverted metamorphic multijunction (IMM) cell technology. PV Research Other Materials & Devices pages: High

The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma.

PubMed

Suarez-Kelly, Lorena P; Kemper, Gregory M; Duggan, Megan C; Stiff, Andrew; Noel, Tiffany C; Markowitz, Joseph; Luedke, Eric A; Yildiz, Vedat O; Yu, Lianbo; Jaime-Ramirez, Alena Cristina; Karpa, Volodymyr; Zhang, Xiaoli; Carson, William E

2016-12-06

The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed. Apoptosis induced by ixazomib was first observed at 12 hours and was maximal at 48 hours with similar levels of cell death compared to bortezomib. IFN-α alone had little effect on cell viability in vitro. However, the combination of ixazomib with IFN-α significantly enhanced ixazomib's ability to induce apoptotic cell death in BRAF V600E mutant and BRAF wild-type human melanoma tumor cells. The combination of ixazomib and IFN-α also enhanced inhibition of cell proliferation in BRAF V600E mutant melanoma tumor cells; however, this was not seen in BRAF wild-type cells. Ixazomib-induced apoptosis was associated with processing of the pro-apoptotic proteins procaspase-3, -7, -8, and -9, and cleavage of poly-ADP-ribose polymerase (PARP). In an in vivo xenograft model of human melanoma, combination treatment with IFN-α-2b and ixazomib demonstrated a significant reduction in tumor volume when compared to vehicle (p = 0.005) and single therapy ixazomib (p = 0.017) and IFN-α-2b (p = 0.036). These pre-clinical results support further evaluation of combination treatment with ixazomib and IFN-α for the treatment of advanced BRAF V600E mutant melanoma.

Cloned Hemoglobin Genes Enhance Growth Of Cells

NASA Technical Reports Server (NTRS)

Khosla, Chaitan; Bailey, James E.

1991-01-01

Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

Heteromerization and colocalization of TrpV1 and TrpV2 in mammalian cell lines and rat dorsal root ganglia.

PubMed

Rutter, A Richard; Ma, Qing-Ping; Leveridge, Mathew; Bonnert, Timothy P

2005-11-07

Coassociation of the vanilloid transient receptor potential (Trp) ion channels, TrpV1 and TrpV2, was investigated by immunoprecipitation and immunofluorescence in transfected mammalian cell lines, rat dorsal root ganglia and spinal cord. TrpV1/TrpV2 heteromeric complexes were coimmunoprecipitated from human embryonic kidney cells and F-11 dorsal root ganglion hybridoma cells following their transient coexpression. Immunofluorescent labelling of transfected F-11 cells revealed colocalization of TrpV1 and TrpV2 at the cell surface. Immunoprecipitation from rat dorsal root ganglion lysates identified a minor population of receptor complexes composed of TrpV1/TrpV2 heteromers, consistent with a small proportion of cells double-labelled with TrpV1 and TrpV2 antibodies in rat dorsal root ganglion sections. TrpV1/TrpV2 receptor complexes may represent a functionally distinct ion channel complex that may increase the diversity observed within the Trp ion channel family.

Bruton's tyrosine kinase and protein kinase C µ are required for TLR7/9-induced IKKα and IRF-1 activation and interferon-β production in conventional dendritic cells.

PubMed

Li, Yan-Feng; Lee, Koon-Guan; Ou, Xijun; Lam, Kong-Peng

2014-01-01

Stimulation of TLR7/9 by their respective ligands leads to the activation of IκB kinase α (IKKα) and Interferon Regulatory Factor 1 (IRF-1) and results in interferon (IFN)-β production in conventional dendritic cells (cDC). However, which other signaling molecules are involved in IKKα and IRF-1 activation during TLR7/9 signaling pathway are not known. We and others have shown that Bruton's Tyrosine Kinase (BTK) played a part in TLR9-mediated cytokine production in B cells and macrophages. However, it is unclear if BTK participates in TLR7/9-induced IFN-β production in cDC. In this study, we show that BTK is required for IFN-β synthesis in cDC upon TLR7/9 stimulation and that stimulated BTK-deficient cDC are defective in the induction of IKKα/β phosphorylation and IRF-1 activation. In addition, we demonstrate that Protein Kinase C µ (PKCµ) is also required for TLR7/9-induced IRF-1 activation and IFN-β upregulation in cDC and acts downstream of BTK. Taken together, we have uncovered two new molecules, BTK and PKCµ, that are involved in TLR7/9-triggered IFN-β production in cDC.

Strand V: Education for Survival. Safety Education. Health Curriculum Materials. Grades 7-9.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

GRADES OR AGES: Grades 7-9. SUBJECT MATTER: Education for survival and safety education. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into eight sections: accident problems, safe behavior, safety in the home, safety in school, safety at work, safety in physical and recreational activities, safety in driving and walking, and safety in…

Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

PubMed

Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

2015-06-01

Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer. Copyright © 2015 Elsevier B.V. All rights reserved.

Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells.

PubMed

Kim, Hyo-Jin; Hwang, Ki-Eun; Park, Do-Sim; Oh, Seon-Hee; Jun, Hong Young; Yoon, Kwon-Ha; Jeong, Eun-Taik; Kim, Hak-Ryul; Kim, Young-Suk

2017-05-31

Shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in lung cancer are not fully understood. This study was designed to clarify whether shikonin causes necroptosis in non-small cell lung cancer (NSCLC) cells and to investigate the mechanism of action. Multiplex and caspase 8 assays were used to analyze effect of shikonin on A549 cells. Cytometry with annexin V/PI staining and MTT assays were used to analyze the mode of cell death. Western blotting was used to determine the effect of shikonin-induced necroptosis and autophagy. Xenograft and orthotopic models with A549 cells were used to evaluate the anti-tumor effect of shikonin in vivo. Most of the cell death induced by shikonin could be rescued by the specific necroptosis inhibitor necrostatin-1, but not by the general caspase inhibitor Z-VAD-FMK. Tumor growth was significantly lower in animals treated with shikonin than in the control group. Shikonin also increased RIP1 protein expression in tumor tissues. Autophagy inhibitors, including methyladenine (3-MA), ATG5 siRNA, and bafilomycin A, enhanced shikonin-induced necroptosis, whereas RIP1 siRNA had no effect on the apoptotic potential of shikonin. Our data indicated that shikonin treatment induced necroptosis and autophagy in NSCLC cells. In addition, the inhibition of shikonin-induced autophagy enhanced necroptosis, suggesting that shikonin could be a novel therapeutic strategy against NSCLC.

Enhancement of CD8+ T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor

PubMed Central

Ren, Hongwei; Ferguson, Brian J; de Motes, Carlos Maluquer; Sumner, Rebecca P; Harman, Laura E R; Smith, Geoffrey L

2015-01-01

Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8+ T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8+ T-cell populations, increased CD8+ T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8+ memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8+ T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8+ T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8+ T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety. PMID:25382035

Suzaku spectra of a Type-II supernova remnant, Kes 79

NASA Astrophysics Data System (ADS)

Sato, Tamotsu; Koyama, Katsuji; Lee, Shiu-Hang; Takahashi, Tadayuki

2016-06-01

This paper reports on results of a Suzaku observation of the supernova remnant (SNR) Kes 79 (G33.6+0.1). The X-ray spectrum is best fitted by a two-temperature model: a non-equilibrium ionization (NEI) plasma and a collisional ionization equilibrium (CIE) plasma. The NEI plasma is spatially confined within the inner radio shell with kT ˜ 0.8 keV, while the CIE plasma is found in more spatially extended regions associated with the outer radio shell with kT ˜0.2 keV and solar abundance. Therefore, the NEI plasma is attributable to the SN ejecta, and the CIE plasma is the forward shocked interstellar medium. In the NEI plasma, we discovered K-shell lines of Al, Ar, and Ca for the first time. The abundance pattern and estimated mass of the ejecta are consistent with a core-collapse supernova explosion of a ˜30-40M⊙ progenitor star. An Fe line with a center energy of ˜6.4 keV is also found in the southeast (SE) portion of the SNR, a close peripheral region around dense molecular clouds. One possibility is that the line is associated with the ejecta. However, the centroid energy of ˜6.4 keV and the spatial distribution of enhancement near the SE peripheral do not favor this scenario. Since the ˜6.4 keV emitting region coincides with the molecular clouds, we propose another possibility, that the Fe line is due to K-shell ionization of neutral Fe by the interaction of locally accelerated protons (LECRp) with the surrounding molecular cloud. Both of these possibilities, heated ejecta or LECRp origin, are discussed based on the observational facts.

STATs shape the active enhancer landscape of T cell populations.

PubMed

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-Wei; Sartorelli, Vittorio; Kanno, Yuka; O'Shea, John J

2012-11-21

Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. Copyright © 2012 Elsevier Inc. All rights reserved.

STATs Shape the Active Enhancer Landscape of T Cell Populations

PubMed Central

Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Sun, Hong-wei; Sartorelli, Vittorio; Kanno, Yuka; O’Shea, John J.

2012-01-01

SUMMARY Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. PMID:23178119

Simultaneous microbial and electrochemical reductions of vanadium (V) with bioelectricity generation in microbial fuel cells.

PubMed

Zhang, Baogang; Tian, Caixing; Liu, Ying; Hao, Liting; Liu, Ye; Feng, Chuanping; Liu, Yuqian; Wang, Zhongli

2015-03-01

Simultaneous microbial and electrochemical reductions of vanadium (V) with bioelectricity generation were realized in microbial fuel cells (MFCs). With initial V(V) concentrations of 75 mg/l and 150 mg/l in anolyte and catholyte, respectively, stable power output of 419±11 mW/m(2) was achieved. After 12h operation, V(V) concentration in the catholyte decreased to the value similar to that of the initial one in the anolyte, meanwhile it was nearly reduced completely in the anolyte. V(IV) was the main reduction product, which subsequently precipitated, acquiring total vanadium removal efficiencies of 76.8±2.9%. Microbial community analysis revealed the emergence of the new species of Deltaproteobacteria and Bacteroidetes as well as the enhanced Spirochaetes mainly functioned in the anode. This study opens new pathways to successful remediation of vanadium contamination. Copyright © 2014 Elsevier Ltd. All rights reserved.

Betavoltaic Enhancement Using Defect-Engineered TiO2 Nanotube Arrays through Electrochemical Reduction in Organic Electrolytes.

PubMed

Ma, Yang; Wang, Na; Chen, Jiang; Chen, Changsong; San, Haisheng; Chen, Jige; Cheng, Zhengdong

2018-06-19

Utilizing high-energy beta particles emitted from radioisotopes for long-lifetime betavoltaic cells is a great challenge due to low energy conversion efficiency. Here, we report a betavoltaic cell fabricated using TiO 2 nanotube arrays (TNTAs) electrochemically reduced in ethylene glycol electrolyte (EGECR-TNTAs) for the enhancement of the betavoltaic effect. The electrochemical reduction of TNTAs using high cathodic bias in organic electrolytes is indeed a facile and effective strategy to induce in situ self-doping of oxygen vacancy (OV) and Ti 3+ defects. The black EGECR-TNTAs are highly stable with a significantly narrower band gap and higher electrical conductivity as well as UV-vis-NIR light absorption. A 20 mCi of 63 Ni betavoltaic cell based on the reduced TNTAs exhibits a maximum ECE of 3.79% with open-circuit voltage of 1.04 V, short-circuit current density of 117.5 nA cm -2 , and a maximum power density of 39.2 nW cm -2 . The betavoltaic enhancement can be attributed to the enhanced charge carrier transport and separation as well as multiple exciton generation of electron-hole pairs due the generation of OV and Ti 3+ interstitial bands below the conductive band of TiO 2.

CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway

PubMed Central

Jijiwa, Mayumi; Demir, Habibe; Gupta, Snehalata; Leung, Crystal; Joshi, Kaushal; Orozco, Nicholas; Huang, Tiffany; Yildiz, Vedat O.; Shibahara, Ichiyo; de Jesus, Jason A.; Yong, William H.; Mischel, Paul S.; Fernandez, Soledad; Kornblum, Harley I.; Nakano, Ichiro

2011-01-01

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44high GBM but not from CD44low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44high GBM, but not in CD44low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKTpathway. PMID:21915300

Rapid and sensitive phenotypic marker detection on breast cancer cells using surface-enhanced Raman scattering (SERS) imaging.

PubMed

Lee, Sangyeop; Chon, Hyangah; Lee, Jiyoung; Ko, Juhui; Chung, Bong Hyun; Lim, Dong Woo; Choo, Jaebum

2014-01-15

We report a surface-enhanced Raman scattering (SERS)-based cellular imaging technique to detect and quantify breast cancer phenotypic markers expressed on cell surfaces. This technique involves the synthesis of SERS nano tags consisting of silica-encapsulated hollow gold nanospheres (SEHGNs) conjugated with specific antibodies. Hollow gold nanospheres (HGNs) enhance SERS signal intensity of individual particles by localizing surface electromagnetic fields through pinholes in the hollow particle structures. This capacity to enhance imaging at the level of single molecules permits the use of HGNs to detect specific biological markers expressed in living cancer cells. In addition, silica encapsulation greatly enhances the stability of nanoparticles. Here we applied a SERS-based imaging technique using SEHGNs in the multiplex imaging of three breast cancer cell phenotypes. Expression of epidermal growth factor (EGF), ErbB2, and insulin-like growth factor-1 (IGF-1) receptors were assessed in the MDA-MB-468, KPL4 and SK-BR-3 human breast cancer cell lines. SERS imaging technology described here can be used to test the phenotype of a cancer cell and quantify proteins expressed on the cell surface simultaneously. Based on results, this technique may enable an earlier diagnosis of breast cancer than is currently possible and offer guidance in treatment. © 2013 Elsevier B.V. All rights reserved.

Cell-Specific Actions of a Human LHX3 Gene Enhancer During Pituitary and Spinal Cord Development

PubMed Central

Park, Soyoung; Mullen, Rachel D.

2013-01-01

The LIM class of homeodomain protein 3 (LHX3) transcription factor is essential for pituitary gland and nervous system development in mammals. In humans, mutations in the LHX3 gene underlie complex pediatric syndromes featuring deficits in anterior pituitary hormones and defects in the nervous system. The mechanisms that control temporal and spatial expression of the LHX3 gene are poorly understood. The proximal promoters of the human LHX3 gene are insufficient to guide expression in vivo and downstream elements including a conserved enhancer region appear to play a role in tissue-specific expression in the pituitary and nervous system. Here we characterized the activity of this downstream enhancer region in regulating gene expression at the cellular level during development. Human LHX3 enhancer-driven Cre reporter transgenic mice were generated to facilitate studies of enhancer actions. The downstream LHX3 enhancer primarily guides gene transcription in α-glycoprotein subunit -expressing cells secreting the TSHβ, LHβ, or FSHβ hormones and expressing the GATA2 and steroidogenic factor 1 transcription factors. In the developing nervous system, the enhancer serves as a targeting module active in V2a interneurons. These results demonstrate that the downstream LHX3 enhancer is important in specific endocrine and neural cell types but also indicate that additional regulatory elements are likely involved in LHX3 gene expression. Furthermore, these studies revealed significant gonadotrope cell heterogeneity during pituitary development, providing insights into the cellular physiology of this key reproductive regulatory cell. The human LHX3 enhancer-driven Cre reporter transgenic mice also provide a valuable tool for further developmental studies of cell determination and differentiation in the pituitary and nervous system. PMID:24100213

A I-V analysis of irradiated Gallium Arsenide solar cells

NASA Technical Reports Server (NTRS)

Heulenberg, A.; Maurer, R. H.; Kinnison, J. D.

1991-01-01

A computer program was used to analyze the illuminated I-V characteristics of four sets of gallium arsenide (GaAs) solar cells irradiated with 1-MeV electrons and 10-MeV protons. It was concluded that junction regions (J sub r) dominate nearly all GaAs cells tested, except for irradiated Mitsubishi cells, which appear to have a different doping profile. Irradiation maintains or increases the dominance by J sub r. Proton irradiation increases J sub r more than does electron irradiation. The U.S. cells were optimized for beginning of life (BOL) and the Japanese for end of life (EOL). I-V analysis indicates ways of improving both the BOL and EOL performance of GaAs solar cells.

Enhancement of radiosensitivity of melanoma cells by pegylated gold nanoparticles under irradiation of megavoltage electrons.

PubMed

Mousavi, Mehdi; Nedaei, Hassan Ali; Khoei, Samideh; Eynali, Samira; Khoshgard, Karim; Robatjazi, Mostafa; Iraji Rad, Rasoul

2017-02-01

Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of radiosensitization was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams. It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 μM. Pegylated-GNP are taken up by B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV electrons. The radiosensitization effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex

PubMed Central

Poort, Jasper; Self, Matthew W.; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R.

2016-01-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure–ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both. We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression. We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current–source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure–ground organization. PMID:27522074

Mn complex-mediated enhancement of antitumor response through modulating myeloid-derived suppressor cells in drug-resistant tumor.

PubMed

Das, Satyajit; Banerjee, Kaushik; Roy, Susmita; Majumder, Saikat; Chatterjee, Mitali; Majumdar, Subrata; Choudhuri, Soumitra Kumar

2014-01-01

The tumor microenvironment (TME) renders tumor cells more resistant to chemotherapy. However, effective immunomodulators for cancer therapy are still elusive. We hypothesized that Mn-N-(2-hydroxyacetophenone) glycinate (MnNG), reported to be an antitumor agent, can modulate the TME. Immunomodulatory effects of MnNG were performed through assessing Myeloid Derived Suppressor Cells (MDSCs), Interferon-γ (Ifnγ)- and Interleukin-4 (Il4)-secreting Cluster of Differentiation 4 (Cd4)(+) T-cells by annexin V-binding assay in drug-resistant TME and T-cell proliferation following in vitro co-culture assay by flow cytometry. MnNG induced infiltration of Ifnγ-secreting Cd4(+) T-cells and reduces MDSC numbers in vivo. Furthermore, it modulated differentiation of MDSCs towards dendritic cells with up-regulation of co-stimulatory molecules and reversed the suppressive function of MDSC's that enhances T-helper cell 1 (Th1) response. MnNG treatment resulted in reduced expression of IL4, but enhanced expression of Ifnγ when Cd4(+) T-cells were co-cultured with MDSCs. MnNG modulates MDSCs differentiaton towards dendritic cells and enhances Th1 response in drug-resistant TME, leading to immunomodulatory efficacy. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Plasmon Enhanced Hetero-Junction Solar Cell

NASA Astrophysics Data System (ADS)

Long, Gen; Ching, Levine; Sadoqi, Mostafa; Xu, Huizhong

2015-03-01

Here we report a systematic study of plasmon-enhanced hetero-junction solar cells made of colloidal quantum dots (PbS) and nanowires (ZnO), with/without metal nanoparticles (Au). The structure of solar cell devices was characterized by AFM, SEM and profilometer, etc. The power conversion efficiencies of solar cell devices were characterized by solar simulator (OAI TriSOL, AM1.5G Class AAA). The enhancement in the photocurrent due to introduction of metal nanoparticles was obvious. We believe this is due to the plasmonic effect from the metal nanoparticles. The correlation between surface roughness, film uniformity and device performance was also studied.

T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV.

PubMed

Liu, William J; Zhao, Min; Liu, Kefang; Xu, Kun; Wong, Gary; Tan, Wenjie; Gao, George F

2017-01-01

Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

PubMed

Zhu, Ye-Hua; Wang, Xun; Zhang, Jin; Chen, Yong-Hui; Kong, Wen; Huang, Yi-Ran

2014-09-01

The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. Significant differences existed in tumor enhancement among different Fuhrman grades (p < 0.001). High-grade tumors had significantly lower enhancement (p < 0.001). The enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

Suppressor of cytokine signalling (SOCS) 1 and 3 enhance cell adhesion and inhibit migration towards the chemokine eotaxin/CCL11.

PubMed

Stevenson, Nigel J; McFarlane, Cheryl; Ong, Seow Theng; Nahlik, Krystyna; Kelvin, Alyson; Addley, Mark R; Long, Aideen; Greaves, David R; O'Farrelly, Cliona; Johnston, James A

2010-11-05

Suppressors of cytokine signalling (SOCS) proteins regulate signal transduction, but their role in responses to chemokines remains poorly understood. We report that cells expressing SOCS1 and 3 exhibit enhanced adhesion and reduced migration towards the chemokine CCL11. Focal adhesion kinase (FAK) and the GTPase RhoA, control cell adhesion and migration and we show the presence of SOCS1 or 3 regulates expression and tyrosine phosphorylation of FAK, while also enhancing activation of RhoA. Our novel findings suggest that SOCS1 and 3 may control chemotaxis and adhesion by significantly enhancing both FAK and RhoA activity, thus localizing immune cells to the site of allergic inflammation. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Persistence of the Z =28 Shell Gap Around 78Ni: First Spectroscopy of 79Cu

NASA Astrophysics Data System (ADS)

Olivier, L.; Franchoo, S.; Niikura, M.; Vajta, Z.; Sohler, D.; Doornenbal, P.; Obertelli, A.; Tsunoda, Y.; Otsuka, T.; Authelet, G.; Baba, H.; Calvet, D.; Château, F.; Corsi, A.; Delbart, A.; Gheller, J.-M.; Gillibert, A.; Isobe, T.; Lapoux, V.; Matsushita, M.; Momiyama, S.; Motobayashi, T.; Otsu, H.; Péron, C.; Peyaud, A.; Pollacco, E. C.; Roussé, J.-Y.; Sakurai, H.; Santamaria, C.; Sasano, M.; Shiga, Y.; Takeuchi, S.; Taniuchi, R.; Uesaka, T.; Wang, H.; Yoneda, K.; Browne, F.; Chung, L. X.; Dombradi, Z.; Flavigny, F.; Giacoppo, F.; Gottardo, A.; Hadyńska-Klek, K.; Korkulu, Z.; Koyama, S.; Kubota, Y.; Lee, J.; Lettmann, M.; Louchart, C.; Lozeva, R.; Matsui, K.; Miyazaki, T.; Nishimura, S.; Ogata, K.; Ota, S.; Patel, Z.; Sahin, E.; Shand, C.; Söderström, P.-A.; Stefan, I.; Steppenbeck, D.; Sumikama, T.; Suzuki, D.; Werner, V.; Wu, J.; Xu, Z.

2017-11-01

In-beam γ -ray spectroscopy of 79Cu is performed at the Radioactive Isotope Beam Factory of RIKEN. The nucleus of interest is produced through proton knockout from a 80Zn beam at 270 MeV /nucleon . The level scheme up to 4.6 MeV is established for the first time and the results are compared to Monte Carlo shell-model calculations. We do not observe significant knockout feeding to the excited states below 2.2 MeV, which indicates that the Z =28 gap at N =50 remains large. The results show that the 79Cu nucleus can be described in terms of a valence proton outside a 78Ni core, implying the magic character of the latter.

Optical absorption enhancement by inserting ZnO optical spacer in plasmonic organic solar cells

NASA Astrophysics Data System (ADS)

N'Konou, Kekeli; Torchio, Philippe

2018-01-01

Optical absorption enhancement (AE) using coupled optical spacer and plasmonic effects in standard and inverted organic solar cells (OSCs) are demonstrated using the finite-difference time-domain numerical method. The influence of an added zinc oxide (ZnO) optical spacer layer inserted below the active layer in standard architecture is first theoretically investigated while the influence of varying the ZnO cathodic buffer layer thickness in inverted design is studied on AE. Then, the embedding of a square periodic array of core-shell silver-silica nanospheres (Ag@SiO2 NSs) at different positions in standard and inverted OSCs is performed while AE and short-circuit current density (Jsc) are calculated. As a result of previous combined effects, the optimized standard plasmonic OSCs present 15% and 79.45% enhancement in J over the reference with and without ZnO optical spacer layer, respectively, and a 16% increase of AE when Ag@SiO2 NSs are placed on top of the PEDOT:PSS layer. Compared to the inverted OSC reference, the plasmonic OSCs present 26% and 27% enhancement in J and AE, respectively, when the Ag@SiO2 NSs are located on top of the ZnO layer. Furthermore, the spatial position of these NSs in such OSCs is a key parameter for increasing light absorption via enhanced electromagnetic field distribution.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

PubMed

Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

2017-06-01

Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

Single-neutron orbits near 78Ni: Spectroscopy of the N = 49 isotope 79Zn

DOE PAGES

Orlandi, R.; Mücher, D.; Raabe, R.; ...

2014-12-09

Single-neutron states in the Z=30, N=49 isotope 79Zn have been populated using the 78Zn(d, p) 79Zn transfer reaction at REX-ISOLDE, CERN. The experimental setup allowed the combined detection of protons ejected in the reaction, and of γ rays emitted by 79Zn. The analysis reveals that the lowest excited states populated in the reaction lie at approximately 1 MeV of excitation, and involve neutron orbits above the N=50 shell gap. From the analysis of γ -ray data and of proton angular distributions, characteristic of the amount of angular momentum transferred, a 5/2 + configuration was assigned to a state at 983more » keV. Comparison with large-scale-shell-model calculations supports a robust neutron N=50 shell-closure for 78Ni. Finally, these data constitute an important step towards the understanding of the magicity of 78Ni and of the structure of nuclei in the region.« less

[Experimental study and correction of the absorption and enhancement effect between Ti, V and Fe].

PubMed

Tuo, Xian-Guo; Mu, Ke-Liang; Li, Zhe; Wang, Hong-Hui; Luo, Hui; Yang, Jian-Bo

2009-11-01

The absorption and enhancement effects in X-ray fluorescence analysis for Ti, V and Fe elements were studied in the present paper. Three bogus duality systems of Ti-V/Ti-Fe/V-Fe samples were confected and measured by X-ray fluorescence analysis technique using HPGe semiconductor detector, and the relation curve between unitary coefficient (R(K)) of element count rate and element content (W(K)) were obtained after the experiment. Having analyzed the degree of absorption and enhancement effect between every two elements, the authors get the result, and that is the absorption and enhancement effect between Ti and V is relatively distinctness, while it's not so distinctness in Ti-Fe and V-Fe. After that, a mathematics correction method of exponential fitting was used to fit the R(K)-W(K) curve and get a function equation of X-ray fluorescence count rate and content. Three groups of Ti-V duality samples were used to test the fitting method and the relative errors of Ti and V were less than 0.2% as compared to the actual results.

Cyclin D1b splice variant promotes αvβ3-mediated adhesion and invasive migration of breast cancer cells.

PubMed

Wu, Feng-Hua; Luo, Li-Qiong; Liu, Yi; Zhan, Qiu-Xiao; Luo, Chao; Luo, Jing; Zhang, Gui-Mei; Feng, Zuo-Hua

2014-12-01

Cyclin D1b, a splice variant of the cell cycle regulator cyclin D1, holds oncogenic functions in human cancer. However, the mechanisms underlying cyclin D1b function remain poorly understood. Here we introduced wild-type cyclin D1a or cyclin D1b variant into non-metastatic MCF-7 cells. Our results show that ectopic expression of cyclin D1b promotes invasiveness of the cancer cells in a cyclin D1a independent manner. Specifically, cyclin D1b is found to modulate the expression of αvβ3, which characterizes the metastatic phenotype, and enhance tumor cell invasive potential in cooperating with HoxD3. Notably, cyclin D1b promotes αvβ3-mediated adhesion and invasive migration, which are associated with invasive potential of breast cancer cells. Further exploration indicates that cyclin D1b makes breast cancer cells more sensitive to toll-like receptor 4 ligand released from damaged tumor cells. These findings reveal a role of cyclin D1b as a possible mediator of αvβ3 transcription to promote tumor metastasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex.

PubMed

Poort, Jasper; Self, Matthew W; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R

2016-10-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure-ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both.We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression.We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current-source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure-ground organization. © The Author 2016. Published by Oxford University Press.

DOT1L and H3K79 Methylation in Transcription and Genomic Stability.

PubMed

Wood, Katherine; Tellier, Michael; Murphy, Shona

2018-02-27

The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

The indole compound NC009-1 inhibits aggregation and promotes neurite outgrowth through enhancement of HSPB1 in SCA17 cells and ameliorates the behavioral deficits in SCA17 mice.

PubMed

Chen, Chiung-Mei; Chen, Wan-Ling; Hung, Chen-Ting; Lin, Te-Hsien; Chao, Chih-Ying; Lin, Chih-Hsin; Wu, Yih-Ru; Chang, Kuo-Hsuan; Yao, Ching-Fa; Lee-Chen, Guey-Jen; Su, Ming-Tsan; Hsieh-Li, Hsiu Mei

2018-06-21

Spinocerebellar ataxia type 17 (SCA17) is caused by the expansion of translated CAG repeat in the TATA box binding protein (TBP) gene encoding a long polyglutamine (polyQ) tract in the TBP protein, which leads to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On cells with inducible SCA17 TBP/Q 79 -GFP expression to test five in-house NC009 indole compounds for neuroprotection. We found that both aggregation and polyQ-induced reactive oxygen species can be significantly prohibited by the tested NC009 compounds in Tet-On TBP/Q 79 293 cells. Among the five indole compounds, NC009-1 up-regulated expression of heat shock protein family B (small) member 1 (HSPB1) chaperone to reduce polyQ aggregation and promote neurite outgrowth in neuronal differentiated TBP/Q 79 SH-SY5Y cells. The increased HSPB1 thus ameliorated the increased BH3 interacting domain death agonist (BID), cytochrome c (CYCS) release, and caspase 3 (CASP3) activation which result in apoptosis. Knock down of HSPB1 attenuated the effects of NC009-1 on TBP/Q 79 SH-SY5Y cells, suggesting that HSPB1 might be one of the major pathways involved for NC009-1 effects. NC009-1 further reduced polyQ aggregation in Purkinje cells and ameliorated behavioral deficits in SCA17 TBP/Q 109 transgenic mice. Our results suggest that NC009-1 has a neuroprotective effect on SCA17 cell and mouse models to support its therapeutic potential in SCA17 treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

A rare mutation in AgRP, +79G>A, affects promoter activity.

PubMed

Sözen, M A; de Jonge, L H M; Greenway, F; Ravussin, E; Smith, S R; Argyropoulos, G

2007-06-01

The agouti-related protein is a powerful orexigenic peptide. A rare mutation, +79G>A, was identified in its minimal promoter in two white carriers. Comparison of the 45-year-old male proband, who was also a carrier of the common Ala67Thr polymorphism, with an age- and weight-matching wild-type population showed marginal differences for resting metabolic rate (RMR) and body mass index. The second carrier however was an obese 57-year-old female with reduced RMR. Functional analysis in hypothalamus- and periphery-derived cell lines showed reduced promoter activity for the +79A allele in the adrenocortical cells only, suggesting that it could affect the peripheral expression levels of AgRP. The +79G>A mutation could predispose to body weight gain (as suggested by the phenotype of the second carrier), but it could only affect the proband at an older age as he may be protected by the Ala67Thr polymorphism that is associated with resistance to late-onset fatness.

Expression, crystallization and preliminary crystallographic analysis of the extracellular IgV-like domain of the human natural killer cell inhibitory receptor p75/AIRM1.

PubMed

Dimasi, Nazzareno; Moretta, Lorenzo; Biassoni, Roberto; Mariuzza, Roy A

2003-10-01

p75/AIRM1 (Siglec-7) is a sialic acid-binding Ig-like lectin recently identified as an inhibitory receptor on natural killer cells. The expression, in vitro folding, circular-dichroism spectroscopy, crystallization and preliminary X-ray characterization of the Ig-V like domain of p75/AIRM1 are reported. X-ray data were collected from a single crystal at 100 K, with a maximum useful diffraction pattern extending to 1.45 A resolution on a synchrotron source. The crystal belongs to a primitive monoclinic space group, with unit-cell parameters a = 32.65, b = 49.72, c = 39.79 A, alpha = gamma = 90, beta = 113 degrees. The systematic absences indicate that the space group is P2(1). Assuming one molecule per asymmetric unit, V(M) (the Matthews coefficient) was calculated to be 1.879 A(3) Da(-1) and the solvent content was estimated to be 32.01%.

Selective inhibition of tumor cell associated Vacuolar-ATPase 'a2' isoform overcomes cisplatin resistance in ovarian cancer cells.

PubMed

Kulshrestha, Arpita; Katara, Gajendra K; Ginter, Jordyn; Pamarthy, Sahithi; Ibrahim, Safaa A; Jaiswal, Mukesh K; Sandulescu, Corina; Periakaruppan, Ramayee; Dolan, James; Gilman-Sachs, Alice; Beaman, Kenneth D

2016-06-01

Development of resistance to platinum compounds significantly hinders successful ovarian cancer (OVCA) treatment. In tumor cells, dysregulated pH gradient across cell membranes is a key physiological mechanism of metastasis/chemo-resistance. These pH alterations are mediated by aberrant activation of key multi-subunit proton pumps, Vacuolar-ATPases (V-ATPases). In tumor cells, its 'a2' isoform (V-ATPase-V0a2) is a component of functional plasma-membrane complex and promotes tumor invasion through tumor-acidification and immuno-modulation. Its involvement in chemo-resistance has not been studied. Here, we show that V-ATPase-V0a2 is over-expressed in acquired-cisplatin resistant OVCA cells (cis-A2780/cis-TOV112D). Of all the 'a' subunit isoforms, V-ATPase-V0a2 exhibited an elevated expression on plasma membrane of cisplatin-resistant cells compared to sensitive counterparts. Immuno-histochemistry revealed V-ATPase-V0a2 expression in both low grade (highly drug-resistant) and high grade (highly recurrent) human OVCA tissues indicating its role in a centralized mechanism of tumor resistance. In cisplatin resistant cells, shRNA mediated inhibition of V-ATPase-V0a2 enhanced sensitivity towards both cisplatin and carboplatin. This improved cytotoxicity was mediated by enhanced cisplatin-DNA-adduct formation and suppressed DNA-repair pathway, leading to enhanced apoptosis. Suppression of V0a2 activity strongly reduced cytosolic pH in resistant tumor cells, which is known to enhance platinum-associated DNA-damage. As an indicator of reduced metastasis and chemo-resistance, in contrast to plasma membrane localization, a diffused cytoplasmic localization of acidic vacuoles was observed in V0a2-knockdown resistant cells. Interestingly, pre-treatment with monoclonal V0a2-inhibitory antibody enhanced cisplatin cytotoxicity in resistant cells. Taken together, our findings suggest that the isoform specific inhibition of V-ATPase-V0a2 could serve as a therapeutic strategy for chemo

Monomeric cocoa catechins enhance β-cell function by increasing mitochondrial respiration.

PubMed

Rowley, Thomas J; Bitner, Benjamin F; Ray, Jason D; Lathen, Daniel R; Smithson, Andrew T; Dallon, Blake W; Plowman, Chase J; Bikman, Benjamin T; Hansen, Jason M; Dorenkott, Melanie R; Goodrich, Katheryn M; Ye, Liyun; O'Keefe, Sean F; Neilson, Andrew P; Tessem, Jeffery S

2017-11-01

A hallmark of type 2 diabetes (T2D) is β-cell dysfunction and the eventual loss of functional β-cell mass. Therefore, mechanisms that improve or preserve β-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on β-cell function. INS-1 832/13-derived β-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose-stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement. The increased glucose-stimulated insulin secretion in the presence of the monomeric catechin-rich fraction corresponded with enhanced mitochondrial respiration, suggesting improvements in β-cell fuel utilization. Mitochondrial complex III, IV and V components are up-regulated after culture with the monomer-rich fraction, corresponding with increased cellular ATP production. The monomer-rich fraction improved cellular redox state and increased glutathione concentration, which corresponds with nuclear factor, erythroid 2 like 2 (Nrf2) nuclear localization and expression of Nrf2 target genes including nuclear respiratory factor 1 (Nrf1) and GA binding protein transcription factor alpha subunit (GABPA), essential genes for increasing mitochondrial function. We propose a model by which monomeric cocoa catechins improve the cellular redox state, resulting in Nrf2 nuclear migration and up-regulation of genes critical for mitochondrial respiration, glucose-stimulated insulin secretion and ultimately improved β-cell function. These results suggest a mechanism by which monomeric cocoa catechins exert their effects as an effective complementary strategy to benefit T2D patients. Copyright �

40 CFR 86.314-79 - Fuel flow measurement specifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... percent of the measuring weight. (3) If the mass of fuel consumed is measured electronically (load cell... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Fuel flow measurement specifications....314-79 Fuel flow measurement specifications. (a) The fuel flow rate measurement instrument must have a...

40 CFR 86.314-79 - Fuel flow measurement specifications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... percent of the measuring weight. (3) If the mass of fuel consumed is measured electronically (load cell... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Fuel flow measurement specifications....314-79 Fuel flow measurement specifications. (a) The fuel flow rate measurement instrument must have a...

40 CFR 86.314-79 - Fuel flow measurement specifications.

Code of Federal Regulations, 2012 CFR

2012-07-01

... percent of the measuring weight. (3) If the mass of fuel consumed is measured electronically (load cell... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Fuel flow measurement specifications....314-79 Fuel flow measurement specifications. (a) The fuel flow rate measurement instrument must have a...

40 CFR 86.314-79 - Fuel flow measurement specifications.

Code of Federal Regulations, 2011 CFR

2011-07-01

... percent of the measuring weight. (3) If the mass of fuel consumed is measured electronically (load cell... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Fuel flow measurement specifications....314-79 Fuel flow measurement specifications. (a) The fuel flow rate measurement instrument must have a...

Further study of inversion layer MOS solar cells

NASA Technical Reports Server (NTRS)

Ho, Fat Duen

1987-01-01

A group of inversion layer MOS solar cells has been fabricated. The highest value of open-circuit voltage obtained for the cells is 0.568V. One of the cells has produced a short-circuit current of 79.6 mA and an open-circuit voltage of 0.54V. It is estimated that the actual area AMO efficiency of this cell is 6.6 percent with an assumed value of 0.75 for its fill factor. Efforts made for fabricating an IL/MOS cell with reasonable efficiencies are reported. Future work for 4 sq cm IL cells and 25 sq cm IL cells is discussed.

Mifepristone enhances insulin-stimulated Akt phosphorylation and glucose uptake in skeletal muscle cells.

PubMed

Bernal-Sore, Izela; Navarro-Marquez, Mario; Osorio-Fuentealba, César; Díaz-Castro, Francisco; Del Campo, Andrea; Donoso-Barraza, Camila; Porras, Omar; Lavandero, Sergio; Troncoso, Rodrigo

2018-02-05

Mifepristone is the only FDA-approved drug for glycaemia control in patients with Cushing's syndrome and type 2 diabetes. Mifepristone also has beneficial effects in animal models of diabetes and patients with antipsychotic treatment-induced obesity. However, the mechanisms through which Mifepristone produces its beneficial effects are not completely elucidated. To determine the effects of mifepristone on insulin-stimulated glucose uptake on a model of L6 rat-derived skeletal muscle cells. Mifepristone enhanced insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane and Akt Ser 473 phosphorylation in L6 myotubes. In addition, mifepristone reduced oxygen consumption and ATP levels and increased AMPK Thr 172 phosphorylation. The knockdown of AMPK prevented the effects of mifepristone on insulin response. Mifepristone enhanced insulin-stimulated glucose uptake through a mechanism that involves a decrease in mitochondrial function and AMPK activation in skeletal muscle cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells.

PubMed

Law, Betty Yuen Kwan; Chan, Wai Kit; Xu, Su Wei; Wang, Jing Rong; Bai, Li Ping; Liu, Liang; Wong, Vincent Kam Wai

2014-07-01

Resistance of cancer cells to chemotherapy is a significant problem in oncology, and the development of sensitising agents or small-molecules with new mechanisms of action to kill these cells is needed. Autophagy is a cellular process responsible for the turnover of misfolded proteins or damaged organelles, and it also recycles nutrients to maintain energy levels for cell survival. In some apoptosis-resistant cancer cells, autophagy can also enhance the efficacy of anti-cancer drugs through autophagy-mediated mechanisms of cell death. Because the modulation of autophagic processes can be therapeutically useful to circumvent chemoresistance and enhance the effects of cancer treatment, the identification of novel autophagic enhancers for use in oncology is highly desirable. Many novel anti-cancer compounds have been isolated from natural products; therefore, we worked to discover natural, anti-cancer small-molecule enhancers of autophagy. Here, we have identified a group of natural alkaloid small-molecules that function as novel autophagic enhancers. These alkaloids, including liensinine, isoliensinine, dauricine and cepharanthine, stimulated AMPK-mTOR dependent induction of autophagy and autophagic cell death in a panel of apoptosis-resistant cells. Taken together, our work provides novel insights into the biological functions, mechanisms and potential therapeutic values of alkaloids for the induction of autophagy.

Hmga2 promotes the development of myelofibrosis in Jak2V617F knockin mice by enhancing TGF-β1 and Cxcl12 pathways.

PubMed

Dutta, Avik; Hutchison, Robert E; Mohi, Golam

2017-08-17

Myelofibrosis (MF) is a devastating blood disorder. The JAK2V617F mutation has been detected in ∼50% cases of MF. Elevated expression of high-mobility group AT hook 2 (HMGA2) has also been frequently observed in patients with MF. Interestingly, upregulation of HMGA2 expression has been found in association with the JAK2V617F mutation in significant cases of MF. However, the contribution of HMGA2 in the pathogenesis of MF remains elusive. To determine the effects of concurrent expression of HMGA2 and JAK2V617F mutation in hematopoiesis, we transduced bone marrow cells from Jak2 V617F knockin mice with lentivirus expressing Hmga2 and performed bone marrow transplantation. Expression of Hmga2 enhanced megakaryopoiesis, increased extramedullary hematopoiesis, and accelerated the development of MF in mice expressing Jak2 V617F Mechanistically, the data show that expression of Hmga2 enhances the activation of transforming growth factor-β1 (TGF-β1) and Cxcl12 pathways in mice expressing Jak2 V617F In addition, expression of Hmga2 causes upregulation of Fzd2, Ifi27l2a, and TGF-β receptor 2. Forced expression of Cxcl12, Fzd2, or Ifi27l2a increases megakaryocytic differentiation and proliferation in the bone marrow of Jak2 V617F mice, whereas TGF-β1 or Cxcl12 stimulation induces collagen deposition in the bone marrow mesenchymal stromal cells. Together, these findings demonstrate that expression of Hmga2 cooperates with Jak2 V617F in the pathogenesis of MF. © 2017 by The American Society of Hematology.

Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.

PubMed

Wang, Shixia; Goguen, Jon D; Li, Fusheng; Lu, Shan

2011-09-09

Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans. Copyright © 2010 Elsevier Ltd. All rights reserved.

7 CFR 1779.79 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] 1779.79 Section 1779.79 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.79 [Reserved] ...

Cellular cooperation in lymphocyte activation. III. B-cell helper effect in the enhancement of T-cell response.

PubMed

Kasahara, T; Kin, K; Itoh, Y; Kawai, T; Kano, Y; Shioiri-Nakano, K

1979-01-01

T and B cells were purified from human tonsil and peripheral blood by the removal of phagocytic cells, followed by filtration through a nylon fiber column (NC) and E-rosette formation. Purified T and B cells contained less than 1% of other cell types. The responses of T cells to concanavalin A (Con A) and soluble protein A were greatly enhanced in the presence of autologous B cells. Participation of B cells in T-cell enhancement was confirmed by the following observations: (a) purified B copulation, which was separated further from adherent B cells, retained its enhancing activity. (b) Another adherent cell-free B-cell preparation, which was purified from the NC-passed fraction, and (c) no T lymphoid but some B lymphoid cell lines, elicited strong T-cell enhancement. It was also found that the enhancing capacity of B cells required no metabolic activity, but rather an intact cell form and direct cell-to-cell contact with responding cells. The stimulatory determinants on B cells were resistant to trypsin and neuraminidase treatment. In this paper a hypothesis will be presented that at least two signals are prerequisite for the effective activation of T cells.

Enhancement on primate corneal endothelial cell survival in vitro by a ROCK inhibitor.

PubMed

Okumura, Naoki; Ueno, Morio; Koizumi, Noriko; Sakamoto, Yuji; Hirata, Kana; Hamuro, Junji; Kinoshita, Shigeru

2009-08-01

The transplantation of cultivated corneal endothelial cells (CECs) has gained attention recently for the treatment of patients with corneal endothelial dysfunction. However, an efficient culturing technique for human (H)CECs has yet to be properly established. The present study was conducted to investigate the applicability of the Rho kinase (ROCK) inhibitor Y-27632 in promoting cultivation of cynomolgus monkey (M)CECs. MCECs of cynomolgus monkeys were cultured in a medium containing 10 microM Y-27632. The number of viable cells adherent to culture plates were monitored by a luminescent cell-viability assay and colony growth was detected by toluidine blue staining. Proliferating cells were detected by Ki67 expression using flow cytometry and a BrdU-labeling assay for immunocytochemistry. Annexin V-positive apoptotic cells were analyzed by flow cytometry. The number of viable cultivated MCECs was enhanced by Y-27632 addition after 24 hours in culture. The colony area of the culture in the presence of Y-27632 was higher than in the absence of Y-27632 on day 10. In Y-27632-treated cultures, the number of Ki67-positive cells was significantly increased at 24 and 48 hours, and the number of proliferating BrdU-positive cells was increased at 48 hours. The number of Annexin V-positive apoptotic cells was decreased at 24 hours. The inhibition of Rho/ROCK signaling by specific ROCK inhibitor Y-27632 promoted the adhesion of MCECs, inhibited apoptosis, and increased the number of proliferating cells. These results suggest that the ROCK inhibitor may serve as a new tool for cultivating HCECs for transplantation.

33 CFR 159.79 - Terminals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Terminals. 159.79 Section 159.79 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.79 Terminals. Terminals must be solderless lugs...

Enhancing the biocompatibility of microfluidics-assisted fabrication of cell-laden microgels with channel geometry.

PubMed

Kim, Suntae; Oh, Jonghyun; Cha, Chaenyung

2016-11-01

Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion ("single") microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which is shown to have a cytotoxic effect. Therefore, a microfluidic device with a sequential ('double') flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the cells' exposure to the oil phase is minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process. This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels. Copyright © 2016 Elsevier B.V. All rights reserved.

Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8.

PubMed

Delint-Ramirez, Ilse; Willoughby, Debbie; Hammond, Gerald R V; Hammond, Gerald V R; Ayling, Laura J; Cooper, Dermot M F

2011-09-23

PKA anchoring proteins (AKAPs) optimize the efficiency of cAMP signaling by clustering interacting partners. Recently, AKAP79 has been reported to directly bind to adenylyl cyclase type 8 (AC8) and to regulate its responsiveness to store-operated Ca(2+) entry (SOCE). Although AKAP79 is well targeted to the plasma membrane via phospholipid associations with three N-terminal polybasic regions, recent studies suggest that AKAP79 also has the potential to be palmitoylated, which may specifically allow it to target the lipid rafts where AC8 resides and is regulated by SOCE. In this study, we have addressed the role of palmitoylation of AKAP79 using a combination of pharmacological, mutagenesis, and cell biological approaches. We reveal that AKAP79 is palmitoylated via two cysteines in its N-terminal region. This palmitoylation plays a key role in targeting the AKAP to lipid rafts in HEK-293 cells. Mutation of the two critical cysteines results in exclusion of AKAP79 from lipid rafts and alterations in its membrane diffusion behavior. This is accompanied by a loss of the ability of AKAP79 to regulate SOCE-dependent AC8 activity in intact cells and decreased PKA-dependent phosphorylation of raft proteins, including AC8. We conclude that palmitoylation plays a key role in the targeting and action of AKAP79. This novel property of AKAP79 adds an unexpected regulatory and targeting option for AKAPs, which may be exploited in the cellular context.

Protein Z G79A polymorphism in Turkish pediatriccerebral infarct patients.

PubMed

Öztürk, Ayşenur; Eğin, Yonca; Deda, Gülhis; Teber, Serap; Akar, Nejat

2008-09-05

Protein Z (PZ) plays an enhancer role in coagulation as an anticoagulant. This is the first study in which G79A polymorphism investigated in Turkish paediatric stroke patients. Ninety-one paediatric stroke patients with cerebral ischemia and 70 control subjects were analyzed for PZ G79A and also FVL, PT mutations. PZ 79 'A' allele in homozygous state was found in five patients (5,5%), while it was found only in one control subject (1,4%) and it was seemed as a risk factor for peadiatric ischemia [OR=3,94 (0,44-35,1)]. When patients and controls who had FVL and PT carriers were excluded, AA genotype carried a risk [OR=3,88 (0,41-36,5)]. Also plasma protein Z levels measured in 21 stroke patients and 52 controls. Plasma protein Z levels were not different between stroke patients (500,95 ngmL-1±158,35) and controls (447,34 ngmL-1±165,97). But the plasma levels of protein Z was decreased in patients with AA genotype. Our data showed that carrying 79 AA genotype could be a genetic risk factor for cerebral infarct in peadiatric patients.

22 CFR 62.79 - Sanctions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Sanctions. 62.79 Section 62.79 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Student and Exchange Visitor Information System (SEVIS) § 62.79 Sanctions. (a) The Department of State shall impose sanctions...

An atlas of active enhancers across human cell types and tissues

NASA Astrophysics Data System (ADS)

Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Consortium, The Fantom; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin

2014-03-01

Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells.

PubMed

Mudado, M A; Rodrigues, A L; Prado, V F; Beirão, P S L; Cruz, J S

2004-06-01

T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 +/- 1.87 ms (N = 16). The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 +/- 2.4 and 6.7 +/- 0.3 mV (pre-pulse of -120 mV, N = 15), and -27.0 +/- 0.97 and 7.5 +/- 0.7 mV (pre-pulse of -40 mV, N = 9). The 8-mV shift in the activation mid-point was statistically significant (P < 0.05). The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of alpha1G (CaV3.1) and alpha1I (CaV3.3) T-type Ca2+ channel mRNA transcripts.

The silencing suppressor (NSs) protein of the plant virus Tomato spotted wilt virus enhances heterologous protein expression and baculovirus pathogenicity in cells and lepidopteran insects.

PubMed

de Oliveira, Virgínia Carla; da Silva Morgado, Fabricio; Ardisson-Araújo, Daniel Mendes Pereira; Resende, Renato Oliveira; Ribeiro, Bergmann Morais

2015-11-01

In this work, we showed that cell death induced by a recombinant (vAcNSs) Autographa californica multiple nucleopolyhedrovirus (AcMNPV) expressing the silencing suppressor (NSs) protein of Tomato spotted wilt virus (TSWV) was enhanced on permissive and semipermissive cell lines. The expression of a heterologous gene (firefly luciferase) during co-infection of insect cells with vAcNSs and a second recombinant baculovirus (vAgppolhfluc) was shown to increase when compared to single vAgppolhfluc infections. Furthermore, the vAcNSs mean time-to-death values were significantly lower than those for wild-type AcMNPV on larvae of Spodoptera frugiperda and Anticarsia gemmatalis. These results showed that the TSWV-NSs protein could efficiently increase heterologous protein expression in insect cells as well as baculovirus pathogenicity and virulence, probably by suppressing the gene-silencing machinery in insects.

49 CFR 79.9 - Design.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Design. 79.9 Section 79.9 Transportation Office of the Secretary of Transportation MEDALS OF HONOR § 79.9 Design. The Department is authorized to adopt and revise the existing designs for the award, rosette, and ribbon provided for by statute. ...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

45 CFR 79.4 - Investigation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Investigation. 79.4 Section 79.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.4 Investigation. (a) If an investigating official concludes that a subpoena pursuant to the authority conferred by...

7 CFR 1.79 - Credits.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false Credits. 1.79 Section 1.79 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.79 Credits. On films on which the Department or one of its agencies provides special assistance it shall be...

7 CFR 1.79 - Credits.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 1 2011-01-01 2011-01-01 false Credits. 1.79 Section 1.79 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.79 Credits. On films on which the Department or one of its agencies provides special assistance it shall be...

7 CFR 1.79 - Credits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 1 2014-01-01 2014-01-01 false Credits. 1.79 Section 1.79 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.79 Credits. On films on which the Department or one of its agencies provides special assistance it shall be...

7 CFR 1.79 - Credits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false Credits. 1.79 Section 1.79 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.79 Credits. On films on which the Department or one of its agencies provides special assistance it shall be...

49 CFR 79.9 - Design.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Design. 79.9 Section 79.9 Transportation Office of the Secretary of Transportation MEDALS OF HONOR § 79.9 Design. The Department is authorized to adopt and revise the existing designs for the award, rosette, and ribbon provided for by statute. ...

40 CFR 79.31 - Additives.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Additives. 79.31 Section 79.31... OF FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.31 Additives. (a) All additives... persons or property on a street or highway. For purposes of this registration, however, additives...

40 CFR 79.31 - Additives.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Additives. 79.31 Section 79.31... OF FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.31 Additives. (a) All additives... persons or property on a street or highway. For purposes of this registration, however, additives...

40 CFR 79.31 - Additives.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Additives. 79.31 Section 79.31... OF FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.31 Additives. (a) All additives... persons or property on a street or highway. For purposes of this registration, however, additives...

40 CFR 79.31 - Additives.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Additives. 79.31 Section 79.31... OF FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.31 Additives. (a) All additives... persons or property on a street or highway. For purposes of this registration, however, additives...

40 CFR 79.31 - Additives.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Additives. 79.31 Section 79.31... OF FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.31 Additives. (a) All additives... persons or property on a street or highway. For purposes of this registration, however, additives...

7 CFR 1.79 - Credits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Credits. 1.79 Section 1.79 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Cooperative Production of Television Films § 1.79 Credits. On films on which the Department or one of its agencies provides special assistance it shall be...

49 CFR 79.9 - Design.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Design. 79.9 Section 79.9 Transportation Office of the Secretary of Transportation MEDALS OF HONOR § 79.9 Design. The Department is authorized to adopt and revise the existing designs for the award, rosette, and ribbon provided for by statute...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Discovery. 79.21 Section 79.21 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

45 CFR 79.21 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Discovery. 79.21 Section 79.21 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1) Requests for production of documents for...

32 CFR 79.2 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Applicability. 79.2 Section 79.2 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN CHILD DEVELOPMENT PROGRAMS (CDPs) § 79.2 Applicability. This part applies to the Office of the Secretary of Defense...

14 CFR 13.79 - Hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hearing. 13.79 Section 13.79 Aeronautics... AND ENFORCEMENT PROCEDURES Orders of Compliance Under the Hazardous Materials Transportation Act § 13.79 Hearing. If an alleged violator requests a hearing in accordance with § 13.75, the procedure of...

Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca(2+) Influx.

PubMed

Wang, Ke; Zhu, Xue; Zhang, Kai; Wu, Zhifeng; Sun, Song; Zhou, Fanfan; Zhu, Ling

2016-07-11

Glutamate toxicity is estimated to be the key cause of photoreceptor degeneration in the pathogenesis of retinal degenerative diseases. Oxidative stress and Ca(2+) influx induced by glutamate are responsible for the apoptosis process of photoreceptor degeneration. Puerarin, a primary component of Kudzu root, has been widely used in the clinical treatment of retinal degenerative diseases in China for decades; however, the detailed molecular mechanism underlying this effect remains unclear. In this study, the neuroprotective effect of puerarin against glutamate-induced cytotoxicity in the differentiated Y-79 cells was first investigated through cytotoxicity assay. Then the molecular mechanism of this effect regarding anti-oxidative stress and Ca(2+) hemostasis was further explored with indirect immunofluorescence, flow cytometric analysis and western blot analysis. Our study showed that glutamate induced cell viability loss, excessive reactive oxygen species (ROS) generation, calcium overload and up-regulated cell apoptosis in differentiated Y-79 cells, which effect was significantly attenuated with the pre-treatment of puerarin in a dose-dependent manner. Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial-dependent signaling pathway and calmodulin-dependent protein kinase II (CaMKII)-dependent apoptosis signal-regulating kinase 1(ASK-1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases.

45 CFR 79.33 - Witnesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Witnesses. 79.33 Section 79.33 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.33 Witnesses. (a) Except as provided in paragraph (b) of this section, testimony at the hearing shall be given...

45 CFR 79.7 - Complaint.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Complaint. 79.7 Section 79.7 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.7 Complaint. (a) On or after the date the Department of Justice approves the issuance of a complaint in accordance...

45 CFR 79.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Definitions. 79.2 Section 79.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.2 Definitions. ALJ means an Administrative Law Judge in the authority appointed pursuant to 5 U.S.C. 3105 or...

45 CFR 79.29 - Sanctions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Sanctions. 79.29 Section 79.29 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.29 Sanctions. (a) The ALJ may sanction a person, including any party or representative, for— (1) Failing to comply...

45 CFR 79.34 - Evidence.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Evidence. 79.34 Section 79.34 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.34 Evidence. (a) The ALJ shall determine the admissibility of evidence. (b) Except as provided in this part, the...

45 CFR 79.47 - Limitations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Limitations. 79.47 Section 79.47 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.47 Limitations. (a) The notice of hearing with respect to a claim or statement must be served in the manner...

40 CFR 79.30 - Scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.30 Scope. Fuels and additives designated and dates prescribed by the Administrator for the registration of such fuels and additives... requirements under §§ 79.11(f) and 79.21(e) are set forth for each designated fuel or additive. Additional...

40 CFR 79.30 - Scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.30 Scope. Fuels and additives designated and dates prescribed by the Administrator for the registration of such fuels and additives... requirements under §§ 79.11(f) and 79.21(e) are set forth for each designated fuel or additive. Additional...

40 CFR 79.30 - Scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.30 Scope. Fuels and additives designated and dates prescribed by the Administrator for the registration of such fuels and additives... requirements under §§ 79.11(f) and 79.21(e) are set forth for each designated fuel or additive. Additional...

40 CFR 79.30 - Scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.30 Scope. Fuels and additives designated and dates prescribed by the Administrator for the registration of such fuels and additives... requirements under §§ 79.11(f) and 79.21(e) are set forth for each designated fuel or additive. Additional...

40 CFR 79.30 - Scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... FUELS AND FUEL ADDITIVES Designation of Fuels and Additives § 79.30 Scope. Fuels and additives designated and dates prescribed by the Administrator for the registration of such fuels and additives... requirements under §§ 79.11(f) and 79.21(e) are set forth for each designated fuel or additive. Additional...

The I-V Measurement System for Solar Cells Based on MCU

NASA Astrophysics Data System (ADS)

Fengxiang, Chen; Yu, Ai; Jiafu, Wang; Lisheng, Wang

2011-02-01

In this paper, an I-V measurement system for solar cells based on Single-chip Microcomputer (MCU) is presented. According to the test principles of solar cells, this measurement system mainly comprises of two parts—data collecting, data processing and displaying. The MCU mainly used as to acquire data, then the collecting results is sent to the computer by serial port. The I-V measurement results of our test system are shown in the human-computer interaction interface based on our hardware circuit. By comparing the test results of our I-V tester and the results of other commercial I-V tester, we found errors for most parameters are less than 5%, which shows our I-V test result is reliable. Because the MCU can be applied in many fields, this I-V measurement system offers a simple prototype for portable I-V tester for solar cells.

STS-79 Flight Day 5

NASA Technical Reports Server (NTRS)

1996-01-01

On this fifth day of the STS-79 mission, the flight crew, Cmdr. William F. Readdy, Pilot Terrence W. Wilcutt, Mission Specialists, Thomas D. Akers, Shannon Lucid, Jay Apt, and Carl E. Walz, in the first full day of joint Shuttle/Mir operations begin in with the transfer of a biotechnology investigation and logistical supplies from Atlantis to Mir. The Biotechnology System, an investigation that will study the long-term development of cartilage cells in microgravity, was transported to Mir early this morning. During his planned four-month stay on Mir, John Blaha will take weekly samples of the culture which may provide researchers with information on engineering cartilage cells for possible use in transplantation. They also took time out of their schedules to talk with Good Morning America's Elizabeth Vargas in a brief interview. Prior to beginning the day's transfer activities, all nine astronauts and cosmonauts participated in a joint planning session to outline the day's schedule.

45 CFR 79.28 - Motions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Motions. 79.28 Section 79.28 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.28 Motions. (a) Any application to the ALJ for an order or ruling shall be by motion. Motions shall state the...

45 CFR 79.25 - Fees.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Fees. 79.25 Section 79.25 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.25 Fees. The party requesting a subpoena shall pay the cost of the fees and mileage of any witness subpoenaed in the...

45 CFR 79.9 - Answer.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Answer. 79.9 Section 79.9 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.9 Answer. (a) The defendant may request a hearing by filing an answer with the reviewing official within 30 days of...

Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Manaresi, Elisabetta; Gallinella, Giorgio

2016-07-15

Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population. Copyright © 2016 Elsevier B.V. All rights reserved.

RECON-Dependent Inflammation in Hepatocytes Enhances Listeria monocytogenes Cell-to-Cell Spread.

PubMed

McFarland, Adelle P; Burke, Thomas P; Carletti, Alexie A; Glover, Rochelle C; Tabakh, Hannah; Welch, Matthew D; Woodward, Joshua J

2018-05-15

The oxidoreductase RECON is a high-affinity cytosolic sensor of bacterium-derived cyclic dinucleotides (CDNs). CDN binding inhibits RECON's enzymatic activity and subsequently promotes inflammation. In this study, we sought to characterize the effects of RECON on the infection cycle of the intracellular bacterium Listeria monocytogenes , which secretes cyclic di-AMP (c-di-AMP) into the cytosol of infected host cells. Here, we report that during infection of RECON-deficient hepatocytes, which exhibit hyperinflammatory responses, L. monocytogenes exhibits significantly enhanced cell-to-cell spread. Enhanced bacterial spread could not be attributed to alterations in PrfA or ActA, two virulence factors critical for intracellular motility and intercellular spread. Detailed microscopic analyses revealed that in the absence of RECON, L. monocytogenes actin tail lengths were significantly longer and there was a larger number of faster-moving bacteria. Complementation experiments demonstrated that the effects of RECON on L. monocytogenes spread and actin tail lengths were linked to its enzymatic activity. RECON enzyme activity suppresses NF-κB activation and is inhibited by c-di-AMP. Consistent with these previous findings, we found that augmented NF-κB activation in the absence of RECON caused enhanced L. monocytogenes cell-to-cell spread and that L. monocytogenes spread correlated with c-di-AMP secretion. Finally, we discovered that, remarkably, increased NF-κB-dependent inducible nitric oxide synthase expression and nitric oxide production were responsible for promoting L. monocytogenes cell-to-cell spread. The work presented here supports a model whereby L. monocytogenes secretion of c-di-AMP inhibits RECON's enzymatic activity, drives augmented NF-κB activation and nitric oxide production, and ultimately enhances intercellular spread. IMPORTANCE To date, bacterial CDNs in eukaryotes are solely appreciated for their capacity to activate cytosolic sensing

Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins.

PubMed

Carduner, L; Leroy-Dudal, J; Picot, C R; Gallet, O; Carreiras, F; Kellouche, S

2014-08-01

At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence. The presence of ascites, which acts as a dynamic reservoir of active molecules and cellular components, correlates with the OC peritoneal metastasis and is associated with poor prognosis. Since epithelial-mesenchymal transition (EMT) is involved in different phases of OC progression, we have investigated the effect of the unique ascitic tumor microenvironment on the EMT status and the behavior of OC cells. The exposure of three OC cell lines to ascites leads to changes in cellular morphologies. Within ascites, OC cells harboring an initial intermediate epithelial phenotype are characterized by marked dislocation of epithelial markers (E-cadherin, ZO-1 staining) while OC cells initially harboring an intermediate mesenchymal phenotype strengthen their mesenchymal markers (N-cadherin, vimentin). Ascites differentially triggers a dissemination phenotype related to the initial cell features by either allowing the proliferation and the formation of spheroids and the extension of colonies for cells that present an initial epithelial intermediate phenotype, or favoring the migration of cells with a mesenchymal intermediate phenotype. In an ascitic microenvironment, a redeployment of αv integrins into cells was observed and the ascites-induced accentuation of the two different invasive phenotypes (i.e. spheroids formation or migration) was shown to involve αv integrins. Thus, ascites induces a shift toward an unstable intermediate state of the epithelial-mesenchymal spectrum and confers a more aggressive cell behavior that takes on a different pathway based on the initial epithelial-mesenchymal cell features.

CD79B and MYD88 Mutations in Splenic Marginal Zone Lymphoma

PubMed Central

Trøen, Gunhild; Warsame, Abdirashid; Delabie, Jan

2013-01-01

The mutation status of genes involved in the NF-κB signaling pathway in splenic marginal zone lymphoma was examined. DNA sequence analysis of four genes was performed: CD79A, CD79B, CARD11, and MYD88 that are activated through BCR signaling or Toll-like and interleukin signaling. A single point mutation was detected in the CD79B gene (Y196H) in one of ten SMZL cases. Additionally, one point mutation was identified in the MYD88 gene (L265P) in another SMZL case. No mutations were revealed in CD79A or CARD11 genes in these SMZL cases. Neither were mutations detected in these four genes studied in 13 control MZL samples. Interestingly, the two cases with mutations of CD79B and MYD88 showed increased numbers of immunoblasts spread among the smaller and typical marginal zone lymphoma cells. Although SMZL shows few mutations of NF-κB signaling genes, our results indicate that the presence of these mutations is associated with a higher histological grade. PMID:23378931

14 CFR 13.79 - Hearing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Hearing. 13.79 Section 13.79 Aeronautics....79 Hearing. If an alleged violator requests a hearing in accordance with § 13.75, the procedure of subpart D of this part applies. At the close of the hearing, the Hearing Officer, on the record or...

14 CFR 13.79 - Hearing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Hearing. 13.79 Section 13.79 Aeronautics....79 Hearing. If an alleged violator requests a hearing in accordance with § 13.75, the procedure of subpart D of this part applies. At the close of the hearing, the Hearing Officer, on the record or...

Performance, Defect Behavior and Carrier Enhancement in Low Energy, Proton Irradiated p(+)nn(+) InP Solar Cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Rybicki, G. C.; Vargas-Aburto, C.; Jain, R. K.; Scheiman, D.

1994-01-01

InP p(+)nn(+) cells, processed by MOCVD, were irradiated by 0.2 MeV protons and their performance and defect behavior observed to a maximum fluence of 10(exp 13)/sq cm. Their radiation induced degradation, over this fluence range, was considerably+less than observed for similarly irradiated, diffused junction n p InP cells. Significant degradation occurred in both the cell's emitter and base regions the least degradation occurring in the depletion region. A significant increase in series resistance occurs at the highest fluenc.e. Two majority carrier defect levels, E7 and E10, are observed by DLTS with activation energies at (E(sub C) - 0.39)eV and (E(sub C) - 0.74)eV respectively. The relative concentration of these defects differs considerably from that observed after 1 MeV electron irradiation. An increased carrier concentration in the cell's n-region was observed at the highest proton fluence, the change in carrier concentration being insignificant at the lower fluences. In agreement with previous results, for 1 and 1.5 MeV electron irradiated InP p(+)n junctions, the defect level E10 is attributed to a complex between zinc, diffused into the n-region from the zinc doped emitter, and a radiation induced defect. The latter is assumed to be either a phosphorus vacancy or interstitial. The increased, or enhanced carrier concentration is attributed to this complex acting as a donor.

Integrin α(V)β(3)-targeted magnetic nanohybrids with enhanced antitumor efficacy, cell cycle arrest ability, and encouraging anti-cell-migration activity.

PubMed

Ding, Guo-Bin; Wang, Yan; Guo, Yi; Xu, Li

2014-10-08

Organic/inorganic nanohybrids, which integrate advantages of the biocompatibility of organic polymers and diversified functionalities of inorganic nanoparticles, have been extensively investigated in recent years. Herein, we report the construction of arginine-glycine-aspartic acid-cysteine (RGDC) tetrapeptide functionalized and 10-hydroxycamptothecin (HCPT)-encapsulated magnetic nanohybrids (RFHEMNs) for integrin αVβ3-targeted drug delivery. The obtained RFHEMNs were near-spherical in shape with a homogeneous size about 50 nm, and exhibited a superparamagnetic behavior. In vitro drug release study showed a sustained and pH-dependent release profile. Cell viability tests revealed that RFHEMNs displayed a significant enhancement of cytotoxicity against αVβ3-overexpressing A549 cells, as compared to free HCPT and nontargeting micelles. Flow cytometry analysis indicated that this cytotoxic effect was associated with dose-dependent S phase arrest. Finally, RFHEMNs exerted encouraging anti-cell-migration activity as determined by an in vitro wound-healing assay and a transwell assay. Overall, we envision that this tumor-targeting nanoscale drug delivery system may be of great application potential in chemotherapy of primary tumor and their metastases.

Enhancing performance of PEM fuel cells: Using the Au nanoplatelet/Nafion interface to enable CO oxidation under ambient conditions

DOE PAGES

Li, Hongfei; Pan, Cheng; Zhao, Sijia; ...

2016-04-16

We developed a method for fabrication of Au nanoparticle platelets which can be coated onto the Nafion membranes of polymer electrolyte membrane (PEM) fuel cells simply by Langmuir–Blodgett (LB) trough lift off from the air water interface. By incorporating the coated membranes into fuel cells with one membrane electrode assembly (MEA) we enhanced the maximum power output by more than 50% when operated under ambient conditions. An enhancement of more than 200% was observed when 0.1% CO was incorporated into the H 2 input gas stream and minimal enhancement was observed when the PEM fuel cell was operated with 100%more » O 2 gas at the cathode, or when particles were deposited on the electrodes. Density function theory (DFT) calculations were carried out to understand the origin of improved output power. Au NPs with 3-atomic layer in height and 2 nm in size were constructed to model the experimentally synthesized Au NPs. Our results indicated that the Au NPs interacted synergistically with the SO 3 groups, attached at end of Nafion side chains, to reduce the energy barrier for the oxidation of CO occurring at the perimeter of the Au NPs, from 1.292 eV to 0.518 eV, enabling the reaction to occur at T<300 K.« less

Surface vimentin is critical for the cell entry of SARS-CoV.

PubMed

Yu, Yvonne Ting-Chun; Chien, Ssu-Chia; Chen, I-Yin; Lai, Chia-Tsen; Tsay, Yeou-Guang; Chang, Shin C; Chang, Ming-Fu

2016-01-22

Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.

Differentiation of V2a interneurons from human pluripotent stem cells

PubMed Central

Butts, Jessica C.; McCreedy, Dylan A.; Martinez-Vargas, Jorge Alexis; Mendoza-Camacho, Frederico N.; Hookway, Tracy A.; Gifford, Casey A.; Taneja, Praveen; Noble-Haeusslein, Linda; McDevitt, Todd C.

2017-01-01

The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+ V2a interneurons from human pluripotent stem cells (hPSCs). Signaling pathways (retinoic acid, sonic hedgehog, and Notch) that pattern the neural tube were sequentially perturbed to identify an optimized combination of small molecules that yielded ∼25% CHX10+ cells in four hPSC lines. Differentiated cultures expressed much higher levels of V2a phenotypic markers (CHX10 and SOX14) than other neural lineage markers. Over time, CHX10+ cells expressed neuronal markers [neurofilament, NeuN, and vesicular glutamate transporter 2 (VGlut2)], and cultures exhibited increased action potential frequency. Single-cell RNAseq analysis confirmed CHX10+ cells within the differentiated population, which consisted primarily of neurons with some glial and neural progenitor cells. At 2 wk after transplantation into the spinal cord of mice, hPSC-derived V2a cultures survived at the site of injection, coexpressed NeuN and VGlut2, extended neurites >5 mm, and formed putative synapses with host neurons. These results provide a description of V2a interneurons differentiated from hPSCs that may be used to model central nervous system development and serve as a potential cell therapy for SCI. PMID:28438991

Integrin αv in the mechanical response of osteoblast lineage cells.

PubMed

Kaneko, Keiko; Ito, Masako; Naoe, Yoshinori; Lacy-Hulbert, Adam; Ikeda, Kyoji

2014-05-02

Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhancing the efficiency of planar heterojunction perovskite solar cells via interfacial engineering with 3-aminopropyl trimethoxy silane hydrolysate

PubMed Central

Wang, Ya-Qiong; Xu, Shou-Bin; Deng, Jian-Guo

2017-01-01

The interfacial compatibility between compact TiO2 and perovskite layers is critical for the performance of planar heterojunction perovskite solar cells (PSCs). A compact TiO2 film employed as an electron-transport layer (ETL) was modified using 3-aminopropyl trimethoxy silane (APMS) hydrolysate. The power conversion efficiency (PCE) of PSCs composed of an APMS-hydrolysate-modified TiO2 layer increased from 13.45 to 15.79%, which was associated with a significant enhancement in the fill factor (FF) from 62.23 to 68.04%. The results indicate that APMS hydrolysate can enhance the wettability of γ-butyrolactone (GBL) on the TiO2 surface, form a perfect CH3NH3PbI3 film, and increase the recombination resistance at the interface. This work demonstrates a simple but efficient method to improve the TiO2/perovskite interface that can be greatly beneficial for developing high-performance PSCs. PMID:29308238

Enhancing the efficiency of planar heterojunction perovskite solar cells via interfacial engineering with 3-aminopropyl trimethoxy silane hydrolysate

NASA Astrophysics Data System (ADS)

Wang, Ya-Qiong; Xu, Shou-Bin; Deng, Jian-Guo; Gao, Li-Zhen

2017-12-01

The interfacial compatibility between compact TiO2 and perovskite layers is critical for the performance of planar heterojunction perovskite solar cells (PSCs). A compact TiO2 film employed as an electron-transport layer (ETL) was modified using 3-aminopropyl trimethoxy silane (APMS) hydrolysate. The power conversion efficiency (PCE) of PSCs composed of an APMS-hydrolysate-modified TiO2 layer increased from 13.45 to 15.79%, which was associated with a significant enhancement in the fill factor (FF) from 62.23 to 68.04%. The results indicate that APMS hydrolysate can enhance the wettability of γ-butyrolactone (GBL) on the TiO2 surface, form a perfect CH3NH3PbI3 film, and increase the recombination resistance at the interface. This work demonstrates a simple but efficient method to improve the TiO2/perovskite interface that can be greatly beneficial for developing high-performance PSCs.

Enhancing the efficiency of planar heterojunction perovskite solar cells via interfacial engineering with 3-aminopropyl trimethoxy silane hydrolysate.

PubMed

Wang, Ya-Qiong; Xu, Shou-Bin; Deng, Jian-Guo; Gao, Li-Zhen

2017-12-01

The interfacial compatibility between compact TiO 2 and perovskite layers is critical for the performance of planar heterojunction perovskite solar cells (PSCs). A compact TiO 2 film employed as an electron-transport layer (ETL) was modified using 3-aminopropyl trimethoxy silane (APMS) hydrolysate. The power conversion efficiency (PCE) of PSCs composed of an APMS-hydrolysate-modified TiO 2 layer increased from 13.45 to 15.79%, which was associated with a significant enhancement in the fill factor (FF) from 62.23 to 68.04%. The results indicate that APMS hydrolysate can enhance the wettability of γ-butyrolactone (GBL) on the TiO 2 surface, form a perfect CH 3 NH 3 PbI 3 film, and increase the recombination resistance at the interface. This work demonstrates a simple but efficient method to improve the TiO 2 /perovskite interface that can be greatly beneficial for developing high-performance PSCs.

I-V-T analysis of radiation damage in high efficiency Si solar cells

NASA Technical Reports Server (NTRS)

Banerjee, S.; Anderson, W. A.; Rao, B. B.

1985-01-01

A detailed analysis of current-voltage characteristics of N(+)-P/P solar cells indicate that there is a combination of different mechanisms which results in an enhancement in the dark current and in turn deteriorates the photovoltaic performance of the solar cells after 1 MeV e(-) irradiation. The increase in the dark current is due to three effects, i.e., bulk recombination, space charge recombination by deep traps and space charge recombination through shallow traps. It is shown that the increase in bulk recombination current is about 2 to 3 orders of magnitude whereas space charge recombination current due to shallow traps increases only by an order or so and no space charge recombination through deep traps was observed after irradiation. Thus, in order to improve the radiation hardness of these devices, bulk properties should be preserved.

Enhanced efficiency of hybrid amorphous silicon solar cells based on single-walled carbon nanotubes and polymer composite thin film.

PubMed

Rajanna, Pramod M; Gilshteyn, Evgenia P; Yagafarov, Timur; Aleekseeva, Alena K; Anisimov, Anton S; Neumüller, Alex; Sergeev, Oleg; Bereznev, Sergei; Maricheva, Jelena; Nasibulin, Albert G

2018-01-31

We report a simple approach to fabricate hybrid solar cells (HSCs) based on a single-walled carbon nanotube (SWCNT) film and thin film hydrogenated amorphous silicon (a-Si:H). Randomly oriented high-quality SWCNTs with conductivity enhanced by means of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate are used as a window layer and a front electrode. A series of HSCs are fabricated in ambient conditions with varying SWCNT film thicknesses. The polymethylmethacrylate layer drop-casted on fabricated HSCs reduces the reflection fourfold and enhances the short-circuit J sc , open-circuit V oc , and efficiency by nearly 10%. A state-of-the-art J-V performance is shown for SWCNT/a-Si HSC with an open-circuit voltage of 900 mV and an efficiency of 3.4% under simulated one-sun AM 1.5 G direct illumination.

Enhanced efficiency of hybrid amorphous silicon solar cells based on single-walled carbon nanotubes and polymer composite thin film

NASA Astrophysics Data System (ADS)

Rajanna, Pramod M.; Gilshteyn, Evgenia P.; Yagafarov, Timur; Aleekseeva, Alena K.; Anisimov, Anton S.; Neumüller, Alex; Sergeev, Oleg; Bereznev, Sergei; Maricheva, Jelena; Nasibulin, Albert G.

2018-03-01

We report a simple approach to fabricate hybrid solar cells (HSCs) based on a single-walled carbon nanotube (SWCNT) film and thin film hydrogenated amorphous silicon (a-Si:H). Randomly oriented high-quality SWCNTs with conductivity enhanced by means of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate are used as a window layer and a front electrode. A series of HSCs are fabricated in ambient conditions with varying SWCNT film thicknesses. The polymethylmethacrylate layer drop-casted on fabricated HSCs reduces the reflection fourfold and enhances the short-circuit J sc , open-circuit V oc , and efficiency by nearly 10%. A state-of-the-art J-V performance is shown for SWCNT/a-Si HSC with an open-circuit voltage of 900 mV and an efficiency of 3.4% under simulated one-sun AM 1.5 G direct illumination.

Cell culture media supplemented with raffinose reproducibly enhances high mannose glycan formation.

PubMed

Brühlmann, David; Muhr, Anais; Parker, Rebecca; Vuillemin, Thomas; Bucsella, Blanka; Kalman, Franka; Torre, Serena; La Neve, Fabio; Lembo, Antonio; Haas, Tobias; Sauer, Markus; Souquet, Jonathan; Broly, Hervé; Hemberger, Jürgen; Jordan, Martin

2017-06-20

Glycosylation plays a pivotal role in pharmacokinetics and protein physiochemical characteristics. In particular, effector functions including antibody-dependent cell-mediated cytotoxicity (ADCC) can be desired, and it has been described that high-mannose species exhibited enhanced ADCC. In this work we present the trisaccharide raffinose as a novel cell culture medium supplement to promote high mannose N-glycans in fed-batch cultures, which is sought after in the development of biosimilars to match the quality profile of the reference medicinal product (RMP) also. Up to six-fold increases of high mannose species were observed with increasing raffinose concentrations in the medium of shaken 96-deepwell plates and shake tubes when culturing two different CHO cell lines in two different media. The findings were confirmed in a pH-, oxygen- and CO 2 -controlled environment in lab-scale 3.5-L bioreactors. To circumvent detrimental effects on cell growth and productivity at high raffinose concentrations, the media osmolality was adjusted to reach the same value independently of the supplement concentration. Interestingly, raffinose predominantly enhanced mannose 5 glycans, and to a considerably smaller degree, mannose 6. While the underlying mechanism is still not fully understood, minor effects on the nucleotide sugar levels have been observed and transcriptomics analysis revealed that raffinose supplementation altered the expression levels of a number of glycosylation related genes. Among many genes, galactosyltransferase was downregulated and sialyltransferase upregulated. Our results highlight the potential of cell culture medium supplementation to modulate product quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations.

PubMed

Cao, Xin-Xin; Li, Jian; Cai, Hao; Zhang, Wei; Duan, Ming-Hui; Zhou, Dao-Bin

2017-11-01

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines.

PubMed

Oktyabri, Dulamsuren; Ishimura, Akihiko; Tange, Shoichiro; Terashima, Minoru; Suzuki, Takeshi

2016-04-01

DOT1L is a histone H3 lysine 79 (H3K79) methyltransferase mainly implicated in leukemia. Here we analyzed the function of DOT1L in breast cancer cells. The expression of DOT1L was up-regulated in malignant breast cancer tissues. Over-expression of DOT1L significantly increased the sphere formation and the cell migration activities of MCF7 breast cancer cell line. In contrast, knockdown of DOT1L reduced the cell migration activity of MDA-MB-231 breast cancer cell line. BCAT1, which encodes a branched-chain amino acid transaminase, was identified as one of the target genes controlled by DOT1L through the regulation of H3K79 methylation. Mechanistic investigation revealed that BCAT1 might be an important regulator responsible for DOT1L-mediated sphere formation and cell migration in breast cancer cells. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture

NASA Astrophysics Data System (ADS)

Islam, Muhymin; Sajid, Adeel; Arif Iftakher Mahmood, M.; Motasim Bellah, Mohammad; Allen, Peter B.; Kim, Young-Tae; Iqbal, Samir M.

2015-06-01

Detection of circulating tumor cells (CTCs) in the early stages of cancer is a great challenge because of their exceedingly small concentration. There are only a few approaches sensitive enough to differentiate tumor cells from the plethora of other cells in a sample like blood. In order to detect CTCs, several antibodies and aptamers have already shown high affinity. Nanotexture can be used to mimic basement membrane to further enhance this affinity. This article reports an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates using micro reactive ion etching (micro-RIE). Three recipes were used to prepare nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided better control on surface properties. Nanotexturing improved the affinity of PDMS surfaces to capture cancer cells using surface immobilized aptamers against cell membrane overexpressed with epidermal growth factor receptors. In all cases, nanotexture of PDMS increased the effective surface area by creating nanoscale roughness on the surface. Nanotexture also enhanced the growth rate of cultured cells compared to plain surfaces. A comparison among the three nanotextured surfaces demonstrated an almost linear relationship between the surface roughness and density of captured tumor cells. The nanotextured PDMS mimicked biophysical environments for cells to grow faster. This can have many implications in microfluidic platforms used for cell handling.

Enhancing Solar Cell Efficiencies through 1-D Nanostructures

PubMed Central

2009-01-01

The current global energy problem can be attributed to insufficient fossil fuel supplies and excessive greenhouse gas emissions resulting from increasing fossil fuel consumption. The huge demand for clean energy potentially can be met by solar-to-electricity conversions. The large-scale use of solar energy is not occurring due to the high cost and inadequate efficiencies of existing solar cells. Nanostructured materials have offered new opportunities to design more efficient solar cells, particularly one-dimensional (1-D) nanomaterials for enhancing solar cell efficiencies. These 1-D nanostructures, including nanotubes, nanowires, and nanorods, offer significant opportunities to improve efficiencies of solar cells by facilitating photon absorption, electron transport, and electron collection; however, tremendous challenges must be conquered before the large-scale commercialization of such cells. This review specifically focuses on the use of 1-D nanostructures for enhancing solar cell efficiencies. Other nanostructured solar cells or solar cells based on bulk materials are not covered in this review. Major topics addressed include dye-sensitized solar cells, quantum-dot-sensitized solar cells, and p-n junction solar cells.

Mitogen-activated Protein Kinase (MAPK) Hyperactivation and Enhanced NRAS Expression Drive Acquired Vemurafenib Resistance in V600E BRAF Melanoma Cells*

PubMed Central

Lidsky, Michael; Antoun, Gamil; Speicher, Paul; Adams, Bartley; Turley, Ryan; Augustine, Christi; Tyler, Douglas; Ali-Osman, Francis

2014-01-01

Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acquisition of resistance to BRAF-targeted therapy in previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem, had higher growth rates and showed differential collateral resistance to cisplatin, melphalan, and temozolomide. The acquisition of vemurafenib resistance was associated with significantly increased NRAS levels in A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells that involves increased activation of all three human MAPKs and the PI3K pathway, as well as increased NRAS expression, which, contrary to previous reports, was not associated with mutations in the NRAS gene. The data highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of optimizing BRAF-targeted therapy in this disease. They also suggest that targeting the MAPKs and/or NRAS may provide a strategy to mitigate such resistance in V600E BRAF+ve melanoma. PMID:25063807

Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.

PubMed

Lidsky, Michael; Antoun, Gamil; Speicher, Paul; Adams, Bartley; Turley, Ryan; Augustine, Christi; Tyler, Douglas; Ali-Osman, Francis

2014-10-03

Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acquisition of resistance to BRAF-targeted therapy in previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem, had higher growth rates and showed differential collateral resistance to cisplatin, melphalan, and temozolomide. The acquisition of vemurafenib resistance was associated with significantly increased NRAS levels in A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells that involves increased activation of all three human MAPKs and the PI3K pathway, as well as increased NRAS expression, which, contrary to previous reports, was not associated with mutations in the NRAS gene. The data highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of optimizing BRAF-targeted therapy in this disease. They also suggest that targeting the MAPKs and/or NRAS may provide a strategy to mitigate such resistance in V600E BRAF+ve melanoma. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes

PubMed Central

Moorthy, Sakthi D.; Davidson, Scott; Shchuka, Virlana M.; Singh, Gurdeep; Malek-Gilani, Nakisa; Langroudi, Lida; Martchenko, Alexandre; So, Vincent; Macpherson, Neil N.; Mitchell, Jennifer A.

2017-01-01

Transcriptional enhancers are critical for maintaining cell-type–specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. PMID:27895109

Stretch-Enhancers Delineate Disease-Associated Regulatory Nodes in T Cells

PubMed Central

Vahedi, Golnaz; Kanno, Yuka; Furumoto, Yasuko; Jiang, Kan; Parker, Stephen C.; Erdos, Michael; Davis, Sean R.; Roychoudhuri, Rahul; Restifo, Nicholas P.; Gadina, Massimo; Tang, Zhonghui; Ruan, Yijun; Collins, Francis S.; Sartorelli, Vittorio; O’Shea, John J.

2014-01-01

Enhancers regulate spatiotemporal gene expression and impart cell-specific transcriptional outputs that drive cell identity1. Stretch- or super-enhancers (SEs) are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease2,3,4,5,6. CD4+ T cells are critical for host defense and autoimmunity. Herein, we analyzed maps of T cell SEs as a non-biased means of identifying key regulatory nodes involved in cell specification. We found that cytokines and cytokine receptors were the dominant class of genes exhibiting SE architecture in T cells. This notwithstanding, the locus encoding Bach2, a key negative regulator of effector differentiation, emerged as the most prominent T cell SE, revealing a network wherein SE-associated genes critical for T cell biology are repressed by BACH2. Disease-associated SNPs for immune-mediated disorders, including rheumatoid arthritis (RA), were highly enriched for T cell-SEs versus typical enhancers (TEs) or SEs in other cell lineages7. Intriguingly, treatment of T cells with the Janus kinase (JAK) inhibitor, tofacitinib, disproportionately altered the expression of RA risk genes with SE structures. Together, these results indicate that genes with SE architecture in T cells encompass a variety of cytokines and cytokine receptors but are controlled by a “guardian” transcription factor, itself endowed with an SE. Thus, enumeration of SEs allows unbiased determination of key regulatory nodes in T cells, which are preferentially modulated by pharmacological intervention. PMID:25686607

JunD/AP-1 Antagonizes the Induction of DAPK1 To Promote the Survival of v-Src-Transformed Cells.

PubMed

Maślikowski, Bart M; Wang, Lizhen; Wu, Ying; Fielding, Ben; Bédard, Pierre-André

2017-01-01

of action determined by the JunD component of AP-1, a factor enhancing cell survival in v-Src-transformed cells. We show that the loss of JunD results in the aberrant activation of a genetic program leading to cell death. This program requires the activation of the tumor suppressor death-associated protein kinase 1 (DAPK1). Since DAPK1 is phosphorylated and inhibited by v-Src, these results highlight the importance of this kinase and the multiple mechanisms controlled by v-Src to antagonize the tumor suppressor function of DAPK1. Copyright © 2016 American Society for Microbiology.

Potentiometric Biosensor for Studying Hydroquinone Cytotoxicity in vitro

PubMed Central

Wang, Yanyan; Chen, Qiang; Zeng, Xiangqun

2009-01-01

Many processes in living cells have electrochemical characteristics that are suitable for measurement by potentiometric biosensors. Potentiometric biosensors allow non invasive, real-time monitoring of the extracellular environment changes by measuring the potential at cell/sensor interface. This can be used as an indicator for overall cell cytotoxicity. The present work employs a potentiometric sensor array to investigate the cytotoxicity of hydroquinone to cultured mammalian V79 cells. Various electrode substrates (Au, PPy-HQ and PPy-PS) used for cell growth were designed and characterized. The controllable release of hydroquinone from PPy substrates was studied. Our results showed that hydroquinone exposure affected cell proliferation and delayed cell growth and attachment in a dose-dependent manner. Additionally, we have shown that exposure of V79 cells to hydroquinone at low doses (i.e 5μM) for more than 15 hours allows V79 cells to gain enhanced adaptability to survive exposure to high toxic HQ doses afterwards. Compared with traditional methods, the potentiometric biosensor not only provides non-invasive and real time monitoring of the cellular reactions but also is more sensitive for in vitro cytotoxicity study. By real time and non-invasive monitoring of the extracellular potential in vitro, the potentiometric sensor system represents a promising biosensor system for drug discovery. PMID:19926470

Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation.

PubMed

Galvez-Contreras, Alma Y; Gonzalez-Castaneda, Rocio E; Campos-Ordonez, Tania; Luquin, Sonia; Gonzalez-Perez, Oscar

2016-01-01

Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Enhancement of T cell recruitment and infiltration into tumours

PubMed Central

Oelkrug, C; Ramage, J M

2014-01-01

Studies have documented that cancer patients with tumours which are highly infiltrated with cytotoxic T lymphocytes show enhanced survival rates. The ultimate goal of cancer immunotherapy is to elicit high-avidity tumour-specific T cells to migrate and kill malignant tumours. Novel antibody therapies such as ipilumimab (a cytotoxic T lymphocyte antigen-4 blocking antibody) show enhanced T cell infiltration into the tumour tissue and increased survival. More conventional therapies such as chemotherapy or anti-angiogenic therapy and recent therapies with oncolytic viruses have been shown to alter the tumour microenvironment and thereby lead to enhanced T cell infiltration. Understanding the mechanisms involved in the migration of high-avidity tumour-specific T cells into tumours will support and provide solutions for the optimization of therapeutic options in cancer immunotherapy. PMID:24828133

Cancer cells cause vascular endothelial cell (vEC) retraction via 12(S)HETE secretion; the possible role of cancer cell derived microparticle.

PubMed

Uchide, Keiji; Sakon, Masato; Ariyoshi, Hideo; Nakamori, Syouji; Tokunaga, Masaru; Monden, Morito

2007-02-01

Cancer cell mediated vascular endothelial cell (vEC) retraction plays a pivotal role in cancer metastasis. The aim of this study is to clarify the biochemical character of vEC retraction factor derived from human breast cancer cell line, MCF-7. In order to estimate vEC retracting activity, transwell chamber assay system was employed. We first tested the effects of trypsin digestion as well as lipid extraction of culture medium (CM). Trypsin digestion of CM resulted in approximately 40% loss of vEC retracting activity and lipid extraction of CM by Brigh and Dyer methods recovered approximately 60% of vEC retracting activity, suggesting that approximately 60% of vEC retracting activity in MCF-7 derived CM is due to lipid. Although Nordihydroguaiaretic acid (NDGA), the specific lipoxygenase inhibitor, suppressed vEC retracting activity in CM, Acetyl salicylic acid (ASA), a specific cyclooxygenase inhibitor, did not affect the activity, suggesting that lipid exerting vEC retracting activity in CM belongs to lipoxygenase mediated arachidonate metabolites. Thin layer chromatography clearly demonstrated that Rf value of lipid vEC retracting factor in CM is identical to 12HETE. Authentic 12(S)HETE, but not 12(R)HETE, showed vEC retracting activity. After the ultracentrifugation of CM, most lipid vEC retracting activity was recovered from the pellet fraction, and flow cytometric analysis using specific antibody against 12(S)HETE clearly showed the association of 12(S)HETE with small particle in CM. These findings suggested the principal involvement of 12(S)HETE in cancer cell derived microparticles in cancer cell mediated vEC retraction.

Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qi; Schneider, Frank; Ma, Lin

Purpose: Intraoperative radiation therapy (IORT) with low-energy x-rays is used to treat the tumor bed during breast-conserving surgery. The purpose was to determine the relative biologic effectiveness (RBE) of 50-kV x-rays for inactivation of cells irradiated in a tumor-bed phantom. Methods and Materials: The RBE was determined for clonogenic inactivation of human tumor and normal cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts), and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a water-equivalent phantom at defined distances (8.1-22.9 mm) from themore » applicator surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were included for comparison; 6-MV x-rays were used as reference radiation. Results: At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x-rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67). No significant dependence of RBE on dose was found for Intrabeam, but RBE decreased at a larger distance (12.7 mm; 9.8 Gy/h). Conclusions: An increased clinically relevant RBE was found for cell irradiation with Intrabeam at depths in the tumor bed targeted by IORT. The reduced RBE values at larger distances may be related to increased repair of sublethal damage during protracted irradiation or to hardening of the photon beam energy.« less

Imatinib Enhances Docetaxel-Induced Apoptosis Through Inhibition of Nuclear Factor-κB Activation in Anaplastic Thyroid Carcinoma Cells

PubMed Central

Kim, EunSook; Matsuse, Michiko; Saenko, Vladimir; Suzuki, Keiji; Ohtsuru, Akira; Yamashita, Shunichi

2012-01-01

Background We previously reported the partial effectiveness of imatinib (also known as STI571, Glivec, or Gleevec) on anaplastic thyroid cancer (ATC) cells. Imatinib is a selective tyrosine kinase inhibitor that has been used for various types of cancer treatments. Recently, several reports have demonstrated that imatinib enhanced the sensitivity of cancer cells to other anticancer drugs. In this study, therefore, we investigated whether imatinib enhances the antitumor activity of docetaxel in ATC cells. Methods Two ATC cell lines, FRO and KTC-2, were treated with imatinib and/or docetaxel. Cell survival assay and flow cytometry for annexin V were used to assess the induction of apoptosis. Changes of pro- and antiapoptotic factors were determined by Western blot. Nuclear factor-κB (NF-κB) activity was measured by DNA-binding assay. Tumor growth was also investigated in vivo. Results The combined treatment significantly enhanced apoptosis compared with single treatment. ATC cells themselves expressed high levels of antiapoptotic factors, X-linked inhibitor of apoptosis (XIAP), and survivin. The treatment with docetaxel alone further increased their expressions; however, the combined treatment blocked the inductions. Although imatinib alone had no effect on NF-κB background levels, combined treatment significantly suppressed the docetaxel-induced NF-κB activation. Further, the combined administration of the drugs also showed significantly greater inhibitory effect on tumor growth in mice xenograft model. Conclusions Imatinib enhanced antitumor activity of docetaxel in ATC cells. Docetaxel seemed to induce both pro- and antiapoptotic signaling pathways in ATC cells, and imatinib blocked the antiapoptotic signal. Thus, docetaxel combined with imatinib emerges as an attractive strategy for the treatment of ATC. PMID:22650230

Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage.

PubMed

Xie, Chengzhi; Edwards, Holly; Caldwell, J Timothy; Wang, Guan; Taub, Jeffrey W; Ge, Yubin

2015-02-01

Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

PubMed

Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

2013-04-03

Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

Engineering Dendritic Cells to Enhance Cancer Immunotherapy

PubMed Central

Boudreau, Jeanette E; Bonehill, Aude; Thielemans, Kris; Wan, Yonghong

2011-01-01

Cancer immunotherapy aims to establish immune-mediated control of tumor growth by priming T-cell responses to target tumor-associated antigens. Three signals are required for T-cell activation: (i) presentation of cognate antigen in self MHC molecules; (ii) costimulation by membrane-bound receptor-ligand pairs; and (iii) soluble factors to direct polarization of the ensuing immune response. The ability of dendritic cells (DCs) to provide all three signals required for T-cell activation makes them an ideal cancer vaccine platform. Several strategies have been developed to enhance and control antigen presentation, costimulation, and cytokine production. In this review, we discuss progress toward developing DC-based cancer vaccines by genetic modification using RNA, DNA, and recombinant viruses. Furthermore, the ability of DC-based vaccines to activate natural killer (NK) and B-cells, and the impact of gene modification strategies on these populations is described. Clinical trials using gene-modified DCs have shown modest results, therefore, further considerations for DC manipulation to enhance their clinical efficacy are also discussed. PMID:21468005

SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khoo, A; Sahoo, N; Krishnan, S

2016-06-15

Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using darkmore » field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm

Resveratrol Enhances Self-Renewal of Mouse Embryonic Stem Cells.

PubMed

Li, Na; Du, Zhaoyu; Shen, Qiaoyan; Lei, Qijing; Zhang, Ying; Zhang, Mengfei; Hua, Jinlian

2017-07-01

Resveratrol (RSV) has been shown to affect the differentiation of several types of stem cells, while the detailed mechanism is elusive. Here, we aim to investigate the function of RSV in self-renewal of mouse embryonic stem cells (ESCs) and the related mechanisms. In contrast with its reported roles, we found unexpectedly that differentiated ESCs or iPSCs treated by RSV would not show further differentiation, but regained a naïve pluripotency state with higher expressions of core transcriptional factors and with the ability to differentiate into all three germ layers when transplanted in vivo. In accordance with these findings, RSV also enhanced cell cycle progression of ESCs via regulating cell cycle-related proteins. Finally, enhanced activation of JAK/STAT3 signaling pathway and suppressed activation of mTOR were found essential in enhancing the self-renewal of ESCs by RSV. Our finding discovered a novel function of RSV in enhancing the self-renewal of ESCs, and suggested that the timing of treatment and concentration of RSV determined the final effect of it. Our work may contribute to understanding of RSV in the self-renewal maintenance of pluripotent stem cells, and may also provide help to the generation and maintenance of iPSCs in vitro. J. Cell. Biochem. 118: 1928-1935, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Variability and repertoire size of T-cell receptor V alpha gene segments.

PubMed

Becker, D M; Pattern, P; Chien, Y; Yokota, T; Eshhar, Z; Giedlin, M; Gascoigne, N R; Goodnow, C; Wolf, R; Arai, K

The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.

Brain-specific enhancers for cell-based therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun

Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

Dissecting engineered cell types and enhancing cell fate conversion via CellNet

PubMed Central

Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

2014-01-01

SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

44 CFR 79.8 - Allowable costs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Allowable costs. 79.8 Section 79.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION GRANTS § 79.8...

44 CFR 79.8 - Allowable costs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Allowable costs. 79.8 Section 79.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION GRANTS § 79.8...

44 CFR 79.8 - Allowable costs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Allowable costs. 79.8 Section 79.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION GRANTS § 79.8...

44 CFR 79.8 - Allowable costs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Allowable costs. 79.8 Section 79.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION GRANTS § 79.8...

STS-79 Mission Insignia

NASA Technical Reports Server (NTRS)

1996-01-01

STS-79 was the fourth in a series of NASA docking missions to the Russian Mir Space Station, leading up to the construction and operation of the International Space Station (ISS). As the first flight of the Spacehab Double Module, STS-79 encompassed research, test and evaluation of ISS, as well as logistics resupply for the Mir Space Station. STS-79 was also the first NASA-Mir American crew member exchange mission, with John E. Blaha (NASA-Mir-3) replacing Shannon W. Lucid (NASA-Mir-2) aboard the Mir Space Station. The lettering of their names either up or down denotes transport up to the Mir Space Station or return to Earth on STS-79. The patch is in the shape of the Space Shuttle's airlock hatch, symbolizing the gateway to international cooperation in space. The patch illustrates the historic cooperation between the United States and Russia in space. With the flags of Russia and the United States as a backdrop, the handshake of Extravehicular Mobility Unit (EMU) which are suited crew members symbolizes mission teamwork, not only of the crew members but also the teamwork between both countries space personnel in science, engineering, medicine and logistics.

Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

PubMed

de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Morgan, Mary E; Muruzabal, Veronica Ayechu; Hofman, Gerard A; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-07-01

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V ( Bb ) (GF/ Bb ) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T reg ) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ Bb during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ Bb reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ Bb also lowered the frequency of activated Th2 cells, while enhancing T reg in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ Bb enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T reg frequency in these mice. © Society for Leukocyte Biology.

Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs.

PubMed

Qazi, Taimoor H; Mooney, David J; Duda, Georg N; Geissler, Sven

2017-09-01

Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell-cell interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiac Stem Cell Hybrids Enhance Myocardial Repair

PubMed Central

Quijada, Pearl; Salunga, Hazel T.; Hariharan, Nirmala; Cubillo, Jonathan D.; El-Sayed, Farid G.; Moshref, Maryam; Bala, Kristin M.; Emathinger, Jacqueline M.; La Torre, Andrea De; Ormachea, Lucia; Alvarez, Roberto; Gude, Natalie A.; Sussman, Mark A.

2015-01-01

Rationale Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results Two distinct and clonally derived CCs, CC1 and CC2 were utilized for this study. CCs improved left ventricular anterior wall thickness (AWT) at 4 weeks post injury, but only CC1 treatment preserved AWT at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC + MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC + MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves upon combinatorial cell approaches to support myocardial regeneration. PMID:26228030

Dual targeting of therapeutics to endothelial cells: collaborative enhancement of delivery and effect

PubMed Central

Greineder, Colin F.; Brenza, Jacob B.; Carnemolla, Ronald; Zaitsev, Sergei; Hood, Elizabeth D.; Pan, Daniel C.; Ding, Bi-Sen; Esmon, Charles T.; Chacko, Ann Marie; Muzykantov, Vladimir R.

2015-01-01

Anchoring pharmacologic agents to the vascular lumen has the potential to modulate critical processes at the blood–tissue interface, avoiding many of the off-target effects of systemically circulating agents. We report a novel strategy for endothelial dual targeting of therapeutics, which both enhances drug delivery and enables targeted agents to partner enzymatically to generate enhanced biologic effect. Based on the recent discovery that paired antibodies directed to adjacent epitopes of platelet endothelial cell adhesion molecule (PECAM)-1 stimulate each other’s binding, we fused single-chain fragments (scFv) of paired anti-mouse PECAM-1 antibodies to recombinant murine thrombomodulin (TM) and endothelial protein C receptor (EPCR), endothelial membrane proteins that partner in activation of protein C (PC). scFv/TM and scFv/EPCR bound to mouse endothelial PECAM-1 with high affinity (EC50 1.5 and 3.8 nM, respectively), and codelivery induced a 5-fold increase in PC activation not seen when TM and EPCR are anchored to distinct cell adhesion molecules. In a mouse model of acute lung injury, dual targeting reduces both the expression of lung inflammatory markers and trans-endothelial protein leak by as much as 40%, as compared to either agent alone. These findings provide proof of principle for endothelial dual targeting, an approach with numerous potential biomedical applications.—Greineder, C. F., Brenza, J. B., Carnemolla, R., Zaitsev, S., Hood, E. D., Pan, D. C., Ding, B.-S., Esmon, C. T., Chacko, A. M., Muzykantov, V. R. Dual targeting of therapeutics to endothelial cells: collaborative enhancement of delivery and effect. PMID:25953848

Recombination imaging of III-V solar cells

NASA Technical Reports Server (NTRS)

Virshup, G. F.

1987-01-01

An imaging technique based on the radiative recombination of minority carriers in forward-biased solar cells has been developed for characterization of III-V solar cells. When used in mapping whole wafers, it has helped identify three independent loss mechanisms (broken grid lines, shorting defects, and direct-to-indirect bandgap transitions), all of which resulted in lower efficiencies. The imaging has also led to improvements in processing techniques to reduce the occurrence of broken gridlines as well as surface defects. The ability to visualize current mechanisms in solar cells is an intuitive tool which is powerful in its simplicity.

45 CFR 79.19 - Prehearing conferences.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Prehearing conferences. 79.19 Section 79.19 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.19 Prehearing conferences. (a) The ALJ may schedule prehearing conferences as appropriate. (b) Upon...

7 CFR 984.79 - Confidential information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Confidential information. 984.79 Section 984.79... Regulating Handling Reports, Books, and Other Records § 984.79 Confidential information. All reports and records submitted by handlers to the Board, which include data or information constituting a trade secret...

Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.

PubMed Central

Goodhardt, M; Babinet, C; Lutfalla, G; Kallenbach, S; Cavelier, P; Rougeon, F

1989-01-01

We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged kappa transgene. Furthermore, unlike endogenous kappa genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage- and lineage- specific regulation of Ig kappa light chain gene rearrangement in vivo. Images PMID:2508061

Enhanced biofilm distribution and cell performance of microfluidic microbial fuel cells with multiple anolyte inlets.

PubMed

Yang, Yang; Ye, Dingding; Liao, Qiang; Zhang, Pengqing; Zhu, Xun; Li, Jun; Fu, Qian

2016-05-15

A laminar-flow controlled microfluidic microbial fuel cell (MMFC) is considered as a promising approach to be a bio-electrochemical system (BES). But poor bacterial colonization and low power generation are two severe bottlenecks to restrict its development. In this study, we reported a MMFC with multiple anolyte inlets (MMFC-MI) to enhance the biofilm formation and promote the power density of MMFCs. Voltage profiles during the inoculation process demonstrated MMFC-MI had a faster start-up process than the conventional microfluidic microbial fuel cell with one inlet (MMFC-OI). Meanwhile, benefited from the periodical replenishment of boundary layer near the electrode, a more densely-packed bacterial aggregation was observed along the flow direction and also the substantially low internal resistance for MMFC-MI. Most importantly, the output power density of MMFC-MI was the highest value among the reported µl-scale MFCs to our best knowledge. The presented MMFC-MI appears promising for bio-chip technology and extends the scope of microfluidic energy. Copyright © 2015 Elsevier B.V. All rights reserved.

Epstein-Barr Virus oncoprotein super-enhancers control B cell growth

PubMed Central

Zhou, Hufeng; Schmidt, Stefanie CS; Jiang, Sizun; Willox, Bradford; Bernhardt, Katharina; Liang, Jun; Johannsen, Eric C; Kharchenko, Peter; Gewurz, Benjamin E; Kieff, Elliott; Zhao, Bo

2015-01-01

Summary Super-enhancers are clusters of gene-regulatory sites bound by multiple transcription factors that govern cell transcription, development, phenotype, and oncogenesis. By examining Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs), we identified four EBV oncoproteins and five EBV-activated NF-κB subunits co-occupying ~1800 enhancer sites. Of these, 187 had markedly higher and broader histone H3K27ac signals characteristic of super-enhancers, and were designated “EBV super-enhancers”. EBV super-enhancer-associated genes included the MYC and BCL2 oncogenes, enabling LCL proliferation and survival. EBV super-enhancers were enriched for B cell transcription factor motifs and had a high co-occupancy of the transcription factors STAT5 and NFAT. EBV super-enhancer-associated genes were more highly expressed than other LCL genes. Disrupting EBV super-enhancers by the bromodomain inhibitor, JQ1 or conditionally inactivating an EBV oncoprotein or NF-κB decreased MYC or BCL2 expression and arrested LCL growth. These findings provide insight into mechanisms of EBV-induced lymphoproliferation and identify potential therapeutic interventions. PMID:25639793

Enhanced Biological Response of AVS-Functionalized Ti-6Al-4V Alloy through Covalent Immobilization of Collagen.

PubMed

Rezvanian, Parsa; Daza, Rafael; López, Patricia A; Ramos, Milagros; González-Nieto, Daniel; Elices, Manuel; Guinea, Gustavo V; Pérez-Rigueiro, José

2018-02-20

This study presents the development of an efficient procedure for covalently immobilizing collagen molecules on AVS-functionalized Ti-6Al-4V samples, and the assessment of the survival and proliferation of cells cultured on these substrates. Activated Vapor Silanization (AVS) is a versatile functionalization technique that allows obtaining a high density of active amine groups on the surface. A procedure is presented to covalently bind collagen to the functional layer using EDC/NHS as cross-linker. The covalently bound collagen proteins are characterized by fluorescence microscopy and atomic force microscopy and their stability is tested. The effect of the cross-linker concentration on the process is assessed. The concentration of the cross-linker is optimized and a reliable cleaning protocol is developed for the removal of the excess of carbodiimide from the samples. The results demonstrate that the covalent immobilization of collagen type I on Ti-6Al-4V substrates, using the optimized protocol, increases the number of viable cells present on the material. Consequently, AVS in combination with the carbodiimide chemistry appears as a robust method for the immobilization of proteins and, for the first time, it is shown that it can be used to enhance the biological response to the material.

Radiation Enhances Regulatory T Cell Representation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei

2011-11-15

Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4{sup +}CD25{sup hi}Foxp3{sup +} lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4{sup +}CD25{sup hi}Foxp3{sup +}more » Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.« less

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

PubMed

Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

2016-06-01

Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fuel cell energy storage for Space Station enhancement

NASA Technical Reports Server (NTRS)

Stedman, J. K.

1990-01-01

Viewgraphs on fuel cell energy storage for space station enhancement are presented. Topics covered include: power profile; solar dynamic power system; photovoltaic battery; space station energy demands; orbiter fuel cell power plant; space station energy storage; fuel cell system modularity; energy storage system development; and survival power supply.

45 CFR 79.37 - Initial decision.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Initial decision. 79.37 Section 79.37 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.37 Initial decision. (a) The ALJ shall issue an initial decision based only on the record, which...

45 CFR 79.35 - The record.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false The record. 79.35 Section 79.35 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.35 The record. (a) The hearing will be recorded and transcribed. Transcripts may be obtained following the...

45 CFR 79.42 - Judicial review.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Judicial review. 79.42 Section 79.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.42 Judicial review. Section 3805 of title 31, United States Code, authorizes judicial review by an...

40 CFR 68.79 - Compliance audits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Compliance audits. 68.79 Section 68.79... ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.79 Compliance audits. (a) The owner or... are being followed. (b) The compliance audit shall be conducted by at least one person knowledgeable...

40 CFR 282.79 - New Hampshire.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false New Hampshire. 282.79 Section 282.79... UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.79 New Hampshire. (a) The State of New....C. 6991 et seq. The State's program, as administered by the New Hampshire Department of...

40 CFR 282.79 - New Hampshire.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 27 2014-07-01 2014-07-01 false New Hampshire. 282.79 Section 282.79... UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.79 New Hampshire. (a) The State of New....C. 6991 et seq. The State's program, as administered by the New Hampshire Department of...

40 CFR 282.79 - New Hampshire.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 27 2011-07-01 2011-07-01 false New Hampshire. 282.79 Section 282.79... UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.79 New Hampshire. (a) The State of New....C. 6991 et seq. The State's program, as administered by the New Hampshire Department of...

40 CFR 282.79 - New Hampshire.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 28 2013-07-01 2013-07-01 false New Hampshire. 282.79 Section 282.79... UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.79 New Hampshire. (a) The State of New....C. 6991 et seq. The State's program, as administered by the New Hampshire Department of...

40 CFR 282.79 - New Hampshire.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 28 2012-07-01 2012-07-01 false New Hampshire. 282.79 Section 282.79... UNDERGROUND STORAGE TANK PROGRAMS Approved State Programs § 282.79 New Hampshire. (a) The State of New....C. 6991 et seq. The State's program, as administered by the New Hampshire Department of...

Enhancing Adoptive Cell Therapy of Cancer through Targeted Delivery of Small-Molecule Immunomodulators to Internalizing or Noninternalizing Receptors.

PubMed

Zheng, Yiran; Tang, Li; Mabardi, Llian; Kumari, Sudha; Irvine, Darrell J

2017-03-28

Adoptive cell therapy (ACT) has achieved striking efficacy in B-cell leukemias, but less success treating other cancers, in part due to the rapid loss of ACT T-cell effector function in vivo due to immunosuppression in solid tumors. Transforming growth factor-β (TGF-β) signaling is an important mechanism of immune suppression in the tumor microenvironment, but systemic inhibition of TGF-β is toxic. Here we evaluated the potential of targeting a small molecule inhibitor of TGF-β to ACT T-cells using PEGylated immunoliposomes. Liposomes were prepared that released TGF-β inhibitor over ∼3 days in vitro. We compared the impact of targeting these drug-loaded vesicles to T-cells via an internalizing receptor (CD90) or noninternalizing receptor (CD45). When lymphocytes were preloaded with immunoliposomes in vitro prior to adoptive therapy, vesicles targeted to both CD45 and CD90 promoted enhanced T-cell expression of granzymes relative to free systemic drug administration, but only targeting to CD45 enhanced accumulation of granzyme-expressing T-cells in tumors, which correlated with the greatest enhancement of T-cell antitumor activity. By contrast, when administered i.v. to target T-cells in vivo, only targeting of a CD90 isoform expressed exclusively by the donor T-cells led to greater tumor regression over equivalent doses of free systemic drug. These results suggest that in vivo, targeting of receptors uniquely expressed by donor T-cells is of paramount importance for maximal efficacy. This immunoliposome strategy should be broadly applicable to target exogenous or endogenous T-cells and defines parameters to optimize delivery of supporting (or suppressive) drugs to these important immune effectors.

Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene.

PubMed

Sun, Mingrui; Kiourti, Asimina; Wang, Hai; Zhao, Shuting; Zhao, Gang; Lu, Xiongbin; Volakis, John L; He, Xiaoming

2016-07-05

Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia.

From coin cells to 400 mAh pouch cells: Enhancing performance of high-capacity lithium-ion cells via modifications in electrode constitution and fabrication

NASA Astrophysics Data System (ADS)

Trask, Stephen E.; Li, Yan; Kubal, Joseph J.; Bettge, Martin; Polzin, Bryant J.; Zhu, Ye; Jansen, Andrew N.; Abraham, Daniel P.

2014-08-01

In this article we describe efforts to improve performance and cycle life of cells containing Li1.2Ni0.15Mn0.55Co0.1O2-based positive and graphite-based negative electrodes. Initial work to identify high-performing materials, compositions, fabrication variables, and cycling conditions is conducted in coin cells. The resulting information is then used for the preparation of double-sided electrodes, assembly of pouch cells, and electrochemical testing. We report the cycling performance of cells with electrodes prepared under various conditions. Our data indicate that cells with positive electrodes containing 92 wt.% Li1.2Ni0.15Mn0.55Co0.1O2, 4 wt.% carbons (no graphite), and 4 wt.% PVdF (92-4-4) show ∼20% capacity fade after 1000 cycles in the 2.5-4.4 V range, significantly better than our baseline cells that show the same fade after only 450 cycles. Our analyses indicate that the major contributors to cell energy fade are capacity loss and impedance rise. Therefore incorporating approaches that minimize capacity fade and impedance rise, such as electrode coatings and electrolyte additives, can significantly enhance calendar and cycle life of this promising cell chemistry.

Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

PubMed

Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

2017-03-01

Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes

PubMed Central

Vaidyanathan, Ravi; Markandeya, Yogananda S.; Kamp, Timothy J.; Makielski, Jonathan C.; January, Craig T.

2016-01-01

Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately −80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms. PMID:27059077

14 CFR 141.79 - Flight training.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight training. 141.79 Section 141.79... OTHER CERTIFICATED AGENCIES PILOT SCHOOLS Operating Rules § 141.79 Flight training. (a) No person other than a certificated flight instructor or commercial pilot with a lighter-than-air rating who has the...

14 CFR 141.79 - Flight training.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight training. 141.79 Section 141.79... OTHER CERTIFICATED AGENCIES PILOT SCHOOLS Operating Rules § 141.79 Flight training. (a) No person other than a certificated flight instructor or commercial pilot with a lighter-than-air rating who has the...

14 CFR 141.79 - Flight training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight training. 141.79 Section 141.79... OTHER CERTIFICATED AGENCIES PILOT SCHOOLS Operating Rules § 141.79 Flight training. (a) No person other than a certificated flight instructor or commercial pilot with a lighter-than-air rating who has the...

14 CFR 141.79 - Flight training.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight training. 141.79 Section 141.79... OTHER CERTIFICATED AGENCIES PILOT SCHOOLS Operating Rules § 141.79 Flight training. (a) No person other than a certificated flight instructor or commercial pilot with a lighter-than-air rating who has the...

45 CFR 79.24 - Protective order.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Protective order. 79.24 Section 79.24 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.24 Protective order. (a) A party or a prospective witness or deponent may file a motion for a...

29 CFR 1919.79 - Wire rope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false Wire rope. 1919.79 Section 1919.79 Labor Regulations...) GEAR CERTIFICATION Certification of Shore-Based Material Handling Devices § 1919.79 Wire rope. (a) Wire rope and replacement wire rope shall be of the same size, same or better grade, and same construction...

29 CFR 1919.79 - Wire rope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Wire rope. 1919.79 Section 1919.79 Labor Regulations...) GEAR CERTIFICATION Certification of Shore-Based Material Handling Devices § 1919.79 Wire rope. (a) Wire rope and replacement wire rope shall be of the same size, same or better grade, and same construction...

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

PubMed Central

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-01-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

PubMed

Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

2014-08-01

A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, Chia-Wen; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Yao, Ju-Hsien

2011-11-15

The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivomore » in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.« less

45 CFR 81.79 - Cross-examination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Cross-examination. 81.79 Section 81.79 Public... UNDER PART 80 OF THIS TITLE Hearing Procedures § 81.79 Cross-examination. A witness may be cross-examined on any matter material to the proceeding without regard to the scope of his direct examination. ...

Dual-junction GaAs solar cells and their application to smart stacked III–V//Si multijunction solar cells

NASA Astrophysics Data System (ADS)

Sugaya, Takeyoshi; Tayagaki, Takeshi; Aihara, Taketo; Makita, Kikuo; Oshima, Ryuji; Mizuno, Hidenori; Nagato, Yuki; Nakamoto, Takashi; Okano, Yoshinobu

2018-05-01

We report high-quality dual-junction GaAs solar cells grown using solid-source molecular beam epitaxy and their application to smart stacked III–V//Si quadruple-junction solar cells with a two-terminal configuration for the first time. A high open-circuit voltage of 2.94 eV was obtained in an InGaP/GaAs/GaAs triple-junction top cell that was stacked to a Si bottom cell. The short-circuit current density of a smart stacked InGaP/GaAs/GaAs//Si solar cell was in good agreement with that estimated from external quantum efficiency measurements. An efficiency of 18.5% with a high open-circuit voltage of 3.3 V was obtained in InGaP/GaAs/GaAs//Si two-terminal solar cells.

Current matching using CdSe quantum dots to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells.

PubMed

Lee, Ya-Ju; Yao, Yung-Chi; Tsai, Meng-Tsan; Liu, An-Fan; Yang, Min-De; Lai, Jiun-Tsuen

2013-11-04

A III-V multi-junction tandem solar cell is the most efficient photovoltaic structure that offers an extremely high power conversion efficiency. Current mismatching between each subcell of the device, however, is a significant challenge that causes the experimental value of the power conversion efficiency to deviate from the theoretical value. In this work, we explore a promising strategy using CdSe quantum dots (QDs) to enhance the photocurrent of the limited subcell to match with those of the other subcells and to enhance the power conversion efficiency of InGaP/GaAs/Ge tandem solar cells. The underlying mechanism of the enhancement can be attributed to the QD's unique capacity for photon conversion that tailors the incident spectrum of solar light; the enhanced efficiency of the device is therefore strongly dependent on the QD's dimensions. As a result, by appropriately selecting and spreading 7 mg/mL of CdSe QDs with diameters of 4.2 nm upon the InGaP/GaAs/Ge solar cell, the power conversion efficiency shows an enhancement of 10.39% compared to the cell's counterpart without integrating CdSe QDs.

Enhanced ADCC Activity of Affinity Maturated and Fc-Engineered Mini-Antibodies Directed against the AML Stem Cell Antigen CD96

PubMed Central

Kellner, Christian; Bräutigam, Joachim; Staudinger, Matthias; Schub, Natalie; Peipp, Matthias; Gramatzki, Martin; Humpe, Andreas

2012-01-01

CD96, a cell surface antigen recently described to be preferentially expressed on acute myeloid leukemia (AML) leukemic stem cells (LSC) may represent an interesting target structure for the development of antibody-based therapeutic approaches. The v-regions from the CD96-specific hybridoma TH-111 were isolated and used to generate a CD96-specific single chain fragment of the variable regions (scFv). An affinity maturated variant resulting in 4-fold enhanced CD96-binding was generated by random mutagenesis and stringent selection using phage display. The affinity maturated scFv CD96-S32F was used to generate bivalent mini-antibodies by genetically fusing an IgG1 wild type Fc region or a variant with enhanced CD16a binding. Antibody dependent cell-mediated cytotoxicity (ADCC) experiments revealed that Fc engineering was essential to trigger significant effector cell-mediated lysis when the wild type scFv was used. The mini-antibody variant generated by fusing the affinity-maturated scFv with the optimized Fc variant demonstrated the highest ADCC activity (2.3-fold enhancement in efficacy). In conclusion, our data provide proof of concept that CD96 could serve as a target structure for effector cell-mediated lysis and demonstrate that both enhancing affinity for CD96 and for CD16a resulted in mini-antibodies with the highest cytolytic potential. PMID:22879978

Reduction of bonding resistance of two-terminal III-V/Si tandem solar cells fabricated using smart-stack technology

NASA Astrophysics Data System (ADS)

Baba, Masaaki; Makita, Kikuo; Mizuno, Hidenori; Takato, Hidetaka; Sugaya, Takeyoshi; Yamada, Noboru

2017-12-01

This paper describes a method that remarkably reduces the bonding resistance of mechanically stacked two-terminal GaAs/Si and InGaP/Si tandem solar cells, where the top and bottom cells are bonded using a Pd nanoparticle array. A transparent conductive oxide (TCO) layer, which partially covers the surface of the Si bottom cell below the electrodes of the III-V top cell, significantly enhances the fill factor (FF) and cell conversion efficiency. The partial TCO layer reduces the bonding resistance and thus, increases the FF and efficiency of InGaP/Si by factors of 1.20 and 1.11, respectively. Eventually, the efficiency exceeds 15%. Minimizing the optical losses at the bonding interfaces of the TCO layer is important in the fabrication of high-efficiency solar cells. To help facilitate this, the optical losses in the tandem solar cells are thoroughly characterized through optical simulations and experimental verifications.

CYP79F1 and CYP79F2 have distinct functions in the biosynthesis of aliphatic glucosinolates in Arabidopsis.

PubMed

Chen, Sixue; Glawischnig, Erich; Jørgensen, Kirsten; Naur, Peter; Jørgensen, Bodil; Olsen, Carl-Erik; Hansen, Carsten H; Rasmussen, Hasse; Pickett, John A; Halkier, Barbara A

2003-03-01

Cytochromes P450 of the CYP79 family catalyze the conversion of amino acids to oximes in the biosynthesis of glucosinolates, a group of natural plant products known to be involved in plant defense and as a source of flavor compounds, cancer-preventing agents and bioherbicides. We report a detailed biochemical analysis of the substrate specificity and kinetics of CYP79F1 and CYP79F2, two cytochromes P450 involved in the biosynthesis of aliphatic glucosinolates in Arabidopsis thaliana. Using recombinant CYP79F1 and CYP79F2 expressed in Escherichia coli and Saccharomyces cerevisiae, respectively, we show that CYP79F1 metabolizes mono- to hexahomomethionine, resulting in both short- and long-chain aliphatic glucosinolates. In contrast, CYP79F2 exclusively metabolizes long-chain elongated penta- and hexahomomethionines. CYP79F1 and CYP79F2 are spatially and developmentally regulated, with different gene expression patterns. CYP79F2 is highly expressed in hypocotyl and roots, whereas CYP79F1 is strongly expressed in cotyledons, rosette leaves, stems, and siliques. A transposon-tagged CYP79F1 knockout mutant completely lacks short-chain aliphatic glucosinolates, but has an increased level of long-chain aliphatic glucosinolates, especially in leaves and seeds. The level of long-chain aliphatic glucosinolates in a transposon-tagged CYP79F2 knockout mutant is substantially reduced, whereas the level of short-chain aliphatic glucosinolates is not affected. Biochemical characterization of CYP79F1 and CYP79F2, and gene expression analysis, combined with glucosinolate profiling of knockout mutants demonstrate the functional role of these enzymes. This provides valuable insights into the metabolic network leading to the biosynthesis of aliphatic glucosinolates, and into metabolic engineering of altered aliphatic glucosinolate profiles to improve nutritional value and pest resistance.

Regional and stage-specific effects of prospectively purified vascular cells on the adult V-SVZ neural stem cell lineage.

PubMed

Crouch, Elizabeth E; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

2015-03-18

Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contribution of pericytes to the neural stem cell niche has not been defined. Here, we describe a rapid FACS purification strategy to simultaneously isolate primary endothelial cells and pericytes from brain microregions of nontransgenic mice using CD31 and CD13 as surface markers. We compared the effect of purified vascular cells from a neurogenic (V-SVZ) and non-neurogenic brain region (cortex) on the V-SVZ stem cell lineage in vitro. Endothelial and pericyte diffusible signals from both regions differentially promote the proliferation and neuronal differentiation of qNSCs, aNSCs, and TACs. Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states. Copyright © 2015 the authors 0270-6474/15/354528-12$15.00/0.

Strand V: Education for Survival. First Aid and Survival Education. Health Curriculum Materials. Grades 7-9.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

GRADES OR AGES: Grades 7-9. SUBJECT MATTER: First aid and survival education. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into five sections: bandaging skills, control of bleeding, conditions caused by extremes in temperatures, foreign substances in body openings, and other common emergencies. The publication format of four columns…

Enhancer of Zeste Homolog 2 Induces Pulmonary Artery Smooth Muscle Cell Proliferation

PubMed Central

Aljubran, Salman A.; Rajanbabu, Venugopal; Bao, Huynh; Mohapatra, Shyam M.; Lockey, Richard; Kolliputi, Narasaiah

2012-01-01

Introduction Pulmonary Arterial Hypertension (PAH) is a progressively devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. The proliferation of cancer cells is mediated by increased expression of Enhancer of Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes. However, the role of EZH2 in PAH has not been studied. In this study, it is hypothesized that EZH2 could play a role in the proliferation of PASMCs. Methods In the present study, the expression patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The effects of EZH2 overexpression on the proliferation of human PASMCs were tested. PASMCs were transfected with EZH2 or GFP using nucleofector system. After transfection, the cells were incubated for 48 hours at 37°C. Proliferation and cell cycle analysis were performed using flow cytometry. Apoptosis of PASMCs was determined using annexin V staining and cell migration was tested by wound healing assay. Results EZH2 protein expression in mouse PASMCs were correlated with an increase in right ventricular systolic pressure and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected cells, there was a 3.5 fold increase in proliferation, while there was a significant decrease in the rate of apoptosis of PASMCs, when compared to control. Conclusion These findings suggest that EZH2 plays a role in the migration and proliferation of PASMCs, which is a major hallmark in PAH. It also suggests that EZH2 could play a role in the development of PAH and can serve as a potential target for new therapies for PAH. PMID:22662197

STS-79 crew insignia

NASA Image and Video Library

1998-09-09

STS79-S-001 (April 1996) --- STS-79 is the fourth in a series of NASA docking missions to the Russian Mir Space Station, leading up to the construction and operation of the International Space Station (ISS). As the first flight of the Spacehab Double Module, STS-79 encompasses research, test and evaluation of ISS, as well as logistics resupply for the Mir Space Station. STS-79 is also the first NASA-Mir American crew member exchange mission, with John E. Blaha (NASA-Mir-3) replacing Shannon W. Lucid (NASA-Mir-2) aboard the Mir Space Station. The lettering of their names either up or down denotes transport up to the Mir Space Station or return to Earth on STS-79. The patch is in the shape of the space shuttle?s airlock hatch, symbolizing the gateway to international cooperation in space. The patch illustrates the historic cooperation between the United States and Russia in space. With the flags of Russia and the United States as a backdrop, the handshake of Extravehicular Mobility Unit (EMU) - suited crew members symbolizes mission teamwork, not only of the crew members but also the teamwork between both countries? space personnel in science, engineering, medicine and logistics. The NASA insignia design for space shuttle flights is reserved for use by the astronauts and for other official use as the NASA Administrator may authorize. Public availability has been approved only in the forms of illustrations by the various news media. When and if there is any change in this policy, which is not anticipated, the change will be publicly announced. Photo credit: NASA

44 CFR 79.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 79.2 Section 79.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... political subdivision, including any Indian Tribe, authorized Tribal organization, Alaska Native village or...

44 CFR 79.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Definitions. 79.2 Section 79.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... political subdivision, including any Indian Tribe, authorized Tribal organization, Alaska Native village or...

Enhanced efficiency of hybrid amorphous silicon solar cells based on single-walled carbon nanotubes/polymer composite thin film.

PubMed

Rajanna, Pramod Mulbagal; Gilshteyn, Evgenia; Yagafarov, Timur; Alekseeva, Alena; Anisimov, Anton; Sergeev, Oleg; Neumueller, Alex; Bereznev, Sergei; Maricheva, Jelena; Nasibulin, Albert

2018-01-09

We report a simple approach to fabricate hybrid solar cells (HSCs) based on a single-walled carbon nanotube (SWCNT) film and a thin film hydrogenated amorphous silicon (a-Si:H). Randomly oriented high quality SWCNTs with an enhanced conductivity by means of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate are used as a window layer and a front electrode. A series of HSCs are fabricated in ambient conditions with different SWCNT film thicknesses. The polymethylmethacrylate layer drop-casted on fabricated HSCs reduces the reflection fourfold and enhances the short-circuit Jsc, open-circuit Voc, and efficiency by nearly 10%. A state-of-the-art J-V performance is shown for SWCNT/a-Si HSC with an open-circuit voltage of 900 mV and efficiency of 3.4% under simulated one-sun AM 1.5G direct illumination. © 2018 IOP Publishing Ltd.

Induction of mutagenesis and alterations in gene expression by tumorigenic chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huberman, E.

1979-01-01

To determine the relationship between mutagenesis and carcinogenesis, a series of eleven polycyclic hydrocarbons with different degrees of carcinogenicity were tested in the cell-mediated mutagenesis assay for the induction of ouabain-resistant mutants. Four carcinogenic hydrocarbons induced ouabain-resistant mutants; five noncarcinogenic hydrocarbons were not mutagenic. Results indicated that there was a relationship between mutagenesis and the degree of carcinogenicity of polycyclic hydrocarbons after enhancement of their metabolism by aminophylline. To study liver carcinogens a system was developed for cocultivating primary liver cells and V79 hamster cells. In this system the nitrosamines and aflatoxins were metabolized by liver cells to intermediates thatmore » were mutagenic to the V79 cells. In experiments using human cells, tumor-promoting phorbol esters induced terminal differentiation while in other studies, in which avian and murine cells were employed, they inhibited differentiation. The results imply that human cells may respond differently from mouse and chicken cells to the biological effects of phorbol diesters. (HLW)« less

Sub-micrometer 20MeV protons or 45MeV lithium spot irradiation enhances yields of dicentric chromosomes due to clustering of DNA double-strand breaks.

PubMed

Schmid, T E; Friedland, W; Greubel, C; Girst, S; Reindl, J; Siebenwirth, C; Ilicic, K; Schmid, E; Multhoff, G; Schmitt, E; Kundrát, P; Dollinger, G

2015-11-01

In conventional experiments on biological effects of radiation types of diverse quality, micrometer-scale double-strand break (DSB) clustering is inherently interlinked with clustering of energy deposition events on nanometer scale relevant for DSB induction. Due to this limitation, the role of the micrometer and nanometer scales in diverse biological endpoints cannot be fully separated. To address this issue, hybrid human-hamster AL cells have been irradiated with 45MeV (60keV/μm) lithium ions or 20MeV (2.6keV/μm) protons quasi-homogeneously distributed or focused to 0.5×1μm(2) spots on regular matrix patterns (point distances up to 10.6×10.6μm), with pre-defined particle numbers per spot to provide the same mean dose of 1.7Gy. The yields of dicentrics and their distribution among cells have been scored. In parallel, track-structure based simulations of DSB induction and chromosome aberration formation with PARTRAC have been performed. The results show that the sub-micrometer beam focusing does not enhance DSB yields, but significantly affects the DSB distribution within the nucleus and increases the chance to form DSB pairs in close proximity, which may lead to increased yields of chromosome aberrations. Indeed, the experiments show that focusing 20 lithium ions or 451 protons per spot on a 10.6μm grid induces two or three times more dicentrics, respectively, than a quasi-homogenous irradiation. The simulations reproduce the data in part, but in part suggest more complex behavior such as saturation or overkill not seen in the experiments. The direct experimental demonstration that sub-micrometer clustering of DSB plays a critical role in the induction of dicentrics improves the knowledge on the mechanisms by which these lethal lesions arise, and indicates how the assumptions of the biophysical model could be improved. It also provides a better understanding of the increased biological effectiveness of high-LET radiation. Copyright © 2015 Elsevier B.V. All

Titania nanotubes with adjustable dimensions for drug reservoir sites and enhanced cell adhesion.

PubMed

Çalışkan, Nazlı; Bayram, Cem; Erdal, Ebru; Karahaliloğlu, Zeynep; Denkbaş, Emir Baki

2014-02-01

This study aims to generate a bactericidal agent releasing surface via nanotube layer on titanium metal and to investigate how aspect ratio of nanotubes affects drug elution time and cell proliferation. Titania nanotube layers were generated on metal surfaces by anodic oxidation at various voltage and time parameters. Gentamicin loading was carried out via simple pipetting and the samples were tested against S. aureus for the efficacy of the applied modification. Drug releasing time and cell proliferation were also tested in vitro. Titania nanotube layers with varying diameters and lengths were prepared after anodization and anodizing duration was found as the most effective parameter for amount of loaded drug and drug releasing time. Drug elution lasted up to 4 days after anodizing for 80 min of the samples, whereas release completed in 24 h when the samples were anodized for 20 min. All processed samples had bactericidal properties against S. aureus organism except unmodified titanium, which was also subjected to drug incorporation step. The anodization also enhanced water wettability and cell adhesion results. Anodic oxidation is an effective surface modification to enhance tissue-implant interactions and also resultant titania layer can act as a drug reservoir for the release of bactericidal agents. The use of implants as local drug eluting devices is promising but further in vivo testing is required. Copyright © 2013 Elsevier B.V. All rights reserved.

Ganoderic acid Me induces the apoptosis of competent T cells and increases the proportion of Treg cells through enhancing the expression and activation of indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells.

PubMed

Que, Zujun; Zou, Fangyuan; Zhang, Anle; Zheng, Yuanhong; Bi, Ling; Zhong, Jianjiang; Tian, Jianhui; Liu, Jianwen

2014-11-01

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. It is known that ganoderic acid Me can enhance IFN-γ expression and IDO is preferentially induced by IFN-γ. However, whether GA-Me can induce IDO expression has not been clarified yet. We established stable clones of IDO-overexpressing 2 LL cells (2LL-EGFP-IDO). After co-culturing with IDO expressing or control vector-transfected 2LL-EGFP cells, T cell apoptosis was determined and the proportion of the regulatory T cells (Tregs) and CD8+ T cell subset was measured. The total cellular protein samples of 2 LL-EGFP-IDO cells were isolated for detecting JAK-STAT1 signalling pathway. Co-culture supernatants were used to detect amino acids and cytokines. IDO transfected 2 LL cells yielded high level of IDO enzymatic activity, resulting in complete depletion of tryptophan from the culture medium. We found that apoptosis occurred in T cells after cocultured with IDO+2LL cells and the proportion of CD4+CD25+ cells and FoxP3+ cells increased while CD8+ cells decreased. The specific inhibitor of IDO, 1-D-MT and GA-Me efficiently enhanced T cell apoptosis, increased Tregs, and reduced CD8+ T cells in vitro. Increased expression of IDO, p-JAK1 and p-STAT1 were confirmed by Western blot analysis. The levels of IFN-γ, IL-10, LDH and kynurenine in co-culture supernatant correspondingly increased, while tryptophan reduced. These results suggest that GA-Me contributing to IDO helps to create a tolerogenic milieu in lung tumors by directly inducing T cell apoptosis, restraining CD8+ T cell activation, and enhancing Treg-mediated immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

14 CFR 13.79 - Hearing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Hearing. 13.79 Section 13.79 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Orders of Compliance Under the Hazardous Materials Transportation Act § 13...

14 CFR 13.79 - Hearing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Hearing. 13.79 Section 13.79 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Orders of Compliance Under the Hazardous Materials Transportation Act § 13...

Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

PubMed

Linhart, B; Narayanan, M; Focke-Tejkl, M; Wrba, F; Vrtala, S; Valenta, R

2014-02-01

Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy. To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses. Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies. Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation. Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation. © 2013 John Wiley & Sons Ltd.

Biomimetic coatings enhance tribocorrosion behavior and cell responses of commercially pure titanium surfaces

PubMed Central

Marques, Isabella da Silva Vieira; Alfaro, Maria Fernanda; Saito, Miki Taketomi; da Cruz, Nilson Cristino; Takoudis, Christos; Landers, Richard; Mesquita, Marcelo Ferraz; Nociti Junior, Francisco Humberto; Mathew, Mathew T.; Sukotjo, Cortino; Barão, Valentim Adelino Ricardo

2016-01-01

Biofunctionalized surfaces for implants are currently receiving much attention in the health care sector. Our aims were (1) to create bioactive Ti-coatings doped with Ca, P, Si, and Ag produced by microarc oxidation (MAO) to improve the surface properties of biomedical implants, (2) to investigate the TiO2 layer stability under wear and corrosion, and (3) to evaluate human mesenchymal stem cells (hMSCs) responses cultured on the modified surfaces. Tribocorrosion and cell experiments were performed following the MAO treatment. Samples were divided as a function of different Ca/P concentrations and treatment duration. Higher Ca concentration produced larger porous and harder coatings compared to the untreated group (p < 0.001), due to the presence of rutile structure. Free potentials experiments showed lower drops (−0.6 V) and higher coating lifetime during sliding for higher Ca concentration, whereas lower concentrations presented similar drops (−0.8 V) compared to an untreated group wherein the drop occurred immediately after the sliding started. MAO-treated surfaces improved the matrix formation and osteogenic gene expression levels of hMSCs. Higher Ca/P ratios and the addition of Ag nanoparticles into the oxide layer presented better surface properties, tribocorrosive behavior, and cell responses. MAO is a promising technique to enhance the biological, chemical, and mechanical properties of dental implant surfaces. PMID:27514370