Sample records for exp cell res

  1. Resveratrol Improves the Mitochondrial Function and Fertilization Outcome of Bovine Oocytes

    PubMed Central

    TAKEO, Shun; SATO, Daichi; KIMURA, Koji; MONJI, Yasunori; KUWAYAMA, Takehito; KAWAHARA-MIKI, Ryoka; IWATA, Hisataka

    2013-01-01

    The aim of the present study was to address the effect of resveratrol-mediated upregulation of sirtuin 1 (SIRT1) during oocyte maturation on mitochondrial function, the developmental ability of oocytes and on mechanisms responsible for blockage of polyspermic fertilization. Oocytes collected from slaughterhouse-derived ovaries were cultured in TCM-199 medium supplemented with 10% FCS and 0 or 20 µM resveratrol (Res). We examined the effect of Res on SIRT1 expression in in vitro-matured oocytes (Exp 1); fertilization and developmental ability (Exp 2); mitochondrial DNA copy number (Mt number), ATP content and mitochondrial membrane potential in matured oocytes (Exp 3); and the time required for proteinase to dissolve the zona pellucida following in vitro fertilization (as a marker of zona pellucida hardening), as well as on the distribution of cortical granules before and after fertilization (Exp 4). In Exp 1, the 20 µM Res treatment upregulated protein expression of SIRT1 in oocytes. In Exp 2, Res treatment improved the ratio of normal fertilization and the total cell number of blastocysts. In Exp 3, Res treatment significantly increased the ATP content in matured oocytes. Additionally, Res increased the overall Mt number and mitochondrial membrane potential, but the effect was donor-dependent. In Exp 4, Res-induced zona hardening improved the distribution and exocytosis of cortical granules after in vitro fertilization. In conclusion, Res improved the quality of oocytes by improving mitochondrial quantity and quality. In addition, Res added to the maturation medium enhanced SIRT1 protein expression in oocytes and improved fertilization via reinforcement of the mechanisms responsible for blockage of polyspermic fertilization. PMID:24390595

  2. Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

    DTIC Science & Technology

    2009-09-01

    C 1999 Sequence requirements for plasmid nuclear import. Exp Cell Res 253(2):713- 22 . 8). Young J L, Benoit J N, Dean D A 2003 Effect of a DNA nuclear...31. Culig Z (2004) Androgen receptor cross-talk with cell signaling pathways. Growth Factors 22 :179–184 382 X. Wang et al.: Effect of Leptin on Bone... Cell Biol. 2003:13:435-446 43. Watanabe N, Higashida C. Formins: processive cappers of growing actin filaments. Exp. Cell Res. 2004:301:16- 22 44

  3. Human Neural Cell-Based Biosensor

    DTIC Science & Technology

    2010-06-11

    stabilizer valproic acid, regulates neurite outgrowth through JNK and the substrate paxillin in N1E - 115 neuroblastoma cells. Exp Cell Res, 313 (9): p...developed methods for directed dopaminergic differentiation using defined medium conditions – all towards the goal of accelerating neuronal... differentiation for biosensor development. Moreover, we have begun an exploration of fluorescence-based assays as a new direction for ‘sensor element’ development

  4. Low Level (Sub Threshold), Large Spot Laser Irradiations of the Foveas of Macaca Mulatta.

    DTIC Science & Technology

    1981-11-01

    light period of the light-dark cycle. GrUn (1980) reported that in adult larval Xenopus and the larvae of the fish, Tilapia , 24 hours of continuous...pulses. Exp. Eye Res. 21 : 457 - 469. 1975. GrUn, G. Developmental dynamic in synaptic ribbons of retinal receptor cells. ( Tilapia , Xenopus). Cell

  5. Exploratory Study on the Stability Characteristics of Commercial Human Keratinocytes

    DTIC Science & Technology

    1990-04-01

    Invest. Dermatol. 75:176- 182; 1980. 16. Hayflick , L. The limited in vitro lifetime of huiran diploid strains. Exp. Cell Res. 37:614-636; 1965. 17...culture keratinocytes were considered by some investigators to have limited proliferative potential, so they used third and fourth passage commercial

  6. The Regulation of Nucleolin Expression in Prostrate Epithelial Cells; Possible Involvement of MYC

    DTIC Science & Technology

    2002-01-01

    SH Yeh, NH (1993). The self-cleaving activity of nucleolin determines its molecular dynamics in relation to cell proliferation. Exp Cell Res 208: 48... complementarity were mixed with a segment encompassing the two Nucleolin domains (p50), the rate with which the strands annealed was significantly enhanced...a recent study (Zhu et al 1999) that Nucleolin with all its phosphorylation sites mutated could localize during mitosis as wild-type Nucleolin did

  7. Genetic Induction of Cytolytic Susceptibility in Breast Cancer Cells

    DTIC Science & Technology

    1999-07-01

    Gryka , M ., Litwak, G., Gebhardt, M ., Bressac, B., Ozturk, M ., Baker, S., Vogelstein, B., and Friend, S. (1990). p5 3 functions as a cell cycle control...Routes, C. Leu, T. Walker, K. Colvin, Exp Cell Res, Submitted for publication (1999). 3. E. White, Genes Dev 10, 1-15 (1996). 4. J. L. Cook, A. M ...6965-6969 (1986). 7. J. L. Cook, D. L. May, A. M . Lewis, Jr., T. A. Walker, J. Virol. 61, 3510-3520 (1987). 8. T. A. Walker, B. A. Wilson, A. M . Lewis

  8. Template Based Design of Anti-Metastatic Drugs from the Active Conformation of Laminin Peptide II

    DTIC Science & Technology

    2001-01-01

    p40 (LBP/p40) gene Maeda, M., Kawasaki, K., Mu, Y., Kamada, H., during sea urchin development. Exp. Cell Res. 221, Tsutsumi, Y., Smith, T. J. & Mayumi...represents the average of six replicates + SEM . minance of putative heparin-binding phage recov- ered from elution with peptide 11. Putative heparin...scrambled sequence peptide, WAQADSTPE, was used as a sequence specificity control. The data shown is the average of six replicate wells ± SEM . Statistics were

  9. Spontaneous Transitional Cell Carcinoma in the Urinary Bladder of a Strain 13 Guinea Pig.

    DTIC Science & Technology

    1985-05-01

    less than I of all canine neoplasms. In the feline , the extremely low incidence of bladder tumors observed may well be due to a difference in...factor of age. Prog Exp Tumor Res 1967;9:261-85. ..................... , 12. Ediger R D, Rabstein M M. Spontaneous leukemia in a Hartley strain guinea pig...Intracisternal virus -like particles in two guinea pig mammary adenocarcinomas. Lab Anim Sci 1976;26:607-9. 17.. Yoshida A, Iqbal Z M, Epstein. S S

  10. A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

    DTIC Science & Technology

    2014-09-01

    810. 22. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A (2009) Invasive cortical stimulation to promote recovery of function after stroke: A critical...stimulation of the motor cortex enhances pro- genitor cell migration in the adult rat brain. Exp Brain Res 231(2):165–177. 28. Edwardson MA, Lucas TH, Carey ...The screws and rod were further secured with dental acrylic (all animals). In both the ADS and OLS groups, a hybrid, 16-channel, single-shank, chronic

  11. Corrigendum to "New Approaches to Inferences for Steep-Sided Domes on Venus" [J. Volcanol. Geotherm. Res. 319 (2016) 93-105

    NASA Technical Reports Server (NTRS)

    Quick, Lynnae C.; Glaze, Lori S.; Baloga, Stephen M.; Stofan, Ellen R.

    2017-01-01

    A typographical error contained in Quick et al. (2016) indicates the incorrect units for the value of the combined quantity (roh(exp. 3)o) that is the basis of Figs. 5, 6, and 7, and Tables 2 and 3. Using the values of ro and ho provided in Table 2, it can easily be shown that the combined quantity is correctly stated as roh(exp. 3)o =0.617 km(exp. 4). As correctly stated in Quick et al. (2016), the combined quantity of (roh(exp. 3)o) determines the family of curves shown in Fig. 5. The derivation of this relationship is shown below for completeness. Note that all results as reported in Quick et al. (2016) remained unchanged.

  12. Contact Lens Anterior Surface pH

    DTIC Science & Technology

    1991-02-01

    greenhouse effect and contact lenses, in Trans- 4. Nom MS: Tear fluid pH in normals, contact lens wearers, actions of the British Contact Lens...Invest 3. Fullard R), Carney LG: Diurnal variation in human tear en- Op/hdanmol Vis Sci 1978;17:810-813. ymes. Exp Eye Res 1984;38:15-26. 20. Efron N: The

  13. Enhancing Technical Skill Learning through Interleaved Mixed-Model Observational Practice

    ERIC Educational Resources Information Center

    Welsher, Arthur; Grierson, Lawrence E. M.

    2017-01-01

    A broad foundation of behavioural (Hayes et al. in "Exp Brain Res" 204(2): 199-206, 2010) and neurophysiological (Kohler et al. in "Science" 297(5582): 846-848, 2002) evidence has revealed that the acquisition of psychomotor skills, including those germane to clinical practice (Domuracki et al. in "Med Educ" 49(2):…

  14. Fundamental Studies in the Molecular Basis of Laser Induced Retinal Damage.

    DTIC Science & Technology

    1983-09-01

    Mandel, P. (1977) Exp. Eye Res. 25, 163-169. 19. Schwabe, U., Puchstein, C. Hannemann , H. and Sochtig, E. (1979) Nature 277, 143-145. 20. Richards, J...Hagins, W. A. and Jennings , W. H. (1959) Discussion Faraday Soc. 27, 180-190. 19. Borwein, B. (1983) Anat. Rec. 205, 363-373. 20. Yoshikami, S

  15. Metabolic status, gonadotropin secretion, and ovarian function during acute nutrient restriction of beef heifers

    USDA-ARS?s Scientific Manuscript database

    The effect of acute nutritional restriction on metabolic status, gonadotropin secretion, and ovarian function of heifers was determined in 2 experiments. In Exp. 1, 14-mo-old heifers were fed a diet supplying 1.2 × maintenance energy requirements (1.2M). After 10 d, heifers were fed 1.2M or were res...

  16. Lorentz Invariance Violation and the Observed Spectrum of Ultrahigh Energy Cosmic Rays

    NASA Technical Reports Server (NTRS)

    Scully, S. T.; Stecker, F. W.

    2009-01-01

    There has been much interest in possible violations of Lorentz invariance, particularly motivated by quantum gravity theories. It has been suggested that a small amount of Lorentz invariance violation (LIV) could turn of photomeson interactions of ultrahigh energy cosmic rays (UHECRs) with photons of the cosmic background radiation and thereby eliminate the resulting sharp steepening in the spectrum of the highest energy CRs predicted by Greisen Zatsepin and Kuzmin (GZK). Recent measurements of the UHECR spectrum reported by the HiRes and Auger collaborations, however, indicate the presence of the GZK effect. We present the results of a detailed calculation of the modification of the UHECR spectrum caused by LIV using the formalism of Coleman and Glashow. We then compare these results with the experimental UHECR data from Auger and HiRes. Based on these data, we find a best fit amount of LIV of 4.5+1:5 ..4:5 x 10(exp -23),consistent with an upper limit of 6 x 10(exp -23). This possible amount of LIV can lead to a recovery of the cosmic ray spectrum at higher energies than presently observed. Such an LIV recovery effect can be tested observationally using future detectors.

  17. Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.

    PubMed

    de Almeida-Paula, Lidiana Duarte; Costa-Lotufo, Leticia V; Silva Ferreira, Zulma; Monteiro, Amanda Elisa G; Isoldi, Mauro Cesar; Godinho, Rosely O; Markus, Regina P

    2005-11-21

    Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and chick retina imposing a diurnal variation in functional responses [Markus, R.P., Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18-22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S., Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine receptors expressed in plasma membrane. In addition, these cells expressed melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However, the pharmacological profile of melatonin analogs regarding the reduction in cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not point to a mechanism mediated by activation of G(i)-protein coupled receptors. On the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a similar manner both effects. Considering that one isoform of adenylyl cyclase present in rat myotubes is regulated by Ca2+/calmodulin, we propose that melatonin modulates the number of nicotinic acetylcholine receptors via reduction in cyclic AMP accumulation.

  18. Animal Preparations to Assess Neurophysiological Effects of Bio-Dynamic Environments.

    DTIC Science & Technology

    1980-07-17

    deprivation in preventing the acquisition of visually-guided behaviors. The next study examined acquisition of visually-guided behaviors in six animals...Maffei, L. and Bisti, S. Binocular interaction in strabismic kittens deprived of vision. Science, 191, 579-580, 1976. Matin, L. A possible hybrid...function in cat visual cortex following prolonged deprivation . Exp. Brain Res., 25 (1976) 139-156. Hein, A. Visually controlled components of movement

  19. Axial resonances a$$_{1}$$(1260), b$$_{1}$$(1235) and their decays from the lattice

    DOE PAGES

    Lang, C. B.; Leskovec, Luka; Mohler, Daniel; ...

    2014-04-28

    The light axial-vector resonancesmore » $$a_1(1260)$$ and $$b_1(1235)$$ are explored in Nf=2 lattice QCD by simulating the corresponding scattering channels $$\\rho\\pi$$ and $$\\omega\\pi$$. Interpolating fields $$\\bar{q} q$$ and $$\\rho\\pi$$ or $$\\omega\\pi$$ are used to extract the s-wave phase shifts for the first time. The $$\\rho$$ and $$\\omega$$ are treated as stable and we argue that this is justified in the considered energy range and for our parameters $$m_\\pi\\simeq 266~$$MeV and $$L\\simeq 2~$$fm. We neglect other channels that would be open when using physical masses in continuum. Assuming a resonance interpretation a Breit-Wigner fit to the phase shift gives the $$a_1(1260)$$ resonance mass $$m_{a1}^{res}=1.435(53)(^{+0}_{-109})$$ GeV compared to $$m_{a1}^{exp}=1.230(40)$$ GeV. The $$a_1$$ width $$\\Gamma_{a1}(s)=g^2 p/s$$ is parametrized in terms of the coupling and we obtain $$g_{a_1\\rho\\pi}=1.71(39)$$ GeV compared to $$g_{a_1\\rho\\pi}^{exp}=1.35(30)$$ GeV derived from $$\\Gamma_{a1}^{exp}=425(175)$$ MeV. In the $$b_1$$ channel, we find energy levels related to $$\\pi(0)\\omega(0)$$ and $$b_1(1235)$$, and the lowest level is found at $$E_1 \\gtrsim m_\\omega+m_\\pi$$ but is within uncertainty also compatible with an attractive interaction. Lastly, assuming the coupling $$g_{b_1\\omega\\pi}$$ extracted from the experimental width we estimate $$m_{b_1}^{res}=1.414(36)(^{+0}_{-83})$$.« less

  20. Anti-hepatocarcinoma effects of resveratrol nanoethosomes against human HepG2 cells

    NASA Astrophysics Data System (ADS)

    Meng, Xiang-Ping; Zhang, Zhen; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2017-02-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Resveratrol (Res) has been widely investigated with its strong anti-tumor activity. However, its low oral bioavailability restricts its wide application. In this study, we prepared resveratrol nanoethosomes (ResN) via ethanol injection method. The in vitro anti-hepatocarcinoma effects of ResN relative to efficacy of bulk Res were evaluated on proliferation and apoptosis of human HepG2 cells. ResN were spherical vesicles and its particle diameter, zeta potential were (115.8 +/- 1.3) nm and (-12.8 +/- 1.9) mV, respectively. ResN exhibited significant inhibitory effects against human HepG2 cells by MTT assay, and the IC50 value was 49.2 μg/ml (105.4 μg/ml of Res bulk solution). By flow cytometry assay, there was an increase in G2/M phase cells treated with ResN. The results demonstrated ResN could effectively block the G2/M phase of HepG2 cells, which can also enhance the inhibitory effect of Res against HepG2 cells.

  1. InGaAs/InP solar cells for space application

    NASA Technical Reports Server (NTRS)

    Karlina, L. B.; Kazantsev, A. B.; Kozlovskii, V. V.; Mokina, I. A.; Shvarts, M. Z.

    1995-01-01

    The effects of irradiation of In(0.53)Ga(0.47)As/InP (InGaAs/InP) solar cells illuminated through a transparent InP substrate with 1 MeV electrons were measured. These solar cells were developed for bottom cells in tandem solar photovoltaic cell structures. Some InGaAs/InP heterostructures with four layers were grown by liquid phase epitaxy. The structure of the solar cells allowed lightly doped materials in n and p photoactive layers to be used. The base dopant levels ranged from 1.10(exp 17) to 5.10(exp 17) cm(exp -3). The open circuit voltage and the short circuit current were moderately degraded after irradiation with 10(exp 16) cm(exp-2) 1 MeV electrons. This behavior is explained in terms of the device structure and the n and p layer thicknesses.

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

    Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon

    Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Resmore » mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI3K, AKT, and NFκB protein expressions in tumor and xenografts. • Res-induced-p21 inhibited DNA repair by modulating Fen-1 binding to PCNA complex.« less

  3. Left-handers show no self-advantage in detecting a delay in visual feedback concerning an active movement.

    PubMed

    Hoover, Adria E N; Elzein, Yasmeenah; Harris, Laurence R

    2016-07-01

    Right-handed people show an advantage in detecting a delay in visual feedback concerning an active movement of their right hand when it is viewed in a natural perspective compared to when it is seen as if viewing another person's hand (Hoover and Harris in Exp Brain Res 233:1053-1060, 2012. doi: 10.1007/s00221-014-4181-9 ; Exp Brain Res 222:389-397, 2015a. doi: 10.1007/s00221-012-3224-3 ). This self-advantage is unique to their dominant hand and may reflect an enhanced sense of ownership which contributes to how right-handed people relate to the world. Here we asked whether left-handers show the same pattern of performance for their dominant hand. We measured the minimum delay that could be detected by 29 left-handers when viewing either their dominant or non-dominant hand from 'self' or 'other' perspectives and compared their thresholds to an age-matched sample of 22 right-handers. Right-handers showed a significant signature self-advantage of 19 ms when viewing their dominant hand in an expected 'self' perspective compared to 'other' perspectives. Left-handers, however, showed no such advantage for either their dominant or non-dominant hand. This lack of self-advantage in detecting delayed visual feedback might indicate a less secure sense of body ownership amongst left-handers.

  4. Les nouveaux critères de la Maladie d’Alzheimer – Perspective gériatrique*

    PubMed Central

    Molin, Pierre; Rockwood, Kenneth

    2016-01-01

    RÉSUMÉ Deux nouvelles séries de critères pour le diagnostic de la maladie d’Alzheimer sont maintenant en vigueur, incluant une série publiée en 2014. Un « nouveau lexique » conceptualisant la maladie a également été proposé. En 2012, la Conférence consensuelle canadienne affirmait que, pour l’instant, ni les nouveaux critères ni la nouvelle terminologie ne modifiaient la pratique en première ligne. Néanmoins, pour les consultants spécialisés en démence, l’avènement de ces critères ouvre la porte à de nombreux défis et occasions. En général, les nouveaux critères accordent une place grandissante aux biomarqueurs. Toutefois, les évidences qui sous-tendent leur utilisation demeurent incomplètes. L’étude de sujets provenant de la communauté ayant raffiné notre compréhension des critères neuropathologiques des démences, il est probable que notre expérience avec les biomarqueurs en bénéficierait également. Pour l’instant, ces critères sont réservés à la recherche. Cependant, leur adoption à plus large échelle est pressentie, particulièrement aux États-Unis. Les gériatres canadiens doivent être conscients de la terminologie maintenant utilisée et du changement fondamental qui en découle : un diagnostic de maladie d’Alzheimer ne requiert plus un diagnostic de démence. Dans l’attente de nouvelles données – auxquelles les gériatres peuvent contribuer – il y a lieu de faire preuve de prudence dans l’adoption des nouveaux critères, car ils sont susceptibles de moins bien s’appliquer aux personnes âgées. PMID:27403215

  5. Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF).

    PubMed

    Vancauwenberghe, Eric; Noyer, Lucile; Derouiche, Sandra; Lemonnier, Loïc; Gosset, Pierre; Sadofsky, Laura R; Mariot, Pascal; Warnier, Marine; Bokhobza, Alexandre; Slomianny, Christian; Mauroy, Brigitte; Bonnal, Jean-Louis; Dewailly, Etienne; Delcourt, Philippe; Allart, Laurent; Desruelles, Emilie; Prevarskaya, Natalia; Roudbaraki, Morad

    2017-08-01

    Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells, and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N-terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co-cultured with CAF, the RES-induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial-stromal crosstalk in the TME leading to resistance to the RES-induced apoptosis. © 2017 Wiley Periodicals, Inc.

  6. Protective effects of resveratrol and its analogs on age-related macular degeneration in vitro.

    PubMed

    Kang, Jung-Hwan; Choung, Se-Young

    2016-12-01

    Damage of retinal pigment epithelial (RPE) cells by A2E may be critical for age-related macular degeneration (AMD) management. Accumulation and photooxidation of A2E are known to be one of the critical causes in AMD. Here, we evaluated the protective effect of resveratrol (RES), piceatannol (PIC) and RES glycones on blue-light-induced RPE cell death caused by A2E photooxidation. A2E treatment followed by blue light exposure caused significant damages on human RPE cells (ARPE-19). But the damages were attenuated by post- and pre-treatment of RES and PIC in our in vitro models. The results of cell free system and FAB-MS analysis clearly showed that the reduction of A2E by blue light exposure was significantly rescued, and that oxidized forms of A2E were significantly reduced by RES or PIC treatment. Besides, RES or PIC inhibited the intracellular accumulation of A2E. Not only RES and PIC but RES glycones showed protection of ARPE-19 cells against A2E and blue-light-induced photo-damage. These findings demonstrate that RES and its analogs may have protective effects against A2E and blue-light-induced ARPE-19 cell death through regulation of A2E accumulation as well as photooxidation of A2E. Thus RES and its analogs may be beneficial for AMD treatment.

  7. Resveratrol Induces Cancer Cell Apoptosis through MiR-326/PKM2-Mediated ER Stress and Mitochondrial Fission.

    PubMed

    Wu, Haili; Wang, Yingying; Wu, Changxin; Yang, Peng; Li, Hanqing; Li, Zhuoyu

    2016-12-14

    Resveratrol (Res), a natural phytoalexin found in a variety of plants, has significant antitumor activity. Pyruvate kinase M2 (PKM2) has abnormally high expression in various tumor cells, and it has been implicated in the survival of tumors. However, whether and how Res inhibits PKM2 expression is poorly understood. In the present study, we found that treatment with Res inhibited cell proliferation and induced cell apoptosis. The IC 50 values of Res against DLD1, HeLa, and MCF-7 cells were 75 ± 4.54, 50 ± 3.65, and 50 ± 3.32 μM, respectively. To elucidate mechanisms underlying its antitumor activities, serial experiments were performed. Results showed that reduction of PKM2 expression in tumor cells by Res treatment increased the expression of ER stress and mitochondrial fission proteins but reduced cell viability and the levels of fusion proteins. These phenomena were reversed by artificial overexpression of PKM2. Quantitative analyses showed that the expression of microRNA-326 (miR-326) was increased upon Res treatment. Treatment with the miR-326 mimic reduced PKM2 expression, promoting recovery from ER stress and mitochondrial fission. Overall, these results demonstrate that miR-326/PKM2-mediated ER stress and mitochondrial dysfunction participate in apoptosis induced by Res. These results provide novel insight into the molecular mechanisms by which Res suppresses tumors and further support for the use of Res as an antitumor drug.

  8. A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

    DTIC Science & Technology

    2015-10-01

    as an oral contraceptive [6, 7]. Recently, its anti-cancer activity has been reported against advanced breast cancer [8] and head and neck squamous...profile of Centchroman--a new post-coital contraceptive . Indian J Exp Biol, 1977. 15(12): p. 1144-50. 7. Misra, N.C., et al., Centchroman--a non-steroidal... contraceptive and for the management of hormone-related clinical disorders. Med Res Rev, 2001. 21(4): p. 302-47. 11. Jaggi, M., et al., Bryostatin 1 modulates

  9. Low-Dose Alcohol Effects on Human Behavior and Performance: A Review of Post-1984 Research

    DTIC Science & Technology

    1994-11-01

    34hangover" effects appear to be more toxicated practice" in alcohol’s performance effects, a severe in FH males (131). Second, further classifica...and piracetam . Blutalkoho124: 333-340, portation, Federal Aviation Administration, p. 1987. 1-18, 1988. 4. BAKER, S. J., G. J. CHRZAN, C. N. PARK, 14...flurazepam hierarchical patterns. A/c: Clin Exp Res 11: 243-248, and zopiclone on the performance of chronic in- 1937. somniac patients: A study of

  10. Anatomical and Physiological Characteristics of the Ferret Lateral Rectus Muscle and Abducena Nucleus

    DTIC Science & Technology

    2007-01-25

    concerned with maintaining gaze control and the ability to acquire visual targets (36). A great deal has been written on the physiology of EOM in animal...borrows, the need for rapid nystagmus control is reduced. The ferret eyes are more laterally placed than either cats or monkeys which increases the visual...20. Hein A, Courjon JH, Flandrin JM and Arzi M. Optokinetic nystagmus in the ferret: including selected comparisons with the cat. Exp Brain Res 79

  11. Neuropeptide-Y both Improves and Impairs Delayed Matching-to-Sample Performance in Rats

    DTIC Science & Technology

    1991-01-01

    Neuropeptide Y distribution in the 422 THOMAS AND AHLERS rat brain. Science 221:877-879; 1983. of animal learning. In: Roitblat , H. L.; Bever, T. G.; Terrace, H...Sources of proactive interference in memory. Hillsdale, NJ: Erlbaum; 1976. animal memory. J. Exp. Psychol. (Anim. Behav.) 1456-70; 1988. 32. Roitblat , H...memory processing by neuropeptide Y varies with brain 33. Roitblat , H. L., Scopatz, R. A. Sequential effects in pigeons de- injection site. Brain Res

  12. The protective effects of resveratrol on Schwann cells with toxicity induced by ethanol in vitro.

    PubMed

    Yuan, Hongtu; Zhang, Jingfen; Liu, Huaxiang; Li, Zhenzhong

    2013-09-01

    Schwann cells (SCs) are the myelin forming cells in the peripheral nervous system, they play a key role in the pathology of various polyneuropathies and provide trophic support to axons via expression of various neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Ethanol (EtOH) adversely affected both SCs proliferation and myelin formation in culture. Resveratrol (Res) has been shown to regulate many cellular processes and to display multiple protective and therapeutic effects. Whether Res has protective effects on SCs with EtOH-induced toxicity is still unclear. The protective efficacy of Res on EtOH-treated SCs in vitro was investigated in the present study. Res improved cell viability of the EtOH-treated SCs. Hoechst 33342 staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling analysis showed that the EtOH-induced apoptosis was inhibited by Res. The effects of Res were blocked by the 5'-adenosine monophosphate-activated protein kinase inhibitor Compound C and the silencing information regulator T1 inhibitor nicotinamide. Res could increase the mRNA and protein levels of BDNF and GDNF in the EtOH-treated SCs. However, the EtOH-induced increase of NGF in the SCs is inhibited by Res. The data from the present study indicate that Res protects SCs from EtOH-induced cell death and regulates the expression of neurotrophicfactors. Res and its derivative may be effective for the treatment of neuropathic diseases induced by EtOH. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Odontoblast-Like Cells Differentiated from Dental Pulp Stem Cells Retain Their Phenotype after Subcultivation

    PubMed Central

    Baldión, Paula A.; Velandia-Romero, Myriam L.

    2018-01-01

    Odontoblasts, the main cell type in teeth pulp tissue, are not cultivable and they are responsible for the first line of response after dental restauration. Studies on dental materials cytotoxicity and odontoblast cells physiology require large quantity of homogenous cells retaining most of the phenotype characteristics. Odontoblast-like cells (OLC) were differentiated from human dental pulp stem cells using differentiation medium (containing TGF-β1), and OLC expanded after trypsinization (EXP-21) were evaluated and compared. Despite a slower cell growth curve, EXP-21 cells express similarly the odontoblast markers dentinal sialophosphoprotein and dentin matrix protein-1 concomitantly with RUNX2 transcripts and low alkaline phosphatase activity as expected. Both OLC and EXP-21 cells showed similar mineral deposition activity evidenced by alizarin red and von Kossa staining. These results pointed out minor changes in phenotype of subcultured EXP-21 regarding the primarily differentiated OLC, making the subcultivation of these cells a useful strategy to obtain odontoblasts for biocompatibility or cell physiology studies in dentistry. PMID:29670655

  14. Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.

    PubMed

    Robb, Ellen L; Moradi, Fereshteh; Maddalena, Lucas A; Valente, Andrew J F; Fonseca, Joao; Stuart, Jeffrey A

    2017-04-01

    Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion. 48 h continuous treatment with 10-20 μM RES stimulated mitochondrial fusion in C2C12 myoblasts, PC3 cancer cells, and mouse embryonic fibroblasts stimulated significant increases in fusion in all instances, resulting in larger and more highly branched mitochondrial networks. Mitofusin-2 (Mfn2) is a key protein facilitating mitochondrial fusion, and its expression was also stimulated by RES. Using Mfn2-null cells we demonstrated that RES's effects on mitochondrial fusion, cellular respiration rates, and cell growth are all dependent upon the presence of Mfn2. Taken together, these results demonstrate that Mfn2 and mitochondrial fusion are affected by RES in ways that appear to relate to RES's known effects on cellular metabolism and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Influence of omega-3 polyunsaturated fatty acids from fish oil or meal on the structure of lipid microdomains in bovine luteal cells.

    PubMed

    Plewes, M R; Burns, P D; Graham, P E; Bruemmer, J E; Engle, T E

    2018-06-01

    Biological membranes are composed of a lipid bilayer and proteins that form lipid microdomains. This study examined the effects of fish byproducts on lipid-protein interactions within lipid microdomains of bovine luteal cells. In Exp. 1 and 2, luteal cells were prepared from corpora lutea (CL; n = 4 to 8) collected at an abattoir. Exp. 1 was conducted to optimize ultrasonication in a detergent-free protocol for isolation of lipid microdomains. A power setting of 10 to 20% was effective in isolating lipid microdomains from bulk lipid. In Exp. 2, cells were cultured in control medium or fish oil to determine influence of fish oil on distribution of lipid microdomain markers and prostaglandin F 2α (FP) receptors. Cells treated with fish oil had a smaller percentage of microdomain markers and FP receptor in microdomains (P < 0.05). In Exp. 3 and 4, cells were prepared from mid-cycle CL obtained from cows supplemented with corn gluten meal (n = 4) or fish meal (n = 4). Exp. 3 examined effects of dietary supplementation on distribution of lipid microdomain markers and FP receptor and Exp. 4 on fatty acid composition within lipid microdomains. A smaller percentage of lipid microdomain markers and FP receptor was detected in microdomains of cells collected from fish meal supplemented animals (P < 0.05). In Exp. 4, a greater percentage of omega-3 polyunsaturated fatty acids was detected in bulk lipid from fish meal supplemented cows (P < 0.05). Results show that fish byproducts influence lipid-protein interactions in lipid microdomains in bovine luteal cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Down-regulation of the IbEXP1 gene enhanced storage root development in sweetpotato

    PubMed Central

    Bae, Jung Myung

    2013-01-01

    The role of an expansin gene (IbEXP1) in the formation of the storage root (SR) was investigated by expression pattern analysis and characterization of IbEXP1-antisense sweetpotato (Ipomoea batatas cv. Yulmi) plants in an attempt to elucidate the molecular mechanism underlying SR development in sweetpotato. The transcript level of IbEXP1 was high in the fibrous root (FR) and petiole at the FR stage, but decreased significantly at the young storage root (YSR) stage. IbEXP1-antisense plants cultured in vitro produced FRs which were both thicker and shorter than those of wild-type (WT) plants. Elongation growth of the epidermal cells was significantly reduced, and metaxylem and cambium cell proliferation was markedly enhanced in the FRs of IbEXP1-antisense plants, resulting in an earlier thickening growth in these plants relative to WT plants. There was a marked reduction in the lignification of the central stele of the FRs of the IbEXP1-antisense plants, suggesting that the FRs of the mutant plants possessed a higher potential than those of WT plants to develop into SRs. IbEXP1-antisense plants cultured in soil produced a larger number of SRs and, consequently, total SR weight per IbEXP1-antisense plant was greater than that per WT plant. These results demonstrate that SR development was accelerated in IbEXP1-antisense plants and suggest that IbEXP1 plays a negative role in the formation of SR by suppressing the proliferation of metaxylem and cambium cells to inhibit the initial thickening growth of SRs. IbEXP1 is the first sweetpotato gene whose role in SR development has been directly identified in soil-grown transgenic sweetpotato plants. PMID:22945944

  17. Isolation and culture of rabbit embryonic stem cells.

    PubMed

    Honda, Arata

    2013-01-01

    Mammalian stem cells are invaluable research resources for the study of cell and embryonic development as well as practical tools for use in the production of genetically engineered animals and further therapeutics. It is important that we further our knowledge and understanding of a variety of stem cells from several different animal species before trials in humans commence. Here we describe methods for establishing rabbit embryonic stem (rES) cell lines with indefinite proliferation potential. rES cells attain maximum proliferation potential when cultured at a feeder cell density of one-sixth of that of full confluency. Higher and lower densities of feeder cells induced ES cell differentiation or division arrest. Fibroblast growth factor (FGF)2 can maintain the undifferentiated status of rES cells; however leukemia inhibitory factor (LIF) is dispensable. Under optimized conditions, rES cells could be passaged by trypsinization 50 times. This culture system enabled efficient gene transduction and clonal expansion from single cells. rES cells grew as flat monolayer cell colonies, as reported for monkey and human ES cells, and expressed pluripotency markers. Embryoid bodies and teratomas formed readily in vitro and in vivo, respectively. Characterization of ES cells from different species is important for establishing common features of pluripotency. We have demonstrated the similarity of ES cells between rabbit and humans. These cell lines could be applied directly using gene-targeting techniques, or in combination with induced pluripotent stem cells. Thus, rES cells are a suitable model for studying human transplantation therapy and disease treatments.

  18. Digital particle image thermometry/velocimetry: a review

    NASA Astrophysics Data System (ADS)

    Dabiri, Dana

    2009-02-01

    Digital particle image thermometry/velocimetry (DPIT/V) is a relatively new methodology that allows for measurements of simultaneous temperature and velocity within a two-dimensional domain, using thermochromic liquid crystal tracer particles as the temperature and velocity sensors. Extensive research has been carried out over recent years that have allowed the methodology and its implementation to grow and evolve. While there have been several reviews on the topic of liquid crystal thermometry (Moffat in Exp Therm Fluid Sci 3:14-32, 1990; Baughn in Int J Heat Fluid Flow 16:365-375, 1995; Roberts and East in J Spacecr Rockets 33:761-768, 1996; Wozniak et al. in Appl Sci Res 56:145-156, 1996; Behle et al. in Appl Sci Res 56:113-143, 1996; Stasiek in Heat Mass Transf 33:27-39, 1997; Stasiek and Kowalewski in Opto Electron Rev 10:1-10, 2002; Stasiek et al. in Opt Laser Technol 38:243-256, 2006; Smith et al. in Exp Fluids 30:190-201, 2001; Kowalewski et al. in Springer handbook of experimental fluid mechanics, 1st edn. Springer, Berlin, pp 487-561, 2007), the focus of the present review is to provide a relevant discussion of liquid crystals pertinent to DPIT/V. This includes a background on liquid crystals and color theory, a discussion of experimental setup parameters, a description of the methodology’s most recent advances and processing methods affecting temperature measurements, and finally an explanation of its various implementations and applications.

  19. Identification and characterization of a newly recognized population of high-Na+, low-K+, low-density sickle and normal red cells.

    PubMed

    Bookchin, R M; Etzion, Z; Sorette, M; Mohandas, N; Skepper, J N; Lew, V L

    2000-07-05

    We describe a population of sickle cell anemia red cells (SS RBCs) ( approximately 4%) and a smaller fraction of normal RBCs (<0.03%) that fail to dehydrate when permeabilized to K(+) with either valinomycin or elevated internal Ca(2+). The nonshrinking, valinomycin-resistant (val-res) fractions, first detected by flow cytometry of density-fractionated SS RBCs, constituted up to 60% of the lightest, reticulocyte-rich (R1) cell fraction, and progressively smaller portions of the slightly denser R2 cells and discocytes. R1 val-res RBCs had a mean cell hemoglobin concentration of approximately 21 g of Hb per dl, and many had an elongated shape like "irreversibly sickled cells," suggesting a dense SS cell origin. Of three possible explanations for val-res cells, failure of valinomycin to K(+)-permeabilize the cells, low co-ion permeability, or reduced driving K(+) gradient, the latter proved responsible: Both SS and normal val-res RBCs were consistently high-Na(+) and low-K(+), even when processed entirely in Na-free media. Ca(2+) + A23187-induced K(+)-permeabilization of SS R1 fractions revealed a similar fraction of cal-res cells, whose (86)Rb uptake showed both high Na/K pump and leak fluxes. val-res/cal-res RBCs might represent either a distinct erythroid genealogy, or an "end-stage" of normal and SS RBCs. This paper focuses on the discovery, basic characterization, and exclusion of artifactual origin of this RBC fraction. Many future studies will be needed to clarify their mechanism of generation and full pathophysiological significance.

  20. Effect of novel chitosan-fluoroaluminosilicate resin modified glass ionomer cement supplemented with translationally controlled tumor protein on pulp cells.

    PubMed

    Wanachottrakul, Nattaporn; Chotigeat, Wilaiwan; Kedjarune-Leggat, Ureporn

    2014-04-01

    Dental materials that can promote cell proliferation and function is required for regenerative pulp therapy. Resin modified glass ionomer cement (RMGIC), a broadly used liner or restorative material, can cause apoptosis to pulp cells mainly due to HEMA (2-hydroxyethyl methacrylate), the released residual monomer. Recent studies found that chitosan and albumin could promote release of protein in GIC while translationally controlled tumor protein (TCTP) has an anti-apoptotic activity against HEMA. The aim of this study was to examine the effect of chitosan and albumin modified RMGIC (Exp-RMGIC) supplemented with TCTP on pulp cell viability and mineralization. Exp-RMGIC+TCTP was composed of RMGIC powder incorporated with 15 % of chitosan, 5 % albumin and supplemented with TCTP mixed with the same liquid components of RMGIC. The effect of each specimen on pulp cells was examined using the Transwell plate. From the MTT assay, Exp-RMGIC+TCTP had the highest percentages of viable cells (P < 0.05) at both 24 and 74 h. Flow cytometry revealed that, after 24 h, Exp-RMGIC+TCTP gave the lowest percentages of apoptotic cells compared to other groups. There was no difference in alkaline phosphatase (ALP) activity among different formula of the specimens, while cells cultured in media with TCTP had higher ALP activity. Von Kossa staining revealed that RMGIC+TCTP, and Exp-RMGIC+TCTP had higher percentages of calcium deposit area compared to those without TCTP. It was concluded that Exp-RMGIC supplemented with TCTP had less cytotoxicity than RMGIC and can protect cells from apoptosis better than RMGIC supplemented with TCTP.

  1. In vitro Catecholamine Exposure Produces Variable Effects on the B7 Costimulatory Pathway in Human Monocytic Cells

    NASA Technical Reports Server (NTRS)

    Salicru, A. N.; Crucian, B.; Sams, Clarence; Actor, J. K.; Marshall, G. D., Jr.

    2006-01-01

    Catecholamines have been associated with immunomodulation of the adaptive immune system towards a Th2 response in vitro. We therefore examined the role of in vitro epinephrine (EPI) and norepinephrine (NE) exposure on the B7 costimulatory expression of antigen presenting cells (APC) from human monocytic cell lines and human peripheral blood mononuclear cells (PBMC). THP1 monocytic cells and CD14+ cells from normal human PBMC were stimulated with lipopolysaccharide (LPS) and incubated with physiologic stress levels (10(exp -6) - 10(exp -8)M) of EPI or NE for 24 hours. Cells were subsequently stained with CD80 FITC, CD86 PE, and CD14 PC5 antibodies and analyzed by flow cytometry for changes in fluorescence and mean fluorescence intensity (MFI). Exposure of THP1 to EPI in vitro at concentrations of 10(exp -6), 10(exp -7) and 10(exp -8)M significantly decreased mean CD80 from 42 plus or minus 0.7% to 11 plus or minus 0.44%, 19.1 plus or minus 2.0%, and 30.7 plus or minus 2.1% expression, respectively (p less than 0.01). In addition, CD86 expression increased with EPI at 10(exp -6), 10(exp -7) and 10(exp -8) M from 9.2 plus or minus 0.52% to 41 plus or minus 3.8%, 26.4 plus or minus 1.9%, and 15.74 plus or minus 1.8% expression, respectively (p less than 0.01). Similar results for mean CD80 and CD86 percent expression were observed for CD14+ cells from PBMC with a sample size of N = 6 and for NE when substituted for EPI. The data show that in vitro exposure to catecholamines significantly decreases %CD86 expression and significantly increases %CD86 expression in THP1 cells and human CD14+ APC. Previous studies have suggested an association between increased CD86 expression and TH2 activity. Thus, these data suggest that immunomodulation by catecholamines results in part by the variable effects of the B7 costimulatory pathway in APC.

  2. Downregulation of the Petunia hybrida alpha-expansin gene PhEXP1 reduces the amount of crystalline cellulose in cell walls and leads to phenotypic changes in petal limbs.

    PubMed

    Zenoni, Sara; Reale, Lara; Tornielli, Giovanni Battista; Lanfaloni, Luisa; Porceddu, Andrea; Ferrarini, Alberto; Moretti, Chiaraluce; Zamboni, Anita; Speghini, Adolfo; Ferranti, Francesco; Pezzotti, Mario

    2004-02-01

    The expansins comprise a family of proteins that appear to be involved in the disruption of the noncovalent bonds between cellulose microfibrils and cross-linking glycans, thereby promoting wall creep. To understand better the expansion process in Petunia hybrida (petunia) flowers, we isolated a cDNA corresponding to the PhEXP1 alpha-expansin gene of P. hybrida. Evaluation of the tissue specificity and temporal expression pattern demonstrated that PhEXP1 is preferentially expressed in petal limbs during development. To determine the function of PhEXP1, we used a transgenic antisense approach, which was found to cause a decrease in petal limb size, a reduction in the epidermal cell area, and alterations in cell wall morphology and composition. The diminished cell wall thickness accompanied by a reduction in crystalline cellulose indicates that the activity of PhEXP1 is associated with cellulose metabolism. Our results suggest that expansins play a role in the assembly of the cell wall by affecting either cellulose synthesis or deposition.

  3. Downregulation of the Petunia hybrida α-Expansin Gene PhEXP1 Reduces the Amount of Crystalline Cellulose in Cell Walls and Leads to Phenotypic Changes in Petal Limbs

    PubMed Central

    Zenoni, Sara; Reale, Lara; Tornielli, Giovanni Battista; Lanfaloni, Luisa; Porceddu, Andrea; Ferrarini, Alberto; Moretti, Chiaraluce; Zamboni, Anita; Speghini, Adolfo; Ferranti, Francesco; Pezzotti, Mario

    2004-01-01

    The expansins comprise a family of proteins that appear to be involved in the disruption of the noncovalent bonds between cellulose microfibrils and cross-linking glycans, thereby promoting wall creep. To understand better the expansion process in Petunia hybrida (petunia) flowers, we isolated a cDNA corresponding to the PhEXP1 α-expansin gene of P. hybrida. Evaluation of the tissue specificity and temporal expression pattern demonstrated that PhEXP1 is preferentially expressed in petal limbs during development. To determine the function of PhEXP1, we used a transgenic antisense approach, which was found to cause a decrease in petal limb size, a reduction in the epidermal cell area, and alterations in cell wall morphology and composition. The diminished cell wall thickness accompanied by a reduction in crystalline cellulose indicates that the activity of PhEXP1 is associated with cellulose metabolism. Our results suggest that expansins play a role in the assembly of the cell wall by affecting either cellulose synthesis or deposition. PMID:14742876

  4. Sleep-dependent consolidation benefits fast transfer of time interval training.

    PubMed

    Chen, Lihan; Guo, Lu; Bao, Ming

    2017-03-01

    Previous study has shown that short training (15 min) for explicitly discriminating temporal intervals between two paired auditory beeps, or between two paired tactile taps, can significantly improve observers' ability to classify the perceptual states of visual Ternus apparent motion while the training of task-irrelevant sensory properties did not help to improve visual timing (Chen and Zhou in Exp Brain Res 232(6):1855-1864, 2014). The present study examined the role of 'consolidation' after training of temporal task-irrelevant properties, or whether a pure delay (i.e., blank consolidation) following pretest of the target task would give rise to improved ability of visual interval timing, typified in visual Ternus display. A procedure of pretest-training-posttest was adopted, with the probe of discriminating Ternus apparent motion. The extended implicit training of timing in which the time intervals between paired auditory beeps or paired tactile taps were manipulated but the task was discrimination of the auditory pitches or tactile intensities, did not lead to the training benefits (Exps 1 and 3); however, a delay of 24 h after implicit training of timing, including solving 'Sudoku puzzles,' made the otherwise absent training benefits observable (Exps 2, 4, 5 and 6). The above improvements in performance were not due to a practice effect of Ternus motion (Exp 7). A general 'blank' consolidation period of 24 h also made improvements of visual timing observable (Exp 8). Taken together, the current findings indicated that sleep-dependent consolidation imposed a general effect, by potentially triggering and maintaining neuroplastic changes in the intrinsic (timing) network to enhance the ability of time perception.

  5. Two-component regulators involved in the global control of virulence in Erwinia carotovora subsp. carotovora.

    PubMed

    Eriksson, A R; Andersson, R A; Pirhonen, M; Palva, E T

    1998-08-01

    Production of extracellular, plant cell wall degrading enzymes, the main virulence determinants of the plant pathogen Erwinia carotovora subsp. carotovora, is coordinately controlled by a complex regulatory network. Insertion mutants in the exp (extracellular enzyme production) loci exhibit pleiotropic defects in virulence and the growth-phase-dependent transcriptional activation of genes encoding extracellular enzymes. Two new exp mutations, designated expA and expS, were characterized. Introduction of the corresponding wild-type alleles to the mutants complemented both the lack of virulence and the impaired production of plant cell wall degrading enzymes. The expA gene was shown to encode a 24-kDa polypeptide that is structurally and functionally related to the uvrY gene product of Escherichia coli and the GacA response regulator of Pseudomonas fluorescens. Functional similarity of expA and uvrY was demonstrated by genetic complementation. The expA gene is organized in an operon together with a uvrC-like gene, identical to the organization of uvrY and uvrC in E. coli. The unlinked expS gene encodes a putative sensor kinase that shows 92% identity to the recently described rpfA gene product from another E. carotovora subsp. carotovora strain. Our data suggest that ExpS and ExpA are members of two-component sensor kinase and response regulator families, respectively. These two proteins might interact in controlling virulence gene expression in E. carotovora subsp. carotovora.

  6. Investigation of the stability and 1.0 MeV proton radiation resistance of commercially produced hydrogenated amorphous silicon alloy solar cells

    NASA Technical Reports Server (NTRS)

    Lord, Kenneth R., II; Walters, Michael R.; Woodyard, James R.

    1994-01-01

    The radiation resistance of commercial solar cells fabricated from hydrogenated amorphous silicon alloys is reported. A number of different device structures were irradiated with 1.0 MeV protons. The cells were annealing at 200 C. The annealing time was dependent on proton fluence. Annealing devices for one hour restores cell parameters or fluences below 1(exp 14) cm(exp -2); fluences above 1(exp 14) cm(exp -2) require longer annealing times. A parametric fitting model was used to characterize current mechanisms observed in dark I-V measurements. The current mechanisms were explored with irradiation fluence, and voltage and light soaking times. The thermal generation current density and quality factor increased with proton fluence. Device simulation shows the degradation in cell characteristics may be explained by the reduction of the electric field in the intrinsic layer.

  7. Role of an expansin-like molecule in Dictyostelium morphogenesis and regulation of its gene expression by the signal transducer and activator of transcription protein Dd-STATa.

    PubMed

    Ogasawara, Shun; Shimada, Nao; Kawata, Takefumi

    2009-02-01

    Expansins are proteins involved in plant morphogenesis, exerting their effects on cellulose to extend cell walls. Dictyostelium is an organism that possesses expansin-like molecules, but their functions are not known. In this study, we analyzed the expL7 (expansin-like 7) gene, which has been identified as a putative target of Dd-STATa, a Dictyostelium homolog of the metazoan signal transducer and activator of transcription (STAT) proteins. Promoter fragments of the expL7 were fused to a lacZ reporter and the expression patterns determined. As expected from the behavior of the endogenous expL7 gene, the expL7/lacZ fusion gene was downregulated in Dd-STATa null slugs. In the parental strain, the expL7 promoter was activated in the anterior tip region. Mutational analysis of the promoter identified a sequence that was necessary for expression in tip cells. In addition, an activator sequence for pstAB cells was identified. These sequences act in combination with the repressor region to prevent ectopic expL7 expression in the prespore and prestalk regions of the slug and culminant. Although the expL7 null mutant showed no phenotypic change, the expL7 overexpressor showed aberrant stalk formation. These results indicate that the expansin-like molecule is important for morphogenesis in Dictyostelium.

  8. Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB

    PubMed Central

    Singh, Narendra P.; Singh, Udai P.; Hegde, Venkatesh L.; Guan, Hongbing; Hofseth, Lorne; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2012-01-01

    Scope Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of Resveratarol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth. Methods and results Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of SIRT1 and downregulation of NF-kB in EL4 cells. SiRNA-mediated down regulation of SIRT1 in EL4 cells increased the activation of NF-kB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-kB. Conclusion These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-kB, leading to suppression of tumor growth. PMID:21520490

  9. Detection of Expansin Proteins and Activity during Tomato Fruit Ontogeny1

    PubMed Central

    Rose, Jocelyn K.C.; Cosgrove, Daniel J.; Albersheim, Peter; Darvill, Alan G.; Bennett, Alan B.

    2000-01-01

    Expansins are plant proteins that have the capacity to induce extension in isolated cell walls and are thought to mediate pH-dependent cell expansion. J.K.C. Rose, H.H. Lee, and A.B. Bennett ([1997] Proc Natl Acad Sci USA 94: 5955–5960) reported the identification of an expansin gene (LeExp1) that is specifically expressed in ripening tomato (Lycopersicon esculentum) fruit where cell wall disassembly, but not cell expansion, is prominent. Expansin expression during fruit ontogeny was examined using antibodies raised to recombinant LeExp1 or a cell elongation-related expansin from cucumber (CsExp1). The LeExp1 antiserum detected expansins in extracts from ripe, but not preripe tomato fruit, in agreement with the pattern of LeExp1 mRNA accumulation. In contrast, antibodies to CsExp1 cross-reacted with expansins in early fruit development and the onset of ripening, but not at a later ripening stage. These data suggest that ripening-related and expansion-related expansin proteins have distinct antigenic epitopes despite overall high sequence identity. Expansin proteins were detected in a range of fruit species and showed considerable variation in abundance; however, appreciable levels of expansin were not present in fruit of the rin or Nr tomato mutants that exhibit delayed and reduced softening. LeExp1 protein accumulation was ethylene-regulated and matched the previously described expression of mRNA, suggesting that expression is not regulated at the level of translation. We report the first detection of expansin activity in several stages of fruit development and while characteristic creep activity was detected in young and developing tomato fruit and in ripe pear, avocado, and pepper, creep activity in ripe tomato showed qualitative differences, suggesting both hydrolytic and expansin activities. PMID:10938374

  10. Synergistic effect of PEGylated resveratrol on delivery of anticancer drugs.

    PubMed

    Wang, Wenlong; Zhang, Liang; Le, Yuan; Chen, Jian-Feng; Wang, Jiexin; Yun, Jimmy

    2016-02-10

    Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The effects of electron and proton radiation on GaSb infrared solar cells

    NASA Technical Reports Server (NTRS)

    Gruenbaum, P. E.; Avery, J. E.; Fraas, L. M.

    1991-01-01

    Gallium antimonide (GaSb) infrared solar cells were exposed to 1 MeV electrons and protons up to fluences of 1 times 10(exp 15) cm (-2) and 1 times 10(exp 12) cm (-2) respectively. In between exposures, current voltage and spectral response curves were taken. The GaSb cells were found to degrade slightly less than typical GaAs cells under electron irradiation, and calculations from spectral response curves showed that the damage coefficient for the minority carrier diffusion length was 3.5 times 10(exp 8). The cells degraded faster than GaAs cells under proton irradiation. However, researchers expect the top cell and coverglass to protect the GaSb cell from most damaging protons. Some annealing of proton damage was observed at low temperatures (80 to 160 C).

  12. Induced mutations in tomato SlExp1 alter cell wall metabolism and delay fruit softening.

    PubMed

    Minoia, Silvia; Boualem, Adnane; Marcel, Fabien; Troadec, Christelle; Quemener, Bernard; Cellini, Francesco; Petrozza, Angelo; Vigouroux, Jacqueline; Lahaye, Marc; Carriero, Filomena; Bendahmane, Abdelhafid

    2016-01-01

    Fruit ripening and softening are key traits for many fleshy fruit. Since cell walls play a key role in the softening process, expansins have been investigated to control fruit over ripening and deterioration. In tomato, expression of Expansin 1 gene, SlExp1, during fruit ripening was associated with fruit softening. To engineer tomato plants with long shelf life, we screened for mutant plants impaired in SlExp1 function. Characterization of two induced mutations, Slexp1-6_W211S, and Slexp1-7_Q213Stop, showed that SlExp1 loss of function leads to enhanced fruit firmness and delayed fruit ripening. Analysis of cell wall polysaccharide composition of Slexp1-7_Q213Stop mutant pointed out significant differences for uronic acid, neutral sugar and total sugar contents. Hemicelluloses chemistry analysis by endo-β-1,4-d-glucanase hydrolysis and MALDI-TOF spectrometry revealed that xyloglucan structures were affected in the fruit pericarp of Slexp1-7_Q213Stop mutant. Altogether, these results demonstrated that SlExp1 loss of function mutants yield firmer and late ripening fruits through modification of hemicellulose structure. These SlExp1 mutants represent good tools for breeding long shelf life tomato lines with contrasted fruit texture as well as for the understanding of the cell wall polysaccharide assembly dynamics in fleshy fruits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Low microchimeric cell density in tumors suggests alternative antineoplastic mechanism.

    PubMed

    Jolis, Timothy W; Brucker, Brenna M; Schorl, Christoph; Butera, James N; Quesenberry, Peter J

    2017-04-01

    Microchimerism has generally been shown to protect against cancer (Gilmore et al. in Exp Hematol 36(9):1073-1077, 2008). The mechanism of how this occurs is an area of intense study, as it may lead to new cancer treatments. The leading theory is that microchimeric cells perform immune surveillance by directly fighting cancerous cells and that they also act as stem cells, repairing damaged tissue (Khosrotehrani et al. in JAMA 292:75-80, 2004). However, there is conflicting evidence to support this theory. Several small studies have found few microchimeric cells in tumor tissue (Gadi in Breast Cancer Res Treat 121(1):241-244, 2010; Cirello et al. in Int J Cancer 126:2874-2878, 2010), while another study contradicted these findings by showing microchimeric cells clustered around tumor tissue (O'Donoghue et al. in Reprod Biomed Online 16:382-390, 2008). To date, we have designed the largest and broadest study to investigate this question of whether microchimeric cells really do cluster at tumor tissue. We analyzed 245 samples from a broad range of cancer types. Using PCR for the male chromosome marker TSPY1, we identified only 12 out of 245 samples with microchimerism for a rate of 4.9% (95% confidence interval 2.2-7.6%). Five of these samples were confirmed using Y fluorescence in situ hybridization. This rate of 4.9% microchimerism is the lowest reported in any study. The low percentage of microchimerism observed in our broad study suggests that microchimeric cells do not invade tumors to fight off neoplasm.

  14. Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB.

    PubMed

    Singh, Narendra P; Singh, Udai P; Hegde, Venkatesh L; Guan, Hongbing; Hofseth, Lorne; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2011-08-01

    Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of resveratrol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth. Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of silent mating type information regulation 2 homolog, 1 (SIRT1) and downregulation of nuclear factor kappa B (NF-κB) in EL4 cells. siRNA-mediated downregulation of SIRT1 in EL4 cells increased the activation of NF-κB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-κB. These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-κB, leading to suppression of tumor growth. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Growth modulation effects of CBM2a under the control of AtEXP4 and CaMV35S promoters in Arabidopsis thaliana, Nicotiana tabacum and Eucalyptus camaldulensis.

    PubMed

    Keadtidumrongkul, Pornthep; Suttangkakul, Anongpat; Pinmanee, Phitsanu; Pattana, Kanokwan; Kittiwongwattana, Chokchai; Apisitwanich, Somsak; Vuttipongchaikij, Supachai

    2017-08-01

    The expression of cell-wall-targeted Carbohydrate Binding Modules (CBMs) can alter cell wall properties and modulate growth and development in plants such as tobacco and potato. CBM2a identified in xylanase 10A from Cellulomonas fimi is of particular interest for its ability to bind crystalline cellulose. However, its potential for promoting plant growth has not been explored. In this work, we tested the ability of CBM2a to promote growth when expressed using both CaMV35S and a vascular tissue-specific promoter derived from Arabidopsis expansin4 (AtEXP4) in three plant species: Arabidopsis, Nicotiana tabacum and Eucalyptus camaldulensis. In Arabidopsis, the expression of AtEXP4pro:CBM2a showed trends for growth promoting effects including the increase of root and hypocotyl lengths and the enlargements of the vascular xylem area, fiber cells and vessel cells. However, in N. tabacum, the expression of CBM2a under the control of either CaMV35S or AtEXP4 promoter resulted in subtle changes in the plant growth, and the thickness of secondary xylem and vessel and fiber cell sizes were generally reduced in the transgenic lines with AtEXP4pro:CBM2a. In Eucalyptus, while transgenics expressing CaMV35S:CBM2a showed very subtle changes compared to wild type, those transgenics with AtEXP4pro:CBM2a showed increases in plant height, enlargement of xylem areas and xylem fiber and vessel cells. These data provide comparative effects of expressing CBM2a protein in different plant species, and this finding can be applied for plant biomass improvement.

  16. Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

    PubMed

    Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

    2014-09-01

    We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

  17. Recycling Endosomes of Polarized Epithelial Cells Actively Sort Apical and Basolateral Cargos into Separate Subdomains

    PubMed Central

    Thompson, Anthony; Nessler, Randy; Wisco, Dolora; Anderson, Eric; Winckler, Bettina

    2007-01-01

    The plasma membranes of epithelial cells plasma membranes contain distinct apical and basolateral domains that are critical for their polarized functions. However, both domains are continuously internalized, with proteins and lipids from each intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs must faithfully recycle membrane proteins back to the correct plasma membrane domains. We examined sorting within REs and found that apical and basolateral proteins were laterally segregated into subdomains of individual REs. Subdomains were absent in unpolarized cells and developed along with polarization. Subdomains were formed by an active sorting process within REs, which precedes the formation of AP-1B–dependent basolateral transport vesicles. Both the formation of subdomains and the fidelity of basolateral trafficking were dependent on PI3 kinase activity. This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity. PMID:17494872

  18. Microorganisms, Organic Carbon, and Their Relationship with Oxidant Activity in Hyper-Arid Mars-Like Soils: Implications for Soil Habitability

    NASA Technical Reports Server (NTRS)

    Valdivia-Silva, Julio E.; Karouia, Fathi; Navarro-Gonzalez, Rafael; McKay, Christopher

    2016-01-01

    Soil samples from the hyper-arid region in the Atacama 23 Desert in Southern Peru (La Joya Desert) were analyzed for total and labile organic carbon (TOC & LOC), phospholipid fatty acids analysis (PLFA), quantitative real time polymerase chain reaction (qRT-PCR), 4',6- diamidino-2-phenylindole (DAPI)-fluorescent microscopy, culturable microorganisms, and oxidant activity, in order to understand the relationship between the presence of organic matter and microorganisms in these types of soils. TOC content levels were similar to the labile pool of carbon suggesting the absence of recalcitrant carbon in these soils. The range of LOC was from 2 to 60 micro-g/g of soil. PLFA analysis indicated a maximum of 2.3 x 10(exp 5) cell equivalents/g. Culturing of soil extracts yielded 1.1 x 10(exp 2)-3.7 x 10(exp 3) CFU/g. qRT-PCR showed between 1.0 x 10(exp 2) and 8 x 10(exp 3) cells/g; and DAPI fluorescent staining indicated bacteria counts up to 5 x 104 cells/g. Arid and semiarid samples (controls) showed values between 10(exp 7) and 10(exp 11) cells/g with all of the methods used. Importantly, the concentration of microorganisms in hyper-arid soils did not show any correlation with the organic carbon content; however, there was a significant dependence on the oxidant activity present in these soil samples evaluated as the capacity to decompose sodium formate in 10 hours. We suggest that the analysis of oxidant activity could be a useful indicator of the microbial habitability in hyper-arid soils, obviating the need to measure water activity over time. This approach could be useful in astrobiological studies on other worlds.

  19. Aging does not affect generalized postural motor learning in response to variable amplitude oscillations of the support surface.

    PubMed

    Van Ooteghem, Karen; Frank, James S; Allard, Fran; Horak, Fay B

    2010-08-01

    Postural motor learning for dynamic balance tasks has been demonstrated in healthy older adults (Van Ooteghem et al. in Exp Brain Res 199(2):185-193, 2009). The purpose of this study was to investigate the type of knowledge (general or specific) obtained with balance training in this age group and to examine whether embedding perturbation regularities within a balance task masks specific learning. Two groups of older adults maintained balance on a translating platform that oscillated with variable amplitude and constant frequency. One group was trained using an embedded-sequence (ES) protocol which contained the same 15-s sequence of variable amplitude oscillations in the middle of each trial. A second group was trained using a looped-sequence (LS) protocol which contained a 15-s sequence repeated three times to form each trial. All trials were 45 s. Participants were not informed of any repetition. To examine learning, participants performed a retention test following a 24-h delay. LS participants also completed a transfer task. Specificity of learning was examined by comparing performance for repeated versus random sequences (ES) and training versus transfer sequences (LS). Performance was measured by deriving spatial and temporal measures of whole body center of mass (COM) and trunk orientation. Both groups improved performance with practice as characterized by reduced COM displacement, improved COM-platform phase relationships, and decreased angular trunk motion. Furthermore, improvements reflected general rather than specific postural motor learning regardless of training protocol (ES or LS). This finding is similar to young adults (Van Ooteghem et al. in Exp Brain Res 187(4):603-611, 2008) and indicates that age does not influence the type of learning which occurs for balance control.

  20. Cone structure and focusing of VLF and LF electromagnetic waves at high altitudes in the ionosphere

    NASA Technical Reports Server (NTRS)

    Alpert, Ya. L.; Green, J. L.

    1994-01-01

    The frequency and angle dependencies of the electric field radiated by an electric dipole E = E(sub 0) cos omega(t) are studied through numerical calculations of absolute value of E in the VLF and LF frequency bands where F is less than or equal 0.02 to 0.05 f(sub b) in a model ionosphere over an altitude region of 800-6000 km where the wave frequency and electron gyrofrequency varies between F approximately 4-500 kHz and f(sub b) is approximately equal (1.1 to 0.2) MHz respectively. It is found that the amplitudes of the electric field have large maxima in four regions: close to the direction of the Earth magnetic field line B(sub 0) (it is called the axis field E(sub 0), in the Storey E(sub St), reversed Storey E(sub RevSt), and resonance E(sub Res) cones. The maximal values of E(sub 0), E(sub Res), and E(sub RevSt) are the most pronounced close to the lower hybrid frequency, F approximately F(sub L). The flux of the electric field is concentrated in very narrow regions, with the apex angles of the cones Delta-B is approximately (0.1-1) deg. The enhancement and focusing of the electric field increases with altitude starting at Z greater than 800 km. At Z greater than or equal to 1000 up to 6000 km, the relative value of absolute value of E, in comparison with its value at Z = 800 km is about (10(exp 2) to 10(exp 4)) times larger. Thus the flux of VLF and LF electromagnetic waves generated at high altitudes in the Earth's ionosphere are trapped into very narrow conical beams similar to laser beams.

  1. Nanoparticle-macrophage interactions: A balance between clearance and cell-specific targeting

    PubMed Central

    Rattan, Rahul; Bhattacharjee, Somnath; Zong, Hong; Swain, Corban; Siddiqui, Muneeb A.; Visovatti, Scott H.; Kanthi, Yogendra; Desai, Sajani; Pinsky, David J.; Goonewardena, Sascha N.

    2017-01-01

    The surface properties of nanoparticles (NPs) are a major factor that influences how these nanomaterials interact with biological systems. Interactions between NPs and macrophages of the reticuloendothelial system (RES) can reduce the efficacy of NP diagnostics and therapeutics. Traditionally, to limit NP clearance by the RES system, the NP surface is neutralized with molecules like poly(ethylene glycol) (PEG) which are known to resist protein adsorption and RES clearance. Unfortunately, PEG modification is not without drawbacks including difficulties with the synthesis and associations with immune reactions. To overcome some of these obstacles, we neutralized the NP surface by acetylation and compared this modification to PEGylation for RES clearance and tumor-specific targeting. We found that acetylation was comparable to PEGylation in reducing RES clearance. Additionally, we found that dendrimer acetylation did not impact folic acid (FA)-mediated targeting of tumor cells whereas PEG surface modification reduced the targeting ability of the NP. These results clarify the impact of different NP surface modifications on RES clearance and cell-specific targeting and provide insights into the design of more effective NPs. PMID:28705434

  2. Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.

    PubMed

    Surya, Sanjna L; Long, Marcus J C; Urul, Daniel A; Zhao, Yi; Mercer, Emily J; EIsaid, Islam M; Evans, Todd; Aye, Yimon

    2018-02-08

    Small heat shock protein (sHSP)-B7 (HSPB7) is a muscle-specific member of the non-ATP-dependent sHSPs. The precise role of HSPB7 is enigmatic. Here, we disclose that zebrafish Hspb7 is a kinetically privileged sensor that is able to react rapidly with native reactive electrophilic species (RES), when only substoichiometric amounts of RES are available in proximity to Hspb7 expressed in living cells. Among the two Hspb7-cysteines, this RES sensing is fulfilled by a single cysteine (C117). Purification and characterizations in vitro reveal that the rate for RES adduction is among the most efficient reported for protein-cysteines with native carbonyl-based RES. Covalent-ligand binding is accompanied by structural changes (increase in β-sheet-content), based on circular dichroism analysis. Among the two cysteines, only C117 is conserved across vertebrates; we show that the human ortholog is also capable of RES sensing in cells. Furthermore, a cancer-relevant missense mutation reduces this RES-sensing property. This evolutionarily conserved cysteine-biosensor may play a redox-regulatory role in cardioprotection.

  3. Simultaneous transgenic suppression of LePG and LeExp1 influences fruit texture and juice viscosity in a fresh market tomato variety.

    PubMed

    Powell, Ann L T; Kalamaki, Mary S; Kurien, Philip A; Gurrieri, Sergio; Bennett, Alan B

    2003-12-03

    Tomatoes are grown for fresh consumption or for processing of the fruit. Some ripening-associated processes of the fruit can either contribute to or degrade attributes associated with both fresh and processing quality. For example, cell wall disassembly is associated with loss of fresh fruit firmness as well as with loss of processed tomato product viscosity. Several enzymes contribute to cell wall polysaccharide disassembly. Polygalacturonase (PG, poly[1,4-alpha-d-galactouronide] glucanohydrolase, EC 3.2.1.15) is among the most abundant polysaccharide hydrolases in ripening tomato fruit and is the major contributor to pectin depolymerization. Expansin (LeExp1) is also abundant in ripening fruit and is proposed to contribute to cell wall disassembly by nonhydrolytic activity, possibly by increasing substrate accessibility to other enzymes. Suppression of either LePG or LeExp1 expression alone results in altered softening and/or shelf life characteristics. To test whether simultaneous suppression of both LePG and LeExp1 expression influences fruit texture in additive or synergistic ways, transgenic Lycopersicon esculentum var. Ailsa Craig lines with reduced expression of either LePG or LeExp1 were crossed. Fruits from the third generation of progeny, homozygous for both transgenic constructs, were analyzed for firmness and other quality traits during ripening on or off the vine. In field-grown transgenic tomato fruit, suppression of LeExp1 or LePG alone did not significantly increase fruit firmness. However, fruits suppressed for both LePG and LeExp1 expression were significantly firmer throughout ripening and were less susceptible to deterioration during long-term storage. Juice prepared from the transgenic tomato fruit with reduced LePG and LeExp1 expression was more viscous than juice prepared from control fruit.

  4. Effects of dietary resveratrol supplementation on hepatic and serum pro-/anti-inflammatory activity in juvenile GIFT tilapia, Oreochromis niloticus.

    PubMed

    Zheng, Yao; Zhao, Zhixiang; Wu, Wei; Song, Chao; Meng, Shunlong; Fan, Limin; Bing, Xuwen; Chen, Jiazhang

    2017-08-01

    Dietary resveratrol (RES) supplementation may have some pharmacological effects including anti-inflammation. Previous studies have shown that Kupffer cell activation and apoptosis induction increases the transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities of 0.1 or 0.3 g/kg RES as a dietary supplement in juvenile freshwater tilapia (Oreochromis niloticus). The results showed that hepatic and serum immunoglobulin M (IgM) significantly decreased and increased while anti- and pro-inflammatory cytokines significantly increased and decreased, respectively, in the RES-treated groups. The expression of serum and hepatic IgM and anti-inflammatory cytokines [interleukin (IL)-10] and its inverse inhibitor interferon (IFN)-γ significantly increased while pro-inflammatory cytokine transcription significantly decreased. Hematoxylin-eosin staining and scanning electron microscopy revealed intestinal deformation, irregular goblet cells, and apoptotic cells in the 0.3 g/kg RES groups. RES (0.3 g/kg) also induced necrosis, apoptosis, reduction in Kupffer cell number, compressed sinusoids, and deformation of epidermal cells in the liver of the treated groups. In conclusion, the results of the present study show that high doses of RES were absorbed in the gut and then damaged the liver and intestinal tissue. Copyright © 2017. Published by Elsevier Ltd.

  5. P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate

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

    Jia, Yongming

    The purpose of present study was to investigate the effect of resveratrol (Res) on altering methotrexate (MTX) pharmacokinetics and clarify the related molecular mechanism. Res significantly increased rat intestinal absorption of MTX in vivo and in vitro. Simultaneously, Res inhibited MTX efflux transport in MDR1-MDCK and MRP2-MDCK cell monolayers, suggesting that the target of drug interaction was MDR1 and MRP2 in the intestine during the absorption process. Furthermore, there was a significant decrease in renal clearance of MTX after simultaneous intravenous administration. Similarly, MTX uptake was markedly inhibited by Res in rat kidney slices and hOAT1/3-HEK293 cell, indicating that OAT1more » and OAT3 were involved in the drug interaction in the kidney. Additionally, concomitant administration of Res decreased cytotoxic effects of MTX in hOAT1/3-HEK293 cells, and ameliorated nephrotoxicity caused by MTX in rats. Conversely, intestinal damage caused by MTX was not exacerbated after Res treatment. In conclusion, Res enhanced MTX absorption in intestine and decreased MTX renal elimination by inhibiting P-gp, MRP2, OAT1 and OAT3 in vivo and in vitro. Res improved MTX-induced renal damage without increasing intestinal toxicity. - Highlights: • DDI between MTX and Res will occur when they are co-administered. • The first targets of the DDI are P-gp and MRP2 located in intestine. • The second targets of the DDI are OAT1 and OAT3 in kidney. • Res improved MTX-induced renal damage without increasing intestinal toxicity.« less

  6. Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines

    PubMed Central

    Caughey, Winslow S.; Raymond, Lynne D.; Horiuchi, Motohiro; Caughey, Byron

    1998-01-01

    A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC50 values of 0.5–1 μM in scrapie-infected mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects on protein biosynthesis in general or PrP-sen biosynthesis in particular. Tetrapyrroles also inhibited PrP-res formation in a cell-free reaction composed predominantly of hamster PrP-res and PrP-sen. Inhibitors were found among phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples included compounds containing anionic, neutral protic, and cationic peripheral substituents and various metals. We conclude that certain tetrapyrroles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects. The inhibition observed in the cell-free conversion reaction suggests that the mechanism involved direct interactions of the tetrapyrrole with PrP-res and/or PrP-sen. These findings introduce a new class of inhibitors of PrP-res formation that represents a potential source of therapeutic agents for transmissible spongiform encephalopathies. PMID:9770449

  7. Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer

    PubMed Central

    Chen, Xiulan; Wei, Shasha; Ma, Ying; Lu, Jie; Niu, Gang; Xue, Yanhong; Chen, Xiaoyuan; Yang, Fuquan

    2014-01-01

    Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOP1MT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. PMID:25285166

  8. Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

    PubMed

    Crook, J; Hendrickson, A; Robinson, F R

    2006-09-15

    Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density of 120 cells/linear mm. Their morphology indicates that they include Golgi and Lugaro cell types with the majority containing both glycine and GABA or glutamic acid decarboxylase. These data are consistent with the proposal that, as in the rat cerebellum, these granular cell layer interneurons corelease glycine and GABA in the primate cerebellum. The patterns of labeling for glycine and GABA within Golgi and Lugaro cells also indicate that there are biochemical sub-types which are morphologically similar. Further, we find that glycine, GABA and glutamic acid decarboxylase identified candelabrum cells adjacent to the Purkinje cells which is the first time that this interneuron has been reported in primate cerebellar cortex. We propose that candelabrum cells, like the majority of Golgi and Lugaro cells, release both glycine and GABA.

  9. Liquid Chromatographic Analysis of the Free Sugars in Sweet Corn: a Method Indicative of Maturity and of Quality Changes Related to Processing Techniques

    DTIC Science & Technology

    1977-07-01

    F. Flora and R. C. Wiley, J . Food Scl., 39, 770 (1974). 2G. Rumpf, J . Mawson and H. Hansen, J . Sci. Food Agric., 23, 193 (1972). L Hough and J . K. N...Clamp, T . Bhatti and R. E. Chambers, Methods Biochem. Anal., 19, 229 (1971). 11 J . M. Richey, H. G. Richey, Jr. and R. Schraer, Analyt. Biochem., 9...C W Culpepper and C, A. Magoon, J . Agr. Res., 28, 403 (1924). -0. M Doty, G. M. Smith, J . R. Roach and J . T . Sullivan, Indiana Agr. Exp. Sta. Bull

  10. Expression and characterization of the Plasmodium translocon of the exported proteins component EXP2.

    PubMed

    Hakamada, Kazuaki; Watanabe, Hirokazu; Kawano, Ryuji; Noguchi, Keiichi; Yohda, Masafumi

    2017-01-22

    The malaria parasite Plasmodium falciparum requires the Plasmodium translocon of exported proteins (PTEX) to proliferate in human red blood cells. During the blood stages of malaria, several hundred parasite-encoded proteins are exported from the parasite into the cytosol of red blood cells. PTEX is the translocon for protein export and comprises 5 proteins: EXP2, PTEX150, PTEX88, Hsp101 and TRX2. Among them, EXP2 is thought to constitute the transmembrane pore, whereas the other components seem to play a role in unfolding the luggage proteins or providing a driving force. However, detailed functional and structural characterizations of PTEX proteins have not been performed. In this study, we expressed and characterized the membrane-associated component EXP2. Because expression of EXP2 is lethal to E. coli, EXP2 was expressed as a fusion protein with GST, and the recombinant EXP2 was obtained by protease digestion. The recombinant EXP2 formed pores in bilayer lipid membranes. The inner diameter of the pore was estimated to be approximately 3.5 nm based on electron microscopy images and channel currents. From this size and the molecular mass as determined by size exclusion chromatography and blue native polyacrylamide gel electrophoresis, we determined that the pore comprises approximately 10-12 EXP2 subunits. However, there is a possibility that the pore structure is different in the PTEX complex. These results provide important insights in the protein transport mechanism of PTEX, which will aid in developing new drugs targeting PTEX. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Trafficking Microenvironmental pHs of Polycationic Gene Vectors in Drug-Sensitive and Multidrug-Resistant MCF7 Breast Cancer Cells

    PubMed Central

    Kang, Han Chang; Samsonova, Olga; Bae, You Han

    2010-01-01

    While multidrug resistance (MDR) has been a significant issue in cancer chemotherapy, delivery resistance to various anticancer biotherapeutics, including genes, has not been widely recognized as a property of MDR. This study aims to provide a better understanding of the transfection characteristics of drug-sensitive and drug-resistant cells by tracing microenvironmental pHs of two representative polymer vectors: poly(l-lysine) and polyethyleneimine. Drug-sensitive breast MCF7 cells had four- to seven-times higher polymeric transfection efficiencies than their counterpart drug-resistant MCF7/ADR-RES cells. Polyplexes in MCF7/ADR-RES cells after endocytosis were exposed to a more acidic microenvironment than those in MCF7 cells; the MDR cells show faster acidification rates in endosomes/lysosomes than the drug-sensitive cells after endocytosis (in the case of PLL/pDNA complexes, ~ pH 5.1 for MCF7/ADR-RES cells vs. ~ pH 6.8 for MCF7 cells at 0.5 hr post-transfection). More polyplexes were identified trapped in acidic subcellular compartments of MCF7/ADR-RES cells than in MCF7 cells, suggesting that they lack endosomal escaping activity. These findings demonstrate that the design of polymer-based gene delivery therapeutics should take into account the pH of subcellular compartments. PMID:20092888

  12. The Orbiting Wide-Angle Light Collectors (OWL) Mission for Charged-Particle Astronomy

    NASA Technical Reports Server (NTRS)

    Mitchell, John; Krizmanic, J. F.; Stecker, F. W.; Streitmatter, R. E.

    2009-01-01

    The space-based OWL mission is designed to perform high-statistics measurements of ultra-high-energy cosmic rays (UHECR) using the Earth's atmosphere as a vast particle calorimeter, furthering the field of charged-particle astronomy. OWL has been developed in formal NASA instrument and mission studies and is comprised of two large telescopes separated by approx.600 km in 1000 km, near-equatorial orbits to stereoscopically image the near-UV air fluorescence emitted by UHECR-induced particle cascades. The High Resolution Fly's Eye (HiRes) Collaboration, and subsequently the Pierre Auger Observatory, recently reported confirmation of the expected Greisen-Zatsepin-Kuzmin (GZK) suppression of the UHECR flux above a few times 10(exp 19) eV. This observation is consistent with the majority of UHECR originating in astrophysical objects and reduces the need to invoke exotic physical processes. Particles observed above the GZK threshold energy must have come from sources within about 100 Mpc from the Earth. The small particle deflection angles expected at UHECR energies, with standard assumptions of extragalactic magnetic fields, are on the order of 1 degree. Thus by observing particles above the GZK threshold with sufficient exposure, there is the potential of identifying and characterizing individual UHECR sources. Auger has reported significant anisotropy in the arrival directions of UHECR at energies above about 6 10(exp 19) eV observed in the South, and a correlation to AGN in the 12th VCV catalog, suggesting that the sources of UHECR are traced by the distribution of luminous matter in the Universe. However, with similar statistics and the same event selection criteria, HiRes observations in the North are consistent with isotropy. Extended observations by Auger-South, by Telescope Array in the North, and possibly by the proposed Auger-North, will further these investigations. However, much greater exposures will be required to fully identify individual sources and measure their cosmic ray spectra. A five-year OWL mission would deliver approximately 10(exp 6)sq km/sr/yr of exposure with full aperture reached at approx. 10(exp 19) eV. The baseline 3 m optical aperture OWL telescopes with 45 degree full field-of-view are easily accomodated on a single conventional launch vehicle. On orbit, the simultaneous viewing of the same volume of atmosphere allows for precise stereo event reconstruction, which is nearly independent of the inclination of the particle track and tolerant of atmospheric conditions. The availability of monocular operation provides increased reliability or can be employed to increase the instantaneous aperture. In stereo mode, OWL is also capable of fully reconstructing horizontal or upward-moving showers and so has unmatched sensitivity to neutrino-induced events. The details of the OWL mission will he presented and its science capabilities will be discussed.

  13. [Apoptosis mechanism of taxol combined with resveratrol on human laryngeal carcinoma Hep-2 cells].

    PubMed

    Lu, Chen-Xin; Sun, Jing-Hui; Wu, Chun-Lian

    2016-02-01

    Laryngeal cancer is one of the most common malignant tumors in the respiratory tumors, and its incidence ranks second highest in the respiratory tumors. Resveratrol (Res) is a kind of polyphenols, which can inhibit nucleotides can inhibit the growth of liver cancer cells, gastric cancer cells, pancreatic cells and other tumor cells by inhibiting ribonucleotide reductase in the cells. Taxol (Tax) is a kind of secondary metabolites of Taxus chinensis, which has anti-tumor activity for breast cancer, cervical cancer, ovarian cancer and other tumors by inhibiting cellular microtubule depolymerization. But at present the effects of resveratrol combined with taxol on human laryngeal carcinoma cell strain Hep-2 and their underlying molecular mechanisms are rarely reported. After human laryngeal cancer cell Hep-2 cells were processed with resveratrol (Res) and taxol (Tax), CCK-8 assay was used to evaluate the effect of these two herbs on the proliferation of cancer cells; AO/PI staining and JC-1 were used to detect Hep-1 cells apoptosis; the expression of Bax, Bcl-2, PARP, TRIB3, and XIAP genes was detected by real time quantitative PCR; the activity of caspase-3 and caspase-8 was determined with quantitative fluorescence method. The experimental results showed that compared with Tax, Res medication alone, joint group significantly enhanced inhibition of Hep-2 cells activity, decreased the dosage of Tax, increased the expression of Bax and PARP, TRIB3, reduced the expression of the Bcl-2 and XIAP, and promoted the activity of caspase-3 and caspase-8. The test results showed that compared with the single medication, combined group could significantly increase the inhibitory effect on Hep-2 cells, significantly reduce Tax dosage, increase expressions of Bax, PARP, TRIB3, reduce expressions of Bcl-2, XIAP, and promote activity of caspase-3, caspase-8. This indicated apoptosis of human laryngeal carcinoma cell strain Hep-2 may be induced with Res, Tax, and the combination of these two herbs by mitochondria pathway. It provides valuable clue for further research on combination of Res and Tax for the treatment of laryngeal cancer, and expanding the combined application of Res and Tax. Copyright© by the Chinese Pharmaceutical Association.

  14. Ozone Correction for AM0 Calibrated Solar Cells for the Aircraft Method

    NASA Technical Reports Server (NTRS)

    Snyder, David B.; Scheiman, David A.; Jenkins, Phillip P.; Rieke, William J.; Blankenship, Kurt S.

    2002-01-01

    The aircraft solar cell calibration method has provided cells calibrated to space conditions for 37 years. However, it is susceptible to systematic errors due to ozone concentrations in the stratosphere. The present correction procedure applies a 1 percent increase to the measured I(sub SC) values. High band-gap cells are more sensitive to ozone absorbed wavelengths (0.4 to 0.8 microns) so it becomes important to reassess the correction technique. This paper evaluates the ozone correction to be 1+O3xFo, where O3 is the total ozone along the optical path, and Fo is 29.8 x 10(exp -6)/du for a Silicon solar cell, 42.6 x 10(exp -6)/du for a GaAs cell and 57.2 x 10(exp -6)/du for an InGaP cell. These correction factors work best to correct data points obtained during the flight rather than as a correction to the final result.

  15. Inhibition of RAD51 by siRNA and Resveratrol Sensitizes Cancer Stem Cells Derived from HeLa Cell Cultures to Apoptosis

    PubMed Central

    Ruíz, Graciela; Valencia-González, Heriberto A.; León-Galicia, Ismael; García-Villa, Enrique

    2018-01-01

    Cervical cancer is the second most frequent tumor type in women worldwide with cases developing clinical recurrence, metastasis, and chemoresistance. The cancer stem cells (CSC) may be implicated in tumor resistance to therapy. RESveratrol (RES), a natural compound, is an antioxidant with multiple beneficial activities. We previously determined that the expression of RAD51 is decreased by RES. The aim of our study was to examine molecular mechanism by which CSC from HeLa cultures exhibit chemoresistance. We hypothesized CSC repair more efficiently DNA breaks and that RAD51 plays an important role in this mechanism. We found that CSC, derived from cervical cancer cell lines, overexpress RAD51 and are less sensitive to Etoposide (VP16). We inhibited RAD51 in CSC-enriched cultures using RES or siRNA against RAD51 messenger RNA and observed a decrease in cell viability and induction of apoptosis when treated simultaneously with VP16. In addition, we found that inhibition of RAD51 expression using RES also sensitizes CSC to VP16 treatment. Our results suggest that resveratrol is effective to sensitize cervical CSC because of RAD51 inhibition, targeting high RAD51 expressing CD49f-positive cells, which supports the possible therapeutic application of RES as a novel agent to treat cancer. PMID:29681946

  16. Electron-irradiated two-terminal, monolithic InP/Ga0.47In0.53As tandem solar cells and annealing of radiation damage

    NASA Technical Reports Server (NTRS)

    Cotal, H. L.; Walters, Robert J.; Summers, Geoffrey P.; Messenger, Scott R.

    1994-01-01

    Radiation damage results from two-terminal monolithic InP/Ga(0.47)In(0.53)As tandem solar cells subject to 1 MeV electron irradiation are presented. Efficiencies greater than 22 percent have been measured by the National Renewable Energy Laboratory from 2x2 sq cm cells at 1 sun, AMO (25 C). The short circuit current density, open circuit voltage and fill factor are found to tolerate the same amount of radiation at low fluences. At high fluence levels, slight differences are observed. Decreasing the base amount of radiation at the Ga(0.47)In(0.53)As bottomcell improved the radiation resistance of J(sub sc) dramatically. This is turn, extended the series current flow through the subcell substantially up to a fluence of 3x10(exp 15) cm(exp -2) compared to 3x10(exp 14) cm(exp -2), as observed previously. The degradation of the maximum power output form tandem device is comparable to that from shallow homojunction (SHJ) InP solar cells, and the mechanism responsible for such degradation is explained in terms of the radiation response of the component cells. Annealing studies revealed that the recovery of the tandem cell response is dictated by the annealing characteristics exhibited by SHJ InP solar cells.

  17. Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin Chemosensitivity in NCI/ADR-RES Ovarian Cancer Cells via Inhibition of P-glycoprotein Expression.

    PubMed

    Choi, Hyeong Sim; Cho, Sung-Gook; Kim, Min Kyoung; Kim, Min Soo; Moon, Seung Hee; Kim, Il Hwan; Ko, Seong-Gyu

    2016-12-01

    Angelica gigas Nakai (AGN, Korean Dang-gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug-resistant phenotype-reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin-resistant NCI/ADR-RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR-RES cells. These combinations increased the number of cells at sub-G1 phase when cells were stained with Annexin V-fluorescein isothiocyanate. We also found that these combinations activated caspase-9, caspase-8, and caspase-3 and increased cleaved PARP level. Moreover, an inhibition of P-glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR-RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin-resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P-glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug-resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways

    PubMed Central

    Singh, Bhupendra; Shoulson, Rivka; Chatterjee, Anwesha; Ronghe, Amruta; Bhat, Nimee K.; Dim, Daniel C.; Bhat, Hari K.

    2014-01-01

    The importance of estrogens in the etiology of breast cancer is widely recognized. Estrogen-induced oxidative stress has been implicated in this carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has chemopreventive effects against a variety of illnesses including cancer. The objective of the present study was to characterize the mechanism(s) of Res-mediated protection against estrogen-induced breast carcinogenesis. Female August Copenhagen Irish rats were treated with 17β-estradiol (E2), Res and Res + E2 for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated proliferative changes in mammary tissues and significantly increased tumor latency and reduced E2-induced breast tumor development. Resveratrol treatment alone or in combination with E2 significantly upregulated expression of nuclear factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of NRF2-regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in protection against oxidative DNA damage was increased in Res- and Res + E2-treated mammary tissues. Resveratrol also prevented E2-mediated inhibition of detoxification genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 promoter methylation and expression of NRF2 targeting miR-93 after Res treatment indicated Res-mediated epigenetic regulation of NRF2 during E2-induced breast carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited E2-mediated increase in DNA damage in mammary tissues. Increased apoptosis and decreased DNA damage, cell migration, colony and mammosphere formation in Res- and Res + E2-treated MCF-10A cells suggested a protective role of Res against E2-induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of NRF2 inhibited Res-mediated preventive effects on the colony and mammosphere formation. Taken together, these results suggest that Res inhibits E2-induced breast carcinogenesis via induction of NRF2-mediated protective pathways. PMID:24894866

  19. 75 FR 11185 - Submission for OMB Review; Comment Request; Reinstatement of OMB No. 0925-0601/exp. 02/28/2010...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ...; Comment Request; Reinstatement of OMB No. 0925-0601/exp. 02/28/2010, Request for Human Embryonic Stem Cell... period seeking public comment for an information collection entitled ``Request for Human Embryonic Stem Cell Line to be Approved for Use in NIH Funded Research''. In the second paragraph of the notice...

  20. A regulatory network to segregate the identity of neuronal subtypes.

    PubMed

    Lee, Seunghee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L; Lee, Jae W; Lee, Soo-Kyung

    2008-06-01

    Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

  1. Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects.

    PubMed

    Ashby, J; Tinwell, H; Pennie, W; Brooks, A N; Lefevre, P A; Beresford, N; Sumpter, J P

    1999-01-01

    It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity of RES was speculated to be relevant to the 'French paradox' in which moderate red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isolated from rat uterus with an affinity approximately 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DES) or oestradiol (E2). In comparison with E2 or DES, RES is only a weak and partial agonist in a yeast hER-alpha transcription assay and in cos-1 cell assays employing transient transfections of ER-alpha or ER-beta associated with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three daily administrations of 0.03-120 mgkg(-1)/day(-1) RES (administered by either oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regarding the extent to which oestrogenicity data derived for a chemical using MCF-7 cells (or any other single in vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans.

  2. Scanning electron microscopy study of neutrophil membrane tubulovesicular extensions (cytonemes) and their role in anchoring, aggregation and phagocytosis. The effect of nitric oxide

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

    Galkina, Svetlana I.; Molotkovsky, Julian G.; Ullrich, Volker

    2005-04-01

    We have shown that human neutrophils develop dynamic thin and very long tubulovesicular extensions (cytonemes) upon adhesion to fibronectin, if cell spreading was blocked by Na{sup +}-free medium or by 4-bromophenacyl bromide, N-ethylmaleimide, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and cytochalasin D (S. I. Galkina, G. F. Sud'ina and V. Ullrich (2001). Exp. Cell Res. 266, 222-228). In the present work we found that similar in size and behavior tubulovesicular extensions were formed on the neutrophil cell bodies upon adhesion to fibronectin-coated substrata in the presence of the nitric oxide donor diethylamine NONOate. In the presence of the nitric oxide synthase inhibitor N-{omega}-nitro-L-arginine methyl ester,more » neutrophils were well spread and had no microextensions. Using scanning electron microscopy, we demonstrated that tubulovesicular extensions of neutrophils executed long-range adhesion and binding objects for phagocytosis, such as serum-opsonized zymosan particles and erythrocytes. Tubulovesicular extensions anchored neutrophils to substrata in a {beta}1 and {beta}2 integrin-independent, but L-selectin-dependent manner. BODIPY-sphingomyelin impaired development of tubulovesicular extension, and heparitinase 1 played a role in their destruction. Membrane tubulovesicular extensions are supposed to represent protrusions of an intracellular exocytotic traffic and serve as cellular sensory and adhesive organelles. Nitric oxide seems to play a role in regulation of tubulovesicular extensions formation, thus affecting neutrophil adhesive interactions and phagocytosis.« less

  3. Evaluation of free radical scavenging capacity and antioxidative damage effect of resveratrol-nanostructured lipid carriers

    NASA Astrophysics Data System (ADS)

    Jin, Ju; Shi, Fan; Li, Qiu-wen; Li, Pei-shan; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Cellular damage induced by free-radicals like reactive oxygen species has been implicated in several diseases. 2, 2-azobis(2-amidino-propane) dihydrochloride(AAPH) generates two potent ROS capable of inducing lipid peroxidation: alkoxy radical(RO-) and peroxy radical(ROO-). These radicals are similar to those that are physiologically active and thus might initiate a cascade of intracellular toxic events leading to oxidation, lipid peroxidation, DNA damage and subsequent cell death. Hence naturally anti-oxidant play a vital role in combating these conditions. In this study, resveratrol loaded nanostructured lipid carriers (Res-NLC) was prepared by hot melting and then high pressure homogenization technique. The effects of Res-NLC on free radical scavenging capacity and antioxidative damage is investigated. The particle size and zeta potential of Res-NLC were 139.3 ± 1.7 nm and -11.21 ± 0.41 mV, respectively. By free radical scavenging assays, the IC50 value of Res-NLC were 19.25, 5.29 μg/mL with DPPH, ABTS assay respectively, and 0.161 mg ferrous sulfate/1 mg Res-NLC with FRAP assay; and by AAPH-induced oxidative injury cell model assay, Res-NLC showed the strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicated that the antioxidant properties of Res-NLC hold great potential used as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetic and pharmaceutical preparations for the oxidative diseases treatment.

  4. Precise small molecule recognition of a toxic CUG RNA repeat expansion

    PubMed Central

    Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

    2017-01-01

    Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

  5. Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

    PubMed

    Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

    2017-02-01

    Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

  6. A very low resistance, non-sintered contact system for use on indium phosphide concentrator/shallow junction solar cells

    NASA Technical Reports Server (NTRS)

    Weizer, Victor G.; Fatemi, Navid S.

    1991-01-01

    An investigation is made into the possibility of providing low resistance contacts to shallow junction InP solar cells which do not require sintering and which do not cause device degradation even when subjected to extended annealing at elevated temperatures. We show that the addition of In to Au contacts in amounts that exceed the solid solubility limit lowers the as-fabricated (unsintered) contact resistivity (R sub c) to the 10(exp -5) ohm cm(exp 2) range. We next consider the contact system Au/Au2P3 which has been shown to exhibit as-fabricated R sub c values in the 10(exp -6) ohm cm(exp 2) range, but which fails quickly when heated. We show that the substitution of a refractory metal (W, Ta) for Au preserves the low R sub c values while preventing the destructive reactions that would normally take place in this system at high temperatures. We show, finally, that R sub c values in the 10(exp -7) ohm cm(exp 2) range can be achieved without sintering by combining the effects of In or Ga additions to Au contacts with the effects of introducing a thin Au2P3 layer at the metal-InP interface.

  7. Plant phenolic volatiles inhibit quorum sensing in pectobacteria and reduce their virulence by potential binding to ExpI and ExpR proteins

    NASA Astrophysics Data System (ADS)

    Joshi, Janak Raj; Khazanov, Netaly; Senderowitz, Hanoch; Burdman, Saul; Lipsky, Alexander; Yedidia, Iris

    2016-12-01

    Quorum sensing (QS) is a population density-dependent regulatory system in bacteria that couples gene expression to cell density through accumulation of diffusible signaling molecules. Pectobacteria are causal agents of soft rot disease in a range of economically important crops. They rely on QS to coordinate their main virulence factor, production of plant cell wall degrading enzymes (PCWDEs). Plants have evolved an array of antimicrobial compounds to anticipate and cope with pathogens, of which essential oils (EOs) are widely recognized. Here, volatile EOs, carvacrol and eugenol, were shown to specifically interfere with QS, the master regulator of virulence in pectobacteria, resulting in strong inhibition of QS genes, biofilm formation and PCWDEs, thereby leading to impaired infection. Accumulation of the signal molecule N-acylhomoserine lactone declined upon treatment with EOs, suggesting direct interaction of EOs with either homoserine lactone synthase (ExpI) or with the regulatory protein (ExpR). Homology models of both proteins were constructed and docking simulations were performed to test the above hypotheses. The resulting binding modes and docking scores of carvacrol and eugenol support potential binding to ExpI/ExpR, with stronger interactions than previously known inhibitors of both proteins. The results demonstrate the potential involvement of phytochemicals in the control of Pectobacterium.

  8. A very low resistance, non-sintered contact system for use on indium phosphide concentrator/shallow junction solar cells

    NASA Technical Reports Server (NTRS)

    Weizer, Victor G.; Fatemi, Navid S.

    1991-01-01

    An investigation is made into the possibility of providing low resistance contacts to shallow junction InP solar cells which do not require sintering and which do not cause device degradation even when subjected to extended annealing at elevated temperatures. We show that the addition of In to Au contacts in amounts that exceed the solid solubility limit lowers the as-fabricated (unsintered) contact resistivity (R sub c) to the 10(exp -5) ohm cm(exp 2) range. We next consider the contact system Au/Au2P3, which has been shown to exhibit as-fabricated R sub c values in the 10(exp -6) ohm cm(exp 2) range, but which fails quickly when heated. We show that the substitution of a refractory metal (W, Ta) for Au preserves the low R sub c values while preventing the destructive reactions that would normally take place in this system at high temperatures. We show, finally, that R sub c values in the 10(exp -7) ohm cm(exp 2) range can be achieved without sintering by combining the effects of In or Ga additions to Au contacts with the effects of introducing a thin Au2P3 layer at the metal-InP interface.

  9. Low-Temperature Rate Coefficients of C2H with CH4 and CD4 from 154 to 359 K

    NASA Technical Reports Server (NTRS)

    Opansky, Brian J.; Leone, Stephen R.

    1996-01-01

    Rate coefficients for the reaction C2H + CH4 yields C2H2 + CH3 and C2H + CD4 yields C2HD + CD3 are measured over the temperature range 154-359 K using transient infrared laser absorption spectroscopy. Ethynyl radicals are produced by pulsed laser photolysis of C2H2 in a variable temperature flow cell, and a tunable color center laser probes the transient removal of C2H (Chi(exp 2) Sigma(+) (0,0,0)) in absorption. The rate coefficients for the reactions of C2H with CH4 and CD4 both show a positive temperature dependence over the range 154-359 K, which can be expressed as k(sub CH4) = (1.2 +/- 0.1) x 10(exp -11) exp((-491 +/- 12)/T) and k(sub CD4) = (8.7 +/- 1.8) x 10(exp -12) exp((-650 +/- 61)/T) cm(exp 3) molecule(exp -1) s(exp -1), respectively. The reaction of C2H + CH4 exhibits a significant kinetic isotope effect at 300 K of k(sub CH4)/k(sub CD4) = 2.5 +/- 0.2. Temperature dependent rate constants for C2H + C2H2 were also remeasured over an increased temperature range from 143 to 359 K and found to show a slight negative temperature dependence, which can be expressed as k(sub C2H2) = 8.6 x 10(exp -16) T(exp 1.8) exp((474 +/- 90)/T) cm(exp 3) molecule(exp -1) s(exp -1).

  10. Quorum sensing in the plant pathogen Erwinia carotovora subsp. carotovora: the role of expR(Ecc).

    PubMed

    Andersson, R A; Eriksson, A R; Heikinheimo, R; Mäe, A; Pirhonen, M; Kõiv, V; Hyytiäinen, H; Tuikkala, A; Palva, E T

    2000-04-01

    The production of the main virulence determinants of the plant pathogen Erwinia carotovora subsp. carotovora, the extracellular cell wall-degrading enzymes, is partly controlled by the diffusible signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). OHHL is synthesized by the product of the expI/carI gene. Linked to expI we found a gene encoding a putative transcriptional regulator of the LuxR-family. This gene, expR(Ecc), is transcribed convergently to the expI gene and the two open reading frames are partially overlapping. The ExpR(Ecc) protein showed extensive amino acid sequence similarity to the repressor EsaR from Pantoea stewartii subsp. stewartii (formerly Erwinia stewartii subsp. stewartii) and to the ExpR(Ech) protein of Erwinia chrysanthemi. Inactivation of the E. carotovora subsp. carotovora expR(Ecc) gene caused no decrease in virulence or production of virulence determinants in vitro. In contrast, there was a slight increase in the maceration capacity of the mutant strain. The effects of ExpR(Ecc) were probably mediated by changes in OHHL levels. Inactivation of expR(Ecc) resulted in increased OHHL levels during early logarithmic growth. In addition, overexpression of expR(Ecc) caused a clear decrease in the production of virulence determinants and part of this effect was likely to be caused by OHHL binding to ExpR(Ecc). ExpR(Ecc) did not appear to exhibit transcriptional regulation of expI, but the effect on OHHL was apparently due to other mechanisms.

  11. Obesity alters immune and metabolic profiles: new insight from obese-resistant mice on high fat diet

    PubMed Central

    Boi, Shannon K.; Buchta, Claire M.; Pearson, Nicole A.; Francis, Meghan B.; Meyerholz, David K.; Grobe, Justin L.; Norian, Lyse A.

    2016-01-01

    Objective Diet-induced obesity has been shown to alter immune function in mice, but distinguishing the effects of obesity from changes in diet composition is complicated. We hypothesized that immunological differences would exist between diet-induced obese (DIO) and obese-resistant (OB-Res) mice fed the same high-fat diet (HFD). Methods BALB/c mice were fed either standard chow or HFD to generate lean or DIO and OB-Res mice, respectively. Resulting mice were analyzed for serum immunologic and metabolic profiles, and cellular immune parameters. Results BALB/c mice on HFD can be categorized as DIO or OB-Res, based on body weight versus lean controls. DIO mice are physiologically distinct from OB-Res mice, whose serum Insulin, Leptin, GIP, and Eotaxin concentrations remain similar to lean controls. DIO mice have increased macrophage+ crown-like structures in white adipose tissue, although macrophage percentages were unchanged from OB-Res and lean mice. DIO mice also have decreased splenic CD4+ T cells, elevated serum GM-CSF, and increased splenic CD11c+ dendritic cells, but impaired dendritic cell stimulatory capacity (p < 0.05 versus lean controls). These parameters were unaltered in OB-Res mice versus lean controls. Conclusions Diet-induced obesity results in alterations in immune and metabolic profiles that are distinct from effects caused by HFD alone. PMID:27515998

  12. Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage/resuscitation.

    PubMed

    Fruchterman, T M; Spain, D A; Wilson, M A; Harris, P D; Garrison, R N

    1998-10-01

    Complement, a nonspecific immune response, is activated during hemorrhage/resuscitation (HEM/RES) and is involved in cellular damage. We hypothesized that activated complement injures endothelial cells (ETCs) and is responsible for intestinal microvascular hypoperfusion after HEM/RES. Four groups of rats were studied by in vivo videomicroscopy of the intestine: SHAM, HEM/RES, HEM/RES + sCR1 (complement inhibitor, 15 mg/kg intravenously given before resuscitation), and SHAM + sCR1. Hemorrhage was to 50% of mean arterial pressure for 60 minutes followed by resuscitation with shed blood plus an equal volume of saline. ETC function was assessed by response to acetylcholine. Resuscitation restored central hemodynamics to baseline after hemorrhage. After resuscitation, inflow A1 and premucosal A3 arterioles progressively constricted (-24% and -29% change from baseline, respectively), mucosal blood flow was reduced, and ETC function was impaired. Complement inhibition prevented postresuscitation vasoconstriction and gut ischemia. This protective effect appeared to involve preservation of ETC function in the A3 vessels (SHAM 76% of maximal dilation, HEM/RES 61%, HEM/RES + sCR1 74%, P < .05). Complement inhibition preserved ETC function after HEM/RES and maintained gut perfusion. Inhibition of complement activation before resuscitation may be a useful adjunct in patients experiencing major hemorrhage and might prevent the sequelae of gut ischemia.

  13. Abilities in tactile discrimination of textures in adult rats exposed to enriched or impoverished environments.

    PubMed

    Bourgeon, Stéphanie; Xerri, Christian; Coq, Jacques-Olivier

    2004-08-12

    In previous studies, we have shown that housing in enriched environment for about 3 months after weaning improved the topographic organization and decreased the size of the receptive fields (RFs) located on the glabrous skin surfaces in the forepaw maps of the primary somatosensory cortex (SI) in rats [Exp. Brain Res. 121 (1998) 191]. In contrast, housing in impoverished environment induced a degradation of the SI forepaw representation, characterized by topographic disruptions, a reduction of the cutaneous forepaw area and an enlargement of the glabrous RFs [Exp. Brain Res. 129 (1999) 518]. Based on these two studies, we postulated that these representational alterations could underlie changes in haptic perception. Therefore, the present study was aimed at determining the influence of housing conditions on the rat's abilities in tactile texture discrimination. After a 2-month exposure to enriched or impoverished environments, rats were trained to perform a discrimination task during locomotion on floorboards of different roughness. At the end of every daily behavioral session, rats were replaced in their respective housing environment. Rats had to discriminate homogeneous (low roughness) from heterogeneous floorboards (combination of two different roughness levels). To determine the maximum performance in texture discrimination, the roughness contrast of the heterogeneous texture was gradually reduced, so that homogeneous and heterogeneous floorboards became harder to differentiate. We found that the enriched rats learned the first steps of the behavioral task faster than the impoverished rats, whereas both groups exhibited similar performances in texture discrimination. An individual "predilection" for either homogeneous or heterogeneous floorboards, presumably reflecting a behavioral strategy, seemed to account for the absence of differences in haptic discrimination between groups. The sensory experience depending on the rewarded texture discrimination task seems to have a greater influence on individual texture discrimination abilities than the sensorimotor experience related to housing conditions.

  14. In vivo levels of diadenosine tetraphosphate and adenosine tetraphospho-guanosine in Physarum polycephalum during the cell cycle and oxidative stress.

    PubMed Central

    Garrison, P N; Mathis, S A; Barnes, L D

    1986-01-01

    Cellular levels of diadenosine tetraphosphate (Ap4A) and adenosine tetraphospho-guanosine (Ap4G) were specifically measured during the cell cycle of Physarum polycephalum by a high-pressure liquid chromatographic method. Ap4A was also measured indirectly by a coupled phosphodiesterase-luciferase assay. No cell cycle-specific changes in either Ap4A or Ap4G were detected in experiments involving different methods of assay, different strains of P. polycephalum, or different methods of fixation of macroplasmodia. Our results on Ap4A are in contrast with those reported previously (C. Weinmann-Dorsch, G. Pierron, R. Wick, H. Sauer, and F. Grummt, Exp. Cell Res. 155:171-177, 1984). Weinmann-Dorsch et al. reported an 8- to 30-fold increase in Ap4A in early S phase in P. polycephalum, as measured by the phosphodiesterase-luciferase assay. We also measured levels of Ap4A, Ap4G, and ATP in macroplasmodia treated with 0.1 mM dinitrophenol. Ap4A and Ap4G transiently increased three- to sevenfold after 1 h and then decreased concomitantly with an 80% decrease in the level of ATP after 2 h in the presence of dinitrophenol. These results do not support the hypothesis that Ap4A is a positive pleiotypic activator that modulates DNA replication, but they are consistent with the hypothesis proposed for procaryotes that Ap4A and Ap4G are signal nucleotides or alarmones of oxidative stress (B.R. Bochner, P.C. Lee, S.W. Wilson, C.W. Cutler, and B.N. Ames, Cell 37:225-232, 1984). PMID:3785160

  15. Matrix metalloproteinase inhibitors disrupt spicule formation by primary mesenchyme cells in the sea urchin embryo.

    PubMed

    Ingersoll, E P; Wilt, F H

    1998-04-01

    The primary mesenchyme cells of the sea urchin embryo construct an elaborate calcareous endoskeletal spicule beginning at gastrulation. This process begins by ingression of prospective primary mesenchyme cells into the blastocoel, after which they migrate and then fuse to form a syncytium. Skeleton deposition occurs in spaces enclosed by the cytoplasmic cables between the cell bodies. Experiments are described which probe the role of proteases in these early events of spicule formation and their role in the continued elaboration of the spicule during later stages of embryogenesis. We find that several inhibitors of metalloproteinases inhibit the continuation of spiculogenesis, an effect first reported by Roe et al. (Exp. Cell Res. 181, 542-550, 1989). A detailed study of one of these inhibitors, BB-94, shows that fusion of primary mesenchyme cells still occurs in the presence of the inhibitor and the formation of the first calcite granule is not impeded. Continued elaboration of the spicule, however, is completely stopped; addition of the inhibitor during the active elongation of the spicule stops further elongation immediately. Removal of the inhibitor allows resumption of spicule growth. The inhibition is accompanied by almost complete cessation of massive Ca ion transport via the primary mesenchyme cells to the spicule. The inhibitor does not prevent the continued synthesis of several spicule matrix proteins. Electron microscopic examination of inhibited primary mesenchyme cells shows an accumulation of characteristic vesicles in the cytoplasm. Gel zymography demonstrates that although most proteases in homogenates of primary mesenchyme cells are not sensitive to the inhibitor in vitro, a protease of low abundance detectable in the medium of cultured primary mesenchyme cells is inhibited by BB-94. We propose that the inhibitor is interfering with the delivery of precipitated calcium carbonate and matrix proteins to the site(s) of spicule growth. Copyright 1998 Academic Press.

  16. The electrolyte challenge for a direct methanol-air polymer electrolyte fuel cell operating at temperatures up to 200 C

    NASA Technical Reports Server (NTRS)

    Savinell, Robert; Yeager, Ernest; Tryk, Donald; Landau, Uziel; Wainright, Jesse; Gervasio, Dominic; Cahan, Boris; Litt, Morton; Rogers, Charles; Scherson, Daniel

    1993-01-01

    Novel polymer electrolytes are being evaluated for use in a direct methanol-air fuel cell operating at temperatures in excess of 100 C. The evaluation includes tests of thermal stability, ionic conductivity, and vapor transport characteristics. The preliminary results obtained to date indicate that a high temperature polymer electrolyte fuel cell is feasible. For example, Nafion 117 when equilibrated with phosphoric acid has a conductivity of at least 0.4 Omega(exp -1)cm(exp -1) at temperatures up to 200 C in the presence of 400 torr of water vapor and methanol vapor cross over equivalent to 1 mA/cm(exp 2) under a one atmosphere methanol pressure differential at 135 C. Novel polymers are also showing similar encouraging results. The flexibility to modify and optimize the properties by custom synthesis of these novel polymers presents an exciting opportunity to develop an efficient and compact methanol fuel cell.

  17. Design of high-efficiency, radiation-hard, GaInP/GaAs solar cells

    NASA Technical Reports Server (NTRS)

    Kurtz, Sarah R.; Bertness, K. A.; Kibbler, A. E.; Kramer, C.; Olson, J. M.

    1994-01-01

    In recently years, Ga(0.5)In((0.5)P/GaAs cells have drawn increased attention both because of their high efficiencies and because they are well suited for space applications. They can be grown and processed as two-junction devices with roughly twice the voltage and half the current of GaAs cells. They have low temperature coefficients, and have good potential for radiation hardness. We have previously reported the effects of electron irradiation on test cells which were not optimally designed for space. From those results we estimated that an optimally designed cell could achieve 20 percent after irradiation with 10(exp 15) cm(exp -2) 1 MeV electrons. Modeling studies predicted that slightly higher efficiencies may be achievable. Record efficiencies for EOL performance of other types of cells are significantly lower. Even the best Si and InP cells have BOL efficiencies lower than the EOL efficiency we report here. Good GaAs cells have an EOL efficiency of 16 percent. The InP/Ga(0.5)In(0.5)As two-junction, two-terminal device has a BOL efficiency as high as 22.2 percent, but radiation results for these cells were limited. In this study we use the previous modeling and irradiation results to design a set of Ga(0.5)In(0.5)P/GaAs cells that will demonstrate the importance of the design parameters and result in high-efficiency devices. We report record AMO efficiencies: a BOL efficiency of 25.7 percent for a device optimized for BOL performance and two of different designs with EOL efficiencies of 19.6 percent (at 10(exp 15) cm(exp -2) 1MeV electrons). We vary the bottom-cell base doping and the top-cell thickness to show the effects of these two important design parameters. We get an unexpected result indicating that the dopant added to the bottom-cell base also increases the degradation of the top cell.

  18. Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Geng, Le; Wang, Zidun; Cui, Chang; Zhu, Yue; Shi, Jiaojiao; Wang, Jiaxian; Chen, Minglong

    2018-06-15

    Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. On the Discovery of CO Nighttime Emissions on Titan by Cassini/VIMS: Derived Stratospheric Abundances and Geological Implications

    NASA Technical Reports Server (NTRS)

    Bainesa, Kevin H.; Drossart, Pierre; Lopez-Valverde, Miguel A.; Atreya, Sushil K.; Sotin, Christophe; Momary, Thomas W.; Brown, Robert H.; Buratti, Bonnie J.; Clark, Roger N.; Nicholson, Philip D.

    2006-01-01

    We present a quantitative analysis of CO thermal emissions discovered on the nightside of Titan by Baines et al. [2005. The atmospheres of Saturn and Titan in the near-infrared: First results of Cassini/VIMS. Earth, Moon, and Planets, 96, 119-147] in Cassini/VIMS spectral imagery. We identify these emission features as the P and R branches of the 1-0 vibrational band of carbon monoxide (CO) near 4.65 microns. For CH3D, the prominent Q branch of the nu(2) fundamental band of CH3D near 4.55 microns is apparent. CO2 emissions from the strong nu(3) vibrational band are virtually absent, indicating a CO2 abundance several orders of magnitude less than CO, in agreement with previous investigations. Analysis of CO emission spectra obtained over a variety of altitudes on Titan's nightside limb indicates that the stratospheric abundance of CO is 32 +/- 15 ppm, and together with other recent determinations, suggests a vertical distribution of CO nearly constant at this value from the surface throughout the troposphere to at least the stratopause near 300 km altitude. The corresponding total atmospheric content of CO in Titan is similar to 2.9 +/- 1.5 x 10(exp 14) kg. Given the long lifetime of CO in the oxygen-poor Titan atmosphere (similar to 0.5-1.0 Gyr), we find a mean CO atmospheric production rate of 6 +/- 3 x 10(exp 5) kg yr(exp -1). Given the lack of primordial heavy noble gases observed by Huygens [Niemann et al., 2005. The abundances of constituents of Titan's atmosphere from the GCMS on the Huygens probe. Nature, 438, 779-784], the primary source of atmospheric CO is likely surface emissions. The implied CO/CH4 mixing ratio of near-surface material is 1.8 +/- 0.9 x 10(exp -4), based on an average methane surface emission rate over the past 0.5 Gyr of 1.3 x 10(exp -13) gm cm(exp -2) s(exp -1) as required to balance hydrocarbon haze production via methane photolysis [Wilson and Atreya, 2004. Current state of modeling the photochemistry of Titan's mutually dependent atmosphere and ionosphere. J. Geophys. Res. 109, E06002 Doi: 10.1029/2003JE002181]. This low CO/CH4 ratio is much lower than expected for the sub-nebular formation region of Titan and supports the hypothesis [e.g., Atreya et al., 2005. Methane on Titan: photochemical-meteorological-hydrogeochemical cycle. Bull. Am. Astron. Soc. 37, 735] that the conversion of primordial CO and other carbon-bearing materials into CH4-enriched clathrate-hydrates occurs within the deep interior of Titan via the release of hydrogen through the serpentinization process followed by Fischer-Tropsch catalysis. The time-averaged predicted emission rate of methane-rich surface materials is approximately 0.02 km(exp 3) yr (exp -1), a value significantly lower than the rate of silicate lava production for the Earth and Venus, but nonetheless indicative of significant geological processes reshaping the surface of Titan.

  20. Culture of somatic cells isolated from frozen-thawed equine semen using fluorescence-assisted cell sorting.

    PubMed

    Brom-de-Luna, Joao Gatto; Canesin, Heloísa Siqueira; Wright, Gus; Hinrichs, Katrin

    2018-03-01

    Nuclear transfer using somatic cells from frozen semen (FzSC) would allow cloning of animals for which no other genetic material is available. Horses are one of the few species for which cloning is commercially feasible; despite this, there is no information available on the culture of equine FzSC. After preliminary trials on equine FzSC, recovered by density-gradient centrifugation, resulted in no growth, we hypothesized that sperm in the culture system negatively affected cell proliferation. Therefore, we evaluated culture of FzSC isolated using fluorescence-assisted cell sorting. In Exp. 1, sperm were labeled using antibodies to a sperm-specific antigen, SP17, and unlabeled cells were collected. This resulted in high sperm contamination. In Exp. 2, FzSC were labeled using an anti-MHC class I antibody. This resulted in an essentially pure population of FzSC, 13-25% of which were nucleated. Culture yielded no proliferation in any of nine replicates. In Exp. 3, 5 × 10 3 viable fresh, cultured horse fibroblasts were added to the frozen-thawed, washed semen, then this suspension was labeled and sorted as for Exp. 2. The enriched population had a mean of five sperm per recovered somatic cell; culture yielded formation of monolayers. In conclusion, an essentially pure population of equine FzSC could be obtained using sorting for presence of MHC class I antigens. No equine FzSC grew in culture; however, the proliferation of fibroblasts subjected to the same processing demonstrated that the labeling and sorting methods, and the presence of few sperm in culture, were compatible with cell viability. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. SIRT1 activation rescues doxorubicin-induced loss of functional competence of human cardiac progenitor cells.

    PubMed

    De Angelis, Antonella; Piegari, Elena; Cappetta, Donato; Russo, Rosa; Esposito, Grazia; Ciuffreda, Loreta Pia; Ferraiolo, Fiorella Angelica Valeria; Frati, Caterina; Fagnoni, Francesco; Berrino, Liberato; Quaini, Federico; Rossi, Francesco; Urbanek, Konrad

    2015-01-01

    The search for compounds able to counteract chemotherapy-induced heart failure is extremely important at the age of global cancer epidemic. The role of SIRT1 in the maintenance of progenitor cell homeostasis may contribute to its cardioprotective effects. SIRT1 activators, by preserving progenitor cells, could have a clinical relevance for the prevention of doxorubicin (DOXO)-cardiotoxicity. To determine whether SIRT1 activator, resveratrol (RES), interferes with adverse effects of DOXO on cardiac progenitor cells (CPCs): 1) human CPCs (hCPCs) were exposed in vitro to DOXO or DOXO+RES and their regenerative potential was tested in vivo in an animal model of DOXO-induced heart failure; 2) the in vivo effects of DOXO+RES co-treatment on CPCs were studied in a rat model. In contrast to healthy cells, DOXO-exposed hCPCs were ineffective in a model of anthracycline cardiomyopathy. The in vitro activation of SIRT1 decreased p53 acetylation, overcame suppression of the IGF-1/Akt pro-survival and anti-apoptotic signaling, enhanced oxidative stress defense and prevented senescence and growth arrest of hCPCs. Priming with RES counterbalanced the onset of dysfunctional phenotype in DOXO-exposed hCPCs, partly restoring their ability to repair the damage with improvement in cardiac function and animal survival. The in vivo co-treatment DOXO+RES prevented the anthracycline-induced alterations in CPCs, partly preserving cardiac function. SIRT1 activation protects DOXO-exposed CPCs and re-establishes their proper function. Pharmacological intervention at the level of tissue-specific progenitor cells may provide cardiac benefits for the growing population of long-term cancer survivors that are at risk of chemotherapy-induced cardiovascular toxicity. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel

    PubMed Central

    Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

    2015-01-01

    Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy. PMID:25844599

  3. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.

    PubMed

    Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

    2015-08-28

    Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy.

  4. Overexpression of the carbohydrate binding module from Solanum lycopersicum expansin 1 (Sl-EXP1) modifies tomato fruit firmness and Botrytis cinerea susceptibility.

    PubMed

    Perini, M A; Sin, I N; Villarreal, N M; Marina, M; Powell, A L T; Martínez, G A; Civello, P M

    2017-04-01

    Firmness, one of the major determinants of postharvest quality and shelf life of fruits is determined by the mechanical resistance imposed by the plant cell wall. Expansins (EXP) are involved in the non-hydrolytic metabolic disassembly of plant cell walls, particularly in processes where relaxation of the wall is necessary, such as fruit development and ripening. As many carbohydrate-associated proteins, expansins have a putative catalytic domain and a carbohydrate-binding module (CBM). Several strategies have been pursued to control the loss of fruit firmness during storage. Most of the approaches have been to suppress the expression of key enzymes involved in the cell wall metabolism, but this is the first time that a CBM was overexpressed in a fruit aimed to control cell wall degradation and fruit softening. We report the constitutive overexpression of the CBM of Solanum lycopersicum expansin 1 (CBM-SlExp1) in the cell wall of tomato plants, and its effects on plant and fruit phenotype. Overexpression of CBM-SlExp1 increased the mechanical resistance of leaves, whereas it did not modify plant growth and general phenotype. However, transgenic plants showed delayed softening and firmer fruits. In addition, fruits were less susceptible to Botrytis cinerea infection, and the "in vitro" growth of the fungus on media containing AIR from the pericarp of transgenic fruits was lower than controls. The possibility of overexpressing a CBM of a fruit-specific expansin to control cell wall degradation and fruit softening is discussed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Menadione serves as a substrate for P-glycoprotein: implication in chemosensitizing activity.

    PubMed

    Oh, Seok-Jeong; Han, Hyo-Kyung; Kang, Keon-Wook; Lee, Young-Joo; Lee, Moo-Yeol

    2013-04-01

    Based on its chemosensitizing effect, we questioned whether menadione is an inhibitor or a substrate of P-glycoprotein (P-gp). To test this hypothesis, we assessed the effect of menadione on P-gp activity and examined the P-gp-dependency of cellular accumulation and cytotoxicity of menadione as well. Treatment with menadione resulted in the concentration-dependent increase of rhodamine 123 (Rh123) accumulation in P-gp-overexpressing MDCKII/MDR1 and NCI/ADR-RES cells, suggesting that menadione inhibits Rh123 extrusion by P-gp. Compared with MDCKII or MCF-7, intracellular distribution of [(3)H]-menadione was significantly lower in MDCKII/MDR1 or NCI/ADR-RES cells, which could be restored by the P-gp inhibitors, verapamil and quinidine. Consistent with these results, MDCKII/MDR1 or NCI/ADR-RES cells were more resistant to the cytotoxicity of menadione than MDCKII or MCF-7 cells, respectively. Such resistance was abolished by the combined treatment of verapamil and quinidine in NCI/ADR-RES cells. Our study identified menadione as a substrate of P-gp, which presumably, acts as the mechanism for the chemosensitizing effect. Menadione may be a promising chemotherapeutic enhancer by its ability of circumventing drug resistance, in addition to its own anti-cancer activity.

  6. Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis.

    PubMed

    Roum, J H; Borok, Z; McElvaney, N G; Grimes, G J; Bokser, A D; Buhl, R; Crystal, R G

    1999-07-01

    Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased (P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated superoxide anion (O2-.) release by ELF inflammatory cells decreased after GSH therapy (P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2-. release (P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation.

  7. UV testing of solar cells: Effects of antireflective coating, prior irradiation, and UV source

    NASA Technical Reports Server (NTRS)

    Meulenberg, A.

    1993-01-01

    Short-circuit current degradation of electron irradiated double-layer antireflective-coated cells after 3000 hours ultraviolet (UV) exposure exceeds 3 percent; extrapolation of the data to 10(exp 5) hours (11.4 yrs.) gives a degradation that exceeds 10 percent. Significant qualitative and quantitative differences in degradation were observed in cells with double- and single-layer antireflective coatings. The effects of UV-source age were observed and corrections were made to the data. An additional degradation mechanism was identified that occurs only in previously electron-irradiated solar cells since identical unirradiated cells degrade to only 6 +/- 3 percent when extrapolated 10(exp 5) hours of UV illumination.

  8. Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse.

    PubMed

    Buff, P R; Morrison, C D; Ganjam, V K; Keisler, D H

    2005-05-01

    Leptin is a protein hormone produced by adipose tissue that influences hypothalamic mechanisms regulating appetite and energy balance. In species tested thus far, including horses, concentrations of leptin increase as animal fat mass increases. The variables and mechanisms that influence the secretion of leptin are not well known, nor is it known in equine species how the secretion of leptin is influenced by acute alterations in energy balance, circadian patterns, and/or reproductive competence. Our objectives were to determine in horses: 1) whether plasma concentrations of leptin are secreted in a circadian and/or a pulsatile pattern; 2) whether a 48-h period of feed restriction would alter plasma concentrations of leptin, growth hormone, or insulin; and 3) whether ovariectomy and/or a melatonin implant would affect leptin. In Exp. 1, mares exposed to ambient photoperiod of visible light (11 h, 33 min to 11 h, 38 min), received treatments consisting of a 48-h feed restriction (RES) or 48 h of alfalfa hay fed ad libitum (FED). Mares were maintained in a dry lot before sampling and were tethered to a rail during sampling. Analyses revealed that leptin was not secreted in a pulsatile manner, and that mean leptin concentrations were greater (P < 0.001) in FED vs. RES mares (17.20 +/- 0.41 vs. 7.29 +/- 0.41 ng/mL). Plasma growth hormone was pulsatile, and mean concentrations were greater in RES than FED mares (2.15 +/- 0.31 vs. 1.08 +/- 0.31 ng/mL; P = 0.05). Circadian patterns of leptin secretion were observed, but only in FED mares (15.39 +/- 0.58 ng/mL for morning vs. 19.00 +/- 0.58 ng/mL for evening; P < 0.001). In Exp. 2, mares that were ovariectomized or intact received either a s.c. melatonin implant or a sham implant. Thereafter, blood was sampled at weekly intervals at 1000 and 1700. Concentrations of leptin in samples collected at 1700 were greater (P < 0.001) than in those collected at 1000 (28.24 +/- 1.7 vs. 22.07 +/- 1.7 ng/mL). Neither ovariectomy nor chronic treatment with melatonin affected plasma concentrations of leptin or the circadian pattern of secretion. These data provide evidence that plasma leptin concentrations in the equine are sensitive to acute changes in nutritional status and vary in a circadian pattern that is sensitive to fasting but not to melatonin treatment or ovariectomy.

  9. Resveratrol Ameliorates Microcystin-LR-Induced Testis Germ Cell Apoptosis in Rats via SIRT1 Signaling Pathway Activation.

    PubMed

    Liu, Haohao; Zhang, Shenshen; Liu, Chuanrui; Wu, Jinxia; Wang, Yueqin; Yuan, Le; Du, Xingde; Wang, Rui; Marwa, Phelisters Wegesa; Zhuang, Donggang; Cheng, Xuemin; Zhang, Huizhen

    2018-06-09

    Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli⁻germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli⁻germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli⁻germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.

  10. Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway.

    PubMed

    Feng, Jing; Liu, Shuai; Ma, Sai; Zhao, Jian; Zhang, Wei; Qi, Wei; Cao, Pengchong; Wang, Zheng; Lei, Wei

    2014-12-01

    Postmenopausal osteoporosis severely jeopardizes human health. Seeking for therapeutic drugs without side effects is of great necessity. Our study was designed to investigate whether resveratrol, an agonist of SIRT1, could have favorable effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model (ovariectomy group, OVX) was established by bilateral ovariectomy. Three different doses of resveratrol were used: 5 mg/kg/d (low-dosed, RES(LD)), 25 mg/kg/d (medium-dosed, RES(MD)), and 45 mg/kg/d (high-dosed, RES(HD)). Results showed that RES(LD) did not show any significant effect on OVX alterations, while RES(MD) and RES(HD) significantly elevated the decreased bone mineral density induced by osteoporosis (RES(MD) 0.205 ± 0.023, RES(HD) 0.214 ± 0.053 vs. OVX 0.165 ± 0.050 g/cm(2) respectively; P < 0.05). Serum markers alkaline phosphatase (ALP) and osteocalcin were moderately restored by resveratrol. Moreover, resveratrol improved bone structure in OVX rats, demonstrated by hematoxylin-eosin staining and micro-computed tomographic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesenchymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 (P < 0.05; RES(MD), RES(HD) vs. control group). SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol (P < 0.05; RES + SIRT1(KD) vs. RES(HD)). Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-κB with decreased expression level of p-IκBα and NF-κB p65 (P < 0.05). Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-κB signaling pathway. This study suggested the therapeutic potential of resveratrol against osteoporosis and stressed the importance of effective doses. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  11. The Fanconi anemia protein interaction network: casting a wide net.

    PubMed

    Rego, Meghan A; Kolling, Frederick W; Howlett, Niall G

    2009-07-31

    It has long been hypothesized that a defect in the repair of damaged DNA is central to the etiology of Fanconi anemia (FA). Indeed, an increased sensitivity of FA patient-derived cells to the lethal effects of various forms of DNA damaging agents was described over three decades ago [A.J. Fornace, Jr., J.B. Little, R.R. Weichselbaum, DNA repair in a Fanconi's anemia fibroblast cell strain, Biochim. Biophys. Acta 561 (1979) 99-109; Y. Fujiwara, M. Tatsumi, Repair of mitomycin C damage to DNA in mammalian cells and its impairment in Fanconi's anemia cells, Biochem. Biophys. Res. Commun. 66 (1975) 592-598; A.J. Rainbow, M. Howes, Defective repair of ultraviolet- and gamma-ray-damaged DNA in Fanconi's anaemia, Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 31 (1977) 191-195]. Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial chromosome formation, exemplifies an innate impairment in the repair of these particularly cytotoxic DNA lesions [A.D. Auerbach, Fanconi anemia diagnosis and the diepoxybutane (DEB) test, Exp. Hematol. 21 (1993) 731-733]. Precisely defining the collective role of the FA proteins in DNA repair, however, continues to be one of the most enigmatic and challenging questions in the FA field. The first six identified FA proteins (A, C, E, F, G, and D2) harbored no recognizable enzymatic features, precluding association with a specific metabolic process. Consequently, our knowledge of the role of the FA proteins in the DNA damage response has been gleaned primarily through biochemical association studies with non-FA proteins. Here, we provide a chronological discourse of the major FA protein interaction network discoveries, with particular emphasis on the DNA damage response, that have defined our current understanding of the molecular basis of FA.

  12. The role of Her2-Nrf2 axis in induction of oxaliplatin resistance in colon cancer cells.

    PubMed

    Pirpour Tazehkand, Abbas; Akbarzadeh, Maryam; Velaie, Kobra; Sadeghi, Mohammad Reza; Samadi, Nasser

    2018-04-20

    Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in promoting chemoresistance by regulation of antioxidants and detoxification enzymes. Her2 is a member of tyrosine kinase receptor family with a key function in resistance of cancer cells to chemotherapeutics. The aim of this study was to investigate the possible cross talk between Nrf2 and Her2 mediated signaling pathways in development of oxaliplatin resistance in colon cancer cells. We first generated oxaliplatin-resistant LS174T and SW480 colon cancer cells with different Her2 expression levels by employing IC50 concentrations followed by a resting period. We evaluated the viability and apoptosis of the cells by MTT and flow cytometry assays, respectively. Nrf2 and Her2 gene expression levels were examined by qRT-PCR. The morphology analysis and combination index calculation were performed using the ImagJ and CompuSyn softwares, respectively. Development of resistant cells revealed a marked increase in half maximal inhibitory concentration (IC50) value from 3.95 ± 0.92 μM to 29.27 ± 3.13 μM in SW480 cells and 377 ± 46 nM to 9.59 ± 0.76 μM in LS174T cells with a significant change in morphology of the cells from elongated to small round shape (p < 0.05). Her2 expression level was increased in both types of resistant cells, but the Nrf2 expression was increased in LS174T resistant (LS174T/Res) cells and decreased in SW480/Res cells which were consistent with the level of resistance in these cells (25 fold increase in IC50 value in LS174T/Res cells versus 7 fold increase in this value in SW480/Res cells). Inhibition of either Nrf2 or Her2 alone and in combination caused a significant increase in oxaliplatin-induced cytotoxicity and apoptosis with maximum effects in SW480/Res cells with low Her2 and Nrf2 expression levels. Altogether, our results suggest that inhibition of Nrf2 signaling in colon cancer patients with Her2 overexpression can be considered as an important strategy to overcome oxaliplatin resistance. Copyright © 2018. Published by Elsevier Masson SAS.

  13. The tomato res mutant which accumulates JA in roots in non-stressed conditions restores cell structure alterations under salinity.

    PubMed

    Garcia-Abellan, José O; Fernandez-Garcia, Nieves; Lopez-Berenguer, Carmen; Egea, Isabel; Flores, Francisco B; Angosto, Trinidad; Capel, Juan; Lozano, Rafael; Pineda, Benito; Moreno, Vicente; Olmos, Enrique; Bolarin, Maria C

    2015-11-01

    Jasmonic acid (JA) regulates a wide spectrum of plant biological processes, from plant development to stress defense responses. The role of JA in plant response to salt stress is scarcely known, and even less known is the specific response in root, the main plant organ responsible for ionic uptake and transport to the shoot. Here we report the characterization of the first tomato (Solanum lycopersicum) mutant, named res (restored cell structure by salinity), that accumulates JA in roots prior to exposure to stress. The res tomato mutant presented remarkable growth inhibition and displayed important morphological alterations and cellular disorganization in roots and leaves under control conditions, while these alterations disappeared when the res mutant plants were grown under salt stress. Reciprocal grafting between res and wild type (WT) (tomato cv. Moneymaker) indicated that the main organ responsible for the development of alterations was the root. The JA-signaling pathway is activated in res roots prior to stress, with transcripts levels being even higher in control condition than in salinity. Future studies on this mutant will provide significant advances in the knowledge of JA role in root in salt-stress tolerance response, as well as in the energy trade-off between plant growth and response to stress. © 2015 Scandinavian Plant Physiology Society.

  14. Combinatorial resveratrol and quercetin polymeric micelles mitigate doxorubicin induced cardiotoxicity in vitro and in vivo.

    PubMed

    Cote, Brianna; Carlson, Lisa Janssen; Rao, Deepa A; Alani, Adam W G

    2015-09-10

    Doxorubicin hydrochloride (ADR) is an anthracycline antibiotic used to treat various cancers. However, due to its extensive cardiotoxic side effects a lifetime cumulative dose limit of 450-550 mg/m2 exists. The postulated mechanism of the cardiotoxicity is generation of reactive oxygen and nitrogen species. Natural products like resveratrol (RES), and quercetin (QUE) are known free radical scavengers and have shown cardioprotective effects. However, concurrent dosing of these natural products with ADR is limited due to their low solubility, and low oral bioavailability. We hypothesize that the combination of RES and QUE in Pluronic® F127 micelles (mRQ) when co-administered with ADR, will be cardioprotective in vitro and in vivo, while maintaining or increasing the efficacy of ADR against cancer cell lines in vitro. We prepared mRQ micelles capable of retaining 1.1mg/mL and 1.42 mg/mL of RES and QUE respectively. The in vitro release of RES and QUE from the micelles followed first order kinetics over 48h. In vitro cell viability and combination index analysis studies in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2) showed that RES:QUE: ADR at 10:10:1 ratio was synergistic in SKOV-3 cells and antagonistic in H9C2 cells. Caspase 3/7 activity studies indicated that mRQ did not interfere with ADR caspase activity in SKOV-3 cells but significantly decreased it in H9C2 cells. The generation of reactive oxygen species (ROS) in SKOV-3 and H9C2 cells in the presence of mRQ also indicated no changes in ROS activity in SKOV-3 cells but significant scavenging in H9C2 cells. Healthy mice were exposed to acute doses of ADR and ADR with mRQ. Based on biochemical estimations the presence of mRQ with ADR conferred full cardioprotection in these mice. Concurrent administration of mRQ with ADR at 10:10:1 ratio provides a viable strategy to mitigate acute ADR induced cardiotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. La contribution de la diversité des expériences littéraires préscolaires aux habiletés émergentes en littéracie

    PubMed Central

    PARENT, Sophie; MONTÉSINOS-GELET, Isabelle; SÉGUIN, Jean R.; ZELAZO, Philip David; TREMBLAY, Richard E.

    2017-01-01

    RÉSUMÉ Les études antérieures montrent que les facteurs langagiers et cognitifs chez le jeune enfant ne suffisent pas pour expliquer les différences individuelles dans l’acquisition des compétences relatives à la langue écrite (Sénéchal et LeFevre, 2002). S’inspirant de l’éthologie et de la sociologie, Pellegrini (2001) propose que l’exposition à une plus grande variété d’interlocuteurs et de contextes sociaux pour l’exercice des compétences liées à l’écrit favorise l’acquisition du langage littéraire et des compétences en lecture/écriture. La présente étude a pour but de vérifier cette contribution de la variété des opportunités sociales reliées à l’écrit à l’acquisition des compétences émergentes en littéracie à 5 ans. Cette contribution est examinée de concert avec les ressources financières familiales, l’éducation parentale, la fréquence des activités mère-enfant de lecture/écriture et les compétences verbales et mnémoniques de l’enfant. Les résultats confirment partiellement l’hypothèse de Pellegrini et appuient la pertinence de considérer plusieurs dimensions des expériences sociales préscolaires. La contribution unique de la diversité des activités littéraires de l’enfant à 48 mois s’avère de taille similaire à celle du vocabulaire réceptif évalué à 42 mois et de la mémoire à court terme à 42 mois. La diversité des interlocuteurs n’ajoute toutefois pas au modèle. PMID:28566801

  16. High-Density Spot Seeding for Tissue Model Formation

    NASA Technical Reports Server (NTRS)

    Marquette, Michele L. (Inventor); Sognier, Marguerite A. (Inventor)

    2016-01-01

    A model of tissue is produced by steps comprising seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any cells that have not partially attached, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1 x 10(exp 5) cells/ml to about 1 x 10(exp 6) cells/ml. The tissue formed may be a muscle tissue or other tissue depending on the cells seeded.

  17. Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture

    PubMed Central

    Miyazawa, Kohtaro; Emmerling, Kaitlin

    2011-01-01

    Transmissible Spongiform Encephalopathy (TSE) agents are defined by their virulence for particular species, their spread in the population, their incubation time to cause disease, and their neuropathological sequelae. Murine adapted human agents, including sporadic CJD (sCJD), New Guinea kuru, and Japanese CJD agents, display particularly distinct incubation times and maximal infectious brain titers. They also induce agent-specific patterns of neurodegeneration. When these TSE agents are transmitted to cultured hypothalamic GT1 cells they maintain their unique identities. Nevertheless, the human kuru (kCJD) and Japanese FU-CJD agents, as well as the sheep 22L and 263K scrapie agents display doubling times that are 8× to 33× faster in cells than in brain, indicating release from complex innate immune responses. These data are most consistent with a foreign viral structure, rather than an infectious form of host prion protein (PrP-res). Profound agent-specific inhibitory effects are also apparent in GT1 cells, and maximal titer plateau in kCJD and FU-CJD differed by 1,000-fold in a cell-based assay. Remarkably, the lower titer kCJD agent rapidly induced de novo PrP-res in GT1 cells, whereas the high titer FU-CJD agent replicated silently for multiple passages. Although PrP-res is often considered to be toxic, PrP-res instead may be part of a primal defense and/or clearance mechanism against TSE environmental agents. Limited spread of particular TSE agents through nanotubes and cell-to-cell contacts probably underlies the long peripheral phase of human CJD. PMID:21527829

  18. Aboveground Biomass Variability Across Intact and Degraded Forests in the Brazilian Amazon

    NASA Technical Reports Server (NTRS)

    Longo, Marcos; Keller, Michael; Dos-Santos, Maiza N.; Leitold, Veronika; Pinage, Ekena R.; Baccini, Alessandro; Saatchi, Sassan; Nogueira, Euler M.; Batistella, Mateus; Morton, Douglas C.

    2016-01-01

    Deforestation rates have declined in the Brazilian Amazon since 2005, yet degradation from logging, re, and fragmentation has continued in frontier forests. In this study we quantified the aboveground carbon density (ACD) in intact and degraded forests using the largest data set of integrated forest inventory plots (n 359) and airborne lidar data (18,000 ha) assembled to date for the Brazilian Amazon. We developed statistical models relating inventory ACD estimates to lidar metrics that explained70 of the variance across forest types. Airborne lidar-ACD estimates for intact forests ranged between 5.0 +/- 2.5 and 31.9 +/- 10.8 kg C m(exp -2). Degradation carbon losses were large and persistent. Sites that burned multiple times within a decade lost up to 15.0 +/- 0.7 kg C m(-2)(94%) of ACD. Forests that burned nearly15 years ago had between 4.1 +/- 0.5 and 6.8 +/- 0.3 kg C m(exp -2) (22-40%) less ACD than intact forests. Even for low-impact logging disturbances, ACD was between 0.7 +/- 0.3 and 4.4 +/- 0.4 kg C m(exp -2)(4-21%) lower than unlogged forests. Comparing biomass estimates from airborne lidar to existing biomass maps, we found that regional and pan-tropical products consistently overestimated ACD in degraded forests, under-estimated ACD in intact forests, and showed little sensitivity to res and logging. Fine-scale heterogeneity in ACD across intact and degraded forests highlights the benefits of airborne lidar for carbon mapping. Differences between airborne lidar and regional biomass maps underscore the need to improve and update biomass estimates for dynamic land use frontiers, to better characterize deforestation and degradation carbon emissions for regional carbon budgets and Reduce Emissions from Deforestation and forest Degradation(REDD+).

  19. High-Density Spot Seeding for Tissue Model Formation

    NASA Technical Reports Server (NTRS)

    Marquette, Michele L. (Inventor); Sognier, Marguerite A. (Inventor)

    2014-01-01

    A method for making a tissue includes seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any unattached cells, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1 x 10(exp 5) cells/ml to about 1 x 10(exp 6) cells/ml. The tissue formed may be a skeletal muscle tissue, a cardiac muscle tissue, nerve tissue, or a bone tissue.

  20. The response regulator expM is essential for the virulence of Erwinia carotovora subsp. carotovora and acts negatively on the sigma factor RpoS (sigma s).

    PubMed

    Andersson, R A; Palva, E T; Pirhonen, M

    1999-07-01

    The main virulence factors of Erwinia carotovora subsp. carotovora, the secreted, extracellular cell-wall-degrading enzymes, are controlled by several regulatory mechanisms. We have isolated transposon mutants with reduced virulence on tobacco. One of these mutants, with a mutation in a gene designated expM, was characterized in this study. This mutant produces slightly reduced amounts of extracellular enzymes in vitro and the secretion of the enzymes is also affected. The expM wild-type allele was cloned together with an upstream gene, designated expL, that has an unknown function. The expM gene was sequenced and found to encode a protein with similarity to the RssB/SprE protein of Escherichia coli and the MviA protein of Salmonella typhimurium. These proteins belong to a new type of two-component response regulators that negatively regulate the stability of the Sigma factor RpoS (sigma s) at the protein level. The results of this study suggest that ExpM has a similar function in E. carotovora subsp. carotovora. We also provide evidence that the overproduction of RpoS in the expM mutant is an important factor for the reduced virulence phenotype and that it partly causes the observed phenotype seen in vitro. However, an expM/rpoS double mutant is still affected in secretion of extracellular enzymes, suggesting that ExpM in addition to RpoS also acts on other targets.

  1. Global regulators ExpA (GacA) and KdgR modulate extracellular enzyme gene expression through the RsmA-rsmB system in Erwinia carotovora subsp. carotovora.

    PubMed

    Hyytiäinen, H; Montesano, M; Palva, E T

    2001-08-01

    The production of the main virulence determinants, the extracellular plant cell wall-degrading enzymes, and hence virulence of Erwinia carotovora subsp. carotovora is controlled by a complex regulatory network. One of the global regulators, the response regulator ExpA, a GacA homolog, is required for transcriptional activation of the extracellular enzyme genes of this soft-rot pathogen. To elucidate the mechanism of ExpA control as well as interactions with other regulatory systems, we isolated second-site transposon mutants that would suppress the enzyme-negative phenotype of an expA (gacA) mutant. Inactivation of kdgR resulted in partial restoration of extracellular enzyme production and virulence to the expA mutant, suggesting an interaction between the two regulatory pathways. This interaction was mediated by the RsmA-rsmB system. Northern analysis was used to show that the regulatory rsmB RNA was under positive control of ExpA. Conversely, the expression of rsmA encoding a global repressor was under negative control of ExpA and positive control of KdgR. This study indicates a central role for the RsmA-rsmB regulatory system during pathogenesis, integrating signals from the ExpA (GacA) and KdgR global regulators of extracellular enzyme production in E. carotovora subsp. carotovora.

  2. Electron temperature response to ECRH on FTU tokamak in transient conditions.

    NASA Astrophysics Data System (ADS)

    Jacchia, A.; Bruschi, A.; Cirant, S.; Granucci, G.; Sozzi, C.; de Luca, F.; Amadeo, P.; Bracco, G.; Tudisco, O.

    2001-10-01

    Steady-state electron heat transport analysis of FTU high density plasmas under Electron Cyclotron Heating (ECRH) shows "stiff" electron temperature profiles [1,2,3]. Plasma response to off-axis EC heating, in fact, exibits a lower limit to electron temperature gradient length, Lc , below which electron thermal conductivity switches to higher values. Stiffness, however, is attenuated in the plasma core of saw-tooth free discharges with flat-hollow temperature profile and during current ramp-up [3,4,5], in which cases the temperature gradient length can be brought to very low values by means of on-axis ECH. Steady and current ramp-up discharges probed by steady and modulated ECH are analyzed in terms of stiffnes. Critical gradient length dependence on local features of computed current density profile is discussed. [1] Sozzi, C. et al., Paper EXP5/13, Plasma Phys. Contr. Fus. Res., Proc.18th IAEA Conf., Sorrento, 2000. [2] Jacchia, A. et al. Topical Conference on Radio Frequency Power in Plasmas, Oxnard, USA, (2001). [3] Cirant, S. et al. Topical Conference on Radio Frequency Power in Plasmas, Oxnard, USA, (2001). [4] Sozzi, C. et al., EPS, Madeira 2001. [5] Bracco, G. et al.,Plasma Phys. Contr. Fus. Res., Proc.18th IAEA Conf., Sorrento, 2000.

  3. A comparison of cosmological hydrodynamic codes

    NASA Technical Reports Server (NTRS)

    Kang, Hyesung; Ostriker, Jeremiah P.; Cen, Renyue; Ryu, Dongsu; Hernquist, Lars; Evrard, August E.; Bryan, Greg L.; Norman, Michael L.

    1994-01-01

    We present a detailed comparison of the simulation results of various hydrodynamic codes. Starting with identical initial conditions based on the cold dark matter scenario for the growth of structure, with parameters h = 0.5 Omega = Omega(sub b) = 1, and sigma(sub 8) = 1, we integrate from redshift z = 20 to z = O to determine the physical state within a representative volume of size L(exp 3) where L = 64 h(exp -1) Mpc. Five indenpendent codes are compared: three of them Eulerian mesh-based and two variants of the smooth particle hydrodynamics 'SPH' Lagrangian approach. The Eulerian codes were run at N(exp 3) = (32(exp 3), 64(exp 3), 128(exp 3), and 256(exp 3)) cells, the SPH codes at N(exp 3) = 32(exp 3) and 64(exp 3) particles. Results were then rebinned to a 16(exp 3) grid with the exception that the rebinned data should converge, by all techniques, to a common and correct result as N approaches infinity. We find that global averages of various physical quantities do, as expected, tend to converge in the rebinned model, but that uncertainites in even primitive quantities such as (T), (rho(exp 2))(exp 1/2) persists at the 3%-17% level achieve comparable and satisfactory accuracy for comparable computer time in their treatment of the high-density, high-temeprature regions as measured in the rebinned data; the variance among the five codes (at highest resolution) for the mean temperature (as weighted by rho(exp 2) is only 4.5%. Examined at high resolution we suspect that the density resolution is better in the SPH codes and the thermal accuracy in low-density regions better in the Eulerian codes. In the low-density, low-temperature regions the SPH codes have poor accuracy due to statiscal effects, and the Jameson code gives the temperatures which are too high, due to overuse of artificial viscosity in these high Mach number regions. Overall the comparison allows us to better estimate errors; it points to ways of improving this current generation ofhydrodynamic codes and of suiting their use to problems which exploit their best individual features.

  4. Low power test architecture for dynamic read destructive fault detection in SRAM

    NASA Astrophysics Data System (ADS)

    Takher, Vikram Singh; Choudhary, Rahul Raj

    2018-06-01

    Dynamic Read Destructive Fault (dRDF) is the outcome of resistive open defects in the core cells of static random-access memories (SRAMs). The sensitisation of dRDF involves either performing multiple read operations or creation of number of read equivalent stress (RES), on the core cell under test. Though the creation of RES is preferred over the performing multiple read operation on the core cell, cell dissipates more power during RES than during the read or write operation. This paper focuses on the reduction in power dissipation by optimisation of number of RESs, which are required to sensitise the dRDF during test mode of operation of SRAM. The novel pre-charge architecture has been proposed in order to reduce the power dissipation by limiting the number of RESs to an optimised number of two. The proposed low power architecture is simulated and analysed which shows reduction in power dissipation by reducing the number of RESs up to 18.18%.

  5. Self-Broadening and Self-Shift Coefficients in the Fundamental Band of 12C 16O

    NASA Technical Reports Server (NTRS)

    Devi, Malathy V.; Benner, D. Chris; Smith, Mary Ann H.; Rinsland, Curtis P.

    1998-01-01

    High quality and precise measurements of self-broadened and self-shift coefficients in the fundamental band of C-12O-16 were made using spectra recorded at room temperature with the high-resolution (0.0027 cm(exp -1)) McMath-Pierce Fourier transform spectrometer located at the National Solar Observatory on Kitt Peak, Arizona. The spectral region under investigation (2008-2247 cm(exp -1)) contains the P(31) to R(31) transitions. The data were obtained using a high-purity natural isotopic sample ofcarbon monoxide and two absorption cells with pathlengths of 4.08 and 9.98 cm, respectively. Various pressures of CO were used, ranging between 0.25 and 201.2 Torr. The results were obtained by analyzing five spectra simultaneously, using a multispectrum nonlinear least-squares fitting technique. The self-broadened coefficients ranged from 0.0426(2) cm(exp -1) atm(exp -1) at 296 K to 0.0924(2) cm(exp -1) atm(exp -1) at 296 K, while the pressure-induced shift coefficients varied between -0.0042(3) cm(exp -1) atm(exp -1) at 296 K and +0.0005(l) cm(exp -1) atm(exp -1) at 296 K. The value in parentheses is the estimated uncertainty in units of the last digit. The self-broadened coefficients of lines with same values of m in the P and R branches agree close to within experimental uncertainties while the self-shift coefficients showed considerable variation within and between the two branches. The mean value of the ratios of P branch to R branch self-broadened coefficients was found to be 1.01 with a standard deviation of + or - 0.01. Comparisons of the results with other published data were made.

  6. Resveratrol-decreased hyperalgesia mediated by the P2X7 receptor in gp120-treated rats.

    PubMed

    Wu, Bing; Ma, Yucheng; Yi, Zhihua; Liu, Shuangmei; Rao, Shenqiang; Zou, Lifang; Wang, Shouyu; Xue, Yun; Jia, Tianyu; Zhao, Shanhong; Shi, Liran; Li, Lin; Yuan, Huilong; Liang, Shangdong

    2017-01-01

    Background Chronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120 (gp120) can directly cause hyperalgesia by stimulating primary sensory afferent nerves. The P2X 7 receptor in the dorsal root ganglia (DRG) is closely related to neuropathic and inflammatory pain. In this study, we aimed to explore the effect of resveratrol (RES) on gp120-induced neuropathic pain that is mediated by the P2X 7 receptor in the rat DRG. Results Mechanical hyperalgesia in rats treated with gp120 was increased compared with that in the sham group. The P2X 7 expression levels in rats treated with gp120 were higher than those in the sham group. Co-localization of the P2X 7 receptor and glial fibrillary acidic protein (GFAP, a marker of satellite glial cells [SGCs]) in the DRG SGCs of the gp120 group exhibited more intense staining than that of the sham group. RES decreased the mechanical hyperalgesia and P2X 7 expression levels in gp120 treatment rats. Co-localization of the P2X 7 receptor and GFAP in the gp120+ RES group was significantly decreased compared to the gp120 group. RES decreased the IL-1β and TNF-α receptor (R) expression levels and ERK1/2 phosphorylation levels as well as increased IL-10 expression in the DRG of gp120-treated rats. Whole cell clamping demonstrated that RES significantly inhibited adenosine triphosphate-activated currents in HEK293 cells that were transfected with the P2X 7 plasmid. Conclusions RES relieved mechanical hyperalgesia in gp120-treated rats by inhibiting the P2X 7 receptor.

  7. Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

    PubMed Central

    Vert, Anna; Castro, Jessica; Ribó, Marc; Vilanova, Maria; Benito, Antoni

    2018-01-01

    Background Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance. Methods NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8. Results Gene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK–Akt, Wnt, and Notch. Conclusion Our findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs. PMID:29379303

  8. L’expression verbale de la douleur chez l’enfant : Comparaison intermodale entre sensation de douleur et manipulation tactile

    PubMed Central

    Bienvenu, Margaux; Jacquet, Denis; Michelutti, Marjolaine; Wood, Chantal

    2011-01-01

    HISTORIQUE: La présente étude se situe dans le contexte de l’expression verbale de la douleur chez l’enfant. Elle porte plus particulièrement sur la dimension qualitative de la sensation de douleur. OBJECTIF: Nous cherchons à repérer les particularités de l’expression verbale relativement à l’aspect qualitatif de la douleur. MÉTHODOLOGIE: La recherche a été menée auprès de 60 patients de quatre à 18 ans ressentant de la douleur, rencontrés dans un hôpital universitaire pédiatrique. Elle confirme en premier lieu l’origine des descripteurs sensoriels de la douleur, qui renvoient aux expériences perceptives passées de l’enfant, non nécessairement liées à la douleur. Ces expériences sont qualifiées de prototypiques, dans la mesure où, bien qu’elles soient liées à des contextes de vie variés, le type de rapport au monde qu’elles provoquent ne varie pas. RÉSULTATS: Dans ce cadre, le pincement, le tiraillement, le tapement, l’écrasement et l’appuiement, le picotement et le serrement constituent chacune des expériences sensorielles et motrices particulières dont la structure de base ne varie pas d’un contexte à l’autre. En second lieu, les résultats obtenus montrent que dès quatre ans, l’enfant est en mesure de comparer, puis de reconnaître une analogie entre une expérience exclusivement tactile et sa sensation de douleur. CONCLUSION: Ces résultats mettent en lumière le rôle primordial du raisonnement analogique dans l’expression verbale de la douleur, ce qui amène à affirmer que le niveau de développement cognitif de l’enfant n’est pas une variable a priori déterminante lorsqu’il s’agit de qualifier sa douleur. PMID:21766069

  9. Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

    PubMed

    Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

    2018-05-01

    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

  10. Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan.

    PubMed

    Wang, Tso-Jen; Huang, San-Yuan; Lin, Wei-Wen; Lo, Hsin-Yi; Wu, Pei-Lin; Wang, Yu-Shan; Wu, Yi-Syuan; Ko, Huei-Chen; Shih, Jean-Chen; Lu, Ru-Band

    2007-01-30

    Both monoamine oxidase A (MAOA) and dopamine D(2) receptor (DRD2) genes have been considered as candidate genes for antisocial personality disorder with alcoholism (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls. Genomics. 45, 290-295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V., Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67-72.; Schmidt, L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J., Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural .Transm. 107, 681-689.]. However, the association between alcoholism and MAOA or DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C., Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between DRD(2) locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592-599.; Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality disorder nor antisocial alcoholism association with MAOA gene among Han Chinese males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889-893.]. Since dopamine is metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its metabolite in predominantly noradrenergic innervated brain areas. Brain. Res. 330, 164-166.], the interaction between MAOA and DRD2 genes might be related to Antisocial ALC. The present study aimed to determine whether Antisocial ALC might be associated with the possible interactions of DRD2 gene with MAOA gene. Of the 231 Han Chinese subjects who were recruited for the study, 73 participants were diagnosed with Antisocial ALC and 158 subjects were diagnosed with antisocial personality disorder without alcoholism (Antisocial Non-ALC). The DRD2 TaqI A and MAOA-uVNTR (variable number of tandem repeat located upstream) polymorphisms were not found to be associated with Antisocial ALC. However, an association between DRD2 TaqI A polymorphisms and Antisocial ALC was shown only after stratification for the MAOA-uVNTR 4-repeat polymorphism. Additionally, after multiple logistic regressions, we found that, under stratification of MAOA-uVNTR 4-repeat polymorphism and in comparison with the DRD2 A1/A1 genotype as a reference group, the DRD2 A1/A2 genotype has a possible protective effect against alcoholism in individuals with antisocial personality disorder (ASPD). We concluded that the possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan.

  11. Development of an enzyme-linked immunoelectrotransfer blot (EITB) assay using two baculovirus expressed recombinant antigens for diagnosis of Taenia solium taeniasis.

    PubMed

    Levine, Min Z; Lewis, Melissa M; Rodriquez, Silvia; Jimenez, Juan A; Khan, Azra; Lin, Sehching; Garcia, Hector H; Gonzales, Armando E; Gilman, Robert H; Tsang, Victor C W

    2007-04-01

    Taeniasis diagnosis is an important step in the control and elimination of both cysticercosis and taeniasis. We report the development of 2 serological taeniasis diagnostic tests using recombinant antigens rES33 and rES38 expressed by baculovirus in insect cells in an EITB format. In laboratory testing with defined sera from nonendemic areas, rES33 has a sensitivity of 98% (n = 167) and a specificity of 99% (n = 310) (J index: 0.97); rES38 has a sensitivity of 99% (n = 146) and a specificity of 97% (n = 275) (J index: 0.96). Independent field testing in Peru showed 97% (n = 203) of the taeniasis sera were positive with rES33, and 100% of the nontaeniasis sera (n = 272) were negative with rES33; 98% (n = 198) of taeniasis sera were positive with rES38, and 91% (n = 274) of the nontaeniasis sera were negative with rES38. Among the Peruvian sera tested, 17 of 26 Peruvian Taenia saginata sera were false positive with rES38 test. Both tests were also examined with cysticercosis sera, with a positive rate ranging from 21% to 46%. rES33 and rES38 tests offer sensitive and specific diagnosis of taeniasis and easy sample collection through finger sticks that can be used in large-scale studies. They are currently being used in cysticercosis elimination programs in Peru.

  12. Advanced driver assistance systems: Using multimodal redundant warnings to enhance road safety.

    PubMed

    Biondi, Francesco; Strayer, David L; Rossi, Riccardo; Gastaldi, Massimiliano; Mulatti, Claudio

    2017-01-01

    This study investigated whether multimodal redundant warnings presented by advanced assistance systems reduce brake response times. Warnings presented by assistance systems are designed to assist drivers by informing them that evasive driving maneuvers are needed in order to avoid a potential accident. If these warnings are poorly designed, they may distract drivers, slow their responses, and reduce road safety. In two experiments, participants drove a simulated vehicle equipped with a forward collision avoidance system. Auditory, vibrotactile, and multimodal warnings were presented when the time to collision was shorter than five seconds. The effects of these warnings were investigated with participants performing a concurrent cell phone conversation (Exp. 1) or driving in high-density traffic (Exp. 2). Braking times and subjective workload were measured. Multimodal redundant warnings elicited faster braking reaction times. These warnings were found to be effective even when talking on a cell phone (Exp. 1) or driving in dense traffic (Exp. 2). Multimodal warnings produced higher ratings of urgency, but ratings of frustration did not increase compared to other warnings. Findings obtained in these two experiments are important given that faster braking responses may reduce the potential for a collision. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Three-dimensional Numerical Simulation of Venus' Cloud-level Convection

    NASA Astrophysics Data System (ADS)

    Sugiyama, K. I.; Nakajima, K.; Odaka, M.; Imamura, T.; Hayashi, Y. Y.; Ishiwatari, M.; Kawabata, T.

    2015-12-01

    Although some observational evidences have suggested the occurrence of convection in the lower part of Venus' cloud layer, its structure remains to be clarified. To date, a few numerical studies have examined the structure of convective motion (Baker et al., 1998, 2000; Imamura et al., 2014), but the model they utilized is two-dimensional. Here we report on the results of our numerical calculations performed in order to investigate possible three-dimensional structure of the convection. We use a convection resolving model developed by Sugiyama et al. (2009), which is used in the simulations of the atmospheric convection of Jupiter (Sugiyama et al., 2011,2014) and Mars (Yamashita et al., submitted). We perform two experiments. The first one, which we call Ext.B, is based on Baker et al. (1998). A constant turbulent mixing coefficient is used in the whole domain, and a constant thermal flux is given at the upper and lower boundaries as a substitute for infrared heating. The second one, which we call Exp.I, is based on Imamura et al. (2014). The sub-grid turbulence process is implemented by Klemp and Wilhelmson (1989), and an infrared heating profile obtained in a radiative-convective equilibrium calculation (Ikeda, 2011) is used. In both experiments, the averaged solar heating profile is used. The spatial resolution is 200 m in the horizontal direction and 125 m in the vertical direction. The domain covers 128km x 128km horizontally and altitudes from 40 km to 60 km. Obtained structures of convection moderately differ in the two experiments. Although the depth of convection layer is almost the same, the horizontal cell size of Exp.B is larger than that of Exp.I; the cell sizes in Exp.B and Exp.I are about 40 km and 25 km, respectively. The vertical motion in Exp.B is asymmetric; updrafts are widespread and weak (~3m/s), whereas downdrafts are narrow and strong (~10m/s). On the other hand, the vertical motion in Exp.I is nearly symmetric and weaker (~2m/s) compared with those in Exp.B. The difference of convective structure results from the different vertical distributions of implemented infrared heating. Namely, the intense downdrafts in Exp.B are forced by the strong cooling concentrated near the top of convection layer. In Exp.I, the heating is distributed in a thick layer, so that relatively symmetric vertical motion occurs.

  14. Transgenic Tobacco Plants Overexpressing a Grass PpEXP1 Gene Exhibit Enhanced Tolerance to Heat Stress

    PubMed Central

    Xu, Qian; Xu, Xiao; Shi, Yang; Xu, Jichen; Huang, Bingru

    2014-01-01

    Heat stress is a detrimental abiotic stress limiting the growth of many plant species and is associated with various cellular and physiological damages. Expansins are a family of proteins which are known to play roles in regulating cell wall elongation and expansion, as well as other growth and developmental processes. The in vitro roles of expansins regulating plant heat tolerance are not well understood. The objectives of this study were to isolate and clone an expansin gene in a perennial grass species (Poa pratensis) and to determine whether over-expression of expansin may improve plant heat tolerance. Tobacco (Nicotiana tabacum) was used as the model plant for gene transformation and an expansin gene PpEXP1 from Poa pratensis was cloned. Sequence analysis showed PpEXP1 belonged to α-expansins and was closely related to two expansin genes in other perennial grass species (Festuca pratensis and Agrostis stolonifera) as well as Triticum aestivum, Oryza sativa, and Brachypodium distachyon. Transgenic tobacco plants over-expressing PpEXP1 were generated through Agrobacterium-mediated transformation. Under heat stress (42°C) in growth chambers, transgenic tobacco plants over-expressing the PpEXP1 gene exhibited a less structural damage to cells, lower electrolyte leakage, lower levels of membrane lipid peroxidation, and lower content of hydrogen peroxide, as well as higher chlorophyll content, net photosynthetic rate, relative water content, activity of antioxidant enzyme, and seed germination rates, compared to the wild-type plants. These results demonstrated the positive roles of PpEXP1 in enhancing plant tolerance to heat stress and the possibility of using expansins for genetic modification of cool-season perennial grasses in the development of heat-tolerant germplasm and cultivars. PMID:25003197

  15. Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.

    PubMed

    Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F; Bauer, Peter O; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K; Berry, James D; Cudkowicz, Merit E; Boeve, Bradley F; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H; Rothstein, Jeffrey D; Boylan, Kevin B; Petrucelli, Leonard; Disney, Matthew D

    2014-09-03

    A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS

    PubMed Central

    Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F.; Bauer, Peter O.; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V.; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K.; Berry, James D.; Cudkowicz, Merit E.; Boeve, Bradley F.; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J.; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H.; Rothstein, Jeffrey D.; Boylan, Kevin B.; Petrucelli, Leonard; Disney, Matthew D.

    2014-01-01

    Summary A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation producing “c9RAN proteins”. Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons trans-differentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic, and suggest c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. PMID:25132468

  17. Ozone Correction for AM0 Calibrated Solar Cells for the Aircraft Method

    NASA Technical Reports Server (NTRS)

    Snyder, David B.; Scheiman, David A.; Jenkins, Phillip P.; Lyons, Valerie J. (Technical Monitor)

    2002-01-01

    The aircraft solar cell calibration method has provided cells calibrated to space conditions for 37 years. However, it is susceptible to systematic errors due to ozone concentration in the stratosphere. The present correction procedure applies a 1% increase to the measured Isc values. High band-gap cells are more sensitive to ozone adsorbed wavelengths so it has become important to reassess the correction technique. This paper evaluates the ozone correction to be 1+{O3}sup Fo, where Fo is 29.5x10(exp-6)/d.u. for a Silicon solar cell and 42.2xl0(exp -6)/d.u. for a GaAs cell. Results will be presented for high band-gap cells. A comparison with flight data indicates that this method of correcting for the ozone density improves the uncertainty of AM0 Isc to 0.5%.

  18. Genetic and Environmental Pathways in Type 1 Diabetes Complication

    DTIC Science & Technology

    2008-06-01

    obese diabetic mice. Biochem Biophys Res Commun 2002. 294:592-596. 4. Beyan H, Goodier MR, Nawroly NS, Hawa MI, Bustin SA, Ogunkolade WB, Londei M...peroxidation in patients with hyperglycemic crisis . Diabetes 2004. 53:2079-2086. 14 In our second quarterly scientific progress report (09/01/07 – 11...cells induced to differentiate into insulin-positive cells. Biochem Biophys Res Commun . 2007;357(2):414-20. 44. Takahashi K, Tanabe K, Ohnuki M, Narita

  19. ATGL and CGI-58 are lipid droplet proteins of the hepatic stellate cell line HSC-T6.

    PubMed

    Eichmann, Thomas O; Grumet, Lukas; Taschler, Ulrike; Hartler, Jürgen; Heier, Christoph; Woblistin, Aaron; Pajed, Laura; Kollroser, Manfred; Rechberger, Gerald; Thallinger, Gerhard G; Zechner, Rudolf; Haemmerle, Günter; Zimmermann, Robert; Lass, Achim

    2015-10-01

    Lipid droplets (LDs) of hepatic stellate cells (HSCs) contain large amounts of vitamin A [in the form of retinyl esters (REs)] as well as other neutral lipids such as TGs. During times of insufficient vitamin A availability, RE stores are mobilized to ensure a constant supply to the body. To date, little is known about the enzymes responsible for the hydrolysis of neutral lipid esters, in particular of REs, in HSCs. In this study, we aimed to identify LD-associated neutral lipid hydrolases by a proteomic approach using the rat stellate cell line HSC-T6. First, we loaded cells with retinol and FAs to promote lipid synthesis and deposition within LDs. Then, LDs were isolated and lipid composition and the LD proteome were analyzed. Among other proteins, we found perilipin 2, adipose TG lipase (ATGL), and comparative gene identification-58 (CGI-58), known and established LD proteins. Bioinformatic search of the LD proteome for α/β-hydrolase fold-containing proteins revealed no yet uncharacterized neutral lipid hydrolases. In in vitro activity assays, we show that rat (r)ATGL, coactivated by rat (r)CGI-58, efficiently hydrolyzes TGs and REs. These findings suggest that rATGL and rCGI-58 are LD-resident proteins in HSCs and participate in the mobilization of both REs and TGs. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  20. Cis-acting regulatory sequences promote high-frequency gene conversion between repeated sequences in mammalian cells.

    PubMed

    Raynard, Steven J; Baker, Mark D

    2004-01-01

    In mammalian cells, little is known about the nature of recombination-prone regions of the genome. Previously, we reported that the immunoglobulin heavy chain (IgH) mu locus behaved as a hotspot for mitotic, intrachromosomal gene conversion (GC) between repeated mu constant (Cmu) regions in mouse hybridoma cells. To investigate whether elements within the mu gene regulatory region were required for hotspot activity, gene targeting was used to delete a 9.1 kb segment encompassing the mu gene promoter (Pmu), enhancer (Emu) and switch region (Smu) from the locus. In these cell lines, GC between the Cmu repeats was significantly reduced, indicating that this 'recombination-enhancing sequence' (RES) is necessary for GC hotspot activity at the IgH locus. Importantly, the RES fragment stimulated GC when appended to the same Cmu repeats integrated at ectopic genomic sites. We also show that deletion of Emu and flanking matrix attachment regions (MARs) from the RES abolishes GC hotspot activity at the IgH locus. However, no stimulation of ectopic GC was observed with the Emu/MARs fragment alone. Finally, we provide evidence that no correlation exists between the level of transcription and GC promoted by the RES. We suggest a model whereby Emu/MARS enhances mitotic GC at the endogenous IgH mu locus by effecting chromatin modifications in adjacent DNA.

  1. Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome.

    PubMed

    Yang, Wang-Yong; He, Fang; Strack, Rita L; Oh, Seok Yoon; Frazer, Michelle; Jaffrey, Samie R; Todd, Peter K; Disney, Matthew D

    2016-09-16

    RNA transcripts containing expanded nucleotide repeats cause many incurable diseases via various mechanisms. One such disorder, fragile X-associated tremor ataxia syndrome (FXTAS), is caused by a noncoding r(CGG) repeat expansion (r(CGG)(exp)) that (i) sequesters proteins involved in RNA metabolism in nuclear foci, causing dysregulation of alternative pre-mRNA splicing, and (ii) undergoes repeat associated non-ATG translation (RANT), which produces toxic homopolymeric proteins without using a start codon. Here, we describe the design of two small molecules that inhibit both modes of toxicity and the implementation of various tools to study perturbation of these cellular events. Competitive Chemical Cross Linking and Isolation by Pull Down (C-Chem-CLIP) established that compounds bind r(CGG)(exp) and defined small molecule occupancy of r(CGG)(exp) in cells, the first approach to do so. Using an RNA GFP mimic, r(CGG)(exp)-Spinach2, we observe that our optimal designed compound binds r(CGG)(exp) and affects RNA localization by disrupting preformed RNA foci. These events correlate with an improvement of pre-mRNA splicing defects caused by RNA gain of function. In addition, the compounds reduced levels of toxic homopolymeric proteins formed via RANT. Polysome profiling studies showed that small molecules decreased loading of polysomes onto r(CGG)(exp), explaining decreased translation.

  2. Diffusion length damage coefficient and annealing studies in proton-irradiated InP

    NASA Technical Reports Server (NTRS)

    Hakimzadeh, Roshanak; Vargas-Aburto, Carlos; Bailey, Sheila G.; Williams, Wendell

    1993-01-01

    We report on the measurement of the diffusion length damage coefficient (K(sub L)) and the annealing characteristics of the minority carrier diffusion length (L(sub n)) in Czochralski-grown zinc-doped indium phosphide (InP), with a carrier concentration of 1 x 10(exp l8) cm(exp -3). In measuring K(sub L) irradiations were made with 0.5 MeV protons with fluences ranging from 1 x 10(exp 11) to 3 x 10(exp 13) cm(exp -2). Pre- and post-irradiation electron-beam induced current (EBIC) measurements allowed for the extraction of L(sub n) from which K(sub L) was determined. In studying the annealing characteristics of L(sub n) irradiations were made with 2 MeV protons with fluence of 5 x 10(exp 13) cm(exp -2). Post-irradiation studies of L(sub n) with time at room temperature, and with minority carrier photoinjection and forward-bias injection were carried out. The results showed that recovery under Air Mass Zero (AMO) photoinjection was complete. L(sub n) was also found to recover under forward-bias injection, where recovery was found to depend on the value of the injection current. However, no recovery of L(sub n) after proton irradiation was observed with time at room temperature, in contrast to the behavior of 1 MeV electron-irradiated InP solar cells reported previously.

  3. New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species.

    PubMed

    Johnson, Michael E; Katiyar, Santosh K; Edlind, Thomas D

    2011-08-01

    Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two "hot spot" regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new "hot spot 3" in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES.

  4. Microgravity can activate signals urging cells to S-phase entry during tissue and organ regeneration in Urodele amphibians exposed to real and simulated microgravity

    NASA Astrophysics Data System (ADS)

    Grigoryan, E.; Anton, H.-J.; Mitashov, V.

    Regenerative response following local injury or tissue removal in urodele amphibians is dependent on cell cycle entry of cells sources for regeneration in the remaining tissue. In a number of our experiments performed aboard biosatellites in orbital flights and fast rotated clinostat we found enhanced proliferative activity and, as a result, regeneration quicker than that in controls. In each investigated case an activity of cell proliferation evaluated by 3H-thymidine radioautography and BrdU assay at the early stages of lens, retina, forelimb and tail regeneration in newts was about 1,2-1,7 fold higher both under conditions of real and physiological weightlessness as compared with controls. Faster S-phase entry under conditions of micro- g was demonstrated by cycling multipotent cells as well as by differentiated postmitotic cells both participated in regeneration. Important, that cycling cells outside areas of regeneration were also found as displayed faster cellular growth. In our papers (1,2,3,4) we offered some hypothesis that could explain mechanisms of low g stimulating effect upon cell growth in regeneration in Urodela. In particular, changes in expression of some growth factors and their receptors, as well as the synthesis of specific range of generalized stress proteins (AGSPs) were proposed. However, in fact, molecular mechanisms of micro- g effect upon cell proliferation are mediated by changes on organismic level induced by micro- g environment. Some of them which are able to trigger off signaling changes on the cellular level that, in turn, evoke cells to grow faster would be represented in our report. 1. Mitashov V. et al. Adv. Space Res. 1996. 17 (6/7): 241-255 2. Anton H.-J. et al. Adv. Space Res. 1996. 17 (6/7): 55-65 3. Grigoryan E. et al. Adv. Space Res. 1998. 22 (2): 293-301 4. Grigoryan E. et al. Adv. Space Res. 2002. 30 (4): 757-764

  5. Tamoxifen synergizes with 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol} and 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, novel azaresveratrol analogs, in inhibiting the proliferation of breast cancer cells

    PubMed Central

    Ronghe, Amruta; Chatterjee, Anwesha; Bhat, Nimee K.; Padhye, Subhash; Bhat, Hari K.

    2016-01-01

    We have recently shown that 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol} (HPIMBD) and 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), novel analogs of resveratrol (Res), selectively inhibited the proliferation of breast cancer cells. In the current study, we tested HPIMBD and TIMBD individually in combination with tamoxifen (Tam) for inhibition of growth of breast cancer cells. Tamoxifen was first tested on non-neoplastic breast epithelial cell lines and its dose that does not inhibit their growth was determined. A combination of this low dose of Tam with either of the Res analogs HPIMBD or TIMBD, resulted in synergistic inhibition of proliferation of breast cancer cells. Both estrogen receptor (ER)-positive and negative breast cancer cell lines responded to the combination. The combination resulted in a substantial decrease in IC50 values of Res analogs in all breast cancer cell lines tested. Mechanistic studies showed a synergistic increase in apoptosis and autophagy genes (beclin-1 and LC3BII/I) with the combination in ER-negative MDA-MB-231 cells. In ER-positive MCF-7 and T47D cells, the mechanism of synergy was found to be inhibition of expression of ERα and oncogene c-Myc. The combination treatment had a synergistic effect in inhibiting the colony forming and spheroid forming ability of cancer cells. Taken together, our findings indicate that a combination of Tam and Res analogs HPIMBD or TIMBD represents a novel approach to enhancing the use of Tam in therapy for breast cancers. Considering the urgent need for novel therapeutic strategies to treat ER-negative breast cancers and overcoming resistance in ER-positive cancers, this combinatorial approach is worthy of continued investigation. PMID:27351134

  6. Automatic white blood cell classification using pre-trained deep learning models: ResNet and Inception

    NASA Astrophysics Data System (ADS)

    Habibzadeh, Mehdi; Jannesari, Mahboobeh; Rezaei, Zahra; Baharvand, Hossein; Totonchi, Mehdi

    2018-04-01

    This works gives an account of evaluation of white blood cell differential counts via computer aided diagnosis (CAD) system and hematology rules. Leukocytes, also called white blood cells (WBCs) play main role of the immune system. Leukocyte is responsible for phagocytosis and immunity and therefore in defense against infection involving the fatal diseases incidence and mortality related issues. Admittedly, microscopic examination of blood samples is a time consuming, expensive and error-prone task. A manual diagnosis would search for specific Leukocytes and number abnormalities in the blood slides while complete blood count (CBC) examination is performed. Complications may arise from the large number of varying samples including different types of Leukocytes, related sub-types and concentration in blood, which makes the analysis prone to human error. This process can be automated by computerized techniques which are more reliable and economical. In essence, we seek to determine a fast, accurate mechanism for classification and gather information about distribution of white blood evidences which may help to diagnose the degree of any abnormalities during CBC test. In this work, we consider the problem of pre-processing and supervised classification of white blood cells into their four primary types including Neutrophils, Eosinophils, Lymphocytes, and Monocytes using a consecutive proposed deep learning framework. For first step, this research proposes three consecutive pre-processing calculations namely are color distortion; bounding box distortion (crop) and image flipping mirroring. In second phase, white blood cell recognition performed with hierarchy topological feature extraction using Inception and ResNet architectures. Finally, the results obtained from the preliminary analysis of cell classification with (11200) training samples and 1244 white blood cells evaluation data set are presented in confusion matrices and interpreted using accuracy rate, and false positive with the classification framework being validated with experiments conducted on poor quality blood images sized 320 × 240 pixels. The deferential outcomes in the challenging cell detection task, as shown in result section, indicate that there is a significant achievement in using Inception and ResNet architecture with proposed settings. Our framework detects on average 100% of the four main white blood cell types using ResNet V1 50 while also alternative promising result with 99.84% and 99.46% accuracy rate obtained with ResNet V1 152 and ResNet 101, respectively with 3000 epochs and fine-tuning all layers. Further statistical confusion matrix tests revealed that this work achieved 1, 0.9979, 0.9989 sensitivity values when area under the curve (AUC) scores above 1, 0.9992, 0.9833 on three proposed techniques. In addition, current work shows negligible and small false negative 0, 2, 1 and substantial false positive with 0, 0, 5 values in Leukocytes detection.

  7. Hydrogen passivation of n+p and p+n heteroepitaxial InP solar cell structures

    NASA Technical Reports Server (NTRS)

    Chatterjee, B.; Ringel, S. A.; Hoffman, R., Jr.

    1995-01-01

    High-efficiency, heteroepitaxial (HE) InP solar cells, grown on GaAs, Si or Ge substrates, are desirable for their mechanically strong, light-weight and radiation-hard properties. However, dislocations, caused by lattice mismatch, currently limit the performance of the HE cells. This occurs through shunting paths across the active photovoltaic junction and by the formation of deep levels. In previous work we have demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of dislocations in specially designed HE InP test structures. In this work, we present the first report of successful hydrogen passivation in actual InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in HE n+n InP cell structures from as-grown values of approximately 10(exp 15)/cm(exp -3), down to 1-2 x 10(exp 13)/cm(exp -3). The deep levels in the p-type base region of the cell structure match those of our earlier p-type test structures, which were attributed to dislocations or related point defect complexes. All dopants were successfully reactivated by a 400 C, 5 minute anneal with no detectable activation of deep levels. I-V analysis indicated a subsequent approximately 10 fold decrease in reverse leakage current at -1 volt reverse bias, and no change in the forward biased series resistance of the cell structure which indicates complete reactivation of the n+ emitter. Furthermore, electrochemical C-V profiling indicates greatly enhanced passivation depth, and hence hydrogen diffusion, for heteroepitaxial structures when compared with identically processed homoepitaxial n+p InP structures. An analysis of hydrogen diffusion in dislocated InP will be discussed, along with comparisons of passivation effectiveness for n+p versus p+n heteroepitaxial cell configurations. Preliminary hydrogen-passivated HE InP cell results will also be presented.

  8. Modulation of Breast Cancer Cell Functions by Intracellular Signaling Through the Membrane Type-1 Matrix Metalloproteinase

    DTIC Science & Technology

    2002-10-01

    Liotta, L. A., Nicolson, G L. and Rao , J. S. (1996) Cancer Res. 56, 384-392 4. Yoshizaki, T., Sato, HR, Maruyama, Y, Murono, S., Furukawa, M., Park, C...lukocyte lineage. Cell Res 271:17119-17123. 9291-30o. Yamamoto M, . Mohana S, Saway -, Fuller G, Sei M, Sato H, Pei D, Weiss SJ. 1996. Transmembrane...deletion mutants of the Gokasla Z 4 IUotta LA, licolson GL, Rao JS. 1996. Diffeorential membrane-type mari metafloproteinase-1 process progelatinase A

  9. Dietary Regulation of PTEN Signaling and Mammary Tumor Initiating Cells: Implications for Breast Cancer Prevention

    DTIC Science & Technology

    2012-07-01

    1999 Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Bio- phys Res Commun 257:79–83 10. Barb D, Pazaitou...Y, Pecquery R 2006 Adiponectin mediates antiproliferative and ap- optotic responses in human MCF7 breast cancer cells. Biochem Bio- phys Res Commun ...Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA 2002 Estrogen receptor in breast cancer. Endocr Relat Cancer 9:1–13 29. Esslimani-Sahla M

  10. Resveratrol and Cardiovascular Diseases

    PubMed Central

    Bonnefont-Rousselot, Dominique

    2016-01-01

    The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials. PMID:27144581

  11. Hydrogen passivation of N(+)-P and P(+)-N heteroepitaxial InP solar cell structures

    NASA Technical Reports Server (NTRS)

    Chatterjee, Basab; Davis, William C.; Ringel, Steve A.; Hoffman, Richard, Jr.

    1996-01-01

    Dislocations and related point defect complexes caused by lattice mismatch currently limit the performance of heteroepitaxial InP cells by introducing shunting paths across the active junction and by the formation of deep traps within the base region. We have previously demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of such defects in specially designed heteroepitaxial InP test structures to probe hydrogen passivation at typical base depths within a cell structure. In this work, we present our results on the hydrogen passivation of actual heteroepitaxial n-p and p-n InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in the base regions of both n(+)-p and p(+)-n heteroepitaxial InP cell structures from as-grown values of 5-7 x 10(exp 14) cm(exp -3), down to 3-5 x 10(exp 12) cm(exp -3). All dopants were successfully reactivated by a 400 C, 5 minute anneal with no detectable activation of deep levels. One to five analysis indicated a subsequent approximately 100 fold decrease in reverse leakage current at -1 volt reverse bias, and an improved built in voltage for the p(+)-n structures. In addition to being passivated, dislocations are also shown to participate in secondary interactions during hydrogenation. We find that the presence of dislocations enhances hydrogen diffusion into the cell structure, and lowers the apparent dissociation energy of Zn-H complexes from 1.19 eV for homoepitaxial Zn-doped InP to 1.12 eV for heteroepitaxial Zn-doped InP. This is explained by additional hydrogen trapping at dislocations subsequent to the reactivation of Zn dopants after hydrogenation.

  12. Influence of liposome charge on the association of liposomes with Kupffer cells in vitro. Effects of divalent cations and competition with latex particles.

    PubMed

    Dijkstra, J; van Galen, M; Scherphof, G

    1985-03-14

    We studied the interaction of large unilamellar liposomes carrying different surface charges with rat Kupffer cells in maintenance culture. In addition to 14C-labeled phosphatidylcholine, all liposome preparations contained either 3H-labeled inulin or 125I-labeled bovine serum albumin as a non-degradable or a degradable aqueous space marker, respectively. With vesicles carrying no net charge, intracellular processing of internalized liposomes caused nearly complete release of protein label into the medium in acid-soluble form, while phospholipid label was predominantly retained by the cells, only about one third being released. The presence of the lysosomotropic agent, ammonia, inhibited the release of both labels from the cells. At 4 degrees C, the association and degradation of the vesicles were strongly reduced. These results are very similar to what we reported on negatively charged liposomes (Dijkstra, J., Van Galen, W.J.M., Hulstaert, C.E., Kalicharan, D., Roerdink, F.H. and Scherphof, G.L. (1984) Exp. Cell Res. 150, 161-176). The interaction of both types of vesicles apparently proceeds by adsorption to the cell surface followed by virtually complete internalization by endocytosis. Similar experiments with positively charged vesicles indicated that only about half of the liposomes were taken up by the endocytic route, the other half remaining adsorbed to the cell-surface. Attachment of all types of liposomes to the cells was strongly dependent on the presence of divalent cations; Ca2+ appeared to be required for optimal binding. Neutral liposomes only slightly competed with the uptake of negatively charged vesicles, both at 4 degrees and 37 degrees C, whereas negatively charged small unilamellar vesicles and negatively charged latex beads were found to compete very effectively with the large negatively charged liposomes. Neutral vesicles competed effectively for uptake with positively charged ones. These results suggest that neutral and positively charged liposomes are largely bound by the same cell-surface binding sites, while negatively charged vesicles attach mainly to other binding sites.

  13. Ethanol and Acetic Acid Production from Carbon Monoxide in a Clostridium Strain in Batch and Continuous Gas-Fed Bioreactors

    PubMed Central

    Nalakath Abubackar, Haris; Veiga, María C.; Kennes, Christian

    2015-01-01

    The effect of different sources of nitrogen as well as their concentrations on the bioconversion of carbon monoxide to metabolic products such as acetic acid and ethanol by Clostridium autoethanogenum was studied. In a first set of assays, under batch conditions, either NH4Cl, trypticase soy broth or yeast extract (YE) were used as sources of nitrogen. The use of YE was found statistically significant (p < 0.05) on the product spectrum in such batch assays. In another set of experiments, three bioreactors were operated with continuous CO supply, in order to estimate the effect of running conditions on products and biomass formation. The bioreactors were operated under different conditions, i.e., EXP1 (pH = 5.75, YE 1g/L), EXP2 (pH = 4.75, YE 1 g/L) and EXP3 (pH = 5.75, YE 0.2 g/L). When compared to EXP2 and EXP3, it was found that EXP1 yielded the maximum biomass accumulation (302.4 mg/L) and products concentrations, i.e., acetic acid (2147.1 mg/L) and ethanol (352.6 mg/L). This can be attributed to the fact that the higher pH and higher YE concentration used in EXP1 stimulated cell growth and did, consequently, also enhance metabolite production. However, when ethanol is the desired end-product, as a biofuel, the lower pH used in EXP2 was more favourable for solventogenesis and yielded the highest ethanol/acetic acid ratio, reaching a value of 0.54. PMID:25608591

  14. Ethanol and acetic acid production from carbon monoxide in a Clostridium strain in batch and continuous gas-fed bioreactors.

    PubMed

    Abubackar, Haris Nalakath; Veiga, María C; Kennes, Christian

    2015-01-20

    The effect of different sources of nitrogen as well as their concentrations on the bioconversion of carbon monoxide to metabolic products such as acetic acid and ethanol by Clostridium autoethanogenum was studied. In a first set of assays, under batch conditions, either NH4Cl, trypticase soy broth or yeast extract (YE) were used as sources of nitrogen. The use of YE was found statistically significant (p < 0.05) on the product spectrum in such batch assays. In another set of experiments, three bioreactors were operated with continuous CO supply, in order to estimate the effect of running conditions on products and biomass formation. The bioreactors were operated under different conditions, i.e., EXP1 (pH = 5.75, YE 1g/L), EXP2 (pH = 4.75, YE 1 g/L) and EXP3 (pH = 5.75, YE 0.2 g/L). When compared to EXP2 and EXP3, it was found that EXP1 yielded the maximum biomass accumulation (302.4 mg/L) and products concentrations, i.e., acetic acid (2147.1 mg/L) and ethanol (352.6 mg/L). This can be attributed to the fact that the higher pH and higher YE concentration used in EXP1 stimulated cell growth and did, consequently, also enhance metabolite production. However, when ethanol is the desired end-product, as a biofuel, the lower pH used in EXP2 was more favourable for solventogenesis and yielded the highest ethanol/acetic acid ratio, reaching a value of 0.54.

  15. Characterization of endocrine disruption potentials of coastal sediments of Taean, Korea employing H295R and MVLN assays-Reconnaissance at 5years after Hebei Spirit oil spill.

    PubMed

    Liu, Xiaoshan; Jung, Dawoon; Zhou, Kairu; Lee, Sangwoo; Noh, Kiwan; Khim, Jong Seong; Giesy, John P; Yim, Un Hyuk; Shim, Won Joon; Choi, Kyungho

    2018-02-01

    Endocrine disrupting potentials were assessed for sediment samples collected near Hebei Spirit oil spill (HSOS) site, between December 2007 and January 2012. For comparison, major crude oil (CO) of HSOS, or its weathered form were assessed. Both raw extracts (REs) and their fractionated samples were tested using H295R and MVLNluc bioassays. In H295R cells, REs of crude and weathered oil (WO), and nine of 14 sediments significantly increased E2 levels, which were correlated with the concentrations of PAHs. Steroidogenic disruption potentials of the sediments generally decreased over time. Among silica fractions of all REs, aromatic hydrocarbons (F2) and polar compounds (F3) caused greater E2 levels. While, in MVLN cell bioassay, only three of 14 sediment REs showed estrogen receptor binding potencies, and no temporal trend was observed. In conclusion, oil spill can cause endocrine disruption in the affected ecosystem through steroidogenic alteration for years, and such potencies attenuate over time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Modulation of photochemical damage in normal and malignant cells by naturally occurring compounds.

    PubMed

    Lee, Yuan-Hao; Kumar, Neeru C; Glickman, Randolph D

    2012-01-01

    Certain phytochemicals, such as the stilbene, resveratrol (RES, found in red grapes and berries), and the triterpenoid, ursolic acid (UA, found in waxy berries and herbs such as rosemary and oregano), have antioxidant, anti-inflammatory and antiproliferative effects. Two human-derived cell lines, hTERT-RPE with a nonmalignant phenotype derived from retinal pigment epithelium, and ATCC CRL-11147 derived from a malignant skin melanoma, were used as in vitro models of photooxidative stress produced by exposure to the broadband output of a 150 W Hg vapor arc lamp at an irradiance of 19-26 mW cm(-2). In untreated cells, UV-VIS broadband light exposure produced a loss of proliferative ability, an activation of NF-κB and an increase in protein carbonyl adducts at 24 h postexposure. Pretreatment of the cells with RES or UA at 1-2 μmsignificantly reduced the amount of phosphorylated NF-κB at 24 h postexposure. RES pretreatment reduced the burden of light-induced protein carbonyl adducts by up to 25% in exposed cells. UA treatment markedly increased the sensitivity of melanoma cells to UV radiation, while conferring some photoprotection to RPE cells. These observations indicate that phytochemicals modulate the cellular response to photochemical stress by interacting with specific cell-signaling pathways. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  17. Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

    PubMed Central

    Sá e Cunha, Cláudia; Nyboer, Britta; Heiss, Kirsten; Sanches-Vaz, Margarida; Fontinha, Diana; Wiedtke, Ellen; Grimm, Dirk; Przyborski, Jude Marek; Mota, Maria M.; Prudêncio, Miguel; Mueller, Ann-Kristin

    2017-01-01

    The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite’s hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host–parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies. PMID:28137845

  18. Uptake and Dissolution of Gaseous Ethanol in Sulfuric Acid

    NASA Technical Reports Server (NTRS)

    Michelsen, Rebecca R.; Staton, Sarah J. R.; Iraci, Laura T.

    2006-01-01

    The solubility of gas-phase ethanol (ethyl alcohol, CH3CH2OH, EtOH) in aqueous sulfuric acid solutions was measured in a Knudsen cell reactor over ranges of temperature (209-237 K) and acid composition (39-76 wt % H2SO4). Ethanol is very soluble under these conditions: effective Henry's law coefficients, H*, range from 4 x 10(exp 4) M/atm in the 227 K, 39 wt % acid to greater than 10(exp 7) M/atm in the 76 wt % acid. In 76 wt % sulfuric acid, ethanol solubility exceeds that which can be precisely determined using the Knudsen cell technique but falls in the range of 10(exp 7)-10(exp 10) M/atm. The equilibrium concentration of ethanol in upper tropospheric/lower stratospheric (UT/LS) sulfate particles is calculated from these measurements and compared to other small oxygenated organic compounds. Even if ethanol is a minor component in the gas phase, it may be a major constituent of the organic fraction in the particle phase. No evidence for the formation of ethyl hydrogen sulfate was found under our experimental conditions. While the protonation of ethanol does augment solubility at higher acidity, the primary reason H* increases with acidity is an increase in the solubility of molecular (i.e., neutral) ethanol.

  19. New Fks Hot Spot for Acquired Echinocandin Resistance in Saccharomyces cerevisiae and Its Contribution to Intrinsic Resistance of Scedosporium Species▿

    PubMed Central

    Johnson, Michael E.; Katiyar, Santosh K.; Edlind, Thomas D.

    2011-01-01

    Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two “hot spot” regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new “hot spot 3” in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES. PMID:21576441

  20. Docetaxel chronopharmacology in mice.

    PubMed

    Tampellini, M; Filipski, E; Liu, X H; Lemaigre, G; Li, X M; Vrignaud, P; François, E; Bissery, M C; Lévi, F

    1998-09-01

    Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P < 0.01). Granulocytopenia at nadir was -49 +/- 14% at 7 HALO compared with -84 +/- 3% at 19 HALO (Exp 2 and 3, P < 0.029), and severe jejunal mucosa necrosis occurred in 5 of 8 mice treated at 23 HALO as opposed to 2 of 18 receiving docetaxel at 7, 11, or 19 HALO (Exp 2 and 3, P < 0.02). The time of least docetaxel toxicity corresponded to the circadian nadir in S or G2-M phase and to the circadian maximum in BCL-2 immunofluorescence in bone marrow. Docetaxel increased the median survival of tumor-bearing mice in a dose-dependent manner (controls: 24 days; 20 mg/kg weekly, 33 days; 30 mg/kg weekly or day 1, 3, 5 schedule, 44 or 46 days, respectively; Exp 5-7). Survival curves of treated mice differed significantly according to dosing time for each dose and schedule (P from log rank <0.003 to P < 0.03). In Exp 5 and 6, the percentage of increase in life span was largest if docetaxel was administered weekly at 7 HALO (20 mg/kg, 220%; 30 mg/kg, 372%) and lowest after docetaxel dosing at 19 HALO (80% with 20 mg/kg) or at 15 HALO (78% with 30 mg/kg). In Exp 7, (day 1, 3, 5 schedule), docetaxel was most active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms underlying the tolerability rhythm likely involved the circadian organization of cell cycle regulation. Docetaxel therapeutic index may be improved with an administration at night in cancer patients, when fewest bone marrow cells are in S or G2-M phase.

  1. Coffee Ingestion Suppresses Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

    PubMed

    Kobayashi, Misato; Kurata, Takao; Hamana, Yoshiki; Hiramitsu, Masanori; Inoue, Takashi; Murai, Atsushi; Horio, Fumihiko

    2017-01-01

    Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic β-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic β-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents.

  2. Change in nomenclature for the immunologic synapse from Troxis Necrosis to trogocytosis.

    PubMed

    French, Samuel W

    2017-10-01

    The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte. This process is performed by the immunologic synapse now called trogocytosis meaning "gnaw" (Martinez-Martin N et al., Immunity 2011, 35: 208-222 and Dustin ML, Cancer Immunol Res 2014, 2: 1023-1033). The repeated episodes of uptake of the hepatocyte bite by bite causes the hepatocyte to slowly disappear like the Cheshire cat. This immunological synapse process is also involved in drug hepatitis, Hashimoto's thyroiditis, type I diabetes, autoimmune adrenalitis, autoimmune gastritis and cancer therapy. Treatment of Alzheimer's disease is also now being studied with PD-L1 antibody as used in the treatment of cancer allowing recruitment of disease modifying leukocytes to the sites of brain pathology (Schwartz M. Science 2017, 357: 254-255). Acknowledgement: Supported by a Grant from NIAAAUO1-021898. Copyright © 2017. Published by Elsevier Inc.

  3. Effect of Gravity on the Mammalian Cell Deformation

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Tsao, Y.; Gonda, Steven

    1995-01-01

    The effect of human cell immersed in culture liquid under a micro-gravity environment has been investigated. The study is based on the numerical simulation of the configuration of human cell affected by the time dependent variation of gravity acceleration ranging from 10(exp -3) to 2 g(sub o) (g(sub o) = 9.81 m/s(exp 2)) in 15 seconds. Both the free floating cell and the cell contacted to the upper and lower inclined walls imposed by the time-dependent reduced gravity acceleration are considered in this study. The results show that the cell configuration changes from spherical to horizontally elongated ellipsoid for both the free floating cell and the cell sitting on the lower inclined wall while the cell configuration varies from spherical to vertically elongated ellipsoid for the cell hanging to the upper inclined wall when the gravity acceleration increases. Experimental observations, carried out of human cells exposed to the variation of gravity levels, show that the results of experimental observations agree exactly with the theoretical model computation described in this paper. These results sre significant for humans exposed to the micro-gravity environment.

  4. Natural antioxidants exhibit chemopreventive characteristics through the regulation of CNC b-Zip transcription factors in estrogen-induced breast carcinogenesis.

    PubMed

    Chatterjee, Anwesha; Ronghe, Amruta; Singh, Bhupendra; Bhat, Nimee K; Chen, Jie; Bhat, Hari K

    2014-12-01

    The objective of the present study was to characterize the role of resveratrol (Res) and vitamin C (VC) in prevention of estrogen-induced breast cancer through regulation of cap "n"collar (CNC) b-zip transcription factors. Human breast epithelial cell line MCF-10A was treated with 17β-estradiol (E2) and VC or Res with or without E2. mRNA and protein expression levels of CNC b-zip transcription factors nuclear factor erythroid 2-related factor 1 (Nrf1), nuclear factor erythroid 2 related factor 2 (Nrf2), nuclear factor erythroid 2 related factor 3 (Nrf3), and Nrf2-regulated antioxidant enzymes superoxide dismutase 3 (SOD3) and quinone oxidoreductase 1 (NQO1) were quantified. The treatment with E2 suppressed, whereas VC and Res prevented E2-mediated decrease in the expression levels of SOD3, NQO1, Nrf2 mRNA, and protein in MCF-10A cells. The treatment with E2, Res, or VC significantly increased mRNA and protein expression levels of Nrf1. 17β-Estradiol treatment significantly increased but VC or Res decreased Nrf3 mRNA and protein expression levels. Our studies demonstrate that estrogen-induced breast cancer might be prevented through upregulation of antioxidant enzymes via Nrf-dependent pathways. © 2014 Wiley Periodicals, Inc.

  5. Rate Coefficients for Reactions of Ethynyl Radical (C2H) With HCN and CH3CN: Implications for the Formation of Comples Nitriles on Titan

    NASA Technical Reports Server (NTRS)

    Hoobler, Ray J.; Leone, Stephen R.

    1997-01-01

    Rate coefficients for the reactions of C2H + HCN yields products and C2H + CH3CN yields products have been measured over the temperature range 262-360 K. These experiments represent an ongoing effort to accurately measure reaction rate coefficients of the ethynyl radical, C2H, relevant to planetary atmospheres such as those of Jupiter and Saturn and its satellite Titan. Laser photolysis of C2H2 is used to produce C2H, and transient infrared laser absorption is employed to measure the decay of C2H to obtain the subsequent reaction rates in a transverse flow cell. Rate constants for the reaction C2H + HCN yields products are found to increase significantly with increasing temperature and are measured to be (3.9-6.2) x 10(exp 13) cm(exp 3) molecules(exp -1) s(exp -1) over the temperature range of 297-360 K. The rate constants for the reaction C2H + CH3CN yields products are also found to increase substantially with increasing temperature and are measured to be (1.0-2.1) x 10(exp -12) cm(exp 3) molecules(exp -1) s(exp -1) over the temperature range of 262-360 K. For the reaction C2H + HCN yields products, ab initio calculations of transition state structures are used to infer that the major products form via an addition/elimination pathway. The measured rate constants for the reaction of C2H + HCN yields products are significantly smaller than values currently employed in photochemical models of Titan, which will affect the HC3N distribution.

  6. Dietary Regulation of PTEN Signaling and Mammary Tumor Initiating Cells: Implications for Breast Cancer Prevention

    DTIC Science & Technology

    2012-01-01

    adiponectin, in obesity. Biochem Bio- phys Res Commun 257:79–83 10. Barb D, Pazaitou-Panayiotou K, Mantzoros CS 2006 Adiponectin: a link between obesity and...optotic responses in human MCF7 breast cancer cells. Biochem Bio- phys Res Commun 345:271–279 17. Liu J, Lam JB, Chow KH, Xu A, Lam KS, Moon RT...220 28. Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Wärri A, Weihua Z, Van Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA 2002

  7. Salt stress differentially affects growth-mediating β-expansins in resistant and sensitive maize (Zea mays L.).

    PubMed

    Geilfus, Christoph-Martin; Zörb, Christian; Mühling, Karl H

    2010-12-01

    Salinity mainly reduces shoot growth by the inhibition of cell division and elongation. Expansins loosen plant cell walls. Moreover, the expression of some isoforms is clearly correlated with growth. Effects of salinity on β-expansin transcripts protein abundance were recently reported for different crop species. This study provides a broad analysis of the impact of an 8-day 100mM NaCl stress treatment on the mRNA expression of different maize (Zea mays L.) β-Expansin isoforms using real-time quantitative RT-PCR. The composite β-expansin protein expression was analyzed by western blotting using an anti-peptide antibody raised against a conserved 15-amino-acid region shared by vegetatively expressed β-expansin isoforms. For the first time, changes in β-expansin transcript and protein abundance have been analyzed together with the salinity-induced inhibition of shoot growth. A salt-resistant and a salt-sensitive cultivar were compared in order to elucidate physiological changes. Genotypic differences in the relative concentration of six β-expansin transcripts together with differences in the abundance β-expansin protein are shown in response NaCl stress. In salt-sensitive Lector, reduced β-expansin protein expression was found to correlate positively with reduced shoot growth under stress. A down-regulation of ZmExpB2, ZmExpB6, and ZmExpB8 transcripts possibly contribute to this decrease in protein abundance. In contrast, the maintenance of shoot growth in salt-resistant SR03 might be related to an unaffected abundance of growth-mediating β-expansin proteins in the shoot. Our data suggest that the up-regulation of ZmExpB2, ZmExpB6, and ZmExpB8 may sustain the stable expression of β-expansin protein under conditions of salt stress. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  8. Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate.

    PubMed

    Pulliero, Alessandra; Wu, Yun; Fenoglio, Daniela; Parodi, Alessia; Romani, Massimo; Soares, Christiane P; Filaci, Gilberto; Lee, James L; Sinkam, Patrick N; Izzotti, Alberto

    2015-03-01

    Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Antagonistic interactions of an arsenic-containing mixture in a multiple organ carcinogenicity bioassay.

    PubMed

    Pott, W A; Benjamin, S A; Yang, R S

    1998-11-27

    Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and trichloroethylene (TCE) are frequently identified as groundwater contaminants near hazardous waste disposal sites. While the carcinogenicity of each of these chemicals has been extensively studied individually, little information exists regarding their carcinogenic potential in combination. Therefore, we investigated the carcinogenic promoting potential of chemical mixtures containing arsenic, DCE, VC and TCE following multiple initiator administration in a multiple organ carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.), Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57, Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of this four-chemical mixture on the development of preneoplastic hepatic lesions (altered hepatocellular foci and glutathione S-transferase pi positive foci) as well as bronchioalveolar hyperplasia and adenoma formation.

  10. Social power, product conspicuousness, and the demand for luxury brand counterfeit products.

    PubMed

    Bian, Xuemei; Haque, Sadia; Smith, Andrew

    2015-03-01

    The aim of this article is twofold: (1) to achieve a better understanding of the psychological determinants of the demand for luxury brand counterfeit products (LBCP) through exploring the effects of social power; (2) to extend power literature by identifying boundary conditions of the relationship between social power and compensatory consumption identified by Rucker and Galinsky (2008, J. Consum. Res., 35, 257-267) and Rucker and Galinsky (2009, J. Exp. Soc. Psychol., 45, 549-555). Findings from three experiments demonstrate that social power holds key insights into understanding consumers' purchase propensity for LBCP; product conspicuousness moderates the effects of social power on purchase propensity for status products; these moderation effects are only observed when the status products are LBCP but not genuine products. This article, therefore, contributes to the literature regarding the demand for counterfeits as well as the social power and compensatory consumption literature. © 2014 The British Psychological Society.

  11. Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

    PubMed

    Favia, Angelo D; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

    2012-10-25

    Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.

  12. Carcinoid Tumour of Caecum: an Unusual Palpable Mass in the Right Iliac Fossa.

    PubMed

    Agrawal, Mohit M; Sude, Nandkishor S

    2016-04-01

    Carcinoid tumour represents 0.8-1.5 % of malignant digestive tumours. Gastrointestinal (GI) carcinoids account for 95 % of all the carcinoids, and caecal carcinoids account for 5 % of all the carcinoids. These tumours are frequent in women (2-4:1) as reported by Spallitta and Termine (Minerva Chir 55:77-87, 2002). In order of frequency, they may occur in the appendix (35 %), ileum (28 %), rectum (13 %) and bronchi. Incidence is less than 1 % in the pancreas, gall bladder, liver, larynx, testes and ovaries. The colon and ileocaecal region are rare sites of origin for gastrointestinal carcinoids as reported by Soga (J Exp Clin Cancer Res 17:139-48, 1998). They remain asymptomatic for years and many a times are diagnosed endoscopically, intraoperatively or during autopsy, based on their histopathological findings. We present a rare case of caecal carcinoid.

  13. Molecular basis of 'hypoxic' breast cancer cell radio-sensitization: phytochemicals converge on radiation induced Rel signaling.

    PubMed

    Aravindan, Sheeja; Natarajan, Mohan; Herman, Terence S; Awasthi, Vibhudutta; Aravindan, Natarajan

    2013-03-04

    Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers (BCa) and generally associated with therapeutic resistance, metastases, and poor patient survival. About 50% of locally advanced BCa, where radiotherapy is less effective are suggested to be due to hypoxic regions. In this study, we investigated the potential of bioactive phytochemicals in radio-sensitizing hypoxic BCa cells. Hypoxic (O2-2.5%; N2-92.5%; CO2-5%) MCF-7 cells were exposed to 4 Gy radiation (IR) alone or after pretreatment with Curcumin (CUR), curcumin analog EF24, neem leaf extract (NLE), Genistein (GEN), Resveratrol (RES) or raspberry extract (RSE). The cells were examined for inhibition of NFκB activity, transcriptional modulation of 88 NFκB signaling pathway genes, activation and cellular localization of radio-responsive NFκB related mediators, eNos, Erk1/2, SOD2, Akt1/2/3, p50, p65, pIκBα, TNFα, Birc-1, -2, -5 and associated induction of cell death. EMSA revealed that cells exposed to phytochemicals showed complete suppression of IR-induced NFκB. Relatively, cells exposed EF24 revealed a robust inhibition of IR-induced NFκB. QPCR profiling showed induced expression of 53 NFκB signaling pathway genes after IR. Conversely, 53, 50, 53, 53, 53 and 53 of IR-induced genes were inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. In addition, 25, 29, 24, 16, 11 and 21 of 35 IR-suppressed genes were further inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. Immunoblotting revealed a significant attenuating effect of IR-modulated radio-responsive eNos, Erk1/2, SOD2, Akt1/2/3, p50, p65, pIκBα, TNFα, Birc-1, -2 and -5 with EF24, NLE, CUR, GEN, RES or RSE. Annexin V-FITC staining showed a consistent and significant induction of IR-induced cell death with these phytochemicals. Notably, EF24 robustly conferred IR-induced cell death. Together, these data identifies the potential hypoxic cell radio-sensitizers and further implies that the induced radio-sensitization may be exerted by selectively targeting IR-induced NFκB signaling.

  14. Optimal and Local Connectivity Between Neuron and Synapse Array in the Quantum Dot/Silicon Brain

    NASA Technical Reports Server (NTRS)

    Duong, Tuan A.; Assad, Christopher; Thakoor, Anikumar P.

    2010-01-01

    This innovation is used to connect between synapse and neuron arrays using nanowire in quantum dot and metal in CMOS (complementary metal oxide semiconductor) technology to enable the density of a brain-like connection in hardware. The hardware implementation combines three technologies: 1. Quantum dot and nanowire-based compact synaptic cell (50x50 sq nm) with inherently low parasitic capacitance (hence, low dynamic power approx.l0(exp -11) watts/synapse), 2. Neuron and learning circuits implemented in 50-nm CMOS technology, to be integrated with quantum dot and nanowire synapse, and 3. 3D stacking approach to achieve the overall numbers of high density O(10(exp 12)) synapses and O(10(exp 8)) neurons in the overall system. In a 1-sq cm of quantum dot layer sitting on a 50-nm CMOS layer, innovators were able to pack a 10(exp 6)-neuron and 10(exp 10)-synapse array; however, the constraint for the connection scheme is that each neuron will receive a non-identical 10(exp 4)-synapse set, including itself, via its efficacy of the connection. This is not a fully connected system where the 100x100 synapse array only has a 100-input data bus and 100-output data bus. Due to the data bus sharing, it poses a great challenge to have a complete connected system, and its constraint within the quantum dot and silicon wafer layer. For an effective connection scheme, there are three conditions to be met: 1. Local connection. 2. The nanowire should be connected locally, not globally from which it helps to maximize the data flow by sharing the same wire space location. 3. Each synapse can have an alternate summation line if needed (this option is doable based on the simple mask creation). The 10(exp 3)x10(exp 3)-neuron array was partitioned into a 10-block, 10(exp 2)x10(exp 3)-neuron array. This building block can be completely mapped within itself (10,000 synapses to a neuron).

  15. Transparent conducting thin films for spacecraft applications

    NASA Technical Reports Server (NTRS)

    Perez-Davis, Marla E.; Malave-Sanabria, Tania; Hambourger, Paul; Rutledge, Sharon K.; Roig, David; Degroh, Kim K.; Hung, Ching-Cheh

    1994-01-01

    Transparent conductive thin films are required for a variety of optoelectronic applications: automotive and aircraft windows, and solar cells for space applications. Transparent conductive coatings of indium-tin-oxide (ITO)-magnesium fluoride (MgF2) and aluminum doped zinc oxide (AZO) at several dopant levels are investigated for electrical resistivity (sheet resistance), carrier concentration, optical properties, and atomic oxygen durability. The sheet resistance values of ITO-MgF2 range from 10(exp 2) to 10(exp 11) ohms/square, with transmittance of 75 to 86 percent. The AZO films sheet resistances range from 10(exp 7) to 10(exp 11) ohms/square with transmittances from 84 to 91 percent. It was found that in general, with respect to the optical properties, the zinc oxide (ZnO), AZO, and the high MgF2 content ITO-MgF2 samples, were all durable to atomic oxygen plasma, while the low MgF2 content of ITO-MgF2 samples were not durable to atomic oxygen plasma exposure.

  16. Hot gas in the cold dark matter scenario: X-ray clusters from a high-resolution numerical simulation

    NASA Technical Reports Server (NTRS)

    Kang, Hyesung; Cen, Renyue; Ostriker, Jeremiah P.; Ryu, Dongsu

    1994-01-01

    A new, three-dimensional, shock-capturing hydrodynamic code is utilized to determine the distribution of hot gas in a standard cold dark matter (CDM) model of the universe. Periodic boundary conditions are assumed: a box with size 85 h(exp -1) Mpc having cell size 0.31 h(exp -1) Mpc is followed in a simulation with 270(exp 3) = 10(exp 7.3) cells. Adopting standard parameters determined from COBE and light-element nucleosynthesis, sigma(sub 8) = 1.05, omega(sub b) = 0.06, and assuming h = 0.5, we find the X-ray-emitting clusters and compute the luminosity function at several wavelengths, the temperature distribution, and estimated sizes, as well as the evolution of these quantities with redshift. We find that most of the total X-ray emissivity in our box originates in a relatively small number of identifiable clusters which occupy approximately 10(exp -3) of the box volume. This standard CDM model, normalized to COBE, produces approximately 5 times too much emission from clusters having L(sub x) is greater than 10(exp 43) ergs/s, a not-unexpected result. If all other parameters were unchanged, we would expect adequate agreement for sigma(sub 8) = 0.6. This provides a new and independent argument for lower small-scale power than standard CDM at the 8 h(exp -1) Mpc scale. The background radiation field at 1 keV due to clusters in this model is approximately one-third of the observed background, which, after correction for numerical effects, again indicates approximately 5 times too much emission and the appropriateness of sigma(sub 8) = 0.6. If we have used the observed ratio of gas to total mass in clusters, rather than basing the mean density on light-element nucleosynthesis, then the computed luminosity of each cluster would have increased still further, by a factor of approximately 10. The number density of clusters increases to z approximately 1, but the luminosity per typical cluster decreases, with the result that evolution in the number density of bright clusters is moderate in this redshift range, showing a broad peak near z = 0.7, and then a rapid decline above redshift z = 3. Detailed computations of the luminosity functions in the range L(sub x) = 10(exp 40) - 10(exp 44) ergs/s in various energy bands are presented for both cluster central regions and total luminosities to be used in comparison with ROSAT and other observational data sets. The quantitative results found disagree significantly with those found by other investigators using semianalytic techniques. We find little dependence of core radius on cluster luminosity and a dependence of temperature on luminosity given by log kT(sub x) = A + B log L(sub x), which is slightly steeper (B = 0.38) than is indicated by observations. Computed temperatures are somewhat higher than observed, as expected, in that COBE-normalized CDM has too much power on the relevant scales. A modest average temperature gradient is found, with temperatures dropping to 90% of central values at 0.4 h(exp -1) Mpc and 70% of central values at 0.9 h(exp -1) Mpc. Examining the ratio of gas to total mass in the clusters normalized to Omega(sub B) h(exp 2) = 0.015, and comparing with observations, we conclude, in agreement with White (1991), that the cluster observations argue for an open universe.

  17. Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1.

    PubMed

    Childs-Disney, Jessica L; Parkesh, Raman; Nakamori, Masayuki; Thornton, Charles A; Disney, Matthew D

    2012-12-21

    Myotonic dystrophy type 1 (DM1) is caused when an expanded r(CUG) repeat (r(CUG)(exp)) binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1) as well as other proteins. Previously, we reported that modularly assembled small molecules displaying a 6'-N-5-hexynoate kanamycin A RNA-binding module (K) on a peptoid backbone potently inhibit the binding of MBNL1 to r(CUG)(exp). However, these parent compounds are not appreciably active in cell-based models of DM1. The lack of potency was traced to suboptimal cellular permeability and localization. To improve these properties, second-generation compounds that are conjugated to a d-Arg(9) molecular transporter were synthesized. These modified compounds enter cells in higher concentrations than the parent compounds and are efficacious in cell-based DM1 model systems at low micromolar concentrations. In particular, they improve three defects that are the hallmarks of DM1: a translational defect due to nuclear retention of transcripts containing r(CUG)(exp); pre-mRNA splicing defects due to inactivation of MBNL1; and the formation of nuclear foci. The best compound in cell-based studies was tested in a mouse model of DM1. Modest improvement of pre-mRNA splicing defects was observed. These studies suggest that a modular assembly approach can afford bioactive compounds that target RNA.

  18. Rational Design of Bioactive, Modularly Assembled Aminoglycosides Targeting the RNA that Causes Myotonic Dystrophy Type 1

    PubMed Central

    Childs-Disney, Jessica L.; Parkesh, Raman; Nakamori, Masayuki; Thornton, Charles A.; Disney, Matthew D.

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is caused when an expanded r(CUG) repeat (r(CUG)exp) binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1) as well as other proteins. Previously, we reported that modularly assembled small molecules displaying a 6′-N-5-hexynoate kanamycin A RNA-binding module (K) on a peptoid backbone potently inhibit the binding of MBNL1 to r(CUG)exp. However, these parent compounds are not appreciably active in cell-based models of DM1. The lack of potency was traced to suboptimal cellular permeability and localization. To improve these properties, second-generation compounds that are conjugated to a D-Arg9 molecular transporter were synthesized. These modified compounds enter cells in higher concentrations than the parent compounds and are efficacious in cell-based DM1 model systems at low micromolar concentrations. In particular, they improve three defects that are the hallmarks of DM1: a translational defect due to nuclear retention of transcripts containing r(CUG)exp; pre-mRNA splicing defects due to inactivation of MBNL1; and the formation of nuclear foci. The best compound in cell-based studies was tested in a mouse model of DM1. Modest improvement of pre-mRNA splicing defects was observed. These studies suggest that a modular assembly approach can afford bioactive compounds that target RNA. PMID:23130637

  19. Global-scale regionalization of hydrological model parameters using streamflow data from many small catchments

    NASA Astrophysics Data System (ADS)

    Beck, Hylke; de Roo, Ad; van Dijk, Albert; McVicar, Tim; Miralles, Diego; Schellekens, Jaap; Bruijnzeel, Sampurno; de Jeu, Richard

    2015-04-01

    Motivated by the lack of large-scale model parameter regionalization studies, a large set of 3328 small catchments (< 10000 km2) around the globe was used to set up and evaluate five model parameterization schemes at global scale. The HBV-light model was chosen because of its parsimony and flexibility to test the schemes. The catchments were calibrated against observed streamflow (Q) using an objective function incorporating both behavioral and goodness-of-fit measures, after which the catchment set was split into subsets of 1215 donor and 2113 evaluation catchments based on the calibration performance. The donor catchments were subsequently used to derive parameter sets that were transferred to similar grid cells based on a similarity measure incorporating climatic and physiographic characteristics, thereby producing parameter maps with global coverage. Overall, there was a lack of suitable donor catchments for mountainous and tropical environments. The schemes with spatially-uniform parameter sets (EXP2 and EXP3) achieved the worst Q estimation performance in the evaluation catchments, emphasizing the importance of parameter regionalization. The direct transfer of calibrated parameter sets from donor catchments to similar grid cells (scheme EXP1) performed best, although there was still a large performance gap between EXP1 and HBV-light calibrated against observed Q. The schemes with parameter sets obtained by simultaneously calibrating clusters of similar donor catchments (NC10 and NC58) performed worse than EXP1. The relatively poor Q estimation performance achieved by two (uncalibrated) macro-scale hydrological models suggests there is considerable merit in regionalizing the parameters of such models. The global HBV-light parameter maps and ancillary data are freely available via http://water.jrc.ec.europa.eu.

  20. High-efficiency, radiation-resistant GaAs space cells

    NASA Technical Reports Server (NTRS)

    Bertness, K. A.; Ristow, M. Ladle; Grounner, M.; Kuryla, M. S.; Werthen, J. G.

    1991-01-01

    Although many GaAs solar cells are intended for space applicatons, few measurements of cell degradation after radiation are available, particularly for cells with efficiencies exceeding 20 percent (one-sun, AMO). Often the cell performance is optimized for the highest beginning-of-life (BOL) efficiency, despite the unknown effect of such design on end-of-life (EOL) efficiencies. The results of a study of the radiation effects on p-n GaAs cells are presented. The EOL efficiency of GaAs space cell can be increased by adjusting materials growth parameters, resulting in a demonstration of 16 percent EOL efficiency at one-sun, AMO. Reducing base doping levels to below 3 x 10(exp 17)/cu m and decreasing emitter thickness to 0.3 to 0.5 micron for p-n cells led to significant improvements in radiation hardness as measured by EOL/BOL efficiency ratios for irradiation of 10(exp -15)/sq cm electrons at 1 MeV. BOL efficiency was not affected by changes in emitter thickness but did improve with lower base doping.

  1. Reproductive and growth responses of gilts to exogenous porcine pituitary growth hormone.

    PubMed

    Bryan, K A; Hammond, J M; Canning, S; Mondschein, J; Carbaugh, D E; Clark, A M; Hagen, D R

    1989-01-01

    Forty gilts (mean wt = 72 kg) were administered daily either vehicle (C = control) or 70 micrograms porcine growth hormone (pGH)/kg BW. After 30 d of treatment, eight gilts per group (Exp. 1) were slaughtered and blood, uteri and ovaries were collected. Follicular fluid (FFl) was collected and granulosa cells (GC) were cultured. The remaining gilts (Exp. 2) were treated for up to 35 additional days and examined twice daily for estrus. Estrusal gilts were removed from the experiment. Noncyclic gilts (n = 9 of 12 pGH; n = 4 of 12 C) were slaughtered on d 66 and their ovaries were examined. Ovarian weights were not different for pGH and C gilts in either Exp. 1 (P greater than .1) or Exp. 2 (P = .09). Uterine weights were greater for pGH-treated than for C gilts (P less than .007) in Exp. 1, but not in Exp. 2. Concentrations of estradiol (E2) in plasma and FF1 and of progesterone (P) in plasma and FF1 were not different for pGH and C gilts. Concentrations of insulin-like growth factor-I (IGF-I) in FF1 and in serum were greater for pGH than for C gilts (P less than .01). Concentration of P in serum-free medium of cultured GC was lower for GH than for C (P less than .05) in the presence or absence of gonadotropins in Exp. 1. The FSH-stimulated secretion of P was also lower for GC of pGH-treated gilts in Exp. 2, indicating a failure of GC to differentiate in culture. Only one pGH gilts in Exp. 2 manifested estrus, compared with seven C gilts (P less than .025). In Exp. 1, ADG was higher (P less than .03) and feed/gain lower (P less than .07) for pGH gilts. Longissimus muscle area (LMA) was not different (P = .19) between groups. Backfat thickness (BF) was lower (P less than .005) in pGH than in C in both Exp. 1 and 2. We conclude that exogenous pGH increased growth rate, improved feed efficiency and altered carcass traits in gilts. However, these effects were associated with impaired ovarian development of prepubertal gilts and a low incidence of estrus.

  2. Monitoring Cellular Interactions during T Cell Activation at the Single Molecule Level Using Semiconductor Quantum-Dots

    DTIC Science & Technology

    2005-05-10

    avidin-fusion constructs in mammalian immune cells. To facilitate detection, an epitope tag (HA, derived from the influenza A virus haemagglutinin...Enhanced Green Fluorescent protein (EGFP) cassette. The IRES element (internal ribosome entry site of the encephalomyocarditis virus ) permits both the...AVIDIN CD4 4 AVIDIN tAT .RES’ EGFP TRES’ EGFP IRES’ EGFp 1RES. EGFP g9K LP tar LP gK LP ITTK LIP IE "M33 Ee TM NAMI IAV ~ 𔃺M A ,A,0,, MIMI, A161 TM

  3. Mini-dystrophin Expression Down-regulates IP3-mediated Calcium Release Events in Resting Dystrophin-deficient Muscle Cells

    PubMed Central

    Balghi, Haouaria; Sebille, Stéphane; Mondin, Ludivine; Cantereau, Anne; Constantin, Bruno; Raymond, Guy; Cognard, Christian

    2006-01-01

    We present here evidence for the enhancement, at rest, of an inositol 1,4,5-trisphosphate (IP3)–mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(−)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, the number of sites discharging calcium (release site density [RSD]) was quantified and found more elevated in SolC1(−) than in SolD(+) myotubes. Variations of membrane potential had no significant effect on this difference, and higher resting [Ca2+]i in SolC1(−) (Marchand, E., B. Constantin, H. Balghi, M.C. Claudepierre, A. Cantereau, C. Magaud, A. Mouzou, G. Raymond, S. Braun, and C. Cognard. 2004. Exp. Cell Res. 297:363–379) cannot explain alone higher RSD. The exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) and phospholipase C inhibitor (U73122) significantly reduced RSD in both cell types but with a stronger effect in dystrophin-deficient SolC1(−) myotubes. Immunocytochemistry allowed us to localize ryanodine receptors (RyRs) as well as IP3 receptors (IP3Rs), IP3R-1 and IP3R-2 isoforms, indicating the presence of both RyRs-dependent and IP3-dependent release systems in both cells. We previously reported evidence for the enhancement, through a Gi protein, of the IP3-mediated calcium signaling pathway in SolC1(−) as compared to SolD(+) myotubes during a high K+ stimulation (Balghi, H., S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard. 2006. J. Gen. Physiol. 127:171–182). Here we show that, at rest, these regulation mechanisms are also involved in the modulation of calcium release activities. The enhancement of resting release activity may participate in the calcium overload observed in dystrophin-deficient myotubes, and our findings support the hypothesis of the regulatory role of mini-dystrophin on intracellular signaling. PMID:16847098

  4. Ingestion of a Multi-Ingredient Supplement Does Not Alter Exercise-Induced Satellite Cell Responses in Older Men.

    PubMed

    Snijders, Tim; Bell, Kirsten E; Nederveen, Joshua P; Saddler, Nelson I; Mazara, Nicole; Kumbhare, Dinesh A; Phillips, Stuart M; Parise, Gianni

    2018-06-01

    Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown. We assessed whether a multi-ingredient protein-based supplement taken over a prolonged period of time could alter the muscle satellite cell response after exercise in older men. Twenty-seven older men [mean ± SD age: 73 ± 1 y; mean ± SD body mass index (kg/m2): 28 ± 1] participated in a randomized double-blind experiment. Participants were randomly divided into an experimental (EXP) group (n = 13) who consumed a multi-ingredient protein-based supplement [30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg Ca, and 1500 mg n-3 (ω-3) polyunsaturated fatty acids] 2 times/d for 7 wk or a control (CON; 22 g maltodextrin) group (n = 14). After 7 wk of supplementation, all participants performed a single resistance exercise session, and muscle biopsy samples were taken from the vastus lateralis before and 24 and 48 h after exercise. Immunohistochemistry was used to assess the change in type I and II muscle fiber satellite cell content and activation status of the cells. In addition, mRNA expression of the myogenic regulatory factors was determined by using reverse transcriptase-polymerase chain reaction. In response to the single bout of exercise, type I muscle fiber satellite cell content was significantly increased at 24 h (0.132 ± 0.015 and 0.131 ± 0.011 satellite cells/fiber in CON and EXP groups, respectively) and 48 h (0.126 ± 0.010 and 0.120 ± 0.012 satellite cells/fiber in CON and EXP groups, respectively) compared with pre-exercise (0.092 ± 0.007 and 0.118 ± 0.017 satellite cells/fiber in CON and EXP groups, respectively) muscle biopsy samples (P < 0.01), with no difference between the 2 groups. In both groups, we observed no significant changes in type II muscle fiber satellite cell content after exercise. Ingesting a multi-ingredient protein-based supplement for 7 wk did not alter the type I or II muscle fiber satellite cell response during postexercise recovery in older men. This trial was registered at www.clinicaltrials.gov as NCT02281331.

  5. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    PubMed Central

    Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

    2014-01-01

    Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and scanning electron microscope (SEM) study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS) was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer circulation and biodistrbution study confirmed high RES uptake (75%) in RES organs like liver lung spleen etc. Conclusion: The high RES uptake suggests BPQ SLN as a promising approach for targeted and improved delivery in theileriosis. PMID:24459400

  6. Capacitor-Chain Successive-Approximation ADC

    NASA Technical Reports Server (NTRS)

    Cunningham, Thomas

    2003-01-01

    A proposed successive-approximation analog-to-digital converter (ADC) would contain a capacitively terminated chain of identical capacitor cells. Like a conventional successive-approximation ADC containing a bank of binary-scaled capacitors, the proposed ADC would store an input voltage on a sample-and-hold capacitor and would digitize the stored input voltage by finding the closest match between this voltage and a capacitively generated sum of binary fractions of a reference voltage (Vref). However, the proposed capacitor-chain ADC would offer two major advantages over a conventional binary-scaled-capacitor ADC: (1) In a conventional ADC that digitizes to n bits, the largest capacitor (representing the most significant bit) must have 2(exp n-1) times as much capacitance, and hence, approximately 2(exp n-1) times as much area as does the smallest capacitor (representing the least significant bit), so that the total capacitor area must be 2(exp n) times that of the smallest capacitor. In the proposed capacitor-chain ADC, there would be three capacitors per cell, each approximately equal to the smallest capacitor in the conventional ADC, and there would be one cell per bit. Therefore, the total capacitor area would be only about 3(exp n) times that of the smallest capacitor. The net result would be that the proposed ADC could be considerably smaller than the conventional ADC. (2) Because of edge effects, parasitic capacitances, and manufacturing tolerances, it is difficult to make capacitor banks in which the values of capacitance are scaled by powers of 2 to the required precision. In contrast, because all the capacitors in the proposed ADC would be identical, the problem of precise binary scaling would not arise.

  7. SIRT1 activation attenuates diastolic dysfunction by reducing cardiac fibrosis in a model of anthracycline cardiomyopathy.

    PubMed

    Cappetta, Donato; Esposito, Grazia; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Berrino, Liberato; Rossi, Francesco; De Angelis, Antonella; Urbanek, Konrad

    2016-02-15

    Doxorubicin (DOXO) is an effective anti-neoplastic drug but its clinical benefits are hampered by cardiotoxicity. Oxidative stress, apoptosis and myocardial fibrosis mediate the anthracycline cardiomyopathy. ROS trigger TGF-β pathway that activates cardiac fibroblasts promoting fibrosis. Myocardial stiffness contributes to diastolic dysfunction, less studied aspect of anthracycline cardiomyopathy. Considering the role of SIRT1 in the inhibition of the TGF-β/SMAD3 pathway, resveratrol (RES), a SIRT1 activator, might improve cardiac function by interfering with the development of cardiac fibrosis in a model of DOXO-induced cardiomyopathy. F344 rats received a cumulative dose of 15 mg/kg of DOXO in 2 weeks or DOXO+RES (DOXO and RES, 2.5mg/kg/day, concomitantly for 2 weeks and then RES alone for 1 more week). The effects of RES on cardiac fibroblasts were also tested in vitro. Along with systolic dysfunction, DOXO was also responsible of diastolic abnormalities. Myocardial stiffness correlated with fibroblast activation and collagen deposition. DOXO+RES co-treatment significantly improved ± dP/dt and, more interestingly, ameliorated end-diastolic pressure/volume relationship. Treatment with RES resulted in reduced fibrosis and fibroblast activation and, most importantly, the mortality rate was significantly reduced in DOXO+RES group. Fibroblasts isolated from DOXO+RES-treated rats, in which SIRT1 was upregulated, showed decreased levels of TGF-β and pSMAD3/SMAD3 when compared to cells isolated from DOXO-exposed hearts. Our findings reveal a key role of SIRT1 in supporting animal survival and functional parameters of the heart. SIRT1 activation by interfering with fibrogenesis can improve relaxation properties of myocardium and attenuate myocardial remodeling related to chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Stem Cell-Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2014-10-01

    of human hematopoietic cells for extracellular matrix protein deficiency in epidermolysis bullosa. Stem Cells 2011, 29:900–906. 18. Di Nicola M...promotes cardiogenic gene expression in mesenchymal stem cells. Stem Cell Res Ther 2013, 4:43. 57. Herrmann JL, Wang Y, Abarbanell AM, Weil BR, Tan J

  9. Absolute determination of local tropospheric OH concentrations

    NASA Technical Reports Server (NTRS)

    Armerding, Wolfgang; Comes, Franz-Josef

    1994-01-01

    Long path absorption (LPA) according to Lambert Beer's law is a method to determine absolute concentrations of trace gases such as tropospheric OH. We have developed a LPA instrument which is based on a rapid tuning of the light source which is a frequency doubled dye laser. The laser is tuned across two or three OH absorption features around 308 nm with a scanning speed of 0.07 cm(exp -1)/microsecond and a repetition rate of 1.3 kHz. This high scanning speed greatly reduces the fluctuation of the light intensity caused by the atmosphere. To obtain the required high sensitivity the laser output power is additionally made constant and stabilized by an electro-optical modulator. The present sensitivity is of the order of a few times 10(exp 5) OH per cm(exp 3) for an acquisition time of a minute and an absorption path length of only 1200 meters so that a folding of the optical path in a multireflection cell was possible leading to a lateral dimension of the cell of a few meters. This allows local measurements to be made. Tropospheric measurements have been carried out in 1991 resulting in the determination of OH diurnal variation at specific days in late summer. Comparison with model calculations have been made. Interferences are mainly due to SO2 absorption. The problem of OH self generation in the multireflection cell is of minor extent. This could be shown by using different experimental methods. The minimum-maximum signal to noise ratio is about 8 x 10(exp -4) for a single scan. Due to the small size of the absorption cell the realization of an open air laboratory is possible in which by use of an additional UV light source or by additional fluxes of trace gases the chemistry can be changed under controlled conditions allowing kinetic studies of tropospheric photochemistry to be made in open air.

  10. The National Aeronautics and Space Administration's Gilmore Load Cell Machine: Load Cell Calibrations to 2.22 x 10(exp 7) Newtons

    NASA Technical Reports Server (NTRS)

    Haynes, Michael W.

    2000-01-01

    Designed in 1964 and erected in 1966, the mission of the Gilmore Load Cell Machine was to provide highly accurate calibrations for large capacity load cells in support of NASA's Apollo Program. Still in use today, the Gilmore Machine is a national treasure with no equal.

  11. A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora.

    PubMed Central

    Pirhonen, M; Flego, D; Heikinheimo, R; Palva, E T

    1993-01-01

    Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions. Images PMID:8508772

  12. A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora.

    PubMed

    Pirhonen, M; Flego, D; Heikinheimo, R; Palva, E T

    1993-06-01

    Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions.

  13. Use of spray-dried porcine blood by-products in diets for young chickens.

    PubMed

    Jamroz, D; Wiliczkiewicz, A; Orda, J; Kuryszko, J; Stefaniak, T

    2012-04-01

    Spray-dried porcine blood plasma (SDBP) or blood cells (SDBC) at amounts of 20 or 40 g/kg were included to the feed mixtures that were given to young chickens within 1-28 (Exp. 1) or 1-30 (Exp. 2) days post-hatch. In comparison with the group fed mixtures containing plant components, chickens fed mixtures supplemented with 40 g/kg of SDBP significantly (p < 0.01) increased the body weight estimated on 14 day of life (Exp. 1). At the age of 28 or 30 days post-hatch, the body weight was improved significantly (p < 0.01 or 0.05) in both experiments. Significant differences (one-factorial anova) in feed conversion among particular feeding groups were stated in Exp. 1 only; however, calculations using two-factorial anova show insignificant differences depending on the used animal meal. In selected blood parameters (IgG, Ht, Hb), insignificant differences between feeding groups were stated. The use of SDBP in feed mixture significantly increased the Na retention in both experiments, and K accretion in Exp. 1 only. Application of SDBC and 40 g/kg of SDBP significantly or insignificantly improved Fe retention. Insignificant diversification of apparent ileal digestibility of nutrients was stated; the crude fat was significantly better digested in treatments fed mixtures with animal meals but kind of animal meal was without any significant effect. Significant differences in digestibility of amino acids were recorded for Pro, Cys, Val, His, Lys and Arg. In chickens fed mixture with SDBC, higher coefficients of apparent digestibility of Cys, Val and His (Exp. 1) and Cys and His (Exp. 2) than in other feeding groups were obtained. The kind of used blood by-products has not affected the histological structure of intestine wall. © 2011 Blackwell Verlag GmbH.

  14. Experimental Air-Broadened Line Parameters in the nu2 Band of CH3D

    NASA Technical Reports Server (NTRS)

    Cross, Adriana Predoi; Brawley-Tremblay, Shannon; Povey, Chad; Smith, Mary Ann H.

    2007-01-01

    In this study we report the first experimental measurements of air-broadening and air-induced pressure-shift coefficients for approximately 378 transitions in the nu2 fundamental band of CH3D. These results were obtained from analysis of 17 room temperature laboratory absorption spectra recorded at 0.0056 cm(exp -1) resolution using the McMath-Pierce Fourier transform spectrometer located on Kitt Peak, Arizona. Three absorption cells with path lengths of 10.2, 25 and 150 cm were used to record the spectra. The total sample pressures ranged from 0.129x10(exp -2) to 52.855x10(exp -2) atm with CH3D volume mixing ratios of approximately 0.0109 in air. The spectra were analyzed using a multispectrum non-linear least-squares fitting technique. We report measurements for air pressure-broadening coefficients for transitions with quantum numbers as high as J" = 20 and K = 15, where K" = K' equivalent to K (for a parallel band). The measured air broadening coefficients range from 0.0205 to 0.0835 cm(exp -1) atm(exp -1) at 296 K. All the measured pressure-shift coefficients are negative and are found to vary from about -0.0005 to -0.0080 cm(exp -1) atm(exp -1) at the temperature of the spectra. We have examined the dependence of the measured broadening and shift parameters on the J" and K quantum numbers and also developed empirical expressions to describe the broadening coefficients in terms of m (m = -J", J" and J" + 1 in the (sup Q)P- (sup Q)Q-, and (sup Q)R-branch, respectively) and K. On average, the empirical expressions reproduce the measured broadening coefficients to within 4.4%.

  15. Design and simulation of front end power converter for a microgrid with fuel cells and solar power sources

    NASA Astrophysics Data System (ADS)

    Jeevargi, Chetankumar; Lodhi, Anuj; Sateeshkumar, Allu; Elangovan, D.; Arunkumar, G.

    2017-11-01

    The need for Renewable Energy Sources (RES) is increasing due to increased demand for the supply of power and it is also environment friendly.In the recent few years, the cost of generation of the power from the RES has been decreased. This paper aims to design the front end power converter which is required for integrating the fuel cells and solar power sources to the micro grid. The simulation of the designed front end converter is carried out in the PSIM 9.1.1 software. The results show that the designed front end power converter is sufficient for integrating the micro grid with fuel cells and solar power sources.

  16. Identification and characterization of an expansin gene AsEXP1 associated with heat tolerance in C3 Agrostis grass species.

    PubMed

    Xu, Jichen; Tian, Jiang; Belanger, Faith C; Huang, Bingru

    2007-01-01

    Plant tolerance of heat stress involves various changes at physiological and molecular levels. The objective of this study was to examine the expression of a gene encoding expansin protein in relation to heat tolerance in two C(3) grass species and genotypes differing in heat tolerance. Heat-tolerant, thermal Agrostis scabra, adapted to high temperatures in geothermal areas in Yellowstone National Park, was subjected to 20 degrees C (control) or 40 degrees C (heat stress) for 7 d in a growth chamber. Differential display analysis identified that a gene, AsEXP1, encoding an expansin protein, was strongly up-regulated in leaves exposed to heat stress in thermal A. scabra. Virtual northern hybridization and RT-PCR confirmed that AsEXP1 was a heat-inducible gene in leaves. The expression of AsEXP1 was induced at 1 h of plant exposure to heat stress and reached the highest level of expression at 4 h of treatment. A 1.3 kb full-length cDNA of AsEXP1 was isolated, which encodes a 251 amino acid protein. Two ecotypes of thermal A. scabra and 10 genotypes of Agrostis stolonifera (creeping bentgrass), a widely used turfgrass species in cool climatic regions, varying in the level of heat tolerance, were exposed to 40 degrees C for 7 d to examine the level of AsEXP1 expression in relation to heat tolerance. Genetic variation in heat tolerance was evaluated by measuring cell membrane stability, photochemical efficiency, and leaf growth. RT-PCR analysis revealed that the level of AsEXP1 in different genotypes was positively correlated with the level of heat tolerance in both grass species. The results first identified a heat-related expansin gene in grass species and suggest that AsEXP1 may be useful as a molecular marker to select for heat-tolerant grass germplasm.

  17. Design of a TEM cell EMP simulator

    NASA Astrophysics Data System (ADS)

    Sevat, Pete

    1991-06-01

    Electromagnetic pulse (EMP) simulators are designed to simulate the EMP generated by a nuclear weapon and are used to harden equipment against the effects of EMP. A transverse electromagnetic (TEM) cell is a square or rectangular coaxial transmission line tapered at each end to form a closed cell. The cell is fed at one end with a signal generator, a continuous wave or pulse generator, and terminated at the other end with a resistor equal to the characteristic impedance of the line. An advantage of the TEM cell is that the field is well characterized and reasonably uniform. A small, symmetric, TEM cell EMP simulator is described which is intended for applications such as susceptibility testing of small equipment, calibration of sensors, design and testing of countermeasures, measurement of transfer functions, and research and development. A detailed design is presented for a 50 ohm and 100 ohm TEM cell with an inner volume of 4 m(exp 3) and a test volume of 0.24 m(exp 3). The pulse generator and terminating network are integrated into the cell to form a completely shielded structure. In this way no interference from the inside of the cell to the outside, or vice versa, will occur.

  18. Hormonal Involvement in Breast Cancer Gene Amplification

    DTIC Science & Technology

    2008-10-01

    and transcriptome. Genome Res.16: 394-404. Zhu W. and Dutta A. (2006). Activation of Fanconi anemia pathway in cells with re- replicated DNA. Cell Cycle 5: 2306-2309. APPENDICES None SUPPORTING DATA None

  19. Mineralogy and Thermal Properties of V-Type Asteroid 956 Elisa: Evidence for Diogenitic Material from the Spitzer IRS (5-35 Micrometers) Spectrum

    NASA Technical Reports Server (NTRS)

    Lim, Lucy F.; Emery, Joshua P.; Moskovitz, Nicholas A.

    2010-01-01

    We present the thermal infrared (5-35 micrometer) spectrum of 956 Elisa as measured by the Spitzer Infrared Spectrograph ("IRS"; Houck,1.R. et .11. [20041. Astrophys, 1. SuppL 154, 18-24) together with new ground-based lightcurve data and near-IR spectra. From the visible lightcurve photometry, we determine a rotation period of 16.494 +/- 0.001 h, identify the rotational phase of the Spitzer observations, and estimate the visible absolute magnitude (Hv) at that rotational phase to be 12.58 +/- 0.04. From radiometric analysis of the thermal flux spectrum, we find that at the time of observation 956 Elisa had a projected radius of 5.3 +/- 0.4 km with a visible albedo pv = 0.142+/- 0.022, significantly lower than that of the prototype V-type asteroid, 4 Vesta. (This corresponds to a radius of 5.2 +/- 0.4 km at lightcurve mean.) Analysis with the standard thermal model (STM) results in a sub-solar temperature of 292.3 +/- 2.8 K and beaming parameter eta = 1.16 +/- 0.05. Thermophysical modeling places a lower limit of 20 J m(exp -2)K(exp -1)s(exp -1/2) on the thermal inertia of the asteroid's surface layer (if the surface is very smooth) but more likely values fall between 30 and 150 J m(exp -2)K(exp -1)s(exp -1/2) depending on the sense of rotation. The emissivity spectrum, calculated by dividing the measured thermal flux spectrum by the modeled thermal continuum, exhibits mineralogically interpretable spectral features within the 9-12 micrometer reststrahlen band, the 15-16.5 micrometer Si-O-Si stretching region, and the 16-25 micrometer reststrahlen region that are consistent with pyroxene of diogenitic composition: extant diogenitic pyroxenes fall within the narrow compositional range W0(sub 2+/-1)En(sub 74+/-2)Fs(sub 24+/-1). Spectral deconvolution of the 9-12 micrometer reststrahlen features indicates that up to approximately 20% olivine may also be present, suggesting an olivine-diogenite-like mineralogy. The mid-IR spectrum is inconsistent with non-cumulate eucrite as the major component on the surface of 956 Elisa, although cumulate eucrite material may be present at abundances lower than that of the diogenite component. Analysis of new near-IR spectra of 956 Elisa with the Modified Gaussian Model (MGM; Sunshine, J,M., Pieters, C.M., Pratt, S.F.[1990]. J. Geophys. Res, 95 (May), 6955-6966) results in two pyroxene compositions: 75% magnesian low-Ca pyroxene and 25% high-Ca pyroxene. High-Ca pyroxene is not evident in the mid-IR data, but may belong to a component that is underrepresented in the mid-IR spectrum either because of its spatial distribution on the asteroid or because of its particle size. High-Ca pyroxenes that occur as exsolution lamellae may also be more evident spectrally in the NIR than in the mid-IR. In any case, we find that the mid-IR spectrum of 956 Elisa is dominated by emission from material of diogenite- like composition, which has very rarely been observed among asteroids.

  20. Molecular basis of ‘hypoxic’ breast cancer cell radio-sensitization: phytochemicals converge on radiation induced Rel signaling

    PubMed Central

    2013-01-01

    Background Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers (BCa) and generally associated with therapeutic resistance, metastases, and poor patient survival. About 50% of locally advanced BCa, where radiotherapy is less effective are suggested to be due to hypoxic regions. In this study, we investigated the potential of bioactive phytochemicals in radio-sensitizing hypoxic BCa cells. Methods Hypoxic (O2-2.5%; N2-92.5%; CO2-5%) MCF-7 cells were exposed to 4 Gy radiation (IR) alone or after pretreatment with Curcumin (CUR), curcumin analog EF24, neem leaf extract (NLE), Genistein (GEN), Resveratrol (RES) or raspberry extract (RSE). The cells were examined for inhibition of NFκB activity, transcriptional modulation of 88 NFκB signaling pathway genes, activation and cellular localization of radio-responsive NFκB related mediators, eNos, Erk1/2, SOD2, Akt1/2/3, p50, p65, pIκBα, TNFα, Birc-1, -2, -5 and associated induction of cell death. Results EMSA revealed that cells exposed to phytochemicals showed complete suppression of IR-induced NFκB. Relatively, cells exposed EF24 revealed a robust inhibition of IR-induced NFκB. QPCR profiling showed induced expression of 53 NFκB signaling pathway genes after IR. Conversely, 53, 50, 53, 53, 53 and 53 of IR-induced genes were inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. In addition, 25, 29, 24, 16, 11 and 21 of 35 IR-suppressed genes were further inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. Immunoblotting revealed a significant attenuating effect of IR-modulated radio-responsive eNos, Erk1/2, SOD2, Akt1/2/3, p50, p65, pIκBα, TNFα, Birc-1, -2 and −5 with EF24, NLE, CUR, GEN, RES or RSE. Annexin V-FITC staining showed a consistent and significant induction of IR-induced cell death with these phytochemicals. Notably, EF24 robustly conferred IR-induced cell death. Conclusions Together, these data identifies the potential hypoxic cell radio-sensitizers and further implies that the induced radio-sensitization may be exerted by selectively targeting IR-induced NFκB signaling. PMID:23452621

  1. Ammonification in Bacillus subtilis Utilizing Dissimilatory Nitrite Reductase Is Dependent on resDE

    PubMed Central

    Hoffmann, Tamara; Frankenberg, Nicole; Marino, Marco; Jahn, Dieter

    1998-01-01

    During anaerobic nitrate respiration Bacillus subtilis reduces nitrate via nitrite to ammonia. No denitrification products were observed. B. subtilis wild-type cells and a nitrate reductase mutant grew anaerobically with nitrite as an electron acceptor. Oxygen-sensitive dissimilatory nitrite reductase activity was demonstrated in cell extracts prepared from both strains with benzyl viologen as an electron donor and nitrite as an electron acceptor. The anaerobic expression of the discovered nitrite reductase activity was dependent on the regulatory system encoded by resDE. Mutation of the gene encoding the regulatory Fnr had no negative effect on dissimilatory nitrite reductase formation. PMID:9422613

  2. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs.

    PubMed

    McCubrey, James A; Lertpiriyapong, Kvin; Steelman, Linda S; Abrams, Steve L; Yang, Li V; Murata, Ramiro M; Rosalen, Pedro L; Scalisi, Aurora; Neri, Luca M; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

    2017-06-12

    Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric ( Curcuma longa ). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants ( e.g., Coptis chinensis ) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

  3. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

    PubMed Central

    McCubrey, James A.; Lertpiriyapong, Kvin; Steelman, Linda S.; Abrams, Steve L.; Yang, Li V.; Murata, Ramiro M.; Rosalen, Pedro L.; Scalisi, Aurora; Neri, Luca M.; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M.; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

    2017-01-01

    Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health. PMID:28611316

  4. Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.

    PubMed

    Childs-Disney, Jessica L; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z; Hoskins, Jason; Southall, Noel; Marugan, Juan J; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P; Schatz, George C; Sobczak, Krzysztof; Thornton, Charles A; Disney, Matthew D

    2013-01-01

    The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.

  5. Induction and Reversal of Myotonic Dystrophy Type 1 Pre-mRNA Splicing Defects by Small Molecules

    PubMed Central

    Childs-Disney, Jessica L.; Stepniak-Konieczna, Ewa; Tran, Tuan; Yildirim, Ilyas; Park, HaJeung; Chen, Catherine Z.; Hoskins, Jason; Southall, Noel; Marugan, Juan J.; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P.; Schatz, George C.; Sobczak, Krzysztof; Thornton, Charles A.; Disney, Matthew D.

    2013-01-01

    The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 (DM1) is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)exp). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. The thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)exp and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)exp. This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)exp and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of DM1. PMID:23806903

  6. Uptake of Organic Vapors by Sulfate Aerosols: Physical and Chemical Processes

    NASA Technical Reports Server (NTRS)

    Michelsen, R. R.; Ashbourn, S. F. M.; Iraci, L.T.; Staton, S. J. R.

    2003-01-01

    While it is known that upper tropospheric sulfate particles contain a significant amount of organic matter, both the source of the organic fraction and its form in solution are unknown. These studies explore how the chemical characteristics of the molecules and surfaces in question affect heterogeneous interactions. The solubilities of acetaldehyde [CH3CHO] and ethanol [CH3CH20H] in cold, aqueous sulfuric acid solutions have been measured by Knudsen cell studies. Henry's law solubility coefficients range from 10(exp 2) to 10(exp 5) M/atm for acetaldehyde, and from 10(exp 4) to 10(exp 9) M/atm for ethanol under upper tropospheric conditions (210-240 K, 40-80 wt. % H2S04). The multiple solvation pathways (protonation, enolization, etc.) available to these compounds in acidic aqueous environments will be discussed. Preliminary results from the interaction of acetaldehyde with solutions of formaldehyde in sulfuric acid will be presented as well. The physical and chemical processes that affect organic uptake by aqueous aerosols will be explored, with the aim of evaluating organic species not yet studied in low temperature aqueous sulfuric acid.

  7. Genome-wide identification of wheat (Triticum aestivum) expansins and expansin expression analysis in cold-tolerant and cold-sensitive wheat cultivars

    PubMed Central

    Zhang, Jun-Feng; Xu, Yong-Qing; Dong, Jia-Min; Peng, Li-Na; Feng, Xu; Wang, Xu; Li, Fei; Miao, Yu; Yao, Shu-Kuan; Zhao, Qiao-Qin; Feng, Shan-Shan; Hu, Bao-Zhong

    2018-01-01

    Plant expansins are proteins involved in cell wall loosening, plant growth, and development, as well as in response to plant diseases and other stresses. In this study, we identified 128 expansin coding sequences from the wheat (Triticum aestivum) genome. These sequences belong to 45 homoeologous copies of TaEXPs, including 26 TaEXPAs, 15 TaEXPBs and four TaEXLAs. No TaEXLB was identified. Gene expression and sub-expression profiles revealed that most of the TaEXPs were expressed either only in root tissues or in multiple organs. Real-time qPCR analysis showed that many TaEXPs were differentially expressed in four different tissues of the two wheat cultivars—the cold-sensitive ‘Chinese Spring (CS)’ and the cold-tolerant ‘Dongnongdongmai 1 (D1)’ cultivars. Our results suggest that the differential expression of TaEXPs could be related to low-temperature tolerance or sensitivity of different wheat cultivars. Our study expands our knowledge on wheat expansins and sheds new light on the functions of expansins in plant development and stress response. PMID:29596529

  8. Ethanol deregulates Mecp2/MeCP2 in differentiating neural stem cells via interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2 regulatory elements

    PubMed Central

    Liyanage, Vichithra Rasangi Batuwita; Zachariah, Robby Mathew; Davie, James Ronald; Rastegar, Mojgan

    2017-01-01

    Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms. However, the underlying molecular mechanisms of ethanol-induced MeCP2 deregulation remain elusive. To study the effect of ethanol on Mecp2/MeCP2 expression during neurodifferentiation, we established an in vitro model of ethanol exposure, using differentiating embryonic brain-derived neural stem cells (NSC). Previously, we demonstrated the impact of DNA methylation at the Mecp2 regulatory elements (REs) on Mecp2/MeCP2 expression in vitro and in vivo. Here, we studied whether altered DNA methylation at these REs is associated with the Mecp2/MeCP2 misexpression induced by ethanol. Binge-like and continuous ethanol exposure upregulated Mecp2/MeCP2, while ethanol withdrawal downregulated its expression. DNA methylation analysis by methylated DNA immunoprecipitation indicated that increased 5-hydroxymethylcytosine (5hmC) and decreased 5-methylcytosine (5mC) enrichment at specific REs were associated with upregulated Mecp2/MeCP2 following continuous ethanol exposure. The reduced Mecp2/MeCP2 expression upon ethanol withdrawal was associated with reduced 5hmC and increased 5mC enrichment at these REs. Moreover, ethanol altered global DNA methylation (5mC and 5hmC). Under the tested conditions, ethanol had minimal effects on NSC cell fate commitment, but caused changes in neuronal morphology and glial cell size. Taken together, our data represent an epigenetic mechanism for ethanol-mediated misexpression of Mecp2/MeCP2 in differentiating embryonic brain cells. We also show the potential role of DNA methylation and MeCP2 in alcohol-related neurological disorders, specifically Fetal Alcohol Spectrum Disorders. PMID:25620416

  9. Small molecule alteration of RNA sequence in cells and animals.

    PubMed

    Guan, Lirui; Luo, Yiling; Ja, William W; Disney, Matthew D

    2017-10-18

    RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG) exp . The small molecule, 2H-4-Ru, binds to r(CUG) exp and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effects of Tea Phenolics on Iron Uptake from Different Fortificants by Caco-2 cells

    USDA-ARS?s Scientific Manuscript database

    The in vitro effects of tea phenolics on Fe uptake from different fortificants (FeSO4, FeCl3, FeEDTA) by Caco-2 cells were compared. Cell cultures were exposed to catechin, tannic acid, green or black tea solutions added within Fe-containing solution, or used to pre-treat cell cultures before Fe-exp...

  11. Studies of Large-Area Inversion-Layer Metal-Insulator-Semiconductor (IL/MIS) Solar Cells and Arrays

    NASA Technical Reports Server (NTRS)

    Ho, Fat Duen

    1996-01-01

    Many inversion-layer metal-insulator-semiconductor (IL/MIS) solar cells have been fabricated. There are around eighteen 1 cm(exp 2) IL/MIS solar cells which have efficiencies greater than 7%. There are only about three 19 cm(exp 2) IL/MIS cells which have efficiencies greater than 4%. The more accurate control of the thickness of the thin layer of oxide between aluminum and silicon of the MIS contacts has been achieved. A lot of effort and progress have been made in this area. A comprehensive model for MIS contacts under dark conditions has been developed that covers a wide range of parameters. It has been applied to MIS solar cells. One of the main advantages of these models is the prediction of the range of the thin oxide thickness versus the maximum efficiencies of the MIS solar cells. This is particularly important when the thickness is increased to 25 A. This study is very useful for our investigation of the IL/MIS solar cells. The two-dimensional numerical model for the IL/MIS solar cells has been tried to develop and the results are presented in this report.

  12. Radioisotope powered AMTEC systems

    NASA Astrophysics Data System (ADS)

    Ivanenok, Joseph F., III; Sievers, Robert K.

    1994-11-01

    Alkali metal thermal to electric converter (AMTEC) systems are being developed for high performance spacecraft power systems, including small, general purpose heat source (GPHS) powered systems. Several design concepts have been evaluated for the power range from 75 W to 1 kW. The specific power for these concepts has been found to be as high as 18-20 W/kg and 22 kW/m(exp 3). The projected area, including radiators, has been as low as 0.4 m(exp 2)/kW. AMTEC power systems are extremely attractive, relative to other current and projected power systems, because AMTEC offers high power density, low projected area, and low volume. Two AMTEC cell design types have been identified. A single-tube cell is already under development and a multitube cell design, to provide additional power system gains, has undergone proof-of-principle testing. Solar powered AMTEC (SAMTEC) systems are also being developed, and numerous terrestrial applications have been identified for which the same basic AMTEC cells being developed for radioisotope systems are also suitable.

  13. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute Radiation Research (CARR) grant; NSBRI is funded through NASA NCC 9-58. Recent Publications: [1]Cengel K. A. et al. (2010) Radiat Environ Biophys 49(4): 715-21. [2] Ware J. H. et al. (2010) Radiation Res 174: 325-330. [3] Davis J. G. et al. (2010) Radiation Res 173(3):353-61. [4] Sanzari J.K. et al. (2011) Radiation Res 175(5):650-6. [5] Ni H. et al. (2011) Radiation Res 175(4): 485-92. [6] Mao X. W. et al. (2011) Radiation Res 176: 187-197. [7] Maks C. J. et al. (2011) Radiation Res 176: 170-6. [8] Kennedy A. R. et al. (2011) Radiation Res 176: 62-70. [9] Sanzari J. K. et al. (2011) Int J Radiat Biol 87: 1033-8. [10] Wilson J. M. et al. (2011) Radiation Res 176(5):649-59. [11] Kennedy A. R. and Wan X. S. (2011) Advances in Space Res 48: 1460-1479. [12] Gridley D. S. et al. (2011) Int J Radiat Biol 2011 87(12): 1173-81, [13] York J. M., et al. (2012) Brain Behav Immun 26(2): 218-27,[14] Wilson J. M. et al. (2012) Advances in Space Res 49: 237-248. [15] Krigsfeld, G.S. et al. Int J Radiat Biol 2012 Feb 6 [Epub ahead of print

  14. Single-Event Effect Performance of a Conductive-Bridge Memory EEPROM

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Wilcox, Edward; Berg, Melanie; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Seidleck, Christina; LaBel, Kenneth

    2015-01-01

    We investigated the heavy ion SEE characteristics of an EEPROM based on CBRAM technology. SEFI is the dominant type of SEE for each operating mode (standby, read-only, write/read). We also observed single bit upsets in the CBRAM cell, during write/read tests. the SEULET threshold is between 10 and 20 MeV * sq cm/mg, with an upper fluence limit of 3 × 10(exp 6) cm(exp -2) at 10 MeV * sq cm/mg. In the stand by mode, the CBRAM array appears immune to bit upsets.

  15. Inhibition of Non-ATG Translational Events in Cells via Covalent Small Molecules Targeting RNA.

    PubMed

    Yang, Wang-Yong; Wilson, Henry D; Velagapudi, Sai Pradeep; Disney, Matthew D

    2015-04-29

    One major class of disease-causing RNAs is expanded repeating transcripts. These RNAs cause diseases via multiple mechanisms, including: (i) gain-of-function, in which repeating RNAs bind and sequester proteins involved in RNA biogenesis and (ii) repeat associated non-ATG (RAN) translation, in which repeating transcripts are translated into toxic proteins without use of a canonical, AUG, start codon. Herein, we develop and study chemical probes that bind and react with an expanded r(CGG) repeat (r(CGG)(exp)) present in a 5' untranslated region that causes fragile X-associated tremor/ataxia syndrome (FXTAS). Reactive compounds bind to r(CGG)(exp) in cellulo as shown with Chem-CLIP-Map, an approach to map small molecule binding sites within RNAs in cells. Compounds also potently improve FXTAS-associated pre-mRNA splicing and RAN translational defects, while not affecting translation of the downstream open reading frame. In contrast, oligonucleotides affect both RAN and canonical translation when they bind to r(CGG)(exp), which is mechanistically traced to a decrease in polysome loading. Thus, designer small molecules that react with RNA targets can be used to profile the RNAs to which they bind in cells, including identification of binding sites, and can modulate several aspects of RNA-mediated disease pathology in a manner that may be more beneficial than oligonucleotides.

  16. Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

    DTIC Science & Technology

    2014-09-01

    Staszewski, et al., The PHSCN dendrimer as a more potent inhibitor of human breast cancer cell invasion, extravasation, and lung colony formation...the PHSCN dendrimer as an inhibitor of human prostate cancer cell invasion, extravasation, and lung colony formation. Clin Exp Metastasis, 2010. 27(3

  17. Transgenic plants producing the bacterial pheromone N-acyl-homoserine lactone exhibit enhanced resistance to the bacterial phytopathogen Erwinia carotovora.

    PubMed

    Mäe, A; Montesano, M; Koiv, V; Palva, E T

    2001-09-01

    Bacterial pheromones, mainly different homoserine lactones, are central to a number of bacterial signaling processes, including those involved in plant pathogenicity. We previously demonstrated that N-oxoacyl-homoserine lactone (OHL) is essential for quorum sensing in the soft-rot phytopathogen Erwinia carotovora. In this pathogen, OHL controls the coordinate activation of genes encoding the main virulence determinants, extracellular plant cell wall degrading enzymes (PCWDEs), in a cell density-dependent manner. We suggest that E. carotovora employ quorum sensing to avoid the premature production of PCWDEs and subsequent activation of plant defense responses. To test whether modulating this sensory system would affect the outcome of a plant-pathogen interaction, we generated transgenic tobacco, producing OHL. This was accomplished by ectopic expression in tobacco of the E. carotovora gene expI, which is responsible for OHL biosynthesis. We show that expI-positive transgenic tobacco lines produced the active pheromone and partially complemented the avirulent phenotype of expI mutants. The OHL-producing tobacco lines exhibited enhanced resistance to infection by wild-type E. carotovora. The results were confirmed by exogenous addition of OHL to wild-type plants, which also resulted in increased resistance to E. carotovora.

  18. Neurosecretory Cell Types and Distribution in Unfed Female Hyalomma Dromedari (Acari: Ixodoidea: Ixodidae) Synganglion

    DTIC Science & Technology

    1987-01-01

    of the cell in subtype VIh (Fig. 2). Type IX : In these oval celo, 2 subtypes are distinguished according to cell size and NSG distribution. The NSG...1977) : Neurosecretion in Ornithodoros savignyi (Audouin) (Ixodoidea : Arga- sidae ). The distribution of neurosecretory cells in the brain. J. Vet. Res

  19. Volatility and Wear Characteristics of a Variety of Liquid Lubricants for Space Applications

    NASA Technical Reports Server (NTRS)

    Nguyen, QuynhGiao N.; Jones, William R., Jr.

    2001-01-01

    The vapor pressures and wear characteristics are critical properties for liquid lubricants to assure long-term reliability and performance in space applications. Vapor pressures, obtained using a Knudsen cell technique, and wear properties, obtained using a vacuum four-ball apparatus, were measured for a series of unformulated liquid lubricants. These included two multiply alkylated cyclopentanes (MACs) (X-1000 and X2000), two linear perfluoropolyalkylethers (PFPAEs) (Z-25 and 815Z), and four silahydrocarbons (a tri, a tetra, and two pentas). Vapor pressures were measured at three elevated temperatures (423, 448, and 498 K) and extrapolated to room temperature 298 K. The lowest 298 K vapor pressure of 5.7 x 10(exp -14) Pa was obtained with the PFPAE fluid (815Z) and the highest value with the low molecular weight MAC (X-1000) at 3.6 x 10(exp -7) Pa. In addition, vacuum wear rates were determined for some of the lubricants. The lowest wear rates (approximately 3 x 10(exp -11) cubic mm/mm) were observed for three of the silahydrocarbons while the highest wear rates (approximately 2 x 10(exp -9) cubic mm/mm) were observed with the two PFPAE fluids (Z-25 and 815Z). The MAC (X-2000) yielded a wear rate of about 10(exp -10) cubic mm/mm. The results indicated that the silahydrocarbon class of liquid lubricants offers the better potential for space applications.

  20. Volatility and Wear Characteristics of a Variety of Liquid Lubricants for Space Applications

    NASA Technical Reports Server (NTRS)

    Nguyen, Quynhgiao N.; Jones, William R., Jr.

    2001-01-01

    The vapor pressures and near characteristics are critical properties for liquid lubricants to assure long-term reliability and performance in space applications. Vapor pressures, obtained using a Knudsen cell technique, and near properties, obtained using a vacuum four-ball apparatus, were measured for a series of unformulated liquid lubricants. These include: two multiple alkylated cyclopentanes (MACs) (X-1000 and X-2000), two linear perfluoropolyalkylethers (PFPAEs) (Z-25 and 815Z), and four silahydrocarbons (a tri-, a tetra-, and two pentas). Vapor pressures were measured at three elevated temperatures (423, 448, and 498 K) and extrapolated to room temperature 298 K. The lowest 298 K vapor pressure of 5.7 x 10(exp -14) Pa, was obtained with the PFPAE fluid (815Z) and the highest value with the low molecular weight MAC (X-1000) at 3.6 x 10(exp -7) Pa. In addition, vacuum near rates were determined for some of the lubricants. The lowest wear rates (approximately 3 x 10(exp -11) cubic mm/mm) were observed for three of the silahydrocarbons while the highest wear rate (approximately 2 x 10(exp-9) cubic mm/mm) were observed with the two PFPAE fluids (Z-25 and 815Z). The MAC (X-2000) yielded a wear rate of about 10(exp -10) cubic mm/mm. The results indicated that the silahydrocarbon class of liquid lubricants offers the better potential for space applications.

  1. Alleviation of Acute Lung Injury in Rats with Sepsis by Resveratrol via the Phosphatidylinositol 3-Kinase/Nuclear Factor-Erythroid 2 Related Factor 2/Heme Oxygenase-1 (PI3K/Nrf2/HO-1) Pathway.

    PubMed

    Wang, Yu; Wang, Xiaofeng; Zhang, Lichun; Zhang, Rong

    2018-05-30

    BACKGROUND Resveratrol (Res) is a type of polyphenol found in many plants, which can protect important organs from the damage induced by sepsis. However, the exact mechanism of its protective effect has not been established. This study investigated the effect of Res on the PI3K/Nrf2/HO-1 signaling pathway in rats with sepsis-induced acute lung injury (ALI). MATERIAL AND METHODS Male Wistar rats were treated with 30 mg/kg Res by intraperitoneal administration for 1 hour immediately after cecal ligation and puncture. Levels of MIP-2, IL-18, and IL-10 in bronchoalveolar lavage fluid (BALF) were determined. Lung tissues were collected to measure the wet-to-dry (W/D) ratios, oxidative stress index, and lung injury scores. Expression levels of Akt, p-Akt, HO-1, Nrf-2, and active caspase-3 proteins were determined by western blotting; expression of HO-1 mRNA was determined by RT-PCR. RESULTS Treatment with Res significantly decreased the levels of MIP-2 and IL-18 and increased IL-10 in the BALF of rats with sepsis-induced ALI. In addition, Res also effectively reduced the W/D lung weight ratio, lung injury score, and the levels of MDA (malondialdehyde) and 8-OHdG. Conversely, Res increased SOD (superoxide dismutase) activity in the lung tissue. Moreover, Res significantly induced higher HO-1 mRNA expression, upregulated HO-1 and Nrf-2 protein expression, and the phosphorylation of Akt in the lung tissue. In contrast, the levels of activated caspase-3 protein were decreased in Res-treated rats (P<0.05). CONCLUSIONS Res could inhibit inflammation, oxidative stress, and cell apoptosis to alleviate ALI in septic rats through the inhibition of the PI3K/Nrf2/HO-1 signaling pathway.

  2. Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

    DTIC Science & Technology

    2010-01-01

    mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

  3. Markers of Ovarian Cancer Using a Glycoprotein/Antibody Array

    DTIC Science & Technology

    2014-05-01

    Article dx.doi.org/10.1021/pr400169n | J. Proteome Res. 2013, 12, 3342−33523350 osteopontin fragments for ovarian cancer in urine . Clin. Cancer Res. 2006...absorbent under urea /dithiothreitol denatured environment. Anal. Biochem. 2010, 398 (1), 34−44. (26) Chiu, P. C.; Chung, M. K.; Koistinen, R.; Koistinen... Synthesis and functional analyses of nuclear clusterin, a cell death protein. J. Biol. Chem. 2003, 278 (13), 11590−600. (60) Hassan, M. K.; Watari, H

  4. INFLUENCE OF TEMPERATURE ON AN ESTROGEN-RESPONSIVE RAINBOW TROUT CELL TRANSFECTION ASSAY

    EPA Science Inventory

    One uncertainty in extrapolating estrogenic effects in mammalian systems to those in fish and wildlife is the influence that temperature has on these effects. A reporter gene assay in cultured rainbow trout cell lines was used to determine the influence of temperature on the exp...

  5. Immunoreactive serum opsonic alpha 2 sb glycoprotein as a noninvasive index of RES systemic defense after trauma.

    PubMed

    Kaplan, J E; Saba, T M

    1979-01-01

    Reticuloendothelial system (RES) depression has been correlated with diminished resistance to trauma, shock, and sepsis in man and animals. Previous studies have related the depression of RES hepatic Kupffer cell phagocytic function after trauma to diminished bioassayable opsonic activity. The present study determined if the loss of biological activity and RES alteration correlated with immunoreactive serum opsonic alpha 2 SB glycoprotein levels after trauma. Serum opsonic activity was measured by liver slice bioassay, and immunoreactive opsonic protein was measured by rocket electroimmunoassay. RE function was determined by colloid clearance over a 24-hour post-trauma period. Anesthetized rats (250-300 gm) subjected to sublethal or severe (greater than LD50) whole-body NCD trauma were the shock models investigated. Immunoreactive levels in 63 rats prior to injury were 518 +/- 24 microgram/ml. Neither biological nor immunoreactive levels were altered over 24 hours in anesthetized sham-traumatized controls. Temporal alteration in the initial decrease and recovery pattern of biologically active and immunoreactive opsonic protein levels significantly correlated following both sublethal and severe injury. Moreover, the patterns of immunoreactive levels of the opsonic protein correlated with the functional phagocytic activity of the RES as determined by vascular clearance of a test dose of blood-borne radiolabeled particulates. This glycoprotein falls after trauma, and the magnitude and duration of the decline increases with severity of injury. Immunoreactive opsonic alpha 2 SB glycoprotein appears to be an accurate measurement of circulating opsonic activity and RE Kupffer cell function after trauma, especially with respect to clearance. Thus, immunoreactive opsonic protein warrants clinical consideration as a noninvasive measure of reticuloendothelial systemic defense in patients after trauma and burn.

  6. Surveying a supercoil domain by using the gamma delta resolution system in Salmonella typhimurium.

    PubMed Central

    Higgins, N P; Yang, X; Fu, Q; Roth, J R

    1996-01-01

    A genetic system was developed to investigate the supercoil structure of bacterial chromosomes. New res-carrying transposons were derived from MudI1734 (MudJr1 and MudJr2) and Tn10 (Tn10dGn). The MudJr1 and MudJr2 elements each have a res site in opposite orientation so that when paired with a Tn10dGn element in the same chromosome, one MudJr res site will be ordered as a direct repeat. Deletion formation was studied in a nonessential region (approximately 100 kb) that extends from the his operon through the cob operon. Strains with a MudJr insertion in the cobT gene at the 5' end of the cob operon plus a Tn10dGn insertion positioned either clockwise or counterclockwise from cobT were exposed to a burst of RES protein. Following a pulse of resolvase expression, deletion formation was monitored by scoring the loss of the Lac+ phenotype or by loss of tetracycline resistance. In exponentially growing populations, deletion products appeared quickly in some cells (in 10 min) but also occurred more than an hour after RES induction. The frequency of deletion (y) diminished with increasing distance (x) between res sites. Results from 15 deletion intervals fit the exponential equation y = 120 . 10(-0.02x). We found that res sites can be plectonemically interwound over long distances ( > 100 kb) and that barriers to supercoil diffusion are placed stochastically within the 43- to 45-min region of the chromosome. PMID:8631670

  7. p21(WAF1) Mediates Cell-Cycle Inhibition, Relevant to Cancer Suppression and Therapy.

    PubMed

    El-Deiry, Wafik S

    2016-09-15

    p21 (WAF1/CIP1; CDKN1a) is a universal cell-cycle inhibitor directly controlled by p53 and p53-independent pathways. Knowledge of the regulation and function of p21 in normal and cancer cells has opened up several areas of investigation and has led to novel therapeutic strategies. The discovery in 1993 and subsequent work on p21 has illuminated basic cellular growth control, stem cell phenotypes, the physiology of differentiation, as well as how cells respond to stress. There remain open questions in the signaling networks, the ultimate role of p21 in the p53-deficiency phenotype in the context of other p53 target defects, and therapeutic strategies continue to be a work in progress. Cancer Res; 76(18); 5189-91. ©2016 AACRSee related article by El-Deiry et al., Cancer Res 1994;54:1169-74Visit the Cancer Research 75(th) Anniversary timeline. ©2016 American Association for Cancer Research.

  8. Production de faisceaux EPR à l'aide d'un oscillateur paramétrique optique à auto-verrouillage de phase

    NASA Astrophysics Data System (ADS)

    Longchambon, L.; Laurat, J.; Treps, N.; Ducci, S.; Maître, A.; Coudreau, T.; Fabre, C.

    2002-06-01

    Nous étudions théoriquement les propriétés quantiques des faisceaux lumineux continus orthogonalement polarisés émis par un Oscillateur Paramétrique Optique (OPO) de type II contenant une lame biréfringente. Quand les axes optiques de la lame sont tournés par rapport à ceux du cristal paramétrique, un couplage apparaît entre les faisceaux signal et complémentaire qui entraîne un verrouillage de phase entre les deux modes et un fonctionnement à dégénérescence de fréquence à l'intérieur d'une zone d'accrochage. Les corrélations quantiques entre les deux faisceaux permettent de définir les zones dans l'espace des paramètres expérimentaux où les différents critères associés à l'intrication EPR utilisés en information quantique sont vérifiés.

  9. Comportement rhéologique des systèmes mixtes biopolymères / protéines

    NASA Astrophysics Data System (ADS)

    Rebiha, M.; Moulai-Mostefa, N.; Sadok, A. Hadj; Sabri, N.

    2005-05-01

    Dans ce travail, on s'est intéressé à l'étude des effets du caséinate de sodium et du xanthane sur les propriétés rhéologiques des solutions aqueuses, préparées suivant un plan d'expériences. Les caractéristiques mécaniques obtenues sont traduites par les coefficients du modèle rhéologique de Casson, en l'occurrence la contrainte seuil, τ 0, et la viscosité plastique, η _c. Ainsi, à l'issue de la modélisation en surface de réponses, il apparaît une interaction répulsive à l'échelle structurale entre le caséinate de sodium et le xanthane, traduite par un abaissement considérable de τ 0. Cet baissement de la rigidité peut conduire à une séparation de phases, phénomène conditionné par la viscosité limite de Casson,η _c.

  10. Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

    PubMed Central

    Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

    2013-01-01

    Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

  11. Influence of gravity on foams

    NASA Astrophysics Data System (ADS)

    Monnereau, C.; Vignes-Adler, M.; Kronberg, B.

    1999-06-01

    The feasibility of experiments on the physics of foams in microgravity environment was investigated during a parabolic flight campaign. Transient foams from surfactant-free organic liquids and stable foams from a soapy solution of a Sodium Dodecyl Sulfate + Dodecanol mixture were investigated. In 0g, the transient foam is stabilized; whatever the liquid the foam bubbles are spherical and their diameter does not change during the flight. When the gravity constant is equal to 1.8 g, the bubbles of the stable foam become polyhedral and numerous topological transformations could be observed. La faisabilité d'expériences permettant d'étudier la physique de la mousse en microgravité a été démontrée au cours de vols paraboliques. Nous avons testé des mousses de liquides organiques sans tensioactif qui sont éphémères dans le champ terrestre, et des mousses à base d'une solution aqueuse d'un mélange de Dodécyl Sulfate de Sodium et de Dodécanol qui sont au contraire très stables. En microgravité, les mousses éphémères sont stabilisées; quel que soit le liquide, les bulles sont sphériques et leur diamètre reste égal à leur valeur initiale. Lorsqu'au cours de la parabole, la gravité devient égale à 1,8 g, les bulles de la mousse stable dont les films sont très rigides prennent une forme polyédrique ; de très nombreuses transformations topologiques de type T1 ont pu alors être observées.

  12. Expression patterns of cell wall-modifying genes from banana during fruit ripening and in relationship with finger drop

    PubMed Central

    Mbéguié-A-Mbéguié, D.; Hubert, O.; Baurens, F. C.; Matsumoto, T.; Chillet, M.; Fils-Lycaon, B.; Sidibé-Bocs, S.

    2009-01-01

    Few molecular studies have been devoted to the finger drop process that occurs during banana fruit ripening. Recent studies revealed the involvement of changes in the properties of cell wall polysaccharides in the pedicel rupture area. In this study, the expression of cell-wall modifying genes was monitored in peel tissue during post-harvest ripening of Cavendish banana fruit, at median area (control zone) and compared with that in the pedicel rupture area (drop zone). To this end, three pectin methylesterase (PME) and seven xyloglucan endotransglycosylase/hydrolase (XTH) genes were isolated. The accumulation of their mRNAs and those of polygalaturonase, expansin, and pectate lyase genes already isolated from banana were examined. During post-harvest ripening, transcripts of all genes were detected in both zones, but accumulated differentially. MaPME1, MaPG1, and MaXTH4 mRNA levels did not change in either zone. Levels of MaPME3 and MaPG3 mRNAs increased greatly only in the control zone and at the late ripening stages. For other genes, the main molecular changes occurred 1–4 d after ripening induction. MaPME2, MaPEL1, MaPEL2, MaPG4, MaXTH6, MaXTH8, MaXTH9, MaEXP1, MaEXP4, and MaEXP5 accumulated highly in the drop zone, contrary to MaXTH3 and MaXTH5, and MaEXP2 throughout ripening. For MaPG2, MaXET1, and MaXET2 genes, high accumulation in the drop zone was transient. The transcriptional data obtained from all genes examined suggested that finger drop and peel softening involved similar mechanisms. These findings also led to the proposal of a sequence of molecular events leading to finger drop and to suggest some candidates. PMID:19357434

  13. Prion protein conversion induced by trivalent iron in vesicular trafficking.

    PubMed

    Choi, Bo-Ran; Lee, Jeongmin; Kim, Su Yeon; Yim, Inbeen; Kim, Eun-Hee; Woo, Hee-Jong

    2013-03-15

    Iron dyshomeostasis has been observed in prion diseases; however, little is known regarding the contribution of the oxidation state of iron to prion protein (PrP) conversion. In this study, PrP(C)-deficient HpL3-4 cells were exposed to divalent [Fe(II)] or trivalent [Fe(III)] iron, followed by exogenous recombinant PrP (rPrP) treatment. We then analyzed the accumulation of internalized rPrP and its biochemical properties, including its resistance to both proteinase K (PK) digestion and detergent solubility. Fe(III), but not Fe(II), induced the accumulation of internalized rPrP, which was partially converted to detergent-insoluble and PK-resistant PrP (PrP(res)). The Fe(III)-induced PrP(res) generation required an intact cell structure, and it was hindered by U18666A, an inhibitor of vesicular trafficking, but not by NH4Cl, an inhibitor of endolysosomal acidification. These observations implicated that the Fe(III)-mediated PrP(res) conversion likely occurs during endosomal vesicular trafficking rather than in the acidic environment of lysosomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. ExpTreeDB: web-based query and visualization of manually annotated gene expression profiling experiments of human and mouse from GEO.

    PubMed

    Ni, Ming; Ye, Fuqiang; Zhu, Juanjuan; Li, Zongwei; Yang, Shuai; Yang, Bite; Han, Lu; Wu, Yongge; Chen, Ying; Li, Fei; Wang, Shengqi; Bo, Xiaochen

    2014-12-01

    Numerous public microarray datasets are valuable resources for the scientific communities. Several online tools have made great steps to use these data by querying related datasets with users' own gene signatures or expression profiles. However, dataset annotation and result exhibition still need to be improved. ExpTreeDB is a database that allows for queries on human and mouse microarray experiments from Gene Expression Omnibus with gene signatures or profiles. Compared with similar applications, ExpTreeDB pays more attention to dataset annotations and result visualization. We introduced a multiple-level annotation system to depict and organize original experiments. For example, a tamoxifen-treated cell line experiment is hierarchically annotated as 'agent→drug→estrogen receptor antagonist→tamoxifen'. Consequently, retrieved results are exhibited by an interactive tree-structured graphics, which provide an overview for related experiments and might enlighten users on key items of interest. The database is freely available at http://biotech.bmi.ac.cn/ExpTreeDB. Web site is implemented in Perl, PHP, R, MySQL and Apache. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.

    PubMed

    Kumar, Amit; Parkesh, Raman; Sznajder, Lukasz J; Childs-Disney, Jessica L; Sobczak, Krzysztof; Disney, Matthew D

    2012-03-16

    Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)(exp)) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5'CAG/3'GAC motif found in r(CAG)(exp) hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)(exp). The compound was identified by first studying the binding of RNA 1 × 1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5'CAG/3'GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate, a small molecule that improves pre-mRNA splicing defects associated with the r(CAG)(exp)-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)(exp) and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)(exp) toxicity. The approach used in these studies, defining the small RNA motifs that bind small molecules with known affinity for nucleic acids and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in the human genomic sequence.

  16. Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG) transcripts

    PubMed Central

    Kumar, Amit; Parkesh, Raman; Sznajder, Lukasz J.; Childs-Disney, Jessica; Sobczak, Krzysztof; Disney, Matthew D.

    2012-01-01

    Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)exp) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5’CAG/3’GAC motif found in r(CAG)exp hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)exp. The compound was identified by first studying the binding of RNA 1×1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5’CAG/3’GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate as small molecule capable of improving pre-mRNA splicing defects associated with the r(CAG)exp-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)exp and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)exp toxicity. The approach used in these studies, defining the small RNA motifs that bind known nucleic acid binders and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in human genomic sequence. PMID:22252896

  17. The effect of a microgravity (space) environment on the expression of expansins from the peg and root tissues of Cucumis sativus

    NASA Technical Reports Server (NTRS)

    Link, B. M.; Wagner, E. R.; Cosgrove, D. J.

    2001-01-01

    In young cucumber seedlings, the peg is a polar outgrowth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. The development of the peg is thought to be gravity-dependent and has become a model system for plant-gravity response. Peg development requires rapid cell expansion, a process thought to be catalyzed by alpha-expansins, and thus was a good system to identify expansins that were regulated by gravity. This study identified 7 new alpha-expansin cDNAs from cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) and examined their expression patterns. Two alpha-expansins (CsExp3 and CsExp4) were more highly expressed in the peg and the root. Earlier reports stated that pegs tend not to form in the absence of gravity, so the expression levels were compared in the pegs of seedlings grown in space (STS-95), on a clinostat, and on earth (1 g). Pegs were observed to form at high frequency on clinostat and space-grown seedlings, yet on clinostats there was more than a 4-fold reduction in the expression of CsExp3 in the pegs of seedlings grown on clinostats vs. those grown at 1 g, while the CsExp4 gene appeared to be turned off (below detection limits). There were no detectable differences in expansin gene expression levels for the pegs of seedlings grown in space or in the orbiter environmental simulator (OES) (1 g) at NASA. The microgravity environment did not affect the expression of CsExp3 or CsExp4, and the clinostat did not simulate the microgravity environment well.

  18. Hematopoietic Stem Cell and Its Growth Factor

    DTIC Science & Technology

    1988-02-16

    Bamberger and AS Felin . 1981. A multipotential leukemia cell line (K562) of human origin. Proc Soc Exp Biol Med 166:546. 40. Marie JP, CA Izaquirre, CI...at day 12 due to the degeneration of cells in the colonies. Monoclonal antibodies against human nonlymphoid leukemia cell lines which have...granulocyte mAb with acute myclocytic and myelomonocytic and lymphocytic leukemia ................................... 18 A-4 Antigen ML143 is expressed on

  19. Optical Strategies for Studying Metastatic Mechanisms, Tumor Cell Detection and Treatment of Prostate Cancer

    DTIC Science & Technology

    2006-10-01

    Treatment, Photodynamic Therapy, Biological Response 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF...photodynamic therapy in a rat prostate tumor model. Clin Cancer Res 2005;11:720-7. 18 . Fukumura D, Yuan F, Monsky WL, Chen Y, Jain RK. Effect of host...angiogenesis and microvascular functions in human breast cancer xenografts : Mammary fat pad versus cranial tumors. Clin Cancer Res 2002;8:1008-13. 20. Hasan T

  20. Effect of Medium-chain Triglyceride (MCT) on Growth Performance, Nutrient Digestibility, Blood Characteristics in Weanling Pigs

    PubMed Central

    Hong, S. M.; Hwang, J. H.; Kim, I. H.

    2012-01-01

    One hundred and twenty weanling pigs in experiment 1 (Exp. 1) (6.91±0.99 kg; 21 d of age) and Exp. 2 (10.20±1.09 kg; 28 d of age) were used in two 42-d and 35-d experiments to evaluate the effect of medium-chain-triglyceride (MCT) on growth performance, apparent total tract digestibility (ATTD) of nutrients and blood profile. In both of Exp. 1 and Exp. 2, the same dietary treatments were utilized as follows : i) negative control (NC), ii) positive control (PC), NC+antibiotics (40 mg/kg Tiamulin, 110 mg/kg Tylosin, and 10 mg/kg Enramycin, iii) MCT3, NC+0.32% (phase 1, 2 and 3) MCT, and iv) MCT5, NC+0.55% (phase 1), 0.32% (phase 2 and 3) MCT. In Exp. 1, the pigs fed MCT5 diets had higher (p<0.05) ADG compared to NC treatment during the first 2 wk. From d 15 to 28, the ATTD of energy was improved (p<0.05) by MCT3 compared to the PC treatment. No effect has been observed on the blood profiles [red blood cell (RBC), white blood cell (WBC), immunoglobulin-G (IgG), lymphocyte concentration] measured in this study. In Exp. 2, the ADG were increased (p<0.05) by the MCT5 treatment than the PC treatment from d 0 to 14. Pigs fed PC treatment diet had lower ADFI (p<0.05) and better FCR (p<0.05) than NC treatment, whereas no differences were shown between MCT treatments and NC or PC treatment from d 15 to 35 and overall phase. The ATTD of DM and nitrogen were improved (p<0.05) by the effect of MCT5 related to the NC and PC treatment at the end of 2nd and 5th wk. The pigs fed MCT3 had higher (p<0.05) energy digestibility than PC treatment. No effects were seen in the blood profiles we measured (WBC, RBC, lymphocyte and immunoglobulin-G). In conclusion, the addition of MCT in the weanling pigs diet can improve the ADG and digestibility during the earlier period (first 2 wks), but had little effect on the blood characteristics. PMID:25049656

  1. Tetraspanin-3 regulates protective immunity against Eimera tenella infection following immunization with dendritic cell-derived exosomes

    USDA-ARS?s Scientific Manuscript database

    The effects of immunization with dendritic cell (DC) exosomes, which had been incubated or non-incubated with an anti-tetraspanin-3 (Tspan-3) blocking antibody (Ab), were studied using an experimental model of Eimeria tenella avian coccidiosis. Purified exosomes from cecal tonsil and splenic DCs exp...

  2. Radioisotope powered AMTEC systems

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

    Ivanenok, J.F. III; Sievers, R.K.

    1994-11-01

    Alkali metal thermal to electric converter (AMTEC) systems are being developed for high performance spacecraft power systems, including small, general purpose heat source (GPHS) powered systems. Several design concepts have been evaluated for the power range from 75 W to 1 kW. The specific power for these concepts has been found to be as high as 18-20 W/kg and 22 kW/m(exp 3). The projected area, including radiators, has been as low as 0.4 m(exp 2)/kW. AMTEC power systems are extremely attractive, relative to other current and projected power systems, because AMTEC offers high power density, low projected area, and lowmore » volume. Two AMTEC cell design types have been identified. A single-tube cell is already under development and a multitube cell design, to provide additional power system gains, has undergone proof-of-principle testing. Solar powered AMTEC (SAMTEC) systems are also being developed, and numerous terrestrial applications have been identified for which the same basic AMTEC cells being developed for radioisotope systems are also suitable. 35 refs.« less

  3. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

    DTIC Science & Technology

    2005-07-01

    Morris, L. S., Coleman, N., and Alexander, G. J. Compromised lymphocytes infiltrate hepatocellular carcinoma : the role of T-regulatory cells...regulatory T cells in peripheral blood of patients with hepatocellular carcinoma . Cancer Res., 65: 2457-2464, 2005. 18. Schaefer, C., Kim, G. G., Albers, A

  4. Limits on the UV Photodecomposition of Carbonates on Mars

    NASA Technical Reports Server (NTRS)

    Quinn, Richard; Zent, Aaron P.; McKay, Christopher P.; DeVincenzi, Donald L. (Technical Monitor)

    2002-01-01

    The effect of UV (ultraviolet) light on the stability of calcium carbonate in a simulated martian atmosphere was experimentally investigated. Sample cells containing C-13 labeled calcite were irradiated with a Xe arc lamp in 10 mbar of simulated martian atmosphere and a quadrupole mass spectrometer was used to monitor the headspace gases for the production of (13)CO2. We found no experimental evidence of the UV photodecomposition of calcium carbonate in a simulated martian atmosphere. Extrapolating the lower limit of detection of our experimental system to an upper limit of carbonate decomposition on Mars yields a quantum efficiency of 3.5 x 10(exp -8) molecules/photon over the wavelength interval of 190-390 nm and a maximum UV photodecomposition rate of 1.2 x 10(exp -13) kg m(exp -2) s(exp -1) from a calcite surface. The maximum loss of bulk calcite due to this process would be 2.5 nm yr(exp -1). However, calcite is expected to be thermodynamically stable on the surface of Mars and potential UV photodecomposition reaction mechanisms indicate that while calcium carbonate may decompose under vacuum, it would be stable in a CO2 atmosphere. Given the expected stability of carbonate on Mars and our inability to detect carbonate decomposition, we conclude that it is unlikely that the apparent absence of carbonate on the martian surface is due to UV photo decomposition of calcite in the current environment.

  5. Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

    DTIC Science & Technology

    2015-10-01

    osteoblastic differentiation during aging . Rejuvenation Res 2006;9:10–9. 25] Gao FB, Raff M. Cell size control and a cell-intrinsic maturation program in...self- renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10, 556-569 (2012). 8. Rybak, A.P., Bristow, R.G., & Kapoor, A...established clinical tumor is sustained by subpopulations of self- renewing cancer cells operationally called cancer stem cells (CSC) that can generate

  6. Phosphoric acid electric utility fuel cell technology development

    NASA Astrophysics Data System (ADS)

    Breault, R. D.; Briggs, T. A.; Congdon, J. V.; Demarche, T. E.; Gelting, R. L.; Goller, G. J.; Luoma, W. L.; McCloskey, M. W.; Mientek, A. P.; Obrien, J. J.

    1991-04-01

    The major objective of this effort was the advancement of cell and stack technology required to meet performance and cost criteria for fabrication and operation of a prototype large area, full height phosphoric acid fuel cell stack. The performance goal for the cell stack corresponded to a power density of 150 wsf, and the manufactured cost goal was a 510 $/kW reduction (in 1981 dollars) compared to existing 3.7 ft.(exp 2) active area cell stacks.

  7. Synthesis of Large-Size 1T' ReS2x Se2(1-x) Alloy Monolayer with Tunable Bandgap and Carrier Type.

    PubMed

    Cui, Fangfang; Feng, Qingliang; Hong, Jinhua; Wang, Renyan; Bai, Yu; Li, Xiaobo; Liu, Dongyan; Zhou, Yu; Liang, Xing; He, Xuexia; Zhang, Zhongyue; Liu, Shengzhong; Lei, Zhibin; Liu, Zonghuai; Zhai, Tianyou; Xu, Hua

    2017-12-01

    Chemical vapor deposition growth of 1T' ReS 2 x Se 2(1- x ) alloy monolayers is reported for the first time. The composition and the corresponding bandgap of the alloy can be continuously tuned from ReSe 2 (1.32 eV) to ReS 2 (1.62 eV) by precisely controlling the growth conditions. Atomic-resolution scanning transmission electron microscopy reveals an interesting local atomic distribution in ReS 2 x Se 2(1- x ) alloy, where S and Se atoms are selectively occupied at different X sites in each Re-X 6 octahedral unit cell with perfect matching between their atomic radius and space size of each X site. This structure is much attractive as it can induce the generation of highly desired localized electronic states in the 2D surface. The carrier type, threshold voltage, and carrier mobility of the alloy-based field effect transistors can be systematically modulated by tuning the alloy composition. Especially, for the first time the fully tunable conductivity of ReS 2 x Se 2(1- x ) alloys from n-type to bipolar and p-type is realized. Owing to the 1T' structure of ReS 2 x Se 2(1- x ) alloys, they exhibit strong anisotropic optical, electrical, and photoelectric properties. The controllable growth of monolayer ReS 2 x Se 2(1- x ) alloy with tunable bandgaps and electrical properties as well as superior anisotropic feature provides the feasibility for designing multifunctional 2D optoelectronic devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

    PubMed

    Zhu, Ying; Feng, Bing; He, Songmin; Su, Zuqing; Zheng, Guangjuan

    2018-02-01

    To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P < .05). Of note, above all parameters were lower in Res group than aspirin group. The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft. Copyright © 2018 Elsevier GmbH. All rights reserved.

  9. Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy.

    PubMed

    Wojciechowska, Marzena; Sobczak, Krzysztof; Kozlowski, Piotr; Sedehizadeh, Saam; Wojtkowiak-Szlachcic, Agnieszka; Czubak, Karol; Markus, Robert; Lusakowska, Anna; Kaminska, Anna; Brook, J David

    2018-04-12

    Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are human neuromuscular disorders associated with mutations of simple repetitive sequences in affected genes. The abnormal expansion of CTG repeats in the 3'-UTR of the DMPK gene elicits DM1, whereas elongated CCTG repeats in intron 1 of ZNF9/CNBP triggers DM2. Pathogenesis of both disorders is manifested by nuclear retention of expanded repeat-containing RNAs and aberrant alternative splicing. The precise determination of absolute numbers of mutant RNA molecules is important for a better understanding of disease complexity and for accurate evaluation of the efficacy of therapeutic drugs. We present two quantitative methods, Multiplex Ligation-Dependent Probe Amplification and droplet digital PCR, for studying the mutant DMPK transcript (DMPK exp RNA) and the aberrant alternative splicing in DM1 and DM2 human tissues and cells. We demonstrate that in DM1, the DMPK exp RNA is detected in higher copy number than its normal counterpart. Moreover, the absolute number of the mutant transcript indicates its low abundance with only a few copies per cell in DM1 fibroblasts. Most importantly, in conjunction with fluorescence in-situ hybridization experiments, our results suggest that in DM1 fibroblasts, the vast majority of nuclear RNA foci consist of a few molecules of DMPK exp RNA.

  10. Improving oral bioavailability of resveratrol by a UDP-glucuronosyltransferase inhibitory excipient-based self-microemulsion.

    PubMed

    Yang, Fei-Fei; Zhou, Jing; Hu, Xiao; Cong, Zhao-Qing; Liu, Chun-Yu; Pan, Rui-Le; Chang, Qi; Liu, Xin-Min; Liao, Yong-Hong

    2018-03-01

    Self-microemulsifying (SME) drug delivery system has been developed to increase oral bioavailabilities, and inhibitory excipients are capable of improving oral bioavailability by inhibiting enzyme mediated intestinal metabolism. However, the potential of enzyme inhibitory excipients containing SME in boosting resveratrol bioavailability remains largely uninvestigated. In this study, we set out to prepare SME-1 with UGT inhibitory excipients (excipients without inhibitory activities named SME-2 as control) to increase the bioavailability of RES by inhibiting intestinal metabolism. Results demonstrated that similar physicochemical properties such as size, polydistribution index and in vitro release, cellular uptake and permeability in Caco-2 cells as well as in vivo lymphatic distribution between inhibitory SME-1 and non-inhibitory SME-2 were observed. In vivo study demonstrated that the molar ratios of RES-G/RES were 7.25±0.48 and 5.06±2.42 for free drug and SME-2, respectively, and the molar ratio decreased to 0.36±0.10 in SME-1 group. Pharmacokinetic study confirmed that the inhibitory excipients containing SME demonstrated potential in increasing bioavailability of RES from 6.5% for the free RES and 12.9% for SME-2 to 76.1% in SME-1 through modulating the glucuronidation by UGT inhibitory excipients. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cloning and Characterization of a Cell Senescence Gene for Breast Cancer

    DTIC Science & Technology

    2005-07-01

    to investigate signaling pathways. F. References 1. Hayflick , L. (1965). The limited in vitro lifetime of human diploid cell strains. Exp. Cell...16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b... limited proliferative life span in culture (1-3). At the end of the proliferative phase, cells enter a state of irreversible post mitotic growth arrest

  12. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.

    PubMed

    Appel, Elena; Weissmann, Sarit; Salzberg, Yehuda; Orlovsky, Kira; Negreanu, Varda; Tsoory, Michael; Raanan, Calanit; Feldmesser, Ester; Bernstein, Yael; Wolstein, Orit; Levanon, Ditsa; Groner, Yoram

    2016-12-01

    The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3. Using transgenic mice expressing BAC reporters spanning the Runx3 locus, we discovered three REs-dubbed R1, R2, and R3-that cross-talk with promoter-2 (P2) to drive TrkC neuron-specific Runx3 transcription. Deletion of single or multiple elements either in the BAC transgenics or by CRISPR/Cas9-mediated endogenous ablation established the REs' ability to promote and/or repress Runx3 expression in developing sensory neurons. Our analysis reveals that an intricate combinatorial interplay among the three REs governs Runx3 expression in distinct subtypes of TrkC neurons while concomitantly extinguishing its expression in non-TrkC neurons. These findings provide insights into the mechanism regulating cell type-specific expression and subtype diversification of TrkC neurons in developing DRGs. © 2016 Appel et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Chemical Passivation of Li(exp +)-Conducting Solid Electrolytes

    NASA Technical Reports Server (NTRS)

    West, William; Whitacre, Jay; Lim, James

    2008-01-01

    Plates of a solid electrolyte that exhibits high conductivity for positive lithium ions can now be passivated to prevent them from reacting with metallic lithium. Such passivation could enable the construction and operation of high-performance, long-life lithium-based rechargeable electrochemical cells containing metallic lithium anodes. The advantage of this approach, in comparison with a possible alternative approach utilizing lithium-ion graphitic anodes, is that metallic lithium anodes could afford significantly greater energy-storage densities. A major impediment to the development of such cells has been the fact that the available solid electrolytes having the requisite high Li(exp +)-ion conductivity are too highly chemically reactive with metallic lithium to be useful, while those solid electrolytes that do not react excessively with metallic lithium have conductivities too low to be useful. The present passivation method exploits the best features of both extremes of the solid-electrolyte spectrum. The basic idea is to coat a higher-conductivity, higher-reactivity solid electrolyte with a lower-conductivity, lower-reactivity solid electrolyte. One can then safely deposit metallic lithium in contact with the lower-reactivity solid electrolyte without incurring the undesired chemical reactions. The thickness of the lower-reactivity electrolyte must be great enough to afford the desired passivation but not so great as to contribute excessively to the electrical resistance of the cell. The feasibility of this method was demonstrated in experiments on plates of a commercial high-performance solid Li(exp +)- conducting electrolyte. Lithium phosphorous oxynitride (LiPON) was the solid electrolyte used for passivation. LiPON-coated solid-electrolyte plates were found to support electrochemical plating and stripping of Li metal. The electrical resistance contributed by the LiPON layers were found to be small relative to overall cell impedances.

  14. Saturation recovery EPR spin-labeling method for quantification of lipids in biological membrane domains.

    PubMed

    Mainali, Laxman; Camenisch, Theodore G; Hyde, James S; Subczynski, Witold K

    2017-12-01

    The presence of integral membrane proteins induces the formation of distinct domains in the lipid bilayer portion of biological membranes. Qualitative application of both continuous wave (CW) and saturation recovery (SR) electron paramagnetic resonance (EPR) spin-labeling methods allowed discrimination of the bulk, boundary, and trapped lipid domains. A recently developed method, which is based on the CW EPR spectra of phospholipid (PL) and cholesterol (Chol) analog spin labels, allows evaluation of the relative amount of PLs (% of total PLs) in the boundary plus trapped lipid domain and the relative amount of Chol (% of total Chol) in the trapped lipid domain [ M. Raguz, L. Mainali, W. J. O'Brien, and W. K. Subczynski (2015), Exp. Eye Res., 140:179-186 ]. Here, a new method is presented that, based on SR EPR spin-labeling, allows quantitative evaluation of the relative amounts of PLs and Chol in the trapped lipid domain of intact membranes. This new method complements the existing one, allowing acquisition of more detailed information about the distribution of lipids between domains in intact membranes. The methodological transition of the SR EPR spin-labeling approach from qualitative to quantitative is demonstrated. The abilities of this method are illustrated for intact cortical and nuclear fiber cell plasma membranes from porcine eye lenses. Statistical analysis (Student's t -test) of the data allowed determination of the separations of mean values above which differences can be treated as statistically significant ( P ≤ 0.05) and can be attributed to sources other than preparation/technique.

  15. Use of pelleted sericea lespedeza (Lespedeza cuneata) for natural control of coccidia and gastrointestinal nematodes in weaned goats.

    PubMed

    Kommuru, D S; Barker, T; Desai, S; Burke, J M; Ramsay, A; Mueller-Harvey, I; Miller, J E; Mosjidis, J A; Kamisetti, N; Terrill, T H

    2014-08-29

    Infection with Eimeria spp. (coccidia) can be devastating in goats, particularly for young, recently-weaned kids, resulting in diarrhea, dehydration, and even death. Feeding dried sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G. Don.] to young goats has been reported to reduce the effects of internal parasites, including gastrointestinal nematodes (GIN) but there have been no reports of the effects of feeding this forage on Eimeria spp. in goats. Two confinement feeding experiments were completed on recently-weaned intact bucks (24 Kiko-cross, Exp. 1; 20 Spanish, Exp. 2) to determine effects of SL pellets on an established infection of GIN and coccidia. The bucks were assigned to 1 of 2 (Exp. 1) or 3 (Exp. 2) treatment groups based upon the number of Eimeria spp. oocysts per gram (OPG) of feces. In Exp. 1, the kids were fed 1 of 2 pelleted rations ad libitum; 90% SL leaf meal+10% of a liquid molasses/lignin binder mix and a commercial pellet with 12% crude protein (CP) and 24% acid detergent fiber (n=12/treatment group, 2 animals/pen). For Exp. 2, treatment groups were fed (1) 90% SL leaf meal pellets from leaves stored 3 years (n=7), (2) 90% SL pellets from leaf meal stored less than 6 months, (n=7), and the commercial pellets (n=6) ad libitum. For both trials, fecal and blood samples were taken from individual animals every 7 days for 28 days to determine OPG and GIN eggs per gram (EPG) and packed cell volume (PCV), respectively. In Exp. 2, feces were scored for consistency (1=solid pellets, 5=slurry) as an indicator of coccidiosis. In Exp. 1, EPG (P<0.001) and OPG (P<0.01) were reduced by 78.7% and 96.9%, respectively, 7 days after initiation of feeding in goats on the SL pellet diet compared with animals fed the control pellets. The OPG and EPG remained lower in treatment than control animals until the end of the trial. In Exp. 2, goats fed new and old SL leaf meal pellets had 66.2% and 79.2% lower (P<0.05) EPG and 92.2% and 91.2% lower (P<0.05) OPG, respectively, than control animals within 7 days, and these differences were maintained or increased throughout the trial. After 4 weeks of pellet feeding in Exp. 2, fecal scores were lower (P<0.01) in both SL-fed groups compared with control animals, indicating fewer signs of coccidiosis. There was no effect of diet on PCV values throughout either experiment. Dried, pelleted SL has excellent potential as a natural anti-coccidial feed for weaned goats. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Integrating Semiconducting Catalyst of ReS2 Nanosheets into P-silicon Photocathode toward Enhanced Solar Water Reduction.

    PubMed

    Zhao, Heng; Dai, Zhengyi; Xu, Xiaoyong; Pan, Jing; Hu, Jingguo

    2018-06-22

    Loading the electro-catalysts at the semiconductor-electrolyte interface is one of promising strategies to develop photoelectrochemical (PEC) water splitting cells. However, the assembly of compatible and synergistic heterojunction between the semiconductor and the selected catalyst remains challenging. Here, we report a hierarchical p-Si/ReS2 heterojunction photocathode fabricated through uniform growth vertically standing ReS2 nanosheets (NSs) on planar p-Si substrate for solar-driven hydrogen evolution reaction (HER). The laden ReS2 NSs not only serve as a high-activity HER catalyst but also render a suitable electronic band coupled with p-Si into a Ⅱ-type heterojunction, which facilitates the photo-induced charge production, separation and utilization. As a result, the assembled p-Si/ReS2 photocathode exhibits a 23-fold-increased photocurrent density at 0 VRHE and a 35-fold-enhanced photoconversion efficiency compared to pure p-Si counterpart. The bifunctional ReS2 as catalyst and semiconductor enables multi effects in improving light harvesting, charge separation and catalytic kinetics, highlighting the potential of semiconducting catalysts integrated into solar water splitting devices.

  17. Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection

    PubMed Central

    Campbell, Sharon M; Knipper, Johanna A; Ruckerl, Dominik; Finlay, Conor M; Logan, Nicola; Minutti, Carlos M; Mack, Matthias; Jenkins, Stephen J; Taylor, Matthew D

    2018-01-01

    Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, Litomosoides sigmodontis. C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2+ phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome. PMID:29299998

  18. A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells

    DTIC Science & Technology

    2009-05-31

    Konaka H, Sodek J, Zhau HE, Chung LW. Human Osteocalcin and Bone Sialoprotein Mediating Osteomimicry of Prostate Cancer Cells: Role of cAMP... sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent protein kinase A signaling path- way. Cancer Res 2005;65:2303^13

  19. Therapeutic Roles of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells

    DTIC Science & Technology

    2013-10-01

    KW, Suri P, Wicha MS. Hedgehog signaling and Bmi-1 regulate self- renewal of normal and malignant human mammary stem cells. Cancer Res 66:6063-71...ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS. Hedgehog signaling and bmi-1 regulate self-renewal of normal and malignant human mammary stem cells

  20. Decline of the 2-10 keV Emission from Eta Carinae

    NASA Technical Reports Server (NTRS)

    Liburd, Jamar; Corcoran, Michael F.; Hamaguchi, Kenji; Gull, Theodore R.; Madura, Thomas; Teodoro, Mairan; Moffat, Anthony; Richardson, Noel; Russell, Chris; Pollock, Andrew; hide

    2014-01-01

    Analysis of Eta Car's X-ray spectrum in the 2-10 keV band using processed data from the X-ray Telescope on Swift reveals a peak flux on July 16, 2014 of 0.046 photons s(exp -1) cm(exp -2) (3.37+/-0.15×10(exp -10) ergs s(exp -1) cm(exp -2). This flux is similar to the previous maximum flux seen by the XRT, 3.53+/-0.13×10(exp -10) ergs s(exp -1) cm(exp -2) (0.049 photons s(exp -1) cm(exp -2), ATEL #6298). Since this peak on July 16, the most recent Swift XRT quicklook data show a drop in flux. On July 20, 2014 the XRT flux as seen in the quicklook data was 0.011 photons s(exp -1) cm(exp -2) (8.3+/-0.5×10(exp -11) ergs s(exp -1) cm(exp -2)). This most likely indicates that the 2-10 keV flux is in its declining phase as Eta Car approaches its deep X-ray minimum stage (Hamaguchi et al., 2014, ApJ, 784, 125) associated with periastron passage of the 2024-day binary orbit. The column density derived from analysis of the July 20 XRT quicklook data is 7.2×10(exp 22) cm(exp -2). This is consistent with the column density seen near the same orbital phase in 2003 (7.7×10(exp 22) cm(exp -2), Hamaguchi et al., 2007, ApJ, 663, 522). Eta Car's deep X-ray minimum phase is expected to begin on July 30, 2014. Weekly Swift/XRT observations of Eta Car in the 2-10 keV band are planned throughout the X-ray minimum.

  1. Radiation hardness of Ga0.5In0.5 P/GaAs tandem solar cells

    NASA Technical Reports Server (NTRS)

    Kurtz, Sarah R.; Olson, J. M.; Bertness, K. A.; Friedman, D. J.; Kibbler, A.; Cavicchi, B. T.; Krut, D. D.

    1991-01-01

    The radiation hardness of a two-junction monolithic Ga sub 0.5 In sub 0.5 P/GaAs cell with tunnel junction interconnect was investigated. Related single junction cells were also studied to identify the origins of the radiation losses. The optimal design of the cell is discussed. The air mass efficiency of an optimized tandem cell after irradiation with 10(exp 15) cm (-2) 1 MeV electrons is estimated to be 20 percent using currently available technology.

  2. MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and HSP27.

    PubMed

    Pai, Hui Chen; Kumar, Sunil; Shen, Chien-Chang; Liou, Jing Ping; Pan, Shiow Lin; Teng, Che Ming

    2015-01-01

    In this study, the anticancer mechanisms of MT-4 were examined in A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines. To evaluate the activity of MT-4, we performed in vitro cell viability and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin polymerization was determined using a tubulin binding assay. MT-4 (2-Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M arrest followed by caspase-mediated apoptosis. Further studies indicated that MT-4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In addition, we found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. Treatment of cells with SB203580 or overexpression of dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT-4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI-ADR/res cell growth in vitro and in vivo. These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer.

  3. Reconciling the effects of inflammatory cytokines on mesenchymal cell osteogenic differentiation

    PubMed Central

    Deshpande, Sagar; James, Aaron W.; Blough, Jordan; Donneys, Alexis; Wang, Stewart C.; Cederna, Paul S.; Buchman, Steven R.; Levi, Benjamin

    2015-01-01

    Therapies using mesenchymal stem cells are a popular current avenue for development and utilization, especially in the fields of de novo tissue engineering (Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164:247.) or tissue regeneration after physical injury (Kitoh H, Kitakoji T, Tsuchiya H, et al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis—a preliminary result of three cases. Bone 2004;35:892; Shumakov VI, Onishchenko NA, Rasulov MF, Krasheninnikov ME, Zaidenov VA. Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts. Bull Exp Biol Med 2003;136:192; Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 1994;56:283.). The osteogenic potential of these cells is of particular interest, given their recent usage for the closure of critical-sized bone defects and other nonhealing bone scenarios such as a nonunion. Recent literature suggests that inflammatory cytokines can significantly impact the osteogenic potential of these cells. A review of relevant, recent literature is presented regarding the impact of the inflammatory cascade on the osteogenic differentiation of these cells and how this varies across species. Finally, we identify areas of conflicting or absent evidence regarding the behavior of mesenchymal stem cells in response to inflammatory cytokines. PMID:23972621

  4. The SNARC effect in two dimensions: Evidence for a frontoparallel mental number plane.

    PubMed

    Hesse, Philipp Nikolaus; Bremmer, Frank

    2017-01-01

    The existence of an association between numbers and space is known for a long time. The most prominent demonstration of this relationship is the spatial numerical association of response codes (SNARC) effect, describing the fact that participants' reaction times are shorter with the left hand for small numbers and with the right hand for large numbers, when being asked to judge the parity of a number (Dehaene et al., J. Exp. Psychol., 122, 371-396, 1993). The SNARC effect is commonly seen as support for the concept of a mental number line, i.e. a mentally conceived line where small numbers are represented more on the left and large numbers are represented more on the right. The SNARC effect has been demonstrated for all three cardinal axes and recently a transverse SNARC plane has been reported (Chen et al., Exp. Brain Res., 233(5), 1519-1528, 2015). Here, by employing saccadic responses induced by auditory or visual stimuli, we measured the SNARC effect within the same subjects along the horizontal (HM) and vertical meridian (VM) and along the two interspersed diagonals. We found a SNARC effect along HM and VM, which allowed predicting the occurrence of a SNARC effect along the two diagonals by means of linear regression. Importantly, significant differences in SNARC strength were found between modalities. Our results suggest the existence of a frontoparallel mental number plane, where small numbers are represented left and down, while large numbers are represented right and up. Together with the recently described transverse mental number plane our findings provide further evidence for the existence of a three-dimensional mental number space. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Two-Photon/Laser-Induced Fluorescence (TP/LIF) sensor

    NASA Technical Reports Server (NTRS)

    Bradshaw, John D.

    1994-01-01

    The Two-Photon/Laser-Induced Fluorescence (TP/LIF) technique is based on the stepwise excitation of the OH transitions, X(exp 2)II, v(exp '') = 0 yields X(exp 2)II, v(exp '') = 1 (lambda = 2.9 microns) and X(exp 2)II v(exp '') = 1 yields A(exp2)Sigma, v' = 0 (lambda = 345 nm) with background free fluorescence monitoring of the A(exp 2)Sigma, v' = 0 yields X(exp 2)II, v(exp '') = 0 transition near 309 nm. This technique has awaited the advent of a suitable mid-infrared (2.9 microns) laser source. Turnable mid-IR lasers now exist that are capable of meeting the specifications required of a high sensitivity TP/LIF OH sensor.

  6. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    DTIC Science & Technology

    2012-10-01

    2009;27(8):1954-1962. 44. Abarbanell AM, Coffey AC, Fehrenbacher JW, et al. Proinflammatory cytokine effects on mesenchymal stem cell therapy for...signaling pathway functions as a commitment switch for osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) (22). Activation...mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10

  7. Mucin (MUC1) Expression and Function in Prostate Cancer Cells

    DTIC Science & Technology

    2001-09-01

    Interactions at the Cell Surface of Mouse Uterine Epithelial Cells and Periimplantation -Stage Embryos. Trophoblast Res., 4:211-241, 1990. 37. Dutt...and Julian, J. Heparan Sulfate Proteoglycan Expression by Periimplantation Stage Embryos. Dev. Biol. 155:97-106,1993. 56. Rohde, L.H., and Carson...Modulators of Embryo-Uterine Epithelial Cell Attachment. In: S.K. Dey (ed.), Molecular and Cellular Aspects of Periimplantation Processes, Springer

  8. Classification of commutator algebras leading to the new type of closed Baker-Campbell-Hausdorff formulas

    NASA Astrophysics Data System (ADS)

    Matone, Marco

    2015-11-01

    We show that there are {\\it 13 types} of commutator algebras leading to the new closed forms of the Baker-Campbell-Hausdorff (BCH) formula $$\\exp(X)\\exp(Y)\\exp(Z)=\\exp({AX+BZ+CY+DI}) \\ , $$ derived in arXiv:1502.06589, JHEP {\\bf 1505} (2015) 113. This includes, as a particular case, $\\exp(X) \\exp(Z)$, with $[X,Z]$ containing other elements in addition to $X$ and $Z$. The algorithm exploits the associativity of the BCH formula and is based on the decomposition $\\exp(X)\\exp(Y)\\exp(Z)=\\exp(X)\\exp({\\alpha Y}) \\exp({(1-\\alpha) Y}) \\exp(Z)$, with $\\alpha$ fixed in such a way that it reduces to $\\exp({\\tilde X})\\exp({\\tilde Y})$, with $\\tilde X$ and $\\tilde Y$ satisfying the Van-Brunt and Visser condition $[\\tilde X,\\tilde Y]=\\tilde u\\tilde X+\\tilde v\\tilde Y+\\tilde cI$. It turns out that $e^\\alpha$ satisfies, in the generic case, an algebraic equation whose exponents depend on the parameters defining the commutator algebra. In nine {\\it types} of commutator algebras, such an equation leads to rational solutions for $\\alpha$. We find all the equations that characterize the solution of the above decomposition problem by combining it with the Jacobi identity.

  9. Analysis and expression of the alpha-expansin and beta-expansin gene families in maize

    NASA Technical Reports Server (NTRS)

    Wu, Y.; Meeley, R. B.; Cosgrove, D. J.

    2001-01-01

    Expansins comprise a multigene family of proteins in maize (Zea mays). We isolated and characterized 13 different maize expansin cDNAs, five of which are alpha-expansins and eight of which are beta-expansins. This paper presents an analysis of these 13 expansins, as well as an expression analysis by northern blotting with materials from young and mature maize plants. Some expansins were expressed in restricted regions, such as the beta-expansins ExpB1 (specifically expressed in maize pollen) and ExpB4 (expressed principally in young husks). Other expansins such as alpha-expansin Exp1 and beta-expansin ExpB2 were expressed in several organs. The expression of yet a third group was not detected in the selected organs and tissues. An analysis of expansin sequences from the maize expressed sequence tag collection is also presented. Our results indicate that expansin genes may have general, overlapping expression in some instances, whereas in other cases the expression may be highly specific and limited to a single organ or cell type. In contrast to the situation in Arabidopsis, beta-expansins in maize seem to be more numerous and more highly expressed than are alpha-expansins. The results support the concept that beta-expansins multiplied and evolved special functions in the grasses.

  10. Retention of Rotavirus Infectivity in Mussels Heated by Using the French Recipe Moules Marinières.

    PubMed

    Souza, Doris Sobral Marques; Miura, Takayuki; Le Mennec, Cécile; Barardi, Célia Regina Monte; Le Guyader, Françoise S

    2015-11-01

    To evaluate the persistence of infectious virus after heating, mussels contaminated with a rotavirus strain were prepared following the French recipe moules marinières (mariner's mussels). Rotavirus was then quantified by real-time quantitative PCR (RT-qPCR) and a cell culture infectivity assay. Results showed the persistence of infectious virus after 3 min of cooking. After 5 min, when no infectious virus could be detected, the RT-qPCR approach showed a 1-log decrease compared with concentrations detected after 1 min of cooking.

  11. InP tunnel junctions for InP/InGaAs tandem solar cells

    NASA Technical Reports Server (NTRS)

    Vilela, Mauro F.; Freundlich, Alex; Renaud, P.; Medelci, N.; Bensaoula, A.

    1996-01-01

    We report, for the first time, an epitaxially grown InP p(+)/n(++) tunnel junction. A diode with peak current densities up to 1600 A/cm and maximum specific resistivities (Vp/Ip - peak voltage to peak current ratio) in the range of 10(exp -4)Omega cm(exp 2) is obtained. This peak current density is comparable to the highest results previously reported for lattice matched In(0.53)Ga(0.47)As tunnel junctions. Both results were obtained using chemical beam epitaxy (CBE). In this paper we discuss the electrical characteristics of these tunnel diodes and how the growth conditions influence them.

  12. Venusian hydrology: Steady state reconsidered

    NASA Technical Reports Server (NTRS)

    Grinspoon, David H.

    1992-01-01

    In 1987, Grinspoon proposed that the data on hydrogen abundance, isotopic composition, and escape rate were consistent with the hypothesis that water on Venus might be in steady state rather than monotonic decline since the dawn of time. This conclusion was partially based on a derived water lifetime against nonthermal escape of approximately 10(exp 8) yr. De Bergh et al., preferring the earlier Pioneer Venus value of 200 ppm water to the significantly lower value detected by Bezard et al., found H2O lifetimes of greater than 10(exp 9) yr. Donahue and Hodges derived H2O lifetimes of 0.4-5 x 10 (exp 9) yr. Both these analyses used estimates of H escape flux between 0.4 x 10(exp 7) and 1 x 10(exp 7) cm(exp -2)s(exp -1) from Rodriguez et al. Yet in more recent Monte Carlo modeling, Hodges and Tinsley found an escape flux due to charge exchange with hot H(+) of 2.8 x 10(exp 7) cm(exp -2)s(exp -1). McElroy et al. estimated an escape flux of 8 x 10(exp 6) cm(exp -2)s(exp -1) from collisions with hot O produced by dissociative recombination of O2(+). Brace et al. estimated an escape flux of 5 x 10(exp 6) cm(exp -2)s(exp -1) from ion escape from the ionotail of Venus. The combined estimated escape flux from all these processes is approximately 4 x 10(exp 7) cm(exp -2)s(exp -1). The most sophisticated analysis to date of near-IR radiation from Venus' nightside reveals a water mixing ratio of approximately 30 ppm, suggesting a lifetime against escape for water of less than 10(exp 8) yr. Large uncertainties remain in these quantities, yet the data point toward a steady state. Further evaluation of these uncertainties, and new evolutionary modeling incorporating estimates of the outgassing rate from post-Magellan estimates of the volcanic resurfacing rate are presented.

  13. Active Microparticle Media

    DTIC Science & Technology

    1992-09-01

    if a(r,t) is any of these quantitites, then 7 a(r,t) = a0 + al(rwl) exp(- iwlt ) + al(r’w2 ) exp(-iw2 t) + 02 (r,w_) exp(-iwt) + a2 (r,w+) exp(-iw+t...02 (r,o) + a2 (r,2wI) exp(-2iwlt) + a2 (r,2w2 ) exp(-2iw2 t) + 0 3 (r,wl)exp(- iwlt ) + G3 (rgu 2 )exp(-1w2 t) + c.c. (6) where ao is the equilibrium

  14. Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.

    PubMed

    Childs-Disney, Jessica L; Hoskins, Jason; Rzuczek, Suzanne G; Thornton, Charles A; Disney, Matthew D

    2012-05-18

    RNA is an important drug target, but it is difficult to design or discover small molecules that modulate RNA function. In the present study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models. DM1 is caused when an expansion of r(CUG) repeats, or r(CUG)(exp), is present in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) mRNA. r(CUG)(exp) folds into a hairpin with regularly repeating 5'CUG/3'GUC motifs and sequesters muscleblind-like 1 protein (MBNL1). A variety of defects are associated with DM1, including (i) formation of nuclear foci, (ii) decreased translation of DMPK mRNA due to its nuclear retention, and (iii) pre-mRNA splicing defects due to inactivation of MBNL1, which controls the alternative splicing of various pre-mRNAs. Previously, modularly assembled ligands targeting r(CUG)(exp) were designed using information in an RNA motif-ligand database. These studies showed that a bis-benzimidazole (H) binds the 5'CUG/3'GUC motif in r(CUG)(exp.) Therefore, we designed multivalent ligands to bind simultaneously multiple copies of this motif in r(CUG)(exp). Herein, we report that the designed compounds improve DM1-associated defects including improvement of translational and pre-mRNA splicing defects and the disruption of nuclear foci. These studies may establish a foundation to exploit other RNA targets in genomic sequence.

  15. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2014-08-01

    Chemical Society meeting, Baton Rouge, LA, Nov 2012; (3) 19th World Congress on Advances in Oncology conference, Athens, Greece, scheduled for Oct, 2014...dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 2009;69

  16. Detection of New Dissociative Electron Attachment Channels in NO

    NASA Technical Reports Server (NTRS)

    Orient, O. J.; Chutjian, A.

    1995-01-01

    Three dissociative electron attachment channels have been detected and identified in NO via measurement of the O minus (exp 2)P fragment energy. In addition to the known N((exp 2 D(exp 0)) + O minus (exp 2)P channel, two new channels N((exp 1 S(exp 0)) + 0 (2 P) and N(exp 2)P(exp 0) + O(exp 2)P were detected. Cross sections for each of the channels are reported by normalizing the scattering intensities to previously measured total cross sections. The experimental approach uses solenoidal magnetic confinement of the electrons and ions, and trochoidal energy analysis of the low-energy ions.

  17. Precise Heater Controller with rf-Biased Josephson Junctions

    NASA Technical Reports Server (NTRS)

    Green, Colin J.; Sergatskov, Dmitri A.; Duncan, R. V.

    2003-01-01

    Paramagnetic susceptibility thermometers used in fundamental physics experiments are capable of measuring temperature changes with a precision of a part in 2 x 10(exp 10). However, heater controllers are only able to control open-loop power dissipation to about a part in 10(exp 5). We used an array of rf-biased Josephson junctions to precisely control the electrical power dissipation in a heater resistor mounted on a thermally isolated cryogenic platform. Theoretically, this method is capable of controlling the electrical power dissipation to better than a part in 10(exp 12). However, this level has not yet been demonstrated experimentally. The experiment consists of a liquid helium cell that also functions as a high-resolution PdMn thermometer, with a heater resistor mounted on it. The cell is thermally connected to a temperature-controlled cooling stage via a weak thermal link. The heater resistor is electrically connected to the array of Josephson junctions using superconducting wire. An rf-biased array of capacitively shunted Josephson junctions drives the voltage across the heater. The quantized voltage across the resistor is Vn = nf(h/2e), where h is Planck's constant, f is the array biasing frequency, e is the charge of an electron, and n is the integer quantum state of the Josephson array. This results in an electrical power dissipation on the cell of Pn = (Vn)(sup 2/R), where R is the heater resistance. The change of the quantum state of the array changes the power dissipated in the heater, which in turn, results in the change of the cell temperature. This temperature change is compared to the expected values based on the known thermal standoff resistance of the cell from the cooling stage. We will present our initial experimental results and discuss future improvements. This work has been funded by the Fundamental Physics Discipline of the Microgravity Science Office of NASA, and supported by a no-cost equipment loan from Sandia National Laboratories.

  18. Harnessing Autopsied DIPG Tumor Tissues for Orthotopic Xenograft Model Development in the Brain Stems of SCID Mice

    DTIC Science & Technology

    2012-09-01

    patched-1-deficient mouse medulloblastoma . Cancer Res. 2009;69:4682-4690. 14. Mao XG, Zhang X, Xue XY, et al. Brain Tumor Stem-Like Cells Identified by...propagating cells in a mouse model of medulloblastoma . Cancer Cell. 2009;15:135-147. 16. Yagi H, Yanagisawa M, Suzuki Y, et al. HNK-1 epitope-carrying

  19. Exact analytic solutions for a global equation of plant cell growth.

    PubMed

    Pietruszka, Mariusz

    2010-05-21

    A generalization of the Lockhart equation for plant cell expansion in isotropic case is presented. The goal is to account for the temporal variation in the wall mechanical properties--in this case by making the wall extensibility a time dependent parameter. We introduce a time-differential equation describing the plant growth process with some key biophysical aspects considered. The aim of this work was to improve prior modeling efforts by taking into account the dynamic character of the plant cell wall with characteristics reminiscent of damped (aperiodic) motion. The equations selected to encapsulate the time evolution of the wall extensibility offer a new insight into the control of cell wall expansion. We find that the solutions to the time dependent second order differential equation reproduce much of the known experimental data for long- and short-time scales. Additionally, in order to support the biomechanical approach, a new growth equation based on the action of expansin proteins is proposed. Remarkably, both methods independently converge to the same kind, sigmoid-shaped, growth description functional V(t) proportional, exp(-exp(-t)), properly describing the volumetric growth and, consequently, growth rate as its time derivative. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  20. Walter Reed Army Institute of Research Annual Progress Report, Fiscal Year 1980

    DTIC Science & Technology

    1980-10-01

    for Military Medicine. 31. Smith, L.F. and G.H. Lowell. 1980. Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. II...dependent monocyte-mediated antibacterial activity . J. Exp. Med. 152:452-457. 33. Lowell, G.H., L.F. Smith, J.M. Griffiss, B.L. Brandt and R.P...dependent cell-mediated antibacterial activity . K lymphocytes, monocytes and granulocytes are effective against shigella. J. Im- munol. (In press). 35

  1. The Mechanism of Blood Function and Production After Injury.

    DTIC Science & Technology

    1980-02-01

    radioactive 59Fe labeled red cell dilution method described by Garcia7 . Red cell 2,3 diphosphoglycerate levels were measured using a commercial kit...and protein depleted rats was also associated with elevated 2,3 diphosphoglycerate levels (p<.05)(Table IV) suggesting partial compensation for anemic...Brewer, G.J.: The relationship between red cell 2,3 diphosphoglycerate and levels of hemoglobin in the human. Proc.Soc. Exp.Biol.Med. 150(1): 215-9

  2. RAPID COMMUNICATION: Nerve growth factor influences cleavage rate and embryo development in sheep.

    PubMed

    Crispo, M; Dos Santos-Neto, P C; Vilariño, M; Mulet, A P; de León, A; Barbeito, L; Menchaca, A

    2016-10-01

    Recent information about Nerve growth factor (NGF), a protein traditionally associated to the nervous system that regulates survival and maturation of developing neurons, suggests that it may exert action also on different levels in the reproductive system. The aim of this study was to evaluate the effect of NGF added during in vitro oocyte maturation, fertilization or in vitro embryo development in sheep. Nerve growth factor was supplemented to the culture medium at 0, 100, or 1,000 ng/mL, during either in vitro maturation (Exp. 1), in vitro fertilization (Exp. 2), or in vitro culture (Exp. 3). In addition, NGF mRNA expression was determined in cumulus cells and oocytes. Nerve growth factor induced early cleavage when added during oocyte maturation or fertilization, improved embryo development when added during fertilization, and had no significant effect when added during embryo culture. In general, the effect was more evident with 100 rather than 1,000 ng/mL (P < 0.05). Expression of endogenous NGF was not detected in oocytes, and increased in cumulus cells when 1,000 ng/mL of NGF was added during fertilization, but not during maturation and embryo culture. In conclusion, the addition of NGF during oocyte maturation and fertilization affects in vitro cleavage and embryo development in sheep. We suggest a possible effect of this growth factor on oocyte maturation and mainly on the fertilization process.

  3. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule

    PubMed Central

    Gurunathan, Sangiliyandi; Han, Jae Woong; Kim, Eun Su; Park, Jung Hyun; Kim, Jin-Hoi

    2015-01-01

    Objective Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells. Methods The successful reduction of graphene oxide (GO) to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO). Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells. Results The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3. Conclusion Our data demonstrate a single, simple green approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic compound resveratrol, which has similar efficacy in the reduction of GO to rGO. Resveratrol-based GO reduction would facilitate large-scale production of graphene-based materials for the emerging graphene-based technologies and biomedical applications. PMID:25931821

  4. Contrôle cohérent de la dynamique de fragmentation d'agrégats alcalins

    NASA Astrophysics Data System (ADS)

    Lindinger, A.; Lupulescu, C.; Le Roux, J.; Bartelt, A.; Vajda, Š.; Wöste, L.

    2004-11-01

    Les agrégats métalliques présentent des propriétés extraordinaires, en particulier chimiques et catalytiques, qui dépendent fortement de leur taille. Ce comportement en fait des candidats idéaux pour l'analyse en temps réel de processus photo-induits ultrarapides, le but ultime étant la conduite de scénarios de contrôle cohérent. Nous avons réalisé des expériences d'ionisation multiphotonique non stationnaire sur de petits agrégats alcalins de différentes tailles et dans différents états électroniques rovibrationnels, y compris leur état fondamental, sondant ainsi leur dynamique ondulatoire, leur orientation structurelle, leur transfert de charge et leur dissociation. Les processus observés dépendent grandement des paramètres du faisceau laser d'excitation, tels que sa phase, son amplitude et sa durée ; cette sensibilité plaide pour l'emploi d'un système de contrôle rétroactif permettant de générer les formes d'impulsion optimales. Les caractéristiques spectrales et temporelles de ces dernières reflètent les propriétés du système étudié ainsi que les processus photochimiques que l'irradiation y induit. Nous présentons d'abord la dynamique vibrationelle d'états électroniques excités, liés, dissociatifs et prédissociatifs, des dimères et trimères alcalins. Suit une description du principe d'observation par pompage optique par effet Raman stimulé de la dynamique d'un paquet d'onde dans l'état électronique fondamental. Puisque les paramètres de l'impulsion d'excitation influencent de façon significative le poids des différentes trajectoires dans l'espace des phases, nous avons mené des expériences sur les canaux de fragmentation concurrents d'une réaction photo-induite, en étudiant les différents embranchements des voies d'ionisation et de fragmentation de Na{2}K excité électroniquement. L'utilisation d'un algorithme évolutif, pour l'optimisation de la phase et de l'amplitude de l'onde électromagnétique appliquée, permit d'influencer significativement la quantité résultante d'ions parents ou fragments. Des propriétés intéressantes sont déduites de la forme des impulsions laser optimales obtenues, qui révèlent la période de vibration moléculaire et qui, combinées aux courbes de potentiel, permettent de proposer les trajectoires que l'optimisation impose aux paquets d'onde. Pour finir, nous avons étudié comment une variété plus grande d'agrégats, en contribuant au canal de fragmentation NaK, influe sur la forme optimale d'impulsion. Là encore, la structure de cette dernière apporte des éclaircissements sur les canaux de fragmentation empruntés durant le processus de contrôle.

  5. GaP betavoltaic cells as a power source

    NASA Technical Reports Server (NTRS)

    Pool, F. S.; Stella, Paul M.; Anspaugh, B.

    1991-01-01

    Maximum power output for the GaP cells of this study was found to be on the order of 1 microW. This resulted from exposure to 200 and 40 KeV electrons at a flux of 2 x 10(exp 9) electrons/sq cm/s, equivalent to a 54 mCurie source. The efficiencies of the cells ranged from 5 to 9 percent for 200 and 40 KeV electrons respectively. The lower efficiency at higher energy is due to a substantial fraction of energy deposition in the substrate, further than a diffusion length from the depletion region of the cell. Radiation damage was clearly observed in GaP after exposure to 200 KeV electrons at a fluence of 2 x 10(exp 12) electrons/sq cm. No discernable damage was observed after exposure to 40 KeV electrons at the same fluence. Analysis indicates that a GaP betavoltaic system would not be practical if limited to low energy beta sources. The power available would be too low even in the ideal case. By utilizing high activity beta sources, such as Sr-90/Y-90, it may be possible to achieve performance that could be suitable for some space power applications. However, to utilize such a source the problem of radiation damage in the beta cell material must be overcome.

  6. Facteurs de risque dans le trouble déficitaire de l’attention et de l’hyperactivité: étude familiale

    PubMed Central

    Poissant, Hélène; Rapin, Lucile

    2012-01-01

    Résumé Objectif: Notre étude a pour but d’évaluer les facteurs de risque associés au trouble déficitaire de l’attention et de l’hyperactivité (TDAH) en termes de comorbidités et de facteurs d’adversité à l’intérieur des familles avec un TDAH. Méthodologie: 137 parents de 104 enfants avec un TDAH et 40 parents de 34 enfants contrôles ont répondu aux items d’un questionnaire. Des tests Chi-carrés et des tests de Student ont mesuré l’association de chaque item avec les groupes et les différences entre les groupes. Résultats: Les enfants avec un TDAH avaient des performances scolaires plus faibles et une plus forte prévalence des troubles d’apprentissage, oppositionnel, des conduites et anxieux que celle des enfants contrôles. Des difficultés d’apprentissage étaient plus souvent rapportées chez les pères d’enfants avec un TDAH. Par ailleurs, l’isolement social et les accidents de la route étaient davantage présents chez les mères d’enfants avec un TDAH. Ces dernières souffraient plus de dépression et de trouble anxieux et prenaient davantage de médicaments que les mères contrôles. Conclusion: L’étude de facteurs de risque révèle un lien entre les parents et les enfants, spécifiquement la présence de dépression parmi les mères d’enfants avec un TDAH et de difficultés d’apprentissage chez les pères, suggérant une composante familiale dans le trouble. La sous-représentation du TDAH chez les pères d’enfants avec un TDAH est discutée. PMID:23133459

  7. Modulation of Phospholipase A2 Activity by Actin and Myosin.

    DTIC Science & Technology

    1987-04-15

    cord vein. Thromb. Res. 18:787-795. 11. Knull. H.R.. W.F. Taylor. and W.W. Wells. 1974. Insulin effects on brain energy metabolism and the related...cells. Nature 271:549-551. I 14. Martin. T.W.. R.B. Wysolmerski. and D. Lagunoff. 1987. Phosphatidylcholine metabolism in endothelial cells: evidence for

  8. Targeting N-RAS as a Therapeutic Approach for Melanoma

    DTIC Science & Technology

    2014-12-01

    cell death. Sci. World J. 10 (2272−84), 2272−2284. (16) Lonne, G. K., Masoumi, K. C., Lennartsson, J., and Larsson, C. (2009) Protein kinase Cδ supports...dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 2009, 69

  9. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

    DTIC Science & Technology

    2006-07-01

    Davies S, Gibbs P, Morris LS, Coleman N and Alexander GJ. Compromised lymphocytes infiltrate hepatocellular carcinoma : the role of T-regulatory...cells in peripheral blood of patients with hepatocellular carcinoma . Cancer Res., 65: 2457-2464, 2005. (8) Casares N, Arribillaga L, Sarobe P, Dotor J

  10. First measurement of helium on Mars: Implications for the problem of radiogenic gases on the terrestrial planets

    NASA Technical Reports Server (NTRS)

    Bowyer, S.; Chakrabarti, S.; Gladstone, G. R.; Mcdonald, J. S.

    1994-01-01

    The 108 photons of the Martian He 584 A airglow detected by the Extreme Ultraviolet Explorer satellite during a two-day exposure (22-23 Jan. 1993) correspond to the effective disk average intensity of 43 (+/-) 10 Rayleigh. Radiative transfer calculations, using a model atmosphere appropriate to the conditions of the observation and having an exospheric temperature of 210 (+/-) 20 K, result in an He mixing ratio of 1.1 (+/-) 0.4 ppm in the lower atmosphere. Nonthermal escape of helium is due to the following: electron impact ionization and pickup of He(+) by the solar wind; collisions with hot oxygen atoms; and charge exchange with molecular species with corresponding column loss rates of 1.4 x 10(exp 5), 3 x 10(exp 4), and 7 x 10(exp 3) cm(exp -2)s(exp -1), respectively. The lifetime of helium on Mars is 5 x 10(exp 4) yr. The He outgassing rate, coupled with the Ar-40 atmospheric abundance and with the K:U:Th ratio measured in the surface rocks, is used as input to a simple two-reservoir degassing model which presumes the loss of all argon accumulated in the atmosphere during the first Byr by large-scale impacts. The model results in total planet mass ratios of 10(exp -5) g/g for K, 2.3 x 10(exp -9) g/g for U, 8.5 x 10(exp -9) g/g for Th, 4 x 10(exp -10) g/g for He, and 1.5 x 10(exp -9) g/g for Ar-40. The predicted radiogenic heat flux is 2 erg cm(exp -2)s(exp -1). Similar modeling for Venus results in total plant mass ratios of 4.7 x 10(exp -5) g/g for K, 6.7 x 10(exp -9) g/g for U, 2.2 x 10(exp -8) g/g for Th, 1.3 x 10(exp -9) for He, 6.7 x 10(exp -9) g/g for Ar-40, and a radiogenic heat flux of 15 erg cm(exp -2)s(exp -1). The implications of these results are discussed. The modeling shows that the radioactive elements were not distributed uniformly in the protoplanetary nebula, and their relative abundances differ very much in the terrestrial planets.

  11. Friction and Wear Properties of As-Deposited and Carbon Ion-Implanted Diamond Films

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa

    1996-01-01

    Recent work on the friction and wear properties of as-deposited and carbon ion-implanted diamond films was reviewed. Diamond films were produced by the microwave plasma chemical vapor deposition (CVD) technique. Diamond films with various grain sizes and surface roughnesses were implanted with carbon ions at 60 keV ion energy, resulting in a dose of 1.2 x 10(exp 17) carbon ions per cm(exp 2). Various analytical techniques, including Raman spectroscopy, proton recoil analysis, Rutherford backscattering, transmission and scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction, were utilized to characterize the diamond films. Sliding friction experiments were conducted with a polished natural diamond pin in contact with diamond films in the three environments: humid air (40% relative humidity), dry nitrogen (less than 1 percent relative humidity), and ultrahigh vacuum (10(exp -7) Pa). The CVD diamond films indeed have friction and wear properties similar to those of natural diamond in the three environments. The as-deposited, fine-grain diamond films can be effectively used as self-lubricating, wear-resistant coatings that have low coefficients of friction (0.02 to 0.04) and low wear rates (10(exp -7) to lO(exp -8) mm(exp 3) N(exp -1) m(exp -1)) in both humid air and dry nitrogen. However, they have high coefficients of friction (1.5 to 1.7) and a high wear rate (10(exp -4) mm(exp 7) N(exp -1) m(exp -1)) in ultrahigh vacuum. The carbon ion implantation produced a thin surficial layer (less than 0.1 micron thick) of amorphous, non-diamond carbon on the diamond films. In humid air and dry nitrogen, the ion-implanted, fine and coarse-grain diamond films have a low coefficient of friction (around 0.1) and a low wear rate (10(exp -7) mm(exp 3) N(exp -1) m(exp-1)). Even in ultrahigh vacuum, the presence of the non-diamond carbon layer reduced the coefficient of friction of fine-grain diamond films to 0.1 or lower and the wear rate to 10(exp -6) mm(exp 3) N(exp -1) m(exp -1). Thus, the carbon ion-implanted, fine-grain diamond films can be effectively used as wear-resistant, self-lubricating coatings not only in air and dry nitrogen, but also in ultrahigh vacuum.

  12. The symbiotic fauna of the African termite Hodotermes mossambicus identification of four flagellate species of the genera Spironympha, Trichomonoides and Retortamonas.

    PubMed

    Brugerolle, Guy

    2006-02-01

    Two Spironympha species were described by light immunofluorescence and electron microscopy. Spironympha fibrosa n. sp. has a narrow columella, several axostylar fibres and original striated myoneme-like fibres attached to the last basal body of each flagellar line. Spironympha simplex n. sp. is small and has non-striated microfibrils attached to the basal body section and an axostyle composed of two fibres. Trichomonas termitidis, as reported by Dogiel (Researches on parasitic protozoa from the intestine of termites. II. Lophomonadidae. Sci Res Zool Exped Brit E Africa made by Prof. V. Dogiel and I. Sokolow in 1914 10:20-35, 1917), has the features of Trichomonoides trypanoides, as reported by Brugerolle and Bordereau (Eur J Protistol 40:163-174, 2004). Retortamonas hodotermitis n. sp. shares the characteristics of insect retortamonads, as reported by Brugerolle (Protistologica 8:233-240, 1976), but does not correspond to any species described to date. The species identification differs from that of described in Dogiel (Russkii Arkhiv Protistologii 1:172-234, 1922).

  13. Fluid mechanics of the human eye: aqueous humour flow in the anterior chamber.

    PubMed

    Fitt, A D; Gonzalez, G

    2006-01-01

    We consider and compare the various different kinds of flow that may take place in the anterior chamber of a human eye. The physical mechanisms responsible for causing such flows may be classified as follows: (i) buoyancy-driven flow arising from the temperature difference between the anterior surface of the cornea and the iris, (ii) flow generated by the aqueous production of the ciliary body, (iii) flow generated by the interaction between buoyancy and gravity while sleeping while sleeping in a face-up position, (iv) flow generated by phakodenesis (lens tremor), (v) flow generated by Rapid Eye Movement (REM) during sleep. Each flow is studied using a traditional fluid mechanics/asymptotic analysis approach. We also assess the veracity of a hypothesis that was recently advanced [see Maurice, D.M., 1998. The Von Sallman Lecture 1996: An ophthalmological explanation of REM sleep. Exp. Eye. Res. 66, 139-145, for details] to suggest that, contrary to previous opinion, the purpose of REM during sleep is to ensure corneal respiration in the absence of the buoyant mixing that routinely takes place due to (i) above during waking conditions.

  14. The speed-curvature power law of movements: a reappraisal.

    PubMed

    Zago, Myrka; Matic, Adam; Flash, Tamar; Gomez-Marin, Alex; Lacquaniti, Francesco

    2018-01-01

    Several types of curvilinear movements obey approximately the so called 2/3 power law, according to which the angular speed varies proportionally to the 2/3 power of the curvature. The origin of the law is debated but it is generally thought to depend on physiological mechanisms. However, a recent paper (Marken and Shaffer, Exp Brain Res 88:685-690, 2017) claims that this power law is simply a statistical artifact, being a mathematical consequence of the way speed and curvature are calculated. Here we reject this hypothesis by showing that the speed-curvature power law of biological movements is non-trivial. First, we confirm that the power exponent varies with the shape of human drawing movements and with environmental factors. Second, we report experimental data from Drosophila larvae demonstrating that the power law does not depend on how curvature is calculated. Third, we prove that the law can be violated by means of several mathematical and physical examples. Finally, we discuss biological constraints that may underlie speed-curvature power laws discovered in empirical studies.

  15. Temporal guidance of musicians' performance movement is an acquired skill.

    PubMed

    Rodger, M W M; O'Modhrain, S; Craig, C M

    2013-04-01

    The ancillary (non-sounding) body movements made by expert musicians during performance have been shown to indicate expressive, emotional, and structural features of the music to observers, even if the sound of the performance is absent. If such ancillary body movements are a component of skilled musical performance, then it should follow that acquiring the temporal control of such movements is a feature of musical skill acquisition. This proposition is tested using measures derived from a theory of temporal guidance of movement, "General Tau Theory" (Lee in Ecol Psychol 10:221-250, 1998; Lee et al. in Exp Brain Res 139:151-159, 2001), to compare movements made during performances of intermediate-level clarinetists before and after learning a new piece of music. Results indicate that the temporal control of ancillary body movements made by participants was stronger in performances after the music had been learned and was closer to the measures of temporal control found for an expert musician's movements. These findings provide evidence that the temporal control of musicians' ancillary body movements develops with musical learning. These results have implications for other skillful behaviors and nonverbal communication.

  16. Identification of two novel functional p53 responsive elements in the Herpes Simplex Virus-1 genome

    PubMed Central

    Hsieh, Jui-Cheng; Kuta, Ryan; Armour, Courtney R.; Boehmer, Paul E.

    2014-01-01

    Analysis of the herpes simplex virus-1 (HSV-1) genome reveals two candidate p53 responsive elements (p53RE), located in proximity to the replication origins oriL and oriS, referred to as p53RE-L and p53RE-S, respectively. The sequences of p53RE-L and p53RE-S conform to the p53 consensus site and are present in HSV-1 strains KOS, 17, and F. p53 binds to both elements in vitro and in virus-infected cells. Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. Importantly, expression of the essential immediate early viral transactivator ICP4 and the essential DNA replication protein ICP8, that are adjacent to p53RE-S and p53RE-L, are repressed in a p53-dependent manner. Taken together, this study identifies two novel functional p53RE in the HSV-1 genome and suggests a complex mechanism of viral gene regulation by p53 which may determine progression of the lytic viral replication cycle or the establishment of latency. PMID:25010269

  17. Skeletal Muscle Satellite Cell Activation Following Cutaneous Burn in Rats

    DTIC Science & Technology

    2013-12-01

    satellite cell activation and survival during oxidative stress. J Muscle Res Cell Motil 2011;32(2):99–109. [33] Rathbone CR, Booth FW, Lees SJ. Sirt1 ...Skeletal muscle satellite cell activation following cutaneous burn in rats Xiaowu Wu*, Thomas J. Walters, Christopher R. Rathbone Extremity Trauma...f o Article history: Accepted 15 October 2012 Keywords: Muscle precursor cell Thermal injury Atrophy Skeletal muscle Activation a b s t r a c t

  18. Effects of nutritional plane and selenium supply during gestation on visceral organ mass and indices of intestinal growth and vascularity in primiparous ewes at parturition and during early lactation.

    PubMed

    Meyer, A M; Reed, J J; Neville, T L; Taylor, J B; Reynolds, L P; Redmer, D A; Vonnahme, K A; Caton, J S

    2012-08-01

    Objectives were to investigate effects of nutritional plane and Se supply during gestation on visceral organ mass and intestinal growth and vascularization in ewes at parturition and during early lactation. Primiparous Rambouillet ewes (n = 84) were allocated to 2 × 3 × 2 factorial arrangement of treatments. Factors included dietary Se [adequate Se (ASe, 11.5 μg/kg BW) or high Se (HSe, 77.0 μg/kg BW)], nutritional plane [60% (restricted; RES), 100% (control; CON), or 140% (high; HIH)], and physiological stage at necropsy (parturition or d 20 of lactation). At parturition, lambs were removed and 42 ewes (7 per treatment) were necropsied. Remaining ewes were transitioned to a common diet which met lactation requirements and mechanically milked for 20 d. In the absence of interactions (P > 0.10), main effects are reported. At parturition, stomach complex and liver masses were greatest for HIH, intermediate for CON, and least for RES (P < 0.02). Small intestinal mass was greater (P ≤ 0.002) for HIH than RES and CON, and greater (P < 0.01) for ASe than HSe. During early lactation, RES and CON gastrointestinal masses increased disproportionally to BW (P < 0.05). At parturition, jejunal mucosal density was less (P ≤ 0.01) for RES than CON and HIH, whereas CON had greater (P < 0.003) jejunal mucosal RNA concentration and RNA:DNA than RES and HIH. Although there were no differences (P > 0.17) at parturition, jejunal cell percent proliferation was greatest in RES, intermediate in CON, and least in HIH (P ≤ 0.09) at d 20 lactation. At both stages, RES had less (P = 0.01) jejunal capillary area density than HIH and less (P ≤ 0.03) capillary surface density than CON and HIH. During lactation, jejunal capillary size was greater (P = 0.04) for ewes previously fed HSe compared with ASe. At parturition, ASe-HIH had greater (P < 0.02) jejunal mucosal endothelial nitric oxide synthase 3 mRNA than all other treatments and greater (P = 0.10) vascular endothelial growth factor (VEGF) than all treatments, except ASe-RES. In addition, CON had less (P ≤ 0.08) jejunal VEGF receptor-1 (FLT1) mRNA compared with RES and HIH, and ASe had greater (P = 0.003) FLT1 than HSe at parturition. Ewes fed HIH had greater (P = 0.04) jejunal VEGF receptor-2 mRNA compared with RES. Results indicate that maternal intestinal growth and vascularization are responsive to nutritional plane and dietary Se during gestation and undergo changes postpartum when under similar lactational management.

  19. Effect of strain and stress on the relative dimensions of the 'hard' and 'soft' regions in crept NaCl single crystals

    NASA Technical Reports Server (NTRS)

    Raj, S. V.; Freed, Alan D.

    1992-01-01

    It is shown that the L exp h and L exp s ratio, where these are respectively the average dimensions of the hard and soft regions as a function of stress and strain in crept NaCl single crystals, significantly influences the steady-state creep and power-law breakdown in these crystals. This is suggested to be due to a change in the internal stresses of the material. The present observations also indicate that steady-state creep is more likely to be influenced by the degree of refinement in the cell boundaries within the subgrains than by the formation of equiaxed subgrains under power-law conditions.

  20. Electrical characterization of 6H crystalline silicon carbide. M.S. Thesis Final Report

    NASA Technical Reports Server (NTRS)

    Lempner, Stephen E.

    1994-01-01

    Crystalline silicon carbide (SiC) substrates and epilayers, undoped as well as n- and p-doped, have been electrically characterized by performing Hall effect and resistivity measurements (van der Pauw) over the temperature range of approximately 85 K to 650 K (200 K to 500 K for p-type sample). By fitting the measured temperature dependent carrier concentration data to the single activation energy theoretical model: (1) the activation energy for the nitrogen donor ranged from 0.078 eV to 0.101 eV for a doping concentration range of 10(exp 17) cm(exp -3) to 10(exp 18) cm(exp -3) and (2) the activation energy for the aluminum acceptor was 0.252 eV for a doping concentration of 4.6 x 10(exp 18) cm(exp -3). By fitting the measured temperature dependent carrier concentration data to the double activation energy level theoretical model for the nitrogen donor: (1) the activation energy for the hexagonal site was 0.056 eV and 0.093 eV corresponding to doping concentrations of 3.33 x 10 (exp 17) cm(exp -3) and 1.6 x 10(exp 18) cm(exp -3) and (2) the activation energy for the cubic site was 0.113 and 0.126 eV corresponding to doping concentrations of 4.2 x 10(exp 17) cm(exp -3) and 5.4 x 10(exp 18) cm(exp -3).

  1. Changes in ingestive capacity of macrophages from different organs in response to hydrocortisone

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

    Mayanskii, D.N.; Voronin, A.Yu.; Voronina, N.P.

    This paper studies changes in the ingestive capacity of resident macrophages (M) from different organs of the reticuloendothelial system (RES) after a single pharmacologic dose of hydrocortisone (HC) was injected into female rats. In a second series of experiments, mice were given an intravenous injection of 10/sup 8/ sheep's red blood cells (SRBC), labeled with Cr 51 (Cr 51-SRBC) 2, 24, and 72 h after injection of 125 mg/kg of HC. Results indicate that the sensitivity of resident M from different organs to HC differs. It may be possible to modify singificantly hormone-dependent metabolic changes in different versions of acutemore » stress and in the course of long-term adaptation, through modulation of reacitivity of Kupffer cells and of the RES as a whole.« less

  2. A Biophysical-Computational Perspective of Breast Cancer Pathogenesis and Treatment Response

    DTIC Science & Technology

    2009-03-01

    82. A.A. Rasmussen and K.J. Cullen, Breast Cancer Res Treat 47 (1998) 219- 33. 83. C. Kuperwasser, T. Chavarria, M. Wu, G. Magrane, J.W. Gray , L...24-34. 94. C.M. Lo, H.B. Wang, M. Dembo and Y.L. Wang, Biophys J 79 (2000) 144- 52. 95. D.S. Gray , J. Tien and C.S. Chen, J Biomed Mater Res A 66...Muller, G. Inghirami and F.G. Giancotti, Cell 126 (2006) 489-502. 103. C.C. Park, H. Zhang, M. Pallavicini, J.W. Gray , F. Baehner, C.J. Park and M.J

  3. Modelling Temporal Variability in the Carbon Balance of a Spruce/Moss Boreal Forest

    NASA Technical Reports Server (NTRS)

    Frolking, S.; Goulden, M. L.; Wofsy, S. C.; Fan, S.-M.; Sutton, D. J.; Munger, J. W.; Bazzaz, A. M.; Daube, B. C.; Crill, P. M.; Aber, J. D.; hide

    1996-01-01

    A model of the daily carbon balance of a black spruce/feathermoss boreal forest ecosystem was developed and results compared to preliminary data from the 1994 BOREAS field campaign in northern Manitoba, Canada. The model, driven by daily weather conditions, simulated daily soil climate status (temperature and moisture profiles), spruce photosynthesis and respiration, moss photosynthesis and respiration, and litter decomposition. Model agreement with preliminary field data was good for net ecosystem exchange (NEE), capturing both the asymmetrical seasonality and short-term variability. During the growing season simulated daily NEE ranged from -4 g C m(exp -2) d(exp -1) (carbon uptake by ecosystem) to + 2 g C m(exp -2) d(exp -1) (carbon flux to atmosphere), with fluctuations from day to day. In the early winter simulated NEE values were + 0.5 g C m(exp -2) d(exp -1), dropping to + 0.2 g C m(exp -2) d(exp -1) in mid-winter. Simulated soil respiration during the growing season (+ 1 to + 5 g C m(exp -2) d(exp -1)) was dominated by metabolic respiration of the live moss, with litter decomposition usually contributing less than 30% and live spruce root respiration less than 10% of the total. Both spruce and moss net primary productivity (NPP) rates were higher in early summer than late summer. Simulated annual NEE for 1994 was -51 g C m(exp -2) y(exp -1), with 83% going into tree growth and 17% into the soil carbon accumulation. Moss NPP (58 g C m(exp -2) d(exp -1)) was considered to be litter (i.e. soil carbon input; no net increase in live moss biomass). Ecosystem respiration during the snow-covered season (84 g Cm(exp -2)) was 58% of the growing season net carbon uptake. A simulation of the same site for 1968-1989 showed about 10-20% year-to-year variability in heterotrophic respiration (mean of + 113 g C m-2 y@1). Moss NPP ranged from 19 to 114 g C m(exp -2) y(exp -1); spruce NPP from 81 to 150 g C nt-2 y,@l; spruce growth (NPP minus litterfall) from 34 to 103 g C m(exp -2) y(exp -1); NEE ranged from +37 to -142 g C m(exp -2) y(exp -1). Values for these carbon balance terms in 1994 were slightly smaller than the 1969 - 89 means. Higher ecosystem productivity years (more negative NEE) generally had early springs and relatively wet summers; lower productivity years had late springs and relatively dry summers.

  4. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    DTIC Science & Technology

    2013-10-01

    Fehrenbacher JW et al. Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart. Ann Thorac Surg Sep 2009;88:1036–1043. 45 Payne... mesenchymal stem cells (MSCs) (5). Activation of RhoA-ROCK signaling in cultured MSCs in vitro induces their osteogenesis but Figure 5 Angiogenesis...osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10):1858-66. PMCID

  5. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    DTIC Science & Technology

    2014-10-01

    is shown in Figure 1. 2) Effect of hypoxia on the gene expression of human muscle derived stem cells (hMDSCs) Three populations of lenti-GFP...adipogenic differentiation of mesenchymal stem cells (MSCs) (5). Activation of RhoA-ROCK signaling in cultured MSCs in vitro induces their osteogenesis but...reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10):1858-66. PMCID

  6. Targeting Midbodies in Ovarian Cancer Stem Cells as a Therapeutic Strategy

    DTIC Science & Technology

    2014-12-01

    BRCA1, BRCA1, breast cancer 1 gene. MT, microtubules. 3. OVERALL PROJECT SUMMARY: Summarize the progress during appropriate reporting period...Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010; 140:62–73. [PubMed: 20074520] 40. Pardal...cells and contributes to the tolerance to nutrient deprivation. Cancer Res. 2007; 67:9677–84. [PubMed: 17942897] 47. Sarkar S, et al. A rational

  7. CpG-STAT3siRNA for Castration-Resistant Prostate Cancer Therapy

    DTIC Science & Technology

    2015-12-01

    RESULTS TLR9 promotes prostate cancer cell engraftment and progression in vivo Previous studies reported expression of the innate immune receptor...cancer cells express innate immune receptors, such as TLR9, normally restricted to the hematopoietic cell lineage [2, 5, 7]. Rather than becoming... innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells . Cancer Res. 2012; 72:3948–3957. 7. Ilvesaro JM

  8. Perceptions des jeunes victimes de violence sexuelle au sein de leurs relations amoureuses sur leur pire expérience

    PubMed Central

    Van Camp, Tinneke; Hébert, Martine; Fernet, Mylène; Blais, Martin; Lavoie, Francine

    2016-01-01

    Cette étude explore les pires expériences vécues dans les relations amoureuses de jeunes qui ont rapporté avoir vécu de la violence sexuelle dans une relation de couple récente. Quelles sont les situations perçues comme étant les plus difficiles par les jeunes et est-ce que celles-ci se limitent à des incidents violents? Le questionnaire sur les parcours amoureux des jeunes (PAJ) a été complété par des jeunes Québécois âgés de 14 à 18 ans. Au total, plus de 600 participants ont rapporté au moins un épisode de violence sexuelle (souvent en combinaison avec d’autres formes de violence). Nous présentons les résultats de l’analyse qualitative inductive fondée sur une question ouverte concernant la pire expérience vécue. Les observations suggèrent que, en plus des expériences de violence, les difficultés relationnelles, les ruptures amoureuses et les sentiments amoureux non réciproques sont des situations particulièrement difficiles selon les propos des jeunes. Ces différents enjeux vécus par les jeunes devraient être pris en considération dans l’offre de services d’intervention à leur intention. PMID:28191266

  9. Fundamentals of Chemistry at Surfaces and Beyond

    DTIC Science & Technology

    2013-09-23

    results of this research were published in J. Phys. Chem. C.34 B4. Fundamental Theory of Organic/Inorganic Hybrid Solar Cells In the field of...B, 104, 538-547 (2000). 38B. O’Regan, M. Gratzel, “A Low-Cost, High-Efficiency Solar Cell Based on Dye-Sensitized Colloidal TiO2 Films,” Nature...N. Murakami, H. J. Snaith, “Efficient Hybrid Solar Cells Based on Meso-Superstructured Organometal Halide Perovskites,” Sci. Exp., DOI: 10.1126

  10. Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats.

    PubMed

    Zhao, Qingling; Wei, Jinlan; Zhang, Hongying

    2018-06-04

    1. This study investigates the influence of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. 2. The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10 mg/kg) with or without pretreatment with quercetin (20 mg/kg/day for 7 days) were investigated. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism. 3. The results showed that when the rats were pretreated with quercetin, the C max (2.16 ± 0.40 vs. 1.33 ± 0.21 mg/L) and the AUC (0-t) (13.89 ± 1.22 vs. 7.34 ± 0.75 mg·h/L) of losartan increased significantly (p < .05), and while the C max (0.76 ± 0.09 vs. 1.14 ± 0.18 mg/L) of EXP3174 decreased significantly compared to the control (p < .05). The t 1/2 of losartan was prolonged from 3.27 ± 0.45 h to 4.74 ± 0.51 h (p < .05). The results also indicated that quercetin could increase losartan absorption rate by inhibiting the activity of P-gp and decrease its metabolic stability by inhibiting the activity of CYP450 enzyme. 4. These results indicated that the herb-drug interaction between quercetin and losartan might occur when they are co-administered in rats, quercetin could increase the systemic exposure of losartan and decrease the plasma concentration of EXP3174, possibly by inhibiting the activity of P-gp or CYP450 enzyme.

  11. Orosomucoid binds insulin and IGF1 and reduces hormone stimulated protein synthesis and glucose metabolism in C2C12 myotubes

    USDA-ARS?s Scientific Manuscript database

    Previous research has indicated that orosomuciod (ORM1) may enhance insulin response in 3T3-L1 adipocytes. The present study was undertaken to determine if ORM1 can modify muscle metabolism by examining glucose oxidation and protein synthesis in the C2C12 muscle cell line. Cells were used for expe...

  12. microRNA Regulation of DEP-induced Inflammation in Airway Epithelial Cells

    EPA Science Inventory

    Morbidity and mortality attributable to air pollution continues to be a growing problem worldwide. Despite several studies on the health effects of ambient air pollution, underlying molecular mechanisms of susceptibility and disease remain elusive. The epigenome controls gene exp...

  13. A method of solving simple harmonic oscillator Schroedinger equation

    NASA Technical Reports Server (NTRS)

    Maury, Juan Carlos F.

    1995-01-01

    A usual step in solving totally Schrodinger equation is to try first the case when dimensionless position independent variable w is large. In this case the Harmonic Oscillator equation takes the form (d(exp 2)/dw(exp 2) - w(exp 2))F = 0, and following W.K.B. method, it gives the intermediate corresponding solution F = exp(-w(exp 2)/2), which actually satisfies exactly another equation, (d(exp 2)/dw(exp 2) + 1 - w(exp 2))F = 0. We apply a different method, useful in anharmonic oscillator equations, similar to that of Rampal and Datta, and although it is slightly more complicated however it is also more general and systematic.

  14. Indigenous and Contaminant Microbes in Ultradeep Mines

    NASA Technical Reports Server (NTRS)

    Onstott, T. C.; Moser, D. P.; Pfiffner, S. M.; Fredrickson, J. K.; Brockman, F. J.; Phelps, T. J.; White, D. C.; Peacock, A.; Balkwill, D.; Hoover, R. B.; hide

    2003-01-01

    Rock, air and service water samples were collected for microbial analyses from 3.2 kilometers depth in a working Au mine in the Witwatersrand basin, South Africa. The approx. 1 meter wide mined zone was comprised of a carbonaceous, quartz, sulfide, uraninite and Au bearing layer, called the Carbon Leader, sandwiched by quartzite and conglomerates. The microbial community in the service water was dominated by mesophilic aerobic and anaerobic, alpha, beta, and gamma-Proteobacteria with a total biomass concentration approx. 10(exp 4) cells/ml, whereas, that of the mine air was dominated by members of the Chlorobi and Bacteroidetes groups and a fungal component. The microorganisms in the Carbon Leader were predominantly mesophilic, aerobic heterotrophic, nitrate reducing and methylotrophic, beta and gamma-Proteobacteria that were more closely related to service water microorganisms rather than air microbes. Rhodamine WT dye and fluorescent microspheres employed as contaminant tracers, however, indicated that service water contamination of most of the rock samples was < 0.01% during acquisition. The microbial contaminants most likely originated from the service water, infiltrated the low permeability rock through and accumulated within mining-induced fractures where they survived for several days prior to being mined. Combined PLFA and terminal restriction fragment length profile (T-RFLP) analyses suggest that the maximum concentration of indigenous microorganisms in the Carbon Leader was < 10(exp 2) cells/g. PLFA, (35)S autoradiography and enrichments suggest that the adjacent quartzite was less contaminated and contained approx. 10(exp 3) cells/gram of a thermophilic, sulfate reducing bacteria, SRB, some of whom are delta Proteobacteria. Pore water and rock geochemical analyses suggest that these SRB's may have been sustained by sulfate diffusing from the adjacent U-rich, Carbon Leader where it was formed by radiolysis of sulfide.

  15. Indigenous and Contaminant Microbes in Ultradeep Mines

    NASA Technical Reports Server (NTRS)

    Onstott, T. C.; Moser, D. P.; Pfiffner, S. M.; Fredrickson, J. F.; Brockman, F. J.; Phelps, T. J.; White, D. C.; Peacock, A.; Balkwill, D.; Hoover, R.; hide

    2003-01-01

    Rock, air and service water samples were collected for microbial analyses from 3.2 kilometers depth in a working Au mine in the Witwatersrand basin, South Africa. The approx. 1 meter wide mined zone was comprised of a carbonaceous, quartz, sulfide, uraninite and Au bearing layer, called the Carbon Leader, sandwiched by quartzite and conglomerates. The microbial community in the service water was dominated by mesophilic aerobic and anaerobic, alpha, beta and gamma-Proteobacteria with a total biomass concentration approx. l0(exp 4) cells/ ml, whereas, that of the mine air was dominated by members of the Chlorobi and Bacteroidetes groups and a fungal component. The microorganisms in the Carbon Leader were predominantly mesophilic, aerobic heterotrophic, nitrate reducing and methylotrophic, beta and gamma - Proteobacteria that were more closely related to service water microorganisms rather than air microbes. Rhodamine WT dye and fluorescent microspheres employed as contaminant tracers, however, indicated that service water contamination of most of the rock samples was less that 0.01% during acquisition. The microbial contaminants most likely originated from the service water, infiltrated the low permeability rock through and accumulated within mining-induced fractures where they survived for several days prior to being mined. Combined PLFA and terminal restriction fragment length profile (T-RFLP) analyses suggest that the maximum concentration of indigenous microorganisms in the Carbon Leader was less than lo(exp 2) cells/ g. PLFA, S-35 autoradiography and enrichments suggest that the adjacent quartzite was less contaminated and contained -10(exp 3) cells/gram of a thermophilic, sulfate reducing bacteria, SRB, some of who are delta Proteobacteria. Pore water and rock geochemical analyses suggest that these SRB's may have been sustained by sulfate diffusing from the adjacent U-rich, Carbon Leader where it was formed by radiolysis of sulfide.

  16. The Garlic Allelochemical Diallyl Disulfide Affects Tomato Root Growth by Influencing Cell Division, Phytohormone Balance and Expansin Gene Expression

    PubMed Central

    Cheng, Fang; Cheng, Zhihui; Meng, Huanwen; Tang, Xiangwei

    2016-01-01

    Diallyl disulfide (DADS) is a volatile organosulfur compound derived from garlic (Allium sativum L.), and it is known as an allelochemical responsible for the strong allelopathic potential of garlic. The anticancer properties of DADS have been studied in experimental animals and various types of cancer cells, but to date, little is known about its mode of action as an allelochemical at the cytological level. The current research presents further studies on the effects of DADS on tomato (Solanum lycopersicum L.) seed germination, root growth, mitotic index, and cell size in root meristem, as well as the phytohormone levels and expression profile of auxin biosynthesis genes (FZYs), auxin transport genes (SlPINs), and expansin genes (EXPs) in tomato root. The results showed a biphasic, dose-dependent effect on tomato seed germination and root growth under different DADS concentrations. Lower concentrations (0.01–0.62 mM) of DADS significantly promoted root growth, whereas higher levels (6.20–20.67 mM) showed inhibitory effects. Cytological observations showed that the cell length of root meristem was increased and that the mitotic activity of meristematic cells in seedling root tips was enhanced at lower concentrations of DADS. In contrast, DADS at higher concentrations inhibited root growth by affecting both the length and division activity of meristematic cells. However, the cell width of the root meristem was not affected. Additionally, DADS increased the IAA and ZR contents of seedling roots in a dose-dependent manner. The influence on IAA content may be mediated by the up-regulation of FZYs and PINs. Further investigation into the underlying mechanism revealed that the expression levels of tomato EXPs were significantly affected by DADS. The expression levels of EXPB2 and beta-expansin precursor were increased after 3 d, and those of EXP1, EXPB3 and EXLB1 were increased after 5 d of DADS treatment (0.41 mM). This result suggests that tomato root growth may be regulated by multiple expansin genes at different developmental stages. Therefore, we conclude that the effects of DADS on the root growth of tomato seedlings are likely caused by changes associated with cell division, phytohormones, and the expression levels of expansin genes. PMID:27555862

  17. A quorum sensing-defective mutant of Pectobacterium carotovorum ssp. brasiliense 1692 is attenuated in virulence and unable to occlude xylem tissue of susceptible potato plant stems.

    PubMed

    Moleleki, Lucy Novungayo; Pretorius, Rudolph Gustav; Tanui, Collins Kipngetich; Mosina, Gabolwelwe; Theron, Jacques

    2017-01-01

    Pectobacterium carotovorum ssp. brasiliense 1692 (Pcb1692) is an important emerging pathogen of potatoes causing blackleg in the field and soft rot during post-harvest storage. Blackleg diseases involve the bacterial colonization of vascular tissue and the formation of aggregates, also known as biofilms. To understand the role of quorum sensing in vascular colonization by Pcb1692, we generated a Pcb1692ΔexpI mutant strain. Inactivation of expI led to the reduced production of plant cell wall-degrading enzymes (PCWDEs), the inability to produce acyl homoserine lactone (AHL) and reduced virulence in potato tubers and stems. Complementation of the mutant strain with the wild-type expI gene in trans successfully restored AHL and PCWDE production as well as virulence. Transmission electron microscopy and in vitro motility assays demonstrated hyperpiliation and loss of flagella and swimming motility in the mutant strain compared with the wild-type Pcb1692. Furthermore, we noted that, in the early stages of infection, Pcb1692 wild-type cells had intact flagella which were shed at the later stages of infection. Confocal laser microscopy of PcbΔexpI-inoculated plants showed that the mutant strain tended to aggregate in intercellular spaces, but was unable to transit to xylem tissue. On the contrary, the wild-type strain was often observed forming aggregates within xylem tissue of potato stems. Gene expression analyses confirmed that flagella are part of the quorum sensing regulon, whereas fimbriae and pili appear to be negatively regulated by quorum sensing. The relative expression levels of other important putative virulence genes, such as those encoding different groups of PCWDEs, were down-regulated in the mutant compared with the wild-type strain. © 2016 BSPP and John Wiley & Sons Ltd.

  18. X-ray clusters from a high-resolution hydrodynamic PPM simulation of the cold dark matter universe

    NASA Technical Reports Server (NTRS)

    Bryan, Greg L.; Cen, Renyue; Norman, Michael L.; Ostriker, Jermemiah P.; Stone, James M.

    1994-01-01

    A new three-dimensional hydrodynamic code based on the piecewise parabolic method (PPM) is utilized to compute the distribution of hot gas in the standard Cosmic Background Explorer (COBE)-normalized cold dark matter (CDM) universe. Utilizing periodic boundary conditions, a box with size 85 h(exp-1) Mpc, having cell size 0.31 h(exp-1) Mpc, is followed in a simulation with 270(exp 3)=10(exp 7.3) cells. Adopting standard parameters determined from COBE and light-element nucleosynthesis, Sigma(sub 8)=1.05, Omega(sub b)=0.06, we find the X-ray-emitting clusters, compute the luminosity function at several wavelengths, the temperature distribution, and estimated sizes, as well as the evolution of these quantities with redshift. The results, which are compared with those obtained in the preceding paper (Kang et al. 1994a), may be used in conjuction with ROSAT and other observational data sets. Overall, the results of the two computations are qualitatively very similar with regard to the trends of cluster properties, i.e., how the number density, radius, and temeprature depend on luminosity and redshift. The total luminosity from clusters is approximately a factor of 2 higher using the PPM code (as compared to the 'total variation diminishing' (TVD) code used in the previous paper) with the number of bright clusters higher by a similar factor. The primary conclusions of the prior paper, with regard to the power spectrum of the primeval density perturbations, are strengthened: the standard CDM model, normalized to the COBE microwave detection, predicts too many bright X-ray emitting clusters, by a factor probably in excess of 5. The comparison between observations and theoretical predictions for the evolution of cluster properties, luminosity functions, and size and temperature distributions should provide an important discriminator among competing scenarios for the development of structure in the universe.

  19. A hydrodynamic treatment of the tilted cold dark matter cosmological scenario

    NASA Technical Reports Server (NTRS)

    Cen, Renyue; Ostriker, Jeremiah P.

    1993-01-01

    A standard hydrodynamic code coupled with a particle-mesh code is used to compute the evolution of a tilted cold dark matter (TCDM) model containing both baryonic matter and dark matter. Six baryonic species are followed, with allowance for both collisional and radiative ionization in every cell. The mean final Zel'dovich-Sunyaev y parameter is estimated to be (5.4 +/- 2.7) x 10 exp -7, below currently attainable observations, with an rms fluctuation of about (6.0 +/- 3.0) x 10 exp -7 on arcmin scales. The rate of galaxy formation peaks at a relatively late epoch (z is about 0.5). In the case of mass function, the smallest objects are stabilized against collapse by thermal energy: the mass-weighted mass spectrum peaks in the vicinity of 10 exp 9.1 solar masses, with a reasonable fit to the Schechter luminosity function if the baryon mass to blue light ratio is about 4. It is shown that a bias factor of 2 required for the model to be consistent with COBE DMR signals is probably a natural outcome in the present multiple component simulations.

  20. Development of microchannel plates in advanced wind-tunnel instrumentation

    NASA Technical Reports Server (NTRS)

    Feller, W. Bruce

    1990-01-01

    Microchannel plate (MCP) electron multiplier dynamic range has been increased 3 to 4 orders of magnitude at ambient temperatures, through enhanced input count rate capability and reduced background or 'dark' noise. The previous upper limit of roughly 10(exp 7) - 10(exp 8) cm(exp -2)s(exp -1) at ambient has been extended to levels approach 10(exp 10) cm(exp -2)s(exp -1) under continuous dc operation. The lower limit, previously set by an irreducible background component (approximately 0.6 cm(exp -2)s(exp -1)), has been lowered to the cosmic ray limit of .01 cm(exp -2)s(exp -1). The high end improvement was achieved by conductively cooling a very low resistance MCP by bonding it to a heat sink, while maintaining pulse-counting operation with multianode readouts. The low-end improvement was achieved by removing all radioisotopes from the MCP matrix glass. The detectors will benefit optical and mass spectrometry, flow visualization, plasma diagnostics, magnetometry, and other high signal flux applications. Very low MCP background noise will benefit X-ray and UV astronomy, medical imaging, trace isotope mass spectrometry, and other applications where the signal flux is often extremely low.

  1. Aerosol Abundances and Optical Characteristics in the Pacific Basin Free Troposphere

    NASA Technical Reports Server (NTRS)

    Pueschel, R. F.; Livingston, J. M.; Ferry, G. V.; deFelice, T. E.

    1994-01-01

    During NASA's Global Backscatter Experiment (GLOBE) mission flights in November 1989 and May 1990, a DC-8 research aircraft probed the Pacific Basin free troposphere for about 90 flight hours in each month between +72 and -62 degrees latitude, +130 and -120 degrees longitude, and up to 39,000 feet pressure altitudes. Aerosols were sampled continuously in situ by optical particle counters to measure concentration and particle size, and during 48 10-min intervals during each mission by wire impactors for concentration, size, composition, phase and shape analyses. The optical particle counters cover a particle diameter range between 0.3 and 20 microns; wire impactors extend the range down to 0.03 microns. Results of particle number, size, shape, together with the assumption of a refractive index corresponding to (NH4)2SO4 to account for the prevalence of aerosol sulfur, were utilized in a Mie algorithm to calculate aerosol extinction and backscatter for a range of wavelengths (0.385 less than lambda less than 10.64 microns). Computations for 22 randomly selected size distributions yield coefficients of extinction E(0.525) = (2.03 +/- 1.20) x 10(exp -4) km(exp -1) and backscatter beta(0.525) = (6.45 +/- 3.49) x 10(exp -6) km(exp -1) sr(exp -1) in the visible, and E(10.64) = (8.13 +/- 6.47) x 10(exp -6) km(exp -1) and beta(10.64) = (9.98 +/- 10.69) x 10(exp -8) km(exp -1) sr(exp -1) in the infrared, respectively. Large particles (D greater than 0.3 microns) contribute two-thirds to the total extinction in the visible (lambda = 0.525 microns), and almost 100% in the infrared (lambda = 10.64 microns). These results have been used to define an IR optical aerosol climatology of the Pacific Basin free troposphere, from which it follows that the infrared backscatter coefficient at lambda = 9.25 microns wavelength fluctuates between 5.0 x 10(exp -10) and 2.0 x 10(exp -7) km(exp -1) sr(exp -1) with a modal value 2.0 x 10(exp -8) km(exp -1) sr(exp -1).

  2. A hydrodynamic approach to cosmology: The mixed dark matter cosmological scenario

    NASA Technical Reports Server (NTRS)

    Cen, Renyue; Ostriker, Jeremiah P.

    1994-01-01

    We compute the evolution of spatially flat, mixed cold and hot dark matter models containing both baryonic matter and two kinds of dark matter. Hydrodynamics is treated with a highly developed Eulerian hydrodynamic code (see Cen 1992). A standard particle-mesh (PM) code is also used in parallel to calculate the motion of the dark matter components. We adopt the following parameters: h equivalent to (sub 0)/100 km/s Mpc(exp -1) = 0.5, OMEGA(sub C) = 0.3, and OMEGA(sub B) = 0.06, with amplitude of the perturbation spectrum fixed by the Cosmic Background Explorer Satellite (COBE) Dark Matter Radiation (DMR) measurements (Smoot et al. 1992) being sigma (sub 8) = 0.67. Four different boxes are simulated with box sizes of L = (64, 16, 4, 1) h(exp -1) Mpc, respectively, the two small boxes providing good resolution but little valid information due to absence of large-scale power. We use 128(exp 3) approximate 10(exp 6.3) baryonic cells, 128(exp .3) cold dark matter particles, and 2 x 128(exp 3) hot dark matter particles. In addition to the dark matter we follow separately six baryonic species (H, H(+), He, He(+), He(++), e(-)) with allowance for both (nonequilibrium) collisional and radiative ionization in every cell. The background radiation field is also followed in detail with allowance made for both continuum and line processes, to allow nonequilibrium heating and cooling processes to be followed in detail. The mean final Zeldovich-Sunyaev y parameter is estimated to be y Bar = (5.4 + or - 2.7) x 10(exp -7) below currently attainable observations, with a rms fluctuation of approximately delta bar y = (0.6 + or - 3.0) x 10(exp -7) on arcminute scales. The rate of galaxy formation peaks at an even later epoch (z approximate 0.3) than in the standard (OMEGA = 1, sigma sub 8 = 0.67) cold dark matter (CDM) model (z approximate 0.5) and, at a redshift of z = 4, is nearly a factor of 100 lower than for the CDM model with the same value of sigma sub 8. With regard to mass function, the smallest objects are stabilized against collapse by thermal energy: the mass-weighted mass spectrum has a broad peak in the vicinity of M(sub B) = 10(exp 9.5) solar mass with a reasonable fit to the Schechter luminosity function if the ratio of baryon mass to blue light is approximately 4. In addition, one very large PM simulation was made in a box with size (320 h(exp - 1) Mpc) containing 3 x 200(exp 3) = 10(exp 7.4) particles. Utilizing this simulation we find that the model yields a cluster mass function which is about a factor of 4 higher than observed, but a cluster-cluster correlation length marginally lower than observed, but that both are closer to observations than in the (COBE) normalized CDM model. The one-dimensional pairwise velocity dispersion is 605 + or - 8 km/s at 1/h separation, lower than that of the DCM model normalized to COBE, but still significant higher than observations (Davis & Peebles 1983). A plausible velocity bias b(sub v) = 0.8 + or - 0.1 on this scale will reduce but not remove the discrepancy. The velocity auto-correlat ion function has a coherence length of 40/h Mpc, which is somewhat lower than the observed counterpart. In all these respects the model would be improved by decreasing the cold fraction of the dark OMEGA(sub CDM)/ (OMEGA(sub CDM) + OMEGA(sub HDB). But formation of galaxies and clusters of galaxies is much later in this model than in COBE-normalized CDM, perhaps too late. To improve on these constraints a larger ratio of OMEGA(sub CDM)/ (OMEGA(sub CDM) + OMEGA(sub HDM)) is required than the value of 0.67 adopted here. It does not seem possible to find a value for this ratio which would satisfy all tests. Overall, the model is similar both on large and intermediate scales to the standard CDM model normalized to the same value of sigma(sub B), but the problem with regard to late formation of galaxies is more severe in this model than in that CDM model. Adding hot dark matter, significantly improves the ability of the COBE-normalized CDM scenario to fit existing observations, but the model is in fact not as good as the CDM model with the same sigma(sub 8) and is still probably unsatisfactory with regard to several critical tests.

  3. La prise en charge d’une clientèle

    PubMed Central

    Roy, Andréanne; Breton, Mylaine; Loslier, Julie

    2016-01-01

    Résumé Objectif Analyser les facteurs qui incitent les médecins de famille nouvellement autorisés à faire de la prise en charge d’une clientèle en première ligne. Type d’étude Devis mixte séquentiel : questionnaire en ligne auto-administré auprès de médecins de famille, suivi d’entrevues individuelles. Contexte La Montérégie, qui est la deuxième région la plus populeuse du Québec, et qui présente des zones rurales et urbaines. Participants Tous les médecins de famille détenant un poste en Montérégie et ayant moins de 10 années d’expérience ont été sollicités, soit 366 médecins. Parmi eux, 118 ont complété le questionnaire en ligne (taux de réponse de 32,2 %). Parmi les répondants, 10 médecins ayant des profils de prise en charge variés ont été sélectionnés pour les entrevues individuelles. Principaux paramètres à l’étude Le pourcentage de temps de travail consacré à la prise en charge, analysé en parallèle avec différents facteurs facilitants et barrières à la prise en charge aux niveaux contextuel, organisationnel, du médecin de famille et de la clientèle. Résultats Les principaux facteurs facilitant la prise en charge sont la relation médecin-patient, l’intérêt pour les activités cliniques liées à la prise en charge, les modèles de rôles positifs, la collaboration avec une infirmière et l’accès adéquat aux ressources, notamment en santé mentale. Les principales barrières sont l’ampleur des tâches administratives, l’intérêt pour une pratique polyvalente, l’expérience négative de la prise en charge lors de la formation, un sentiment n’inaptitude à l’égard de la prise en charge, la lourdeur de la clientèle et le manque de soutien en début de pratique. Conclusion Certaines pistes de solution pour inciter les nouveaux médecins de famille à prendre en charge une clientèle sont proposées. Des points d’amélioration au niveau de la formation médicale, du soutien administratif et des ressources humaines sont notamment soulevés.

  4. Explicit knowledge about the availability of visual feedback affects grasping with the left but not the right hand.

    PubMed

    Tang, Rixin; Whitwell, Robert L; Goodale, Melvyn A

    2014-01-01

    Previous research (Whitwell et al. in Exp Brain Res 188:603-611, 2008; Whitwell and Goodale in Exp Brain Res 194:619-629, 2009) has shown that trial history, but not anticipatory knowledge about the presence or absence of visual feedback on an upcoming trial, plays a vital role in determining how that feedback is exploited when grasping with the right hand. Nothing is known about how the non-dominant left hand behaves under the same feedback regimens. In present study, therefore, we compared peak grip aperture (PGA) for left- and right-hand grasps executed with and without visual feedback (i.e., closed- vs. open-loop conditions) in right-handed individuals under three different trial schedules: the feedback conditions were blocked separately, they were randomly interleaved, or they were alternated. When feedback conditions were blocked, the PGA was much larger for open-loop trials as compared to closed-loop trials, although this difference was more pronounced for right-hand grasps than left-hand grasps. Like Whitwell et al., we found that mixing open- and closed-loop trials together, compared to blocking them separately, homogenized the PGA for open- and closed-loop grasping in the right hand (i.e., the PGAs became smaller on open-loop trials and larger on closed-loop trials). In addition, the PGAs for right-hand grasps were entirely determined by trial history and not by knowledge of whether or not visual feedback would be available on an upcoming trial. In contrast to grasps made with the right hand, grasps made by the left hand were affected both by trial history and by anticipatory knowledge of the upcoming visual feedback condition. But these effects were observed only on closed-loop trials, i.e., the PGAs of grasps made with the left hand on closed-loop trials were smaller when participants could anticipate the availability of feedback on an upcoming trial (alternating trials) than when they could not (randomized trials). In contrast, grasps made with the left hand on open-loop trials exhibited the same large PGAs under all feedback schedules: blocked, random, or alternating. In other words, there was no evidence for homogenization. Taken together, these results suggest that in addition to the real-time demands of the task, such as the target's size and position and the availability of visual feedback, the initial (i.e., pre-movement) programming of right-hand grasping relies on what happened on the previous trial, whereas the programming of left-hand grasping is more cognitively supervised and exploits explicit information about trial order to prepare for an upcoming trial.

  5. La Station Laser ultra mobile: de l'Obtention d'une Exactitude centimétrique des Mesures à des Applications en Océanographie et Géodésie Spatiales

    NASA Astrophysics Data System (ADS)

    Nicolas, Joëlle

    2000-12-01

    La Station Laser Ultra Mobile est la plus petite station de télémétrie laser au monde, ne pesant que 300 kg, dédiée à la poursuite de satellites équipés de rétroréflecteurs laser. Elle utilise un petit télescope de 13 cm de diamètre placé sur une monture issue d'un théodolite de précision et motorisé, un laser très compact et une photodiode à avalanche permettant la détection au niveau du simple photo-électron. Les premières expériences (Corse, fin 1996) ont révélé de nombreuses instabilités dans la qualité des mesures. Ce travail concerne l'étude et la mise en place de nombreuses modifications techniques afin d'atteindre une exactitude centimétrique des mesures et de pouvoir participer à la campagne de validation des orbites et d'étalonnage de l'altimètre du satellite océanographique JASON-1 (2001). La précision instrumentale souhaitée a été vérifiée avec succès en laboratoire. Outre cet aspect instrumental et métrologique, une analyse a été développée afin de pouvoir estimer l'exactitude et la stabilité des observations de la station mobile après intégration des modifications. A partir d'une expérience de co-localisation entre les deux stations laser fixe du plateau de Calern, l'analyse est basée sur l'ajustement, par station, de coordonnées et d'un biais instrumental moyen à partir d'une orbite de référence des satellites LAGEOS. Des variations saisonnières ont été mises en évidence dans les séries temporelles des différentes composantes. La comparaison locale des déformations de la croûte terrestre se traduisant par des variations d'altitude issues des données laser a montré une cohérence remarquable avec les mesures du gravimètre absolu transportable FG5. Des signaux de même amplitude ont aussi été observés par GPS. Ces variations sont également mises en évidence à l'échelle mondiale et leur interprétation géophysique est faite (combinaison des effets de marées terrestres et polaire et des effets de charge atmosphérique).

  6. Therapeutic Role of Resveratrol and Quercetin on Aortic Fibroblasts of Psammomys obesus After Oxidative Stress by Hydrogen Peroxide.

    PubMed

    Boumaza, Saliha; Belkebir, Aicha; Neggazi, Samia; Sahraoui, Hamid; Berdja, Sihem; Smail, Leila; Benazzoug, Yasmina; Kacimi, Ghoti; Aouichat Bouguerra, Souhila

    In our study, we propose to analyze the effects of resveratrol (RES) and quercetin (QRC) on proliferation markers, oxidative stress, apoptosis, and inflammation of aortic fibroblasts of Psammomys obesus after induced oxidative stress by hydrogen peroxide (H2O2). Fibroblasts were incubated in RES 375 μM and QRC 0.083 μM for 24 hours after exposure to H2O2 1.2 mM for 6 hours. We performed the proliferation rate, cells viability, morphological analyses, cytochrome c, Akt, ERK1/2, and p38 MAPK quantification. The redox status was achieved by proportioning of malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl proteins, catalase, and superoxide dismutase activity. The inflammation was measured by TNFα, MCP1, and NF-kB assay. The extracellular matrix (ECM) remodeling was performed by SDS-PAGE. Stressed fibroblasts showed a decrease of cell proliferation and viability, hypertrophy and oncosis, chromatin hypercondensation and increase of cytochrome c release characteristic of apoptosis, activation of ERK1/2 and Akt pathway, and decreases in p38 MAPK pathways marking the cellular resistance. The redox state was disrupted by increased malondialdehyde, nitric monoxide, advanced oxidation protein products, carbonyl protein production, catalase and superoxide dismutase activity, and a decreased production of proteins including collagens. Inflammation state was marked by MCP-1, TNFα, and NF-kB increase. Treatment of fibroblasts stressed by RES and QRC inverted the oxidative stress situation decreasing apoptosis and inflammation, and improving the altered redox status and rearrangement of disorders observed in extracellular matrix. H2O2 induced biochemical and morphological alterations leading to apoptosis. An improved general condition is observed after treatment with RES and QRC; this explains the antioxidant and antiapoptotic effects of polyphenols.

  7. Frequency and phase effects on cervical vestibular evoked myogenic potentials (cVEMPs) to air-conducted sound.

    PubMed

    Govender, Sendhil; Dennis, Danielle L; Colebatch, James G

    2016-09-01

    Few previous studies of tuning using air-conducted (AC) stimuli and the cervical vestibular evoked myogenic potential (cVEMP) have compensated for the effects of middle ear (ME) attenuation. Zhang et al. (Exp Brain Res 213:111-116, 2011a) who did allow for ME effects were able to show a secondary peak around 100 Hz for the ocular VEMP (oVEMP). Recently, it has become clear that the otolith afferents responsible for the cVEMP and oVEMP differ and thus the nature of tuning may be more related to the reflex studied determining which otolith receptors are activated rather than the properties of the stimulus. We wished to reinvestigate the tuning for the cVEMP using AC stimuli, to establish whether the low-frequency peak is specific for the oVEMP or a consequence of the stimulus modality itself. In response to recent evidence using a 500 Hz AC stimulus that there was no effect of stimulus phase, we also investigated whether phase (condensation or rarefaction) had an effect at any frequency. We measured corrected cVEMP amplitudes and latencies in response to stimuli between 50 and 1200 Hz in 10 normal volunteers using an AC stimulus adjusted for ME attenuation. We confirmed earlier reports of the similarity of the tuning for both the cVEMP and oVEMP reflexes but found no separate 100 Hz peak for the cVEMP. AC stimulus phase did not affect either amplitude or latency. Both the tuning pattern and the phase effects contrast with those previously reported for bone-conducted (BC) stimuli. Unlike BC stimulation, which shows tuning consistent with an action on the otolith membrane, AC stimuli are likely to act through a different mechanism, most likely directly at the hair cell level.

  8. Functional Genomics for Epithelial-Mesenchymal Transition in Breast Cancer

    DTIC Science & Technology

    2011-10-01

    9780521887212) CONFERENCES PRESENTATIONS (Podium) International International Bone & Mineral Society – Cancer and Bone Society meeting, Chicago , IL...bladder. Clin Exp Metastasis. 22: 115– 125. 62. Yates CC, Shepard CR, Stolz DB, Wells A (2007) Co- culturing human prostate carcinoma cells with hepato

  9. Nrf2 Expression Modifies Influenza A Entry and Replication inNasal Epithelial Cells

    EPA Science Inventory

    Influenza infection is a major cause of morbidity and mortality worldwide, especially during pandemics outbreaks. Emerging data indicate that phase II antioxidant enzyme pathways could playa role in virus-associated inflammation and immune clearance. While Nrf2-dependent gene exp...

  10. Mechanism of Hormonal Regulation of CAD Gene Expression in Human Breast Cancer Cells

    DTIC Science & Technology

    2006-05-01

    showed that PGJ2, troglitazone, and ciglitazone inhibit E2-stimulated cell proliferation of a leiomyoma -derived cell line and human primary leiomyoma ...cultures and also inhibit ER-mediated gene expression and protein expression. These results suggested that in uterine leiomyomas PPARγ activation is...peroxisome proliferator-activated receptor gamma ligands in uterine leiomyoma . Cancer Res. 63, 1221-1227. Hulka, BS., Liu, ET., and Lininger, RA., 1994

  11. Progress in p(+)n InP solar cells fabricated by thermal diffusion

    NASA Technical Reports Server (NTRS)

    Flood, D. J.; Brinker, D. J.; Weinberg, I.; Vargas, C.; Faur, Mircea; Faur, Maria; Goradia, C.; Goradia, M.; Fatemi, N. S.

    1993-01-01

    The performance results of our most recently thermally diffused InP solar cells using the p(+)n (Cd,S) structures are presented. We have succeeded in fabricating cells with measured AMO, 25 C V(sub oc) exceeding 880 mV (bare cells) which to the best of our knowledge is higher than previously reported V(sub oc) values for any InP homojunction solar cells. The cells were fabricated by thinning the emitter, after Au-Zn front contacting, from its initial thickness of about 4.5 microns to about 0.6 microns. After thinning, the exposed surface of the emitter was passivated by a thin (approximately 50A) P-rich oxide. Based on the measured EQY and J(sub sc)-V(sub oc) characteristics of our experimental high V(sub oc) p(+)n InP solar cells, we project that reducing the emitter thickness to 0.3 microns, using an optimized AR coating, maintaining the surface hole concentration of 3 x 10(exp 18)cm(sup -3), reducing the grid shadowing from actual 10.55 percent to 6 percent and reducing the contact resistance will increase the actual measured 12.57 percent AMO 25 C efficiency to about 20.1 percent. By using our state-of-the-art p(+)n structures which have a surface hole concentration of 4 x 10(exp 18)cm(sup -3) and slightly improving the front surface passivation, an even higher practically achievable AMO, 25 C efficiency of 21.3 percent is projected.

  12. The Role of the Caspase-8 Inhibitor FLIP in Androgen-Withdrawal Induced Death of Prostate Epithelium

    DTIC Science & Technology

    2007-01-01

    cells. Cancer Res 2000;60:2384-9. 20. Voelkel-Johnson C, King DL, Norris JS. Resistance of prostate cancer cells to soluble TNF-related apoptosis...Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell...ethanol. LY294002 (Cayman) was dissolved in Androgens and FOXO3a regulate FLIP page 7 dimethylsulfoxide (DMSO). Soluble recombinant human TRAIL (Biomol

  13. Shock Tube and Modeling Study of the H + O2 = OH + O Reaction over a Wide Range of Composition, Pressure, and Temperature

    NASA Technical Reports Server (NTRS)

    Ryu, Si-Ok; Hwang, Soon Muk; Rabinowitz, Martin Jay

    1995-01-01

    The rate coefficient of the reaction H + 02 = OH + 0 was determined using OH laser absorption spectroscopy behind reflected shock waves over the temperature range 1050-2500 K and the pressure range 0.7-4.0 atm. Eight mixtures and three stoichiometries were used. Two distinct and independent criteria were employed in the evaluation of k(sub 1). Our recommended expression for k(sub 1) is k(sub 1) = 7.13 x 10(exp 13)exp(-6957 K/T) cm(exp 3)mol(exp -1)s(exp -1) with a statistical uncertainty of 6%. A critical review of recent evaluations of k(sub 1) yields a consensus expression given by k(sub 1) = 7.82 x 10(exp 13)exp(-7105 K/7) cm(exp 3)mol(exp -1)s(exp -1) over the temperature range 960-5300 K. We do not support a non-Arrhenius rate coefficient expression, nor do we find evidence of composition dependence upon the determination of k(sub 1).

  14. Thermochemistry of Calcium-Magnesium-Aluminum-Silicate (CMAS) and Components of Advanced Thermal and Environmental Barrier Coating Systems

    NASA Technical Reports Server (NTRS)

    Costa, Gustavo C. C.; Acosta, Waldo A.; Zhu, Dongming; Ghoshal, Anindya

    2017-01-01

    There is increasing interest in the degradation mechanism studies of thermal and environmental barrier coatings (TEBCs) of gas turbines by molten CaO-MgO-Al(exp. 2)O(exp. 3)-SiO(exp. 2) CMAS). CMAS minerals are usually referred as silicon-containing sand dust and volcano ash materials that are carried by the intake air into gas turbines, e.g. in aircraft engines, and their deposits often react at high temperatures (greater than 1200 degrees C) with the engine turbine coating systems and components. The high temperature reactions causes degradation and accelerated failure of the static and rotating components of the turbine engines. We discuss some results of the reactions between the CMAS and Rare-Earth (RE = Y, Yb, Dy, Gd, Nd and Sm) - oxide stabilized ZrO(exp. 2) or HfO(exp. 2) systems, and the stability of the resulting oxides and silicates. Plasma sprayed hollow tube samples (outside diameter = 4.7 mm, wall thickness = 0.76 mm and = 26 mm height) were half filled with CMAS powder, wrapped and sealed with platinum foil, and heat treated at 1310 degrees C for 5h. Samples were characterized by differential scanning calorimetry (DSC), X-ray diffraction, and cross-section electron microscopy analysis and energy dispersive X-ray spectroscopy. It was found that CMAS penetrated the samples at the grain boundaries and dissolved the TEBC materials to form silicate phases containing the rare-earth elements. Furthermore, it was found that apatite crystalline phases were formed in the samples with total rare-earth content higher than 12 mol% in the reaction zone for the ZrO(exp. 2) system. In general, samples with the nominal compositions (30YSZ), HfO(exp. 2)-7Dy(exp. 2)O(exp. 2) and ZrO(exp. 2)-9.5Y(exp. 2)O(exp. 3)-2.25Gd(exp. 2)O(exp. 3)-2.25Yb(exp. 2)O(exp. 3) exhibited lower reactivity or more resistance to CMAS than the other coating compositions of this work.

  15. Heterogeneous Interactions of Acetaldehyde and Sulfuric Acid

    NASA Technical Reports Server (NTRS)

    Michelsen, R. R.; Ashbourn, S. F. M.; Iraci, L. T.

    2004-01-01

    The uptake of acetaldehyde [CH3CHO] by aqueous sulfuric acid has been studied via Knudsen cell experiments over ranges of temperature (210-250 K) and acid concentration (40-80 wt. %) representative of the upper troposphere. The Henry's law constants for acetaldehyde calculated from these data range from 6 x 10(exp 2) M/atm for 40 wt. % H2SO4 at 228 K to 2 x 10(exp 5) M/atm for 80 wt. % H2SO4 at 212 K. In some instances, acetaldehyde uptake exhibits apparent steady-state loss. The possible sources of this behavior, including polymerization, will be explored. Furthermore, the implications for heterogeneous reactions of aldehydes in sulfate aerosols in the upper troposphere will be discussed.

  16. Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes

    EPA Science Inventory

    Abstract: Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen and has adverse reproductive and developmental toxicities in exp...

  17. A New Method for Estimating Bacterial Abundances in Natural Samples using Sublimation

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Cleaves, H. James; Schubert, Michael; Aubrey, Andrew; Bada, Jeffrey L.

    2004-01-01

    We have developed a new method based on the sublimation of adenine from Escherichia coli to estimate bacterial cell counts in natural samples. To demonstrate this technique, several types of natural samples including beach sand, seawater, deep-sea sediment, and two soil samples from the Atacama Desert were heated to a temperature of 500 C for several seconds under reduced pressure. The sublimate was collected on a cold finger and the amount of adenine released from the samples then determined by high performance liquid chromatography (HPLC) with UV absorbance detection. Based on the total amount of adenine recovered from DNA and RNA in these samples, we estimated bacterial cell counts ranging from approx. l0(exp 5) to l0(exp 9) E. coli cell equivalents per gram. For most of these samples, the sublimation based cell counts were in agreement with total bacterial counts obtained by traditional DAPI staining. The simplicity and robustness of the sublimation technique compared to the DAPI staining method makes this approach particularly attractive for use by spacecraft instrumentation. NASA is currently planning to send a lander to Mars in 2009 in order to assess whether or not organic compounds, especially those that might be associated with life, are present in Martian surface samples. Based on our analyses of the Atacama Desert soil samples, several million bacterial cells per gam of Martian soil should be detectable using this sublimation technique.

  18. Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia.

    PubMed

    Cai, Zhen; Pan, Bo; Jiang, Haiyue; Zhang, Lixia

    2015-06-01

    To evaluate the efficiency of chondrogenesis of human adipose-derived stem cells (ADSCs) induced by auricular chondrocytes from microtia via subcutaneous co-graft in nude mice. Human ADSCs and auricular chondrocytes were mixed at the ratio of 7:3 and suspended in 0.2 ml of Pluronic F-127 (5.0 × 10(7) cells/ml), and injected into Balb/c nude mice as the experimental group (Exp group). The same quantity of auricular chondrocytes (Ctr.1 group) or ADSCs (Ctr.2 group) in 0.2 ml of Pluronic F-127 was set as positive and negative control groups. The mixture of auricular chondrocytes (1.5 × 10(7) cells/ml) in 0.2 ml of Pluronic F-127 was set as the low concentration of chondrocyte control group (Ctr.3). At 8 weeks after grafting, the newly generated tissue pellets were isolated for morphological examination, haematoxylin and eosin staining, toluidine blue staining and safranin O staining of glycosaminoglycan (GAG), Masson's trichrome staining and immunohistochemical staining of type II collagen, and Verhoeff-iron-hematoxylin staining of elastic fibers. GAG content was determined by Alcian blue colorimetric method, and mRNA expression of type II collagen and aggrecan were examined by real-time PCR. Cartilage-like tissue with a white translucent appearance and good elasticity was generated in the Exp and Ctr.1 groups. The tissue pellets in the Ctr.2 and Ctr.3 groups were much smaller than those in the Ctr.1 group. The mature cartilage lacunas could be observed in the Exp and Ctr.1 groups, while were rarely seen in the Ctr.3 group and not observed in the Ctr.2 group. The expression of cartilage-specific extracellular matrix such as type II collagen, GAG content, aggrecan, and elastic fibers in the Exp group was similar to that in the Ctr.1 group, whereas the expression of these extracellular matrix substances was significantly lower in the Ctr.2 and Ctr.3 groups (both P < 0.01). Auricular chondrocytes from microtia can efficiently promote the chondrogenic differentiation and chondrogenesis of ADSCs by co-grafting in vivo. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

  19. High power density proton exchange membrane fuel cells

    NASA Technical Reports Server (NTRS)

    Murphy, Oliver J.; Hitchens, G. Duncan; Manko, David J.

    1993-01-01

    Proton exchange membrane (PEM) fuel cells use a perfluorosulfonic acid solid polymer film as an electrolyte which simplifies water and electrolyte management. Their thin electrolyte layers give efficient systems of low weight, and their materials of construction show extremely long laboratory lifetimes. Their high reliability and their suitability for use in a microgravity environment makes them particularly attractive as a substitute for batteries in satellites utilizing high-power, high energy-density electrochemical energy storage systems. In this investigation, the Dow experimental PEM (XUS-13204.10) and unsupported high platinum loading electrodes yielded very high power densities, of the order of 2.5 W cm(exp -2). A platinum black loading of 5 mg per cm(exp 2) was found to be optimum. On extending the three-dimensional reaction zone of fuel cell electrodes by impregnating solid polymer electrolyte into the electrode structures, Nafion was found to give better performance than the Dow experimental PEM. The depth of penetration of the solid polymer electrolyte into electrode structures was 50-70 percent of the thickness of the platinum-catalyzed active layer. However, the degree of platinum utilization was only 16.6 percent and the roughness factor of a typical electrode was 274.

  20. Interactive effects of betaine and monensin in uninfected and Eimeria acervulina-infected chicks.

    PubMed

    Matthews, J O; Ward, T L; Southern, L L

    1997-07-01

    Three experiments (Exp.) were conducted to evaluate the interactive effects of dietary betaine (BET) and monensin (MON) in uninfected or Eimeria acervulina-infected chicks. The treatments were replicated with six (Exp. 1) or five (Exp. 2 and 3) pens of five chicks each. The experimental periods lasted 9 (Exp. 1 and 2) or 10 (Exp. 3) d each and the coccidiosis infections were established on Day 2 (Exp. 1 and 2) or Day 3 (Exp. 3) of the experiment. Average initial weight of the chicks was 101, 73, and 68 g in Exp. 1 to 3, respectively, and the initial age of the chicks was 5 (Exp. 1) or 4 (Exp. 2 and 3) d. A corn-soybean meal basal diet was used in each experiment. In Exp. 1, the effect of dietary BET (0, 0.1, or 0.5%) in uninfected or coccidiosis-infected (COC; 5 x 10(5) sporulated E. acervulina oocysts) chicks was investigated. In Exp. 2, the interactive effects of BET (0 or 0.1%) and MON (0 or 55 ppm) in uninfected or COC chicks were investigated in a 2 x 2 x 2 factorial arrangement of treatments. Experiment 3 was identical to Exp. 2, except the level of MON was 110 rather than 55 ppm. In Exp. 1, 2, and 3, COC reduced (P < 0.01) gain, feed intake (FI), feed efficiency (GF), and plasma carotenoid concentration (CAR) and increased (P < 0.01) lesion score (LS). In Exp. 1, gain and FI were decreased in uninfected chicks fed 0.1% BET but gain and FI were increased in COC chicks fed 0.1% BET (COC x BET quadratic, P < 0.01). Dietary BET linearly increased (P < 0.05) GF. In Exp. 2 and 3, MON increased (P < 0.01) gain, FI, GF, and CAR and decreased (P < 0.01) LS of COC chicks, but MON had no effect in uninfected chicks (COC x MON, P < 0.01). In Exp. 2, GF was increased more in chicks fed both MON and BET than in chicks fed MON (BET x MON, P < 0.06). In Exp. 3, BET increased GF of uninfected chicks fed MON and of COC chicks not fed MON (COC x BET x MON, P < 0.02). Betaine may have an effect on E. acervulina-infected chicks, but there is no conclusive evidence to indicate that the efficacy of MON is improved when fed in combination with BET.

  1. Identification of two novel functional p53 responsive elements in the herpes simplex virus-1 genome.

    PubMed

    Hsieh, Jui-Cheng; Kuta, Ryan; Armour, Courtney R; Boehmer, Paul E

    2014-07-01

    Analysis of the herpes simplex virus-1 (HSV-1) genome reveals two candidate p53 responsive elements (p53RE), located in proximity to the replication origins oriL and oriS, referred to as p53RE-L and p53RE-S, respectively. The sequences of p53RE-L and p53RE-S conform to the p53 consensus site and are present in HSV-1 strains KOS, 17, and F. p53 binds to both elements in vitro and in virus-infected cells. Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. Importantly, expression of the essential immediate early viral transactivator ICP4 and the essential DNA replication protein ICP8, that are adjacent to p53RE-S and p53RE-L, are repressed in a p53-dependent manner. Taken together, this study identifies two novel functional p53RE in the HSV-1 genome and suggests a complex mechanism of viral gene regulation by p53 which may determine progression of the lytic viral replication cycle or the establishment of latency. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation

    PubMed Central

    2012-01-01

    Background Fluorescence loss in photobleaching (FLIP) is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments. Typically, the user defines regions of interest (ROIs) for further analysis which is subjective and does not allow for comparing different cells and experimental settings. Results We present two complementary methods to detect and quantify protein transport and aggregation in living cells from FLIP image series. In the first approach, a stretched exponential (StrExp) function is fitted to fluorescence loss (FL) inside and outside the bleached region. We show by reaction–diffusion simulations, that the StrExp function can describe both, binding/barrier–limited and diffusion-limited FL kinetics. By pixel-wise regression of that function to FL kinetics of enhanced green fluorescent protein (eGFP), we determined in a user-unbiased manner from which cellular regions eGFP can be replenished in the bleached area. Spatial variation in the parameters calculated from the StrExp function allow for detecting diffusion barriers for eGFP in the nucleus and cytoplasm of living cells. Polyglutamine (polyQ) disease proteins like mutant huntingtin (mtHtt) can form large aggregates called inclusion bodies (IB’s). The second method combines single particle tracking with multi-compartment modelling of FL kinetics in moving IB’s to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt) between aggregates and the cytoplasm. This method is self-calibrating since it relates the FL inside and outside the bleached regions. It makes it therefore possible to compare release kinetics of eGFP-mtHtt between different cells and experiments. Conclusions We present two complementary methods for quantitative analysis of FLIP experiments in living cells. They provide spatial maps of exchange dynamics and absolute binding parameters of fluorescent molecules to moving intracellular entities, respectively. Our methods should be of great value for quantitative studies of intracellular transport. PMID:23148417

  3. Next-Generation Angular Distribution Models for Top-of-Atmosphere Radiative Flux Calculation from CERES Instruments: Validation

    NASA Technical Reports Server (NTRS)

    Su, W.; Corbett, J.; Eitzen, Z.; Liang, L.

    2015-01-01

    Radiative fluxes at the top of the atmosphere (TOA) from the Clouds and the Earth's Radiant Energy System (CERES) instrument are fundamental variables for understanding the Earth's energy balance and how it changes with time. TOA radiative fluxes are derived from the CERES radiance measurements using empirical angular distribution models (ADMs). This paper evaluates the accuracy of CERES TOA fluxes using direct integration and flux consistency tests. Direct integration tests show that the overall bias in regional monthly mean TOA shortwave (SW) flux is less than 0.2Wm(exp -2) and the RMSE is less than 1.1Wm(exp -2). The bias and RMSE are very similar between Terra and Aqua. The bias in regional monthly mean TOA LW fluxes is less than 0.5Wm(exp -2) and the RMSE is less than 0.8Wm(exp -)2 for both Terra and Aqua. The accuracy of the TOA instantaneous flux is assessed by performing tests using fluxes inverted from nadir- and oblique-viewing angles using CERES along-track observations and temporally and spatially matched MODIS observations, and using fluxes inverted from multi-angle MISR observations. The averaged TOA instantaneous SW flux uncertainties from these two tests are about 2.3% (1.9Wm(exp -2) over clear ocean, 1.6% (4.5Wm(exp -2) over clear land, and 2.0% (6.0Wm(exp -) over clear snow/ice; and are about 3.3% (9.0Wm(exp -2), 2.7% (8.4Wm(exp -2), and 3.7% (9.9Wm(exp -2) over ocean, land, and snow/ice under all-sky conditions. The TOA SW flux uncertainties are generally larger for thin broken clouds than for moderate and thick overcast clouds. The TOA instantaneous daytime LW flux uncertainties derived from the CERESMODIS test are 0.5% (1.5Wm(exp -2), 0.8% (2.4Wm(exp -2), and 0.7% (1.3Wm(exp -2) over clear ocean, land, and snow/ice; and are about 1.5% (3.5Wm(exp -2), 1.0% (2.9Wm(exp -2), and 1.1% (2.1Wm(exp -2) over ocean, land, and snow/ice under all-sky conditions. The TOA instantaneous nighttime LW flux uncertainties are about 0.5-1% (<2.0Wm(exp -2) for all surface types. Flux uncertainties caused by errors in scene identification are also assessed by using the collocated CALIPSO, CloudSat, CERES and MODIS data product. Errors in scene identification tend to underestimate TOA SW flux by about 0.6Wm(exp -2) and overestimate TOA daytime (nighttime) LW flux by 0.4 (0.2)Wm(exp -2) when all CERES viewing angles are considered.

  4. Reporting of sex as a variable in cardiovascular studies using cultured cells

    PubMed Central

    2011-01-01

    Background Chromosomal complement, including that provided by the sex chromosomes, influences expression of proteins and molecular signaling in every cell. However, less than 50% of the scientific studies published in 2009 using experimental animals reported sex as a biological variable. Because every cell has a sex, we conducted a literature review to determine the extent to which sex is reported as a variable in cardiovascular studies on cultured cells. Methods Articles from 10 cardiovascular journals with high impact factors (Circulation, J Am Coll Cardiol, Eur Heart J, Circ Res, Arterioscler Thromb Vasc Biol, Cardiovasc Res, J Mol Cell Cardiol, Am J Physiol Heart Circ Physiol, J Heart Lung Transplant and J Cardiovasc Pharmacol) and published in 2010 were searched using terms 'cultured' and 'cells' in any order to determine if the sex of those cells was reported. Studies using established cell lines were excluded. Results Using two separate search strategies, we found that only 25 of 90 articles (28%) and 20 of 101 articles (19.8%) reported the sex of cells. Of those reporting the sex of cells, most (68.9%; n = 31) used only male cells and none used exclusively female cells. In studies reporting the sex of cells of cardiovascular origin, 40% used vascular smooth-muscle cells, and 30% used stem/progenitor cells. In studies using cells of human origin, 35% did not report the sex of those cells. None of the studies using neonatal cardiac myocytes reported the sex of those cells. Conclusions The complement of sex chromosomes in cells studied in culture has the potential to affect expression of proteins and 'mechanistic' signaling pathways. Therefore, consistent with scientific excellence, editorial policies should require reporting sex of cells used in in vitro experiments. PMID:22060014

  5. Development of Antibodies Against Novel Cell Surface Proteins In Hormone Refractory Prostate Cancer. Addendum

    DTIC Science & Technology

    2011-07-01

    marker of hormone refractory metastatic prostate cancer. Clin Cancer Res, 2005. 15: 2237- 43 . 3. Tomita K, van Bokhoven A, van Leenders GJ, Ruijter...Santa Cruz Biotechnology), vimentin, Ki-67 (DakoCytomation) and caspase-3 (Cell Signaling Technology). Flow cytometry was performed with N...transduced cells were labeled with N-cadherin–specific antibody and sorted by flow cytometry , gating for a GFP-positive, N-cadherinlow population. The

  6. A Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers

    DTIC Science & Technology

    2012-05-01

    subset enriched in epithelial-to- mesenchymal transition and stem cell characteristics. Cancer Res 69: 4116–4124. Hoenerhoff MJ, Chu I, Barkan D, Liu ZY...expression of epithelial markers and loss of mesenchymal markers in MB- 231 cells (Task1a) Our analyses of m icroarray data com paring 231-Empty cells ...is considered a hallmark of EMT (Yang and Weinberg 2008). MB-231 cells lack E-cadherin expression and exhibit a more mesenchymal phenotype

  7. LL-37 Recruits Immunosuppressive Regulatory T Cells to Ovarian Tumors

    DTIC Science & Technology

    2009-11-01

    receptor. Western blot analysis of MSC lysates showed that ERK-1 and -2 are robustly phosphorylated beginning 10 minutes after LL-37 treatment and...Carretero, Escamez et al. 2008; von Haussen, Koczulla et al. 2008). Western blot analysis of LL-37-treated SK-OV-3 cell lysates showed the robust...mesenchymal stem cells in the treatment of gliomas ." Cancer Res 65(8): 3307-18. Studeny, M., F. C. Marini, et al. (2004). "Mesenchymal stem cells: potential

  8. Far-Ultraviolet Observations of Comet C 2012 S1 (ISON) From Fortis

    NASA Technical Reports Server (NTRS)

    Mccandiss, Stephan R.; Feldman, Paul D.; Weaver, Harold; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, S. Harvey

    2016-01-01

    We have used the unique far-UV imaging capability offered by a sounding-rocket-borne instrument to acquire observations of C/2012 S1 (ISON) when its angular separation with respect to the Sun was 26 deg.3 on 2013 November 20.49. At the time of observation, the comet's heliocentric distance and velocity relative to the Sun were r h = 0.43 au and r (sub h) = 62.7 km s)exp. -1). Images dominated by C Iota Lambda 1657 and H Iota Lambda 1216 were acquired over a 10(exp. 6) x 10(exp. 6) km(exp. 2) region. The water production rate implied by the Ly Alpha observations is constrained to be Q H2O is much greater than 8 x 10(exp. 29) s(exp. -1) while the neutral carbon production rate was Q(sub c) is much greater than 4 x 10(exp. 28) s(exp. -1). The radial profile of C I was consistent with it being a dissociation product of a parent molecule with a lifetime T is approx. 5 x 10(exp. 4) s, favoring a parent other than CO. We constrain the Q(sub co) production rate to 5(+1.5)(-7.5), 10(exp. 28) s(exp. -1) with 1 sigma errors derived from photon statistics. The upper limit on the Q (sub CO)/Q(sub H2O) is 6%.

  9. 1,2-Dichlorohexafluoro-Cyclobutane (1,2-c-C4F6Cl2, R-316c) a Potent Ozone Depleting Substance and Greenhouse Gas: Atmospheric Loss Processes, Lifetimes, and Ozone Depletion and Global Warming Potentials for the (E) and (Z) stereoisomers

    NASA Technical Reports Server (NTRS)

    Papadimitriou, Vassileios C.; McGillen, Max R.; Smith, Shona C.; Jubb, Aaron M.; Portmann, Robert W.; Hall, Bradley D.; Fleming, Eric L.; Jackman, Charles H.; Burkholder, James B.

    2013-01-01

    The atmospheric processing of (E)- and (Z)-1,2-dichlorohexafluorocyclobutane (1,2-c-C4F6Cl2, R-316c) was examined in this work as the ozone depleting (ODP) and global warming (GWP) potentials of this proposed replacement compound are presently unknown. The predominant atmospheric loss processes and infrared absorption spectra of the R-316c isomers were measured to provide a basis to evaluate their atmospheric lifetimes and, thus, ODPs and GWPs. UV absorption spectra were measured between 184.95 to 230 nm at temperatures between 214 and 296 K and a parametrization for use in atmospheric modeling is presented. The Cl atom quantum yield in the 193 nm photolysis of R- 316c was measured to be 1.90 +/- 0.27. Hexafluorocyclobutene (c-C4F6) was determined to be a photolysis co-product with molar yields of 0.7 and 1.0 (+/-10%) for (E)- and (Z)-R-316c, respectively. The 296 K total rate coefficient for the O(1D) + R-316c reaction, i.e., O(1D) loss, was measured to be (1.56 +/- 0.11) × 10(exp -10)cu cm/ molecule/s and the reactive rate coefficient, i.e., R-316c loss, was measured to be (1.36 +/- 0.20) × 10(exp -10)cu cm/molecule/s corresponding to a approx. 88% reactive yield. Rate coefficient upper-limits for the OH and O3 reaction with R-316c were determined to be <2.3 × 10(exp -17) and <2.0 × 10(exp -22)cu cm/molecule/s, respectively, at 296 K. The quoted uncertainty limits are 2(sigma) and include estimated systematic errors. Local and global annually averaged lifetimes for the (E)- and (Z)-R-316c isomers were calculated using a 2-D atmospheric model to be 74.6 +/- 3 and 114.1 +/-10 years, respectively, where the estimated uncertainties are due solely to the uncertainty in the UV absorption spectra. Stratospheric photolysis is the predominant atmospheric loss process for both isomers with the O(1D) reaction making a minor, approx. 2% for the (E) isomer and 7% for the (Z) isomer, contribution to the total atmospheric loss. Ozone depletion potentials for (E)- and (Z)-R-316c were calculated using the 2-D model to be 0.46 and 0.54, respectively. Infrared absorption spectra for (E)- and (Z)-R-316c were measured at 296 K and used to estimate their radiative efficiencies (REs) and GWPs; 100-year time-horizon GWPs of 4160 and 5400 were obtained for (E)- and (Z)-R-316c, respectively. Both isomers of R-316c are shown in this work to be long-lived ozone depleting substances and potent greenhouse gases.

  10. [Chemotherapy-induced diarrhea].

    PubMed

    Kobayashi, Kunihiko

    2003-06-01

    Chemotherapy-induced diarrhea is a well-documented side effect of many cancer treatments and is associated with increased morbidity and mortality. Chemotherapy-induced diarrhea negatively impacts patient quality of life and treatment outcome by requiring dose limitations or treatment interruption. The chemotherapeutic agent CPT-11 (irinotecan) has shown promising results as a single agent and in combination chemotherapy for the treatment of colorectal and small cell lung cancer. However, delayed onset diarrhea is considered to be its major dose-limiting toxicity. In some cases, it can be life threatening. To prevent CPT-11-induced delayed diarrhea, oral alkalization (OA) and control of defecation (CD) [Int J Cancer 92: 269-275, 2001] were developed based on fundamental studies [Int J Cancer 83: 491-496, 1999; Cancer Res 62: 179-187, 2002]. Oral administration of antibiotics [Cancer Res 56: 3752-3757, 1996; Clin Cancer Res 7: 1136-1141, 2001] or kampo medicine [Jpn J Cancer Res 86: 978-984, 1995; Jpn J Cancer Res 86: 985-989, 1995] to decrease beta-glucuronidase activity derived from bacteria in the large intestine was also reported to be successful in preventing delayed diarrhea. When CPT-11-induced delayed diarrhea occurs, the conventional treatment is loperamide [J Natl Cancer Inst 86: 446-449, 1994], and the early recognition and treatment of diarrhea with this opioid has reduced, although not entirely eliminated, patient morbidity. Other therapies are needed to treat patients with loperamide-refractory CPT-11 induced diarrhea, and the successful use of the somatostatin analogue octreotide has been reported [Support Care Cancer 9: 258-260, 2001; Ann Oncol 12: 227-229, 2001; Proc Am Soc Clin Oncol 21: 387a, 2002].

  11. Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice.

    PubMed

    Campêlo, Clarissa L C; Santos, José R; Silva, Anatildes F; Dierschnabel, Aline L; Pontes, André; Cavalcante, Jeferson S; Ribeiro, Alessandra M; Silva, Regina H

    2017-06-15

    Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson's disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus-maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Rate Coefficients of C2H with C2H4, C2H6, and H2 from 150 to 359 K

    NASA Technical Reports Server (NTRS)

    Opansky, Brian J.; Leone, Stephen R.

    1996-01-01

    Rate coefficients for the reactions C2H with C2H4, C2H6, and H2 are measured over the temperature range 150-359 K using transient infrared laser absorption spectroscopy. The ethynyl radical is formed by photolysis of C2H2 with a pulsed excimer laser at 193 nm, and its transient absorption is monitored with a color center laser on the Q(sub 11)(9) line of the A(sup 2) Pi-Chi(sup 2) Sigma transition at 3593.68 cm(exp -1). Over the experimental temperature range 150-359 K the rate constants of C2H with C2H4, C2H6, and H2 can be fitted to the Arrhenius expressions k(sub C2H4) = (7.8 +/- 0.6) x 10(exp -11) exp[(134 +/- 44)/T], k(sub C2H6) = (3.5 +/- 0.3) x 10(exp -11) exp[(2.9 +/- 16)/T], and k(sub H2) = (1.2 +/- 0.3) x 10(exp -11) exp[(-998 +/- 57)]/T cm(exp 3) molecule(exp -1) sec(exp -1). The data for C2H with C2H4 and C2H6 indicate a negligible activation energy to product formation shown by the mild negative temperature dependence of both reactions. When the H2 data are plotted together with the most recent high-temperature results from 295 to 854 K, a slight curvature is observed. The H2 data can be fit to the non-Arrhenius form k(sub H2) = 9.2 x 10(exp -18) T(sup 2.17 +/- 0.50) exp[(-478 +/- 165)/T] cm(exp 3) molecules(exp -1) sec(exp -1). The curvature in the Arrhenius plot is discussed in terms of both quantum mechanical tunneling of the H atom from H2 to the C2H radical and bending mode contributions to the partition function.

  13. The Role of Acid Sensing Ion Channels in Spinal Cord Injury

    DTIC Science & Technology

    2012-10-01

    ASIC1a is localized to the cell bodies and dendrites of neurons [4]. Pathological cerebral acidosis activates these channels which, in turn, kill...Tripathi, P. Wei, and A.T. Lash, The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury. Exp Neurol

  14. Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

    DTIC Science & Technology

    1994-05-01

    lipopolysaccharide- and TNF-induced cartilage breakdown in bovine nasal cartilage(121’. The use of medications that modulate PGE2 production may have an adverse...Levine, P. Goldhaber. 1972. Evidence that the bone resorption stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2. J. Exp. Med

  15. Wounding-Induced Manifestations of Type 1 Neurofibromatosis

    DTIC Science & Technology

    2001-07-01

    hairless mice induced by topical dimethylbenzanthracene., Exp. Cell Biol. 57: 292-9, 1989. Vogel, K. S., Klesse, L. J., Velasco- Miguel , S., Meyers, K... Santoro IM, Kordich JJ, Gismondi V, Trzepacz C, Badiali M, Giangaspero F, Balko MG, Graham JS, Ratner N, Lowy AM, Varesco L, Groden J. (2001) A

  16. Comparative proteomics analysis of Bacillus amyloliquefaciens SQR9 revealed the key proteins involved in in situ root colonization.

    PubMed

    Qiu, Meihua; Xu, Zhihui; Li, Xingxing; Li, Qing; Zhang, Nan; Shen, Qirong; Zhang, Ruifu

    2014-12-05

    Bacillus Amyloliquefaciens SQR9 is a well-investigated plant growth-promoting rhizobacteria with strong root colonization capability. To identify the key proteins involved in in situ root colonization and biofilm formation, the proteomic profiles of planktonic and root colonized SQR9 cells were compared. A total of 755 proteins were identified, of which 78 and 95 proteins were significantly increased and deceased, respectively, when SQR9 was colonized on the root. The proteins that were closely affiliated with the root colonization belonged to the functional categories of biocontrol, detoxification, biofilm formation, cell motility and chemotaxis, transport, and degradation of plant polysaccharides. A two-component system protein ResE was increased 100-fold when compared to the planktonic status; impairment of the resE gene postponed the formation of cell biofilm and decreased the root colonization capability, which may be regulated through the spo0A-sinI-yqxM pathway. The SQR9 proteomic data provide valuable clues for screening key proteins in the plant-rhizobacteria interaction.

  17. FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway

    PubMed Central

    2014-01-01

    Background Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. Results FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCϒ, NWASP, ARP2/3, and ROCK had no influence this. Conclusions FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies. PMID:24885257

  18. FAP-α (Fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway.

    PubMed

    Jia, Jun; Martin, Tracey Amanda; Ye, Lin; Jiang, Wen Guo

    2014-05-21

    Fibroblast Activation Protein alpha (FAP-α) or seprase is an integral membrane serine peptidase. Previous work has not satisfactorily explained both the suppression and promotion effects that have been observed in cancer. The purpose of this work was to investigate the role of FAP-α in human breast cancer. Expression of FAP-α was characterized in primary tumour samples and in cell lines, along with the effects of FAP-α expression on in vitro growth, invasion, attachment and migration. Furthermore the potential interaction of FAP-α with other signalling pathways was investigated. FAP-α was significantly increased in patients with poor outcome and survival. In vitro results showed that breast cancer cells over expressing FAP-α had increased growth ability and impaired migratory ability. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced by FAP-α expression. Over-expression of FAP-α resulted in a reduction of phosphorylated focal adhesion kinase (FAK) level in both cells cultured in normal media and serum-free media. An inhibitor to FAK restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231exp cells and prevented the change in phosphorylated FAK levels. However, inhibitors to PI3K, ERK, PLCΥ, NWASP, ARP2/3, and ROCK had no influence this. FAP-α in significantly associated with poor outcome in patients with breast cancer. In vitro, FAP-α promotes proliferation and inhibits migration of breast cancer cells, potentially by regulating the FAK pathway. These results suggest FAP-α could be a target for future therapies.

  19. Early feed restriction of lambs modifies ileal epimural microbiota and affects immunity parameters during the fattening period.

    PubMed

    Frutos, J; Andrés, S; Yáñez-Ruiz, D R; Benavides, J; López, S; Santos, A; Martínez-Valladares, M; Rozada, F; Giráldez, F J

    2018-04-22

    Bacteria firmly attached to the gastrointestinal epithelium during the pre-weaning phase may show a significant impact on nutrient processing, immunity parameters, health and feed efficiency of lambs during post-weaning phases. Thus, the aim of this study was to describe the differences in the ileal epimural microbiota (e.g. total bacteria, Prevotella spp., Bifidobacterium spp. and Lactobacillus spp.) of fattening lambs promoted by early feed restriction during the suckling phase trying to elucidate some of the underlying mechanisms behind changes in feed efficiency during the fattening period. A total of 24 Merino lambs (average BW 4.81±0.256 kg) were used, 12 of them (ad libitum, ADL) kept permanently in individual pens with their mothers, whereas the other 12 lambs were separated from their dams for 9 h each day to be exposed to milk restriction (RES). After weaning (BW=15 kg) all the animals were penned individually, offered the same complete pelleted diet (35 g/kg BW per day) and slaughtered at a BW of 27 kg. During the fattening period, reduced gain : feed ratio (0.320 v. 0.261, P<0.001) was observed for the RES group. Moreover, increments of Prevotella spp. were detected in the ileal epimural microbiota of RES lambs (P<0.05). There were also higher numbers of infiltrated lymphocytes (T and B cells) in the ileal lamina propria (P<0.05), a higher M-cell labelling intensity in ileal Peyer's patches domes (P<0.05) and a trend towards a thickening of the submucosa layer when compared with the ADL group (P=0.057). Some other immunological parameters, such as an increased immunoglobulin A (IgA) production (pg IgA/µg total protein) and increments in CD45+ cells were also observed in the ileum of RES group (P<0.05), whereas transforming growth factor β and toll-like receptor gene expression was reduced (P<0.05). In conclusion, early feed restriction during the suckling phase promoted changes in ileal epimural microbiota and several immunity parameters that could be related to differences in feed efficiency traits during the fattening period of Merino lambs.

  20. Tests of the Rockwell Si:As Back-Illuminated Blocked-Impurity Band (BIBIB) detectors

    NASA Technical Reports Server (NTRS)

    Wolf, J.; Groezinger, U.; Burgdorf, M.; Salama, A.

    1989-01-01

    Two arrays of Rockwell's Si:As back-illuminated blocked-impurity-band detectors were tested at the Max-Planck-Institute for Astronomy (MPIA) at low background and low temperature for possible use in the astronomical space experiment ISOPHOT. For these measurements special test equipment was put together. A cryostat was mechanically modified to accommodate the arrays and special peripheral electronics was added to a microprocessor system to drive the cold multiplexer and to acquire the output data. The first device, a 16x50 element array on a fan-out board was used to test individual pixels with a trans-impedance-amplifier at a photon background of 10(exp 8) Ph s(-1)cm(-2) and at temperatures of 2.7 to 4.4 K. The noise-equivalent-power NEP is in the range 5 - 7 x 10(exp -18) WHz(exp -1/2), the responsivity is less than or equal to 100 AW(exp -1)(f = 10 Hz). The second device was a 10x50 array including a cold readout electronics of switched FETs (SWIFET). Measurements of this array were done in a background range of 5 x 10(exp 5) to 5 x 10(exp 11) Ph s(exp-1)cm(exp-2) and at operating temperatures between 3.0 and 4.8 K. The NEP ranges from less than 10(exp -18) at the lowest background to 2 x 10(exp -16) WHz(exp -1/2) at the highest flux.

  1. Biochemical mechanisms of imidacloprid resistance in Nilaparvata lugens: over-expression of cytochrome P450 CYP6AY1.

    PubMed

    Ding, Zhiping; Wen, Yucong; Yang, Baojun; Zhang, Yixi; Liu, Shuhua; Liu, Zewen; Han, Zhaojun

    2013-11-01

    Imidacloprid is a key insecticide extensively used for control of Nilaparvata lugens, and its resistance had been reported both in the laboratory selected strains and field populations. A target site mutation Y151S in two nicotinic acetylcholine receptor subunits and enhanced oxidative detoxification have been identified in the laboratory resistant strain, contributing importantly to imidacloprid resistance in N. lugens. To date, however, imidacloprid resistance in field population is primarily attributable to enhanced oxidative detoxification by over-expressed P450 monooxygenases. A resistant strain (Res), originally collected from a field population and continuously selected in laboratory with imidacloprid for more than 40 generations, had 180.8-fold resistance to imidacloprid, compared to a susceptible strain (Sus). Expression of different putative P450 genes at mRNA levels was detected and compared between Res and Sus strains, and six genes were found expressed significantly higher in Res strain than in Sus strain. CYP6AY1 was found to be the most different expressed P450 gene and its mRNA level in Res strain was 17.9 times of that in Sus strain. By expressing in E. coli cells, CYP6AY1 was found to metabolize imidacloprid efficiently with initial velocity calculated of 0.851 ± 0.073 pmol/min/pmol P450. When CYP6AY1 mRNA levels in Res strain was reduced by RNA interference, imidacloprid susceptibility was recovered. In four field populations with different resistance levels, high levels of CYP6AY1 transcript were also found. In vitro and in vivo studies provided evidences that the over-expression of CYP6AY1 was one of the key factors contributing to imidacloprid resistance in the laboratory selected strain Res, which might also be the important mechanism for imidacloprid resistance in field populations, when the target site mutation was not prevalent at present. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Relationship Between Ecosystem Productivity and Photosynthetically Active Radiation for Northern Peatlands

    NASA Technical Reports Server (NTRS)

    Frolking, S. E.; Bubier, J. L.; Moore, T. R.; Ball, T.; Bellisario, L. M.; Bhardwaj, A.; Carroll, P.; Crill, P. M.; Lafleur, P. M.; McCaughey, J. H.; hide

    1998-01-01

    We analyzed the relationship between net ecosystem exchange of carbon dioxide (NEE) and irradiance (as photosynthetic photon flux density or PPFD), using published and unpublished data that have been collected during midgrowing season for carbon balance studies at seven peatlands in North America and Europe, NEE measurements included both eddy-correlation tower and clear, static chamber methods, which gave very similar results. Data were analyzed by site, as aggregated data sets by peatland type (bog, poor fen, rich fen, and all fens) and as a single aggregated data set for all peatlands. In all cases, a fit with a rectangular hyperbola (NEE = alpha PPFD P(sub max)/(alpha PPFD + P(sub max) + R) better described the NEE-PPFD relationship than did a linear fit (NEE = beta PPFD + R). Poor and rich fens generally had similar NEE-PPFD relationships, while bogs had lower respiration rates (R = -2.0 micro mol m(exp -2) s(exp -1) for bogs and -2.7 micro mol m(exp -2) s(exp -1)) for fens) and lower NEE at moderate and high light levels (P(sub max)= 5.2 micro mol m(exp -2) s(exp -1) for bogs and 10.8 micro mol m(exp -2) s(exp -1) for fens). As a single class, northern peatlands had much smaller ecosystem respiration (R = -2.4 micro mol m(exp -2) s(exp -1)) and NEE rates (alpha = 0.020 and P(sub max)= 9.2 micro mol m(exp -2) s(exp -1)) than the upland ecosystems (closed canopy forest, grassland, and cropland). Despite this low productivity, northern peatland soil carbon pools are generally 5-50 times larger than upland ecosystems because of slow rates of decomposition caused by litter quality and anaerobic, cold soils.

  3. Comparative Studies for the Sodium and Potassium Atmospheres of the Moon and Mercury

    NASA Technical Reports Server (NTRS)

    Smyth, William H.

    1999-01-01

    A summary discussion of recent sodium and potassium observations for the atmospheres of the Moon and Mercury is presented with primary emphasis on new full-disk images that have become available for sodium. For the sodium atmosphere, image observations for both the Moon and Mercury are fitted with model calculations (1) that have the same source speed distribution, one recently measured for electron-stimulated desorption and thought to apply equally well to photon-stimulated desorption, (2) that have similar average surface sodium fluxes, about 2.8 x 10(exp 5) to 8.9 x 10(exp 5) atoms cm(exp -2)s(exp -1) for the Moon and approximately 3.5 x 10(exp 5) to 1.4 x 10(exp 6) atoms cm(exp -2)s(exp -1) for Mercury, but (3) that have very different distributions for the source surface area. For the Moon, a sunlit hemispherical surface source of between approximately 5.3 x 10(exp 22) to 1.2 x 10(exp 23) atoms/s is required with a spatial dependence at least as sharp as the square of the cosine of the solar zenith angle. For Mercury, a time dependent source that varies from 1.5 x 10(exp 22) to 5.8 x l0(exp 22) atoms/s is required which is confined to a small surface area located at, but asymmetrically distributed about, the subsolar point. The nature of the Mercury source suggest that the planetary magnetopause near the subsolar point acts as a time varying and partially protective shield through which charged particles may pass to interact with and liberate gas from the planetary surface. Suggested directions for future research activities are discussed.

  4. 40 CFR Appendix - Tables to Part 132

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... c CMCt=exp {mA[pH]+bA}. The CMCt shall be rounded to two significant digits. Notes: The term “exp...,b 0.846 +2.255 0.998 Pentachlorophenol c 1.005 −4.869 n/a Zinc a,b 0.8473 +0.884 0.978 a CMCtr=exp... CMCt=exp mA {[pH]+bA}. The CMCt shall be rounded to two significant digits. Notes: The term “exp...

  5. MicroRNA Regulation of CD44+ Prostate Tumor Stem/Progenitor Cells and Prostate Cancer Development/Metastasis

    DTIC Science & Technology

    2013-05-01

    prostate cancer stem cells. Cancer Res. 65, 10946–10951 (2005). 18 . Patrawala, L. et al. Highly purified CD44+ prostate cancer cells from xenograft ... xenograft tumors were of the human origin and morphologically epithelial with detectable cytokeratin 8 and 18 . RT-PCR analysis detected AR whereas...miR-301 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT

  6. Compatibility of SYTO 13 and Hoechst 33342 for Longitudinal Imaging of Neuron Viability and Cell Death

    DTIC Science & Technology

    2012-08-14

    Defining the molecular and biochemical pathways re- sponsible for cell death phenotypes is essential for iden- tifying critical points that could be...clearly image nuclear structure resulted in PI-positive nuclei developing an orange hue. (B) Planimetric quantitation of nuclear size measured...metabolites on undifferentiated PC12 cells: a putative structure -toxicity relationship. Chem Res Toxicol 2006, 19(10):1294–1304. 10. McNutt P, Celver J

  7. Breast Cancer Vaccines That Overcome Tolerance and Immune Suppression

    DTIC Science & Technology

    2011-01-01

    activate healthy donor T cells” American Associaiton of Immunolgists 98th Annual meeting. San- Francisco , CA. May 13-17, 2011, abstract submitted. 9...Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67, 4507-4513 12. Rodriguez , P.C., Hernandez, C.P., Quiceno... Santo , J.P., Apte, R.N. and Vosshenrich, C.A. (2010) IL-1beta regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development

  8. A Balloon Sounding Technique for Measuring SO2 Plumes

    NASA Technical Reports Server (NTRS)

    Morris, Gary A.; Komhyr, Walter D.; Hirokawa, Jun; Lefer, Barry; Krotkov, Nicholay; Ngan, Fong

    2010-01-01

    This paper reports on the development of a new technique for inexpensive measurements of SO2 profiles using a modified dual-ozonesonde instrument payload. The presence of SO2 interferes with the standard electrochemical cell (ECC) ozonesonde measurement, resulting in -1 molecule of O3 reported for each molecule of SO2 present (provided [O3] > [SO2]). In laboratory tests, an SO2 filter made with Cr03 placed on the inlet side of the sonde removes nearly 100% of the SO2 present for concentrations up to 60 ppbv and remained effective after exposure to 2.8 X 10(exp 16) molecules of SO2 [equivalent to a column approximately 150 DU (1 DU = 2.69 X 10(exp 20) molecules m(exp -2))]. Flying two ECC instruments on the same payload with one filtered and the other unfiltered yields SO2 profiles, inferred by subtraction. Laboratory tests and field experience suggest an SO2 detection limit of approximately 3 pbb with profiles valid from the surface to the ozonopause [i.e., approximately (8-10 km)]. Two example profiles demonstrate the success of this technique for both volcanic and industrial plumes.

  9. Redetermination of piperidinium hydrogen sulfide structure

    NASA Technical Reports Server (NTRS)

    Andras, Maria T.; Hepp, Aloysius F.; Fanwick, Phillip E.; Duraj, Stan A.; Gordon, Edward M.

    1994-01-01

    The presence of adventitious water in a reaction between dicyclopentamethylene thiuram-disulfide (C5H10NCS2)(sub 2) and a picoline solution of tricyclopentadienyl indium(III) (C5H5)(sub 3). It resulted in the formation of piperidinium hydrogen sulfide (C5H13NS). The piperidinium hydrogen sulfide produced in this way was unambiguously characterized by X-ray crystallography. The structure determination showed that the piperidinium hydrogen sulfide crystal (MW = 119.23 g/mol) has an orthorhombic (Pbcm) unit cell whose parameters are: a = 9.818(2), b = 7.3720(1), c = 9.754(1) A, V = 706.0(3) A(exp 3), Z=4. D(sub chi) = 1.122 g cm(exp -3), Mo K(alpha) (lamda = 0.71073), mu= 3.36 cm(exp -1), F(000) = 264.0, T =293 K, R = 0.036 for 343 reflections with F(sub O)(sup 2) greater than 3 sigma (F(sub O)(sup 2)) and 65 variables. The compound consists of (C5H10NH2)(+) cations and (SH)(-) anions with both species residing on crystallographic mirror planes. N-H -- S hydrogen bonding contributes to the interconnection of neighboring piperidinium components of the compound.

  10. A Weyl-Dirac cosmological model with DM and DE

    NASA Astrophysics Data System (ADS)

    Israelit, Mark

    2011-03-01

    In the Weyl-Dirac (W-D) framework a spatially closed cosmological model is considered. It is assumed that the space-time of the universe has a chaotic Weylian microstructure but is described on a large scale by Riemannian geometry. Locally fields of the Weyl connection vector act as creators of massive bosons having spin 1. It is suggested that these bosons, called weylons, provide most of the dark matter in the universe. At the beginning the universe is a spherically symmetric geometric entity without matter. Primary matter is created by Dirac’s gauge function very close to the beginning. In the early epoch, when the temperature of the universe achieves its maximum, chaotically oriented Weyl vector fields being localized in micro-cells create weylons. In the dust dominated period Dirac’s gauge function is giving rise to dark energy, the latter causing the cosmic acceleration at present. This oscillatory universe has an initial radius identical to the Plank length = 1.616 exp (-33) cm, at present the cosmic scale factor is 3.21 exp (28) cm, while its maximum value is 8.54 exp (28) cm. All forms of matter are created by geometrically based functions of the W-D theory.

  11. The effect of deep frying or conventional oven cooking on inactivation of Shiga toxin-producing cells of Escherichia coli (STEC) in meatballs

    USDA-ARS?s Scientific Manuscript database

    We investigated the effects deep frying or oven cooking on inactivation of Shiga toxin-producing cells of Escherichia coli (STEC) in meatballs. A finely-ground veal and/or a beef-pork-veal mixture were inoculated (ca. 7.0 log CFU/g) with an eight-strain, genetically-marked cocktail of rifampicin-res...

  12. Enhancement of Radiation Therapy in Prostate Cancer by DNA-PKcs Inhibitor

    DTIC Science & Technology

    2014-09-01

    of DAB2IP in chemo- resistance of prostate cancer cells. Clin Cancer Res 2013;19:4740- 4749. POLYMERIC NANOPARTICLES FOR TARGETED... cancer , NU7441, Targeting John Wiley & Sons, Inc. Journal of Biomedical Materials Research: Part A 1 POLYMERIC NANOPARTICLES FOR TARGETED...The University of Texas Southwestern Medical Center, Dallas, TX, 75390 Running Title: Nanoparticles for radiosensitization of prostate cancer cells

  13. Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin-Coated Nanocrystals.

    PubMed

    Gad, Sheryhan F; Park, Joonyoung; Park, Ji Eun; Fetih, Gihan N; Tous, Sozan S; Lee, Wooin; Yeo, Yoon

    2018-01-29

    Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel (DTX) is challenging due to the low bioavailability and the toxicity related to solubilizing excipients. Colloidal nanoparticles are used as alternative carriers, but low drug loading capacity and circulation instability limit their clinical translation. To address these challenges, DTX nanocrystals (NCs) were prepared using Pluronic F127 as an intermediate stabilizer and albumin as a functional surface modifier, which were previously found to be effective in producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs (DTX-F-alb) will remain stable in serum-containing medium so as to effectively leverage the enhanced permeability and retention effect. In addition, the surface-bound albumin, in its native form, may contribute to cellular transport of NCs through interactions with albumin-binding proteins such as secreted protein acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure with an average length, width, and thickness of 284 ± 96, 173 ± 56, and 40 ± 8 nm and remained stable in 50% serum solution at a concentration greater than 10 μg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free) DTX were compared on three cell lines with different levels of SPARC expression and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast, multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with time and responded better to the former. This difference was reduced by SPARC knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.

  14. Growth of potatoes for CELSS

    NASA Technical Reports Server (NTRS)

    Tibbitts, T. W.; Cao, W.; Wheeler, R. M.

    1994-01-01

    This report summarizes research on the utilization of white potatoes (Solanum tuberosum L.) for space life support systems at the University of Wisconsin-Madison over the period of 1984 to 1993. At full maturity the tuber productivity was 37.5 gm(exp -2) d(exp -1), equating to a growing area requirement for one human (2800 kcal d(exp -1)) of 10.1 m(exp -2). A recirculating nutrient system using slanted trays produced best potato growth and tuber yields when a 2-3 cm layer of gravel or arcillite media was utilized. Potato production was close to maximum under lighting levels of 400 micromol m(exp -2) s(exp -1) of photosynthetic photo flux (PPF) for 24 hours or 800 micromol m(exp -2) s(exp -1) for 12 hours, alternating diurnal temperatures of 22 C and 14 C, relative humidity of 85 percent, and a carbon dioxide level of 1000 micromol m(exp -1). The range of effective concentrations of each separate nutrient is reported. The extensive studies with potatoes in this project have demonstrated that this crop has high productivity of nutritous tubers with a high harvest index in controlled environments, and can fulfill a significant portion of the energy and protein requirements for humans in space.

  15. X-ray clusters in a cold dark matter + lambda universe: A direct, large-scale, high-resolution, hydrodynamic simulation

    NASA Technical Reports Server (NTRS)

    Cen, Renyue; Ostriker, Jeremiah P.

    1994-01-01

    A new, three-dimensional, shock-capturing, hydrodynamic code is utilized to determine the distribution of hot gas in a cold dark matter (CDM) + lambda model universe. Periodic boundary conditions are assumed: a box with size 85/h Mpc, having cell size 0.31/h Mpc, is followed in a simulation with 270(exp 3) = 10(exp 7.3) cells. We adopt omega = 0.45, lambda = 0.55, h identically equal to H/100 km/s/Mpc = 0.6, and then, from the cosmic background explorer (COBE) and light element nucleosynthesis, sigma(sub 8) = 0.77, omega(sub b) = 0.043. We identify the X-ray emitting clusters in the simulation box, compute the luminosity function at several wavelength bands, the temperature function and estimated sizes, as well as the evolution of these quantities with redshift. This open model succeeds in matching local observations of clusters in contrast to the standard omega = 1, CDM model, which fails. It predicts an order of magnitude decline in the number density of bright (h nu = 2-10 keV) clusters from z = 0 to z = 2 in contrast to a slight increase in the number density for standard omega = 1, CDM model. This COBE-normalized CDM + lambda model produces approximately the same number of X-ray clusters having L(sub x) greater than 10(exp 43) erg/s as observed. The background radiation field at 1 keV due to clusters is approximately the observed background which, after correction for numerical effects, again indicates that the model is consistent with observations.

  16. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.

    PubMed

    Champiat, Stéphane; Dercle, Laurent; Ammari, Samy; Massard, Christophe; Hollebecque, Antoine; Postel-Vinay, Sophie; Chaput, Nathalie; Eggermont, Alexander; Marabelle, Aurélien; Soria, Jean-Charles; Ferté, Charles

    2017-04-15

    Purpose: While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown. Experimental Design: Medical records from all patients ( N = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed. Results: HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD ( P < 0.05). HPD is associated with a higher age ( P < 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 ( P < 0.05) therapy. Conclusions: A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. Clin Cancer Res; 23(8); 1920-8. ©2016 AACR See related commentary by Sharon, p. 1879 . ©2016 American Association for Cancer Research.

  17. Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures.

    PubMed

    Testa, Claudia M; Sherer, Todd B; Greenamyre, J Timothy

    2005-03-24

    Rotenone, a pesticide and complex I inhibitor, causes nigrostriatal degeneration similar to Parkinson disease pathology in a chronic, systemic, in vivo rodent model [M. Alam, W.J. Schmidt, Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats, Behav. Brain Res. 136 (2002) 317-324; R. Betarbet, T.B. Sherer, G. MacKenzie, M. Garcia-Osuna, A.V. Panov, J.T. Greenamyre, Chronic systemic pesticide exposure reproduces features of Parkinson's disease, Nat. Neurosci. 3 (2000) 1301-1306; S.M. Fleming, C. Zhu, P.O. Fernagut, A. Mehta, C.D. DiCarlo, R.L. Seaman, M.F. Chesselet, Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone, Exp. Neurol. 187 (2004) 418-429; T.B. Sherer, J.H. Kim, R. Betarbet, J.T. Greenamyre, Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation, Exp. Neurol. 179 (2003) 9-16.]. To better investigate the role of mitochondria and complex I inhibition in chronic, progressive neurodegenerative disease, we developed methods for long-term culture of rodent postnatal midbrain organotypic slices. Chronic complex I inhibition over weeks by low dose (10-50 nM) rotenone in this system lead to dose- and time-dependent destruction of substantia nigra pars compacta neuron processes, morphologic changes, some neuronal loss, and decreased tyrosine hydroxylase (TH) protein levels. Chronic complex I inhibition also caused oxidative damage to proteins, measured by protein carbonyl levels. This oxidative damage was blocked by the antioxidant alpha-tocopherol (vitamin E). At the same time, alpha-tocopherol also blocked rotenone-induced reductions in TH protein and TH immunohistochemical changes. Thus, oxidative damage is a primary mechanism of mitochondrial toxicity in intact dopaminergic neurons. The organotypic culture system allows close study of this and other interacting mechanisms over a prolonged time period in mature dopaminergic neurons with intact processes, surrounding glia, and synaptic connections.

  18. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

    PubMed

    Rice, Gillian I; Bond, Jacquelyn; Asipu, Aruna; Brunette, Rebecca L; Manfield, Iain W; Carr, Ian M; Fuller, Jonathan C; Jackson, Richard M; Lamb, Teresa; Briggs, Tracy A; Ali, Manir; Gornall, Hannah; Couthard, Lydia R; Aeby, Alec; Attard-Montalto, Simon P; Bertini, Enrico; Bodemer, Christine; Brockmann, Knut; Brueton, Louise A; Corry, Peter C; Desguerre, Isabelle; Fazzi, Elisa; Cazorla, Angels Garcia; Gener, Blanca; Hamel, Ben C J; Heiberg, Arvid; Hunter, Matthew; van der Knaap, Marjo S; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre G; Lourenco, Charles M; Marom, Daphna; McDermott, Michael F; van der Merwe, William; Orcesi, Simona; Prendiville, Julie S; Rasmussen, Magnhild; Shalev, Stavit A; Soler, Doriette M; Shinawi, Marwan; Spiegel, Ronen; Tan, Tiong Y; Vanderver, Adeline; Wakeling, Emma L; Wassmer, Evangeline; Whittaker, Elizabeth; Lebon, Pierre; Stetson, Daniel B; Bonthron, David T; Crow, Yanick J

    2009-07-01

    Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.

  19. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

    PubMed Central

    Rice, Gillian I; Bond, Jacquelyn; Asipu, Aruna; Brunette, Rebecca L; Manfield, Iain W; Carr, Ian M; Fuller, Jonathan C; Jackson, Richard M; Lamb, Teresa; Briggs, Tracy A; Ali, Manir; Gornall, Hannah; Couthard, Lydia R; Aeby, Alec; Attard-Montalto, Simon P; Bertini, Enrico; Bodemer, Christine; Brockmann, Knut; Brueton, Louise A; Corry, Peter C; Desguerre, Isabelle; Fazzi, Elisa; Cazorla, Angels Garcia; Gener, Blanca; Hamel, Ben C J; Heiberg, Arvid; Hunter, Matthew; van der Knaap, Marjo S; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre G; Lourenco, Charles M; Marom, Daphna; McDermott, Michael F; van der Merwe, William; Orcesi, Simona; Prendiville, Julie S; Rasmussen, Magnhild; Shalev, Stavit A; Soler, Doriette M; Shinawi, Marwan; Spiegel, Ronen; Tan, Tiong Y; Vanderver, Adeline; Wakeling, Emma L; Wassmer, Evangeline; Whittaker, Elizabeth; Lebon, Pierre; Stetson, Daniel B; Bonthron, David T; Crow, Yanick J

    2014-01-01

    Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response. PMID:19525956

  20. Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii)

    DTIC Science & Technology

    2007-05-01

    Burkitts lymphoma associated with Epstein - Barr virus (47); hepatocellular carcinoma associated with hepatitis B and C viruses (48, 49) and cervical...response to Epstein - Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med, 176: 157-168, 1992. 48. Rehermann, B...strategy for the treatment of cancer. To exploit this potential, we have developed cell-based cancer vaccines consisting of tumor cells expressing

  1. Cox-1 Suppression and Follicle Depletion in the Etiology of Menopause- Associated Ovarian Cancer

    DTIC Science & Technology

    2008-04-01

    follicular function (2). Most oocytes are progressively lost by atresia, or apoptosis (3), and the ovary may develop a number of atrophic features...the risk of ovarian epithelial cancers, by far the most predominant form (14), and cause growth inhibition and apoptosis in ovarian cancer cell lines...1990;4:390-400. 8. Mintz B. Embryological development of primordial germ-cells in the mouse: influence of a new mutation, Wj. J Embryol Exp

  2. Effects of rainfall and surface flow on chemical diffusion from soil to runoff water

    USDA-ARS?s Scientific Manuscript database

    Although basic processes of diffusion and convection have been used to quantify chemical transport from soil to surface runoff, there are little research results actually showing how these processes were affected by rainfall and surface flow. We developed a laboratory flow cell and a sequence of exp...

  3. EVIDENCE THAT CA2+ SIGNALING AND TRANSCRIPTION FACTOR (CREB) ACTIVITIES STIMULATED BY POLYCHLORINATED BIPHENYLS ARE LOCALIZED TO DEVELOPING NEURONS.

    EPA Science Inventory

    Using a mixed culture of neonatal cortical cells, we have demonstrated that the polychlorinated biphenyl (PCB) mixture Aroclor 1254 (A1254) induces complex Ca2+i signals involving multiple receptors/channels (Inglefield and Shafer, J.Pharm.Exp.Ther. 295:105) and also activates/ p...

  4. Multispecies Biofilm Development on Space Station Heat Exhanger Core Material

    NASA Technical Reports Server (NTRS)

    Pyle, B. H.; Roth, S. R.; Vega, L. M.; Pickering, K. D.; Alvarez, Pedro J. J.; Roman, M. C.

    2007-01-01

    Investigations of microbial contamination of the cooling system aboard the International Space Station (ISS) suggested that there may be a relationship between heat exchanger (HX) materials and the degree of microbial colonization and biofilm formation. Experiments were undertaken to test the hypothesis that biofilm formation is influenced by the type and previous exposure of HX surfaces. Acidovorax delafieldii, Comamonas acidovorans, Hydrogenophaga pseudoflava, Pseudomonas stutzeri, Sphingomonas paucimobilis, and Stenotrophomonas maltophilia, originally isolated from ISS cooling system fluid, were cultured on R2A agar and suspended separately in fresh filter-sterilized ISS cooling fluid, pH 8.3. Initial numbers in each suspension ranged from 10(exp 6)-10(exp 7) CFU/ml, and a mixture contained greater than 10(exp 7) CFU/ml. Coupons of ISS HX material, previously used on orbit (HXOO) or unused (HXUU), polycarbonate (PC) and 316L polished stainless steel (SS) were autoclaved, covered with multispecies suspension in sterile tubes and incubated in the dark at ambient (22-25 C). Original HX material contained greater than 90% Ni, 4.5% Si, and 3.2% B, with a borate buffer. For approximately 10 weeks, samples of fluid were plated on R2A agar, and surface colonization assessed by SYBR green or BacLight staining and microscopy. Suspension counts for the PC and SC samples remained steady at around 10(exp 7) CFU/ml. HXUU counts declined about 1 log in 21 d then remained steady, and HXOO counts declined 2 logs in 28 d, fluctuated and stabilized about 10(exp 3) CFU/ml from 47-54 d. Predominantly yellow S. paucimobilis predominated on plates from HXOO samples up to 26 d, then white or translucent colonies of other species appeared. All colony types were seen on plates from other samples throughout the trial. Epifluorescence microscopy indicated microbial growth on all surfaces by 21 d, followed by variable colonization. After 54 d, all but the HXOO samples had well-distributed live and dead cells; the HXOO samples had few cells and most were live by BacLight. The results suggest that HX materials themselves are inhibiting microbial growth on the surfaces. The HX exposed on orbit to cooling system fluid inhibited growth of some species originally isolated from the system, whereas the unused HX material had a moderate effect compared to no inhibition with PC or SS controls. It is possible that chemistry or microbiology of the ISS system increased deposition of inhibitory compounds on the HXOO coupon surfaces; these may inhibit inoculated species to differing degrees.

  5. The prevalence effect in lateral masking and its relevance for visual search.

    PubMed

    Geelen, B P; Wertheim, A H

    2015-04-01

    In stimulus displays with or without a single target amid 1,644 identical distractors, target prevalence was varied between 20, 50 and 80 %. Maximum gaze deviation was measured to determine the strength of lateral masking in these arrays. The results show that lateral masking was strongest in the 20 % prevalence condition, which differed significantly from both the 50 and 80 % prevalence conditions. No difference was observed between the latter two. This pattern of results corresponds to that found in the literature on the prevalence effect in visual search (stronger lateral masking corresponding to longer search times). The data add to similar findings reported earlier (Wertheim et al. in Exp Brain Res, 170:387-402, 2006), according to which the effects of many well-known factors in visual search correspond to those on lateral masking. These were the effects of set size, disjunctions versus conjunctions, display area, distractor density, the asymmetry effect (Q vs. O's) and viewing distance. The present data, taken together with those earlier findings, may lend credit to a causal hypothesis that lateral masking could be a more important mechanism in visual search than usually assumed.

  6. Resveratrol and Epigallocatechin-3-gallate addition to thawed boar sperm improves in vitro fertilization.

    PubMed

    Gadani, B; Bucci, D; Spinaci, M; Tamanini, C; Galeati, G

    2017-03-01

    Thawing is one of the most delicate process after semen cryopreservation as spermatozoa pass from a dormant metabolic stage to a sudden awakening in cellular metabolism. The rapid oxygen utilization leads to an overproduction of reactive oxygen species that can damage sperm cells, thus causing a significant decrease of fertilizing potential of frozen-thawed spermatozoa. Resveratrol (Res) is a natural grape-derived phytoalexin and Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea (Camellia sinensis); both molecules are known to possess high levels of antioxidant activity. The objective of the present study was to assess the effect of different concentrations of Res (0.5, 1 or 2 mM; Experiment 1) or EGCG (25, 50 or 100 μM; Experiment 2) supplementation to thawing boar semen extender on sperm quality parameters (viability and acrosome integrity) and in vitro fertilization (IVF). Semen after thawing and dilution with three volumes of Beltsville Thawing Solution (BTS), was immediately divided in control group without antioxidants addition (CTR) and either Res or EGCG groups. Sperm viability and acrosome integrity were evaluated in CTR, Res or EGCG groups after 1 h of incubation at 37 °C. The addition of different doses of Res or EGCG to thawing extender for 1 h did not induce any effect on boar sperm viability and acrosome integrity. However, both Res and EGCG treated samples exhibited a significantly higher penetration rate compared with CTR when used for IVF. In particular the treatment with all the EGCG concentrations increased the penetration rate (P < 0.01) while only Res 2 mM induced a significant increase of this parameter (P < 0.01). In addition, EGCG 25 and 50 μM supplementation significantly increased total fertilization efficiency as compared to control (EGCG 25 μM: 40.3 ± 8.2 vs 26.8 ± 9.5, P < 0.05; EGCG 50 μM: 40.4 ± 7.8 vs 26.8 ± 9.5, P < 0.01). The same effect was observed with Res 2 mM (51.0 ± 7.6 vs 29.6 ± 11.3, P < 0.01). In conclusion, our results indicate that the addition of different doses of the two antioxidants to thawed spermatozoa for one hour, even if does not exert any effect on sperm viability and acrosome integrity, efficiently improves in vitro penetration rate. Moreover, both molecules (EGCG 25 and 50 μM and Res 2 mM) significantly increases the total efficiency of fertilization. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

    PubMed Central

    Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

    2009-01-01

    Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

  8. Superconducting techniques for gravity survey and inertial navigation

    NASA Technical Reports Server (NTRS)

    Chan, H. A.; Moody, M. V.; Paik, H. J.; Parke, J. W.

    1985-01-01

    A three-axis gravity gradiometer is developed, in which the magnetic fields produced by persistent currents are modulated by motions of superconducting proof masses. The common-acceleration-induced errors are compensated for by a six-axis superconducting accelerometer with a single magnetically levitated proof mass, linear acceleration resolution of 4 x 10 to the -12th m/(s exp 2 Hz exp 1/2), and angular acceleration resolution of 3 x 10 to the -11th rad/(s exp 2 Hz exp 1/2). The testing of a prototype gradiometer revealed that the environment-induced noise limits the noise floor to 7 x 10 to the -10th/(s exp 2 Hz exp 1/2).

  9. Measurement of the Specific Heat Using a Gravity Cancellation Approach

    NASA Technical Reports Server (NTRS)

    Zhong, Fang

    2003-01-01

    The specific heat at constant volume C(sob V) of a simple fluid diverges near its liquid-vapor critical point. However, gravity-induced density stratification due to the divergence of isothermal susceptibility hinders the direct comparison of the experimental data with the predictions of renormalization group theory. In the past, a microgravity environment has been considered essential to eliminate the density stratification. We propose to perform specific heat measurements of He-3 on the ground using a method to cancel the density stratification. A He-3 fluid layer will be heated from below, using the thermal expansion of the fluid to cancel the hydrostatic compression. A 6% density stratification at a reduced temperature of 10(exp -5) can be cancelled to better than 0.1% with a steady 1.7 micro K temperature difference across a 0.05 cm thick fluid layer. A conventional AC calorimetry technique will be used to determine the heat capacity. The minimized bulk density stratification with a relaxation time 6500 sec at a reduced temperature of 10(exp -5) will stay unchanged during 1 Hz AC heating. The smear of the specific heat divergence due to the temperature difference across the cell is about 0.1% at a reduced temperature of 10(exp -6). The combination of using High Resolution Thermometry with a 0.5 n K temperature resolution in the AC technique and the cancellation of the density stratification will enable C(sub V) to be measured down to a reduced temperature of 10(exp -6) with less than a 1% systematic error.

  10. A catalogue of potentially bright close binary gravitational wave sources

    NASA Technical Reports Server (NTRS)

    Webbink, Ronald F.

    1985-01-01

    This is a current print-out of results of a survey, undertaken in the spring of 1985, to identify those known binary stars which might produce significant gravitational wave amplitudes at earth, either dimensionless strain amplitudes exceeding a threshold h = 10(exp -21), or energy fluxes exceeding F = 10(exp -12) erg cm(exp -2) s(exp -1). All real or putative binaries brighter than a certain limiting magnitude (calculated as a function of primary spectral type, orbital period, orbital eccentricity, and bandpass) are included. All double degenerate binaries and Wolf-Rayet binaries with known or suspected orbital periods have also been included. The catalog consists of two parts: a listing of objects in ascending order of Right Ascension (Equinox B1950), followed by an index, listing of objects by identification number according to all major stellar catalogs. The object listing is a print-out of the spreadsheets on which the catalog is currently maintained. It should be noted that the use of this spreadsheet program imposes some limitations on the display of entries. Text entries which exceed the cell size may appear in truncated form, or may run into adjacent columns. Greek characters are not available; they are represented here by the first two or three letters of their Roman names, the first letter appearing as a capital or lower-case letter according to whether the capital or lower-case Greek character is represented. Neither superscripts nor subscripts are available; they appear here in normal position and type-face. The index provides the Right Ascension and Declination of objects sorted by catalogue number.

  11. Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

    PubMed

    Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

    2017-02-01

    Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Priming the Tumor Immune Microenvironment Improves Immune Surveillance of Cancer Stem Cells and Prevents Cancer Recurrence

    DTIC Science & Technology

    2013-10-01

    YANG,a DEBBIE LIAO,b CONG CHEN,c YAN LIU,c TSUNG-HSIEN CHUANG,d RONG XIANG,a DOROTHY MARKOWITZ,b RALPH A. REISFELD,b YUNPING LUOb,c aDepartment of...tumor stem cells. Cancer Cell 2007;11:69–82. 27 Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res...polarization and vessel normalization through downregulation of PlGF. Cancer Cell 2011; 19: 31–44. 12 Murdoch C, Lewis CE. Macrophage migration and gene

  13. Initial astronomical results with a new 5-14 micron Si:Ga 58x62 DRO array camera

    NASA Technical Reports Server (NTRS)

    Gezari, Dan; Folz, Walter; Woods, Larry

    1989-01-01

    A new array camera system was developed using a 58 x 62 pixel Si:Ga (gallium doped silicon) DRO (direct readout) photoconductor array detector manufactured by Hughes/Santa Barbara Research Center (SBRC). The camera system is a broad band photometer designed for 5 to 14 micron imaging with large ground-based optical telescopes. In a typical application a 10 micron photon flux of about 10(exp 9) photons sec(exp -1) m(exp -2) microns(exp -1) arcsec(exp -2) is incident in the telescope focal plane, while the detector well capacity of these arrays is 10(exp 5) to 10 (exp 6) electrons. However, when the real efficiencies and operating conditions are accounted for, the 2-channel 3596 pixel array operates with about 1/2 full wells at 10 micron and 10% bandwidth with high duty cycle and no real experimental compromises.

  14. Meteoroid Flux from Lunar Impact Monitoring

    NASA Technical Reports Server (NTRS)

    Suggs, Robert; Moser, Danielle; Cooke, William; Suggs, Ronnie

    2015-01-01

    The flux of kilogram-sized meteoroids has been determined from the first 5 years of observations by NASA's Lunar Impact Monitoring Program (Suggs et al. 2014). Telescopic video observations of 126 impact flashes observed during photometric conditions were calibrated and the flux of meteoroids to a limiting mass of 30 g was determined to be 6.14 x 10(exp -10) m(exp -2) yr(exp -1) at the Moon, in agreement with the Grun et al. (1985) model value of 7.5 x 10(exp -10) m(exp -2) yr(exp -1). After accounting for gravitational focusing effects, the flux at the Earth to a limiting impact energy of 3.0 x10(exp -6) kilotons of TNT (1.3 x 10(exp 7) J) was determined to be consistent with the results in Brown et al. (2002). Approximately 62% of the impact flashes were correlated with major meteor showers as cataloged in visual/optical meteor shower databases. These flux measurements, coupled with cratering and ejecta models, can be used to develop impact ejecta engineering environments for use in lunar surface spacecraft design and risk analyses.

  15. Activation of Myeloid-Derived Suppressor Cells in Bone Marrow

    DTIC Science & Technology

    2013-12-01

    tumormodelwas utilized to establish the causal relationship between PTHrP and CD11bþGr1þ cells. Ace-1 prostate cancer cells produce predominantly osteoblas...2012;19:243–54. 20. Park SI, Kim SJ, McCauley LK, Gallick GE. Pre-clinical mouse models of human prostate cancer and their utility in drug discovery...microenvironment. Clin Cancer Res 2010; 16:924–35. 33. Huang YF, Harrison JR, Lorenzo JA, Kream BE. Parathyroid hor- mone induces interleukin-6

  16. The Role of Polycomb Group Gene Bmi-1 in the Development of Prostate Cancer

    DTIC Science & Technology

    2011-09-01

    new tricks. Cell Div. 2006 Jul 24;1:15. 17. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions... Pestell RG. Signal transduction mediated by cyclin D1: from mitogens to cell proliferation: a molecular target with therapeutic potential. Cancer...Datar 22 R, Cote R, Pestell R, Albanese C. ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. Cancer Res. 2007

  17. Synthetic Lethal Metabolic Targeting of Senescent Cells after Androgen Deprivation Therapy

    DTIC Science & Technology

    2017-07-01

    ORGANIZATION NAME(S) AND ADDRESS(ES) UNIVERSITY OF WISCONSIN, MADISON 8. PERFORMING ORGANIZATION REPORT NUMBER 21 N PARK ST STE 6401 MADISON WI 53715...Avenue, Madison, WI 53705, USA 123 Breast Cancer Res Treat (2017) 163:435–447 DOI 10.1007/s10549-017-4201-0 In an effort to enhance the activity of TRAIL...cells. (Figure 1). A dose–response experiment in MDA-MB-468 cells identi- fied 0.5 mM metformin as the minimal concentration needed to sensitize these

  18. Relation Between Macular Retinal Ganglion Cell/Inner Plexiform Layer Thickness and Multifocal Electroretinogram Measures in Experimental Glaucoma

    PubMed Central

    Luo, Xunda; Patel, Nimesh B.; Rajagopalan, Lakshmi P.; Harwerth, Ronald S.; Frishman, Laura J.

    2014-01-01

    Purpose. We investigated relations between macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) thickness and macular retinal function revealed by multifocal electroretinonography (mfERG) in a nonhuman primate model of experimental glaucoma. Methods. Retinal ganglion cell (RGC) structure and function were followed with spectral-domain optical coherence tomography (SD-OCT) and ERGs in five macaques with unilateral experimental glaucoma. Linear regression was used to study correlations in control (Con) and experimental (Exp) eyes between peripapillary retinal nerve fiber layer (RNFL) thickness, macular RGC+IPL thickness, multifocal photopic negative response (mfPhNR) and high-frequency multifocal oscillatory potentials (mfOP) in slow-sequence mfERG, and low-frequency component (mfLFC) in global-flash mfERG. We used ANOVA and paired t-tests to compare glaucoma-related mfERG changes between superior and inferior hemifields, foveal hexagon, inner three rings, and four quadrants of macula. Results. Average macular RGC+IPL and temporal RNFL thickness were strongly correlated (r2 = 0.90, P < 0.001). In hexagon-by-hexagon analysis, all three mfERG measures were correlated (P < 0.001) with RGC+IPL thickness for Con (r2, 0.33–0.51) and Exp eyes (r2, 0.17–0.35). The RGC structural and functional metrics decreased as eccentricity increased. The reduction in amplitude of mfERG measures in Exp eyes relative to Con eyes was proportionally greater, in general, than the relative thinning of RGC+IPL at the same location for eyes in which structural loss was not evident, or mild to moderate. Although not statistically significant, percent amplitude reduction of mfERG measures was greatest in the inferior temporal quadrant. Conclusions. Macular RGC+IPL thickness and mfERG measures of RGC function can be complementary tools in assessing glaucomatous neuropathy. PMID:24970256

  19. Manufactured and Airborne Nanoparticle Cardiopulmonary Interactions: A Review of Mechanisms and the Possible Contribution of Mast Cells

    EPA Science Inventory

    Human inhalation exposures to manufactured nanoparticles (NP) and airborne ultrafine particles (UFP) continues to increase in both occupational and environmental settings. UFP exposures have been associated with increased cardiovascular mortality and morbidity, while ongoing res...

  20. PSR J2021+4026 in the Gamma Cygni Region: The First Variable Gamma-Ray Pulsar Seen by the Fermi LAT

    NASA Technical Reports Server (NTRS)

    Allafort, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.; Bellazzini, R.; Bonamente, E.; Bottacini, E.; Brandt, T. J.; hide

    2013-01-01

    Long-term monitoring of PSR J2021+4026 in the heart of the Cygnus region with the Fermi Large Area Telescope unveiled a sudden decrease in flux above 100 MeV over a timescale shorter than a week. The "jump" was near MJD 55850 (2011 October 16), with the flux decreasing from (8.33 plus or minus 0.08)×10(exp -10) erg cm(exp -2) s(exp -1) to (6.86 plus or minus 0.13)× 10 (exp -1)0 erg cm (exp -2) s(exp -1). Simultaneously, the frequency spindown rate increased from (7.8 plus or minus 0.1) × 10(exp -13) Hz s(exp -1) to (8.1 plus or minus 0.1) × 10(exp -1)3 Hz s(exp -1). Significant (greater than 5 sigma) changes in the pulse profile and marginal (less than 3 sigma) changes in the emission spectrum occurred at the same time. There is also evidence for a small, steady flux increase over the 3 yr preceding MJD 55850. This is the first observation at gamma-ray energies of mode changes and intermittent behavior, observed at radio wavelengths for other pulsars. We argue that the change in pulsed gamma-ray emission is due to a change in emission beaming and we speculate that it is precipitated by a shift in the magnetic field structure, leading to a change of either effective magnetic inclination or effective current.

  1. Deficits in reticuloendothelial humoral control mechanisms in patients after trauma.

    PubMed

    Scovill, W A; Saba, T M; Kaplan, J E; Bernard, H; Powers, S

    1976-11-01

    Plasma opsonic activity as expressed by an alpha-2-globulin which stimulates hepatic Kupffer cell phagocytosis, and thus modulates RES clearance, was determined in patients at varying intervals following whole-body trauma. Plasma opsonic activity decreased markedly following trauma in both nonsurviving (NS) and surviving (S) trauma patients as compared to an age- and sex-matched group of healthy volunteers. The initial post-traumatic hypoopsonemia (0-72 hr) was more severe (p less than 0.01) in nonsurviving patients than surviving patients. Survivors following trauma manifested restoration of opsonin levels with a definite transient rebound hyperopsonemia during the recovery phase (11-30 days); nonsurviving patients exhibited persistent systemic alpha-2-globulin opsonic deficiency. On the basis of previous animal and human studies, the presently observed humoral deficits following trauma in patients could contribute to impairment of reticuloendothelial Kupffer cell clearance of blood-borne particulate matter such as fibrin, damaged platelets, and other altered autologous tissue. The importance of post-trauma RES dysfunction to survival following severe injury warrants further investigation and clinical consideration.

  2. Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake

    NASA Astrophysics Data System (ADS)

    Rao, Lang; Xu, Jun-Hua; Cai, Bo; Liu, Huiqin; Li, Ming; Jia, Yan; Xiao, Liang; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-02-01

    Suppression of the reticuloendothelial system (RES) uptake is one of the most challenging tasks in nanomedicine. Coating stratagems using polymers, such as poly(ethylene glycol) (PEG), have led to great success in this respect. Nevertheless, recent observations of immunological response toward these synthetic polymers have triggered a search for better alternatives. In this work, natural red blood cell (RBC) membranes are camouflaged on the surface of Fe3O4 nanoparticles for reducing the RES uptake. In vitro macrophage uptake, in vivo biodistribution and pharmacokinetic studies demonstrate that the RBC membrane is a superior alternative to the current gold standard PEG for nanoparticle ‘stealth’. Furthermore, we systematically investigate the in vivo potential toxicity of RBC membrane-coated nanoparticles by blood biochemistry, whole blood panel examination and histology analysis based on animal models. The combination of synthetic nanoparticles and natural cell membranes embodies a novel and biomimetic nanomaterial design strategy and presents a compelling property of functional materials for a broad range of biomedical applications.

  3. Interaction Between Eddies and Mean Flow in Jupiter's Atmosphere: Analysis of Cassini Imaging Data

    NASA Technical Reports Server (NTRS)

    Salyk, Colette; Ingersoll, Andrew P.; Lorre, Jean; Vasavada, Ashwin; DelGenio, Anthony D.

    2006-01-01

    Beebe et al. [Beebe, R.F., et al., 1980. Geophys. Res. Lett. 17, 1-4] and Ingersoll et al. [Ingersoll, A.P., et al., 1981. J. Geophys. Res. 86, 8733-8743] used images from Voyagers 1 and 2 to analyze the interaction between zonal winds and eddies in Jupiter's atmosphere. They reported a high positive correlation between Jupiter's eddy momentum flux, pu'v', and the variation of zonal velocity with latitude, du/dy. This correlation implied a surprisingly high rate of conversion of energy from eddies to zonal flow: approx. 1.5-3.0 W/sq m, a value more than 10% of Jupiter s thermal flux emission. However, Sromovsky et al. [Sromovsky, L.A., et al., 1982. J. Atmos. Sci. 39,1413-1432] argued that possible biases in the analysis could have caused an artificially high correlation. In addition, significant differences in the derived eddy flux between datasets put into question the robustness of any one result. We return to this long-standing puzzle using images of Jupiter from the Cassini flyby of December 2000. Our method is similar to previous analyses, but utilizes an automatic feature tracker instead of the human eye. The number of velocity vectors used in this analysis is over 200,000, compared to the 14,000 vectors used by Ingersoll et al. We also find a positive correlation between u'v' and du/dy and derive a global average power per unit mass, u'v' du/dy, ranging from (7.1-12.3) x 10(exp -5)W/kg. Utilizing Ingersoll et al.'s estimate of the mass per unit area involved in the transport, this would imply a rate of energy conversion of approx.0.7-1.2 W/sq m. We discuss the implications of this result and employ several tests to demonstrate its robustness.

  4. Qualification test results for blue-red reflecting solar covers

    NASA Technical Reports Server (NTRS)

    Beauchamp, W. T.

    1994-01-01

    Recent market forces and design innovations have spurred the development of solar cell covers that significantly reduce the solar absorptance for a cell array. GaAs cells, using Ge as the substrate host material, can have a significantly higher output if the solar absorptance of the cell array is reduced. New optical coating design techniques have allowed the construction of covers that reflect the ultraviolet energy (below 350 nm) and the near infrared energy (above 900 nm) resulting in the beneficial reduction in absorptance. Recent modeling suggests three or more present output increase due to the lowered temperature with such a device. Within the last several months we have completed the testing of production samples of these new covers in a qualification series that included the usual environmental effects associated with the routine testing of solar cell covers and the combined effects of protons, electrons and solar UV as would be encountered in space. For the combined effects testing the samples were exposed to 300 sun days equivalent UV, 5 x 10(exp 14)/sq cm of 0.5 MeV protons and 10(exp 15)/sq cm of 1.0 MeV electrons. Measurements of the reflectance, transmission, emittance and other appropriate parameters were made before and after the testing. As measured by the averaged transmission over the cell operating band, the change in transmission for the samples was less than or about equal to 1 percent. The details of the testing and the results in terms of transmission, reflectance and emittance are discussed in the paper.

  5. Hypergravity Loading the Cultured Osteoblasts: Modeling and Experimental Analysis of Cellular Morphology and the Cytoskeleton

    NASA Technical Reports Server (NTRS)

    Searby, N. D.; Steele, C. R.; Globus, R. K.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Bone forming cells, osteoblasts, respond to various mechanical forces, including mechanical strain and fluid-induced shear stress. This study examined whether osteoblasts detect changes in gravity as a mechanical force, as assessed by cellular morphology and dimensions of the cytoskeletal network. We used modeling to evaluate how gravity influences cell morphology given theoretical differences in densities between the surrounding medium, cytoplasm, and nucleus. A mechanical model was built based on analysis of axisymmetric shell structures (Fast4 software) to study the effects of 10 times gravity (10G) on cell height. The model indicated 0.02% decrease in overall cell height when the medium was 10% denser than the nucleus or cytoplasm, 5.9 x 10(exp-5)% decrease when the nucleus was 10% denser than the cytoplasm or medium, and 1.3 x 10(exp-5)% decrease when the cell cytoplasm was 10% denser than the nucleus or medium. To experimentally evaluate the influence of gravity, cultured primary fetal rat osteoblasts were grown to near confluence and centrifuged at 10G for 3 hours. Actin, microtubules, and nuclei were fluorescently labeled and analyzed by confocal microscopy to determine overall microtubule and actin network height. Centrifugation led to an apparent reduction in height of both the microtubule (-16%) and the actin (-20%) networks relative to stationary controls. Thus, both modeling and experiments indicate that hypergravity reduces the height of the osteoblast cell layer and their microtubule and actin networks. This combination of modeling and experimental analyses will help us to better understand the mechanical loading of osteoblasts.

  6. Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women.

    PubMed

    Messini, Christina I; Malandri, Maria; Anifandis, George; Dafopoulos, Konstantinos; Georgoulias, Panagiotis; Sveronis, Georgios; Garas, Antonios; Daponte, Alexandros; Messinis, Ioannis E

    2017-07-01

    An inhibitory effect of ghrelin on gonadotrophin secretion has been reported in normally menstruating women possibly modulated by endogenous oestrogen. The aim of this study was to examine the effect of ghrelin on gonadotrophin and prolactin (PRL) secretion in oestrogen-deprived postmenopausal women. Prospective intervention study. Ten healthy postmenopausal volunteer women were studied during two 15-days periods of oestrogen treatment (A and B) a month apart. Four experiments (Exp) were performed in total, two on day 1 (Exp 1A and Exp 1B) and two on day 15 (Exp 15A and Exp 15B) of the two periods. The women received in Exp 1A and in Exp 15A two iv injections of ghrelin (0.15 μg/kg at time 0 minute and 0.30 μg/kg at time 90 minutes) and in Exp1B and in Exp 15B normal saline (2 mL), respectively. Blood samples were taken at -15, 0, 30, 60, 90, 120, 150 and 180 minutes. After oestrogen treatment, late follicular phase serum oestradiol levels were attained on day 15 of periods A and B. Ghrelin administration did not affect serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), whereas it increased significantly those of growth hormone (GH) and PRL. In Exp 15A, serum PRL increment in response to ghrelin (area under the curve, net increment) was significantly greater than in Exp 1A (P<.05). This study demonstrates for the first time that in oestrogen-deprived postmenopausal women, ghrelin administration affects neither FSH nor LH levels but stimulates PRL secretion, that is amplified by exogenous oestrogen administration. © 2017 John Wiley & Sons Ltd.

  7. Improved construction materials for polar regions using microcellular thermoplastic foams

    NASA Technical Reports Server (NTRS)

    Cunningham, Daniel J.

    1994-01-01

    Microcellular polymer foams (MCF) are thermoplastic foams with very small cell diameters, less than 10 microns, and very large cell densities, 10(exp 9) to 10(exp 15) cells per cubic centimeter of unfoamed material. The concept of foaming polymers with microcellular voids was conceived to reduce the amount of material used for mass-produced items without compromising the mechanical properties. The reasoning behind this concept was that if voids smaller than the critical flaw size pre-existing in polymers were introduced into the matrix, they would not affect the overall strength of the product. MCF polycarbonate (PC), polystyrene (PS), and polyvinyl chloride (PVC) were examined to determine the effects of the microstructure towards the mechanical properties of the materials at room and arctic temperatures. Batch process parameters were discovered for these materials and foamed samples of three densities were produced for each material. To quantify the toughness and strength of these polymers, the tensile yield strength, tensile toughness, and impact resistance were measured at room and arctic temperatures. The feasibility of MCF polymers has been demonstrated by the consistent and repeatable MCF microstructures formed, but the improvements in the mechanical properties were not conclusive. Therefore the usefulness of the MCF polymers to replace other materials in arctic environments is questionable.

  8. Turbulent Aeroheating Testing of Mars Science Laboratory Entry Vehicle in Perfect-Gas Nitrogen

    NASA Technical Reports Server (NTRS)

    Hollis, Brian R.; Collier, Arnold S.

    2007-01-01

    An experimental investigation of turbulent aeroheating on the Mars Science Laboratory entry vehicle heat shield has been conducted in the Arnold Engineering Development Center Hypervelocity Wind Tunnel No. 9. Testing was performed on a 6-in. (0.1524 m) diameter MSL model in pure N2 gas in the tunnel s Mach 8 and Mach 10 nozzles at free stream Reynolds numbers of 4.1x10(exp 6)/ft to 49x10(exp 6)/ft (1.3x10(exp 7)/m to 16x10(exp 7)/m) and 1.2x10(exp 6)/ft to 19x10(exp 6)/ft (0.39x10(exp 7)/m to 62x10(exp 7)/m), respectively. These conditions were sufficient to span the regime of boundary-layer flow from completely laminar to fully-developed turbulent flow over the entire forebody. A supporting aeroheating test was also conducted in the Langley Research Center 20-Inch Mach 6 Air Tunnel at free stream Reynolds number of 1x10(exp 6)/ft to 7x10(exp 6)/ft (0.36x10(exp 7)/m to 2.2x10(exp 7)/m) in order to help corroborate the Tunnel 9 results. A complementary computational fluid dynamics study was conducted in parallel to the wind tunnel testing. Laminar and turbulent predictions were generated for all wind tunnel test conditions and comparisons were performed with the data for the purpose of helping to define uncertainty margins on predictions for aeroheating environments during entry into the Martian atmosphere. Data from both wind tunnel tests and comparisons with the predictions are presented herein. It was concluded from these comparisons that for perfect-gas conditions, the computational tools could predict fully-laminar or fully-turbulent heating conditions to within 10% of the experimental data

  9. Turbulent Aeroheating Testing of Mars Science Laboratory Entry Vehicle

    NASA Technical Reports Server (NTRS)

    Hollis, Brian R.; Collier, Arnold S.

    2008-01-01

    An experimental investigation of turbulent aeroheating on the Mars Science Laboratory entry vehicle heat shield has been conducted in the Arnold Engineering Development Center Hypervelocity Wind Tunnel No. 9. Testing was performed on a 6-in. (0.1524 m) diameter MSL model in pure N2 gas in the tunnel's Mach 8 and Mach 10 nozzles at free stream Reynolds numbers of 4.1 x 10(exp 6)/ft to 49 x 10(exp 6)/ft (1.3 x 10(exp 7)/m to 19 x 10(exp 6/ft) and 1.2 x 10(exp 6)/ft to 19 x 10(exp 6)/ft (0.39 x 10(exp 7)/m to 62 x 10(exp 7)/m), respectively. These conditions were sufficient to span the regime of boundary-layer flow from completely laminar to fully-developed turbulent flow over the entire forebody. A supporting aeroheating test was also conducted in the Langley Research Center 20-Inch Mach 6 Air Tunnel at free stream Reynolds number of 1 x 10(exp 6)/ft to 7 x 10(exp 6)/ft (0.36 x 10(exp 7)/m to 2.2 x 10(exp 7)/m) in order to help corroborate the Tunnel 9 results. A complementary computational fluid dynamics study was conducted in parallel to the wind tunnel testing. Laminar and turbulent predictions were generated for the wind tunnel test conditions and comparisons were performed with the data for the purpose of helping to define uncertainty margins on predictions for aeroheating environments during entry into the Martian atmosphere. Data from both wind tunnel tests and comparisons with the predictions are presented herein. It was concluded from these comparisons that for perfect-gas conditions, the computational tools could predict fully-laminar or fully-turbulent heating conditions to within 12% or better of the experimental data.

  10. Rice and soy protein isolate in pre-starter diets for broilers.

    PubMed

    Ebling, P D; Kessler, A M; Villanueva, A P; Pontalti, G C; Farina, G; Ribeiro, A M L

    2015-11-01

    Although most industries use a specific diet for the pre-starter phase, ingredients are used in the later phases, primarily corn and soybean meal, which at this stage do not have high digestibility. Three experiments : Exp : were carried out to evaluate the substitution of corn by white or parboiled rice : WR, PR : and the inclusion of 6% soy protein isolate : SPI : in pre-starter diets (1 to 7 d). In Exp 1 (1 to 21 d), WR, PR, and SPI were added to the diets until the birds were 21-day-old, whereas in Exps 2 and 3 (1 to 33 d), only until birds were 7-day-old. Birds were fed a basal diet based on corn and soybean meal until the end of the experimental period. In Exp 1, the coefficients of total tract apparent retention : CTTAR : of the pre-starter and the starter diets, ileal and jejunal digestibility of starch in the starter diets, and broiler performance were measured. Subsequently, the same pre-starter diets Exp 1 were evaluated in pellet (Exp 2) or mash (Exp 3) form and different oil percentage (Exp 2) or not (Exp 3). We hypothesized that the ingredients particle size (Exp 2) and fat content (Exp 3) could influence feed intake. There was no interaction among the evaluated factors (P > 0.05). Rice (WR or PR) promoted better results than corn in terms of CTTAR of dietary components, jejunal and ileal starch digestibility, and broiler performance (P < 0.01). In Exp 1, diets with 6% SPI presented better CTTAR, except Nitrogen ( N: ), but lower feed intake, which negatively affected broiler performance (P < 0.01). In Exps 1, 2, and 3, the inclusion of SPI did not improve broiler performance (P > 0.05), so that SPI may not be the best choice for pre-starter diets. The study also suggests that better growth performance and nutrient digestibility can be obtained in broiler chickens if corn is replaced by rice in pre-starter diets. © 2015 Poultry Science Association Inc.

  11. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

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

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serummore » (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.« less

  12. Comparison of Regulation Mechanisms of Five Mulberry Ingredients on Insulin Secretion under Oxidative Stress.

    PubMed

    Zheng, Yun-Chong; He, Hao; Wei, Xing; Ge, Sheng; Lu, Yan-Hua

    2016-11-23

    The effects of mulberry ingredients including 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) on insulin secretion under oxidative stress were investigated. The results revealed that they had distinct effects on insulin secretion in H 2 O 2 -induced MIN 6 cells, especially DNJ, C3G, and C3R, while RES and OXY showed modest effects in low dose (12.5 μM). The mechanisms were demonstrated in signal pathway that after treatment with DNJ, C3G, and C3R, the expressions of glucokinase (GK) were up-regulated, leading to intracellular ATP accumulation and insulin secretion. They also bound to glucagon-like peptide-1 receptor (GLP-1R), improved GLP-1R, duodenal homeobox factor-1 (PDX-1) expression, and stimulated insulin secretion. Moreover, ROS production was inhibited, followed by a decreasing apoptosis rate, while RES and OXY accelerated the apoptosis at high dose (50 μM). This work expounded the potential mechanisms of mulberry ingredients on insulin secretion, indicating the potential application in the intervention against hyperglycemia.

  13. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-04-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

  14. Largazole as a Novel and Selective Anti-Breast Cancer Agent

    DTIC Science & Technology

    2012-10-01

    shorter median time to relapse and death and significant unmet medical need due to the fact that these cancers do not respond to endocrine therapy or...Overexpression of single HDAC enzyme isoform is insufficient to convert sensitive cells to resistance or vice versa. 13 4. REPORTABLE OUTCOMES...McConkey. 2006. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res 66:3773-81

  15. Modulation of Human Plasma Fibronectin Levels Following Exercise,

    DTIC Science & Technology

    1988-01-01

    forms of this large molecular weight (440 kilodaltons) glycoprotein,(17. While the tissue type is cell-associated and important to cell adhesion and...increased under conditions of pathology, such as in obesity (6). cancer (3). proteinuria (4). diabetic retinopathy (5). and preeclampsia (27). in the absence...Res. 1977: 22:709-716. 27. Stubbs. T.M.. Lazarchick. J.. and Horger. E.O. Plasma fibronectin levels in preeclampsia : A possible biochemical marker

  16. Analysis of Complex Carbohydrate Composition in Plant Cell Wall Using Fourier Transformed Mid-Infrared Spectroscopy (FT-IR).

    PubMed

    Badhan, Ajay; Wang, Yuxi; McAllister, Tim A

    2017-01-01

    Fourier transformed mid-infrared spectroscopy (FTIR) is a powerful tool for compositional analysis of plant cell walls (Acebes et al., Front Plant Sci 5:303, 2014; Badhan et al., Biotechnol Biofuels 7:1-15, 2014; Badhan et al., BioMed Res Int 2015: 562952, 2015; Roach et al., Plant Physiol 156:1351-1363, 2011). The infrared spectrum generates a fingerprint of a sample with absorption peaks corresponding to the frequency of vibrations between the bonds of the atoms making up the material. Here, we describe a method focused on the use of FTIR in combination with principal component analysis (PCA) to characterize the composition of the plant cell wall. This method has been successfully used to study complex enzyme saccharification processes like rumen digestion to identify recalcitrant moieties in low-quality forage which resist rumen digestion (Badhan et al., BioMed Res Int 2015: 562952, 2015), as well as to characterize cell wall mutant lines or transgenic lines expressing exogenous hydrolases (Badhan et al., Biotechnol Biofuels 7:1-15, 2014; Roach et al., Plant Physiol 156:1351-1363, 2011). The FTIR method described here facilitates high-throughput identification of the major compositional differences across a large set of samples in a low cost and nondestructive manner.

  17. The Rovibrational Intensities of the (40 deg 1) and (00 deg 0) Pentad Absorption Bands of 12C16O2 Between 7284 and 7921 cm(exp-1)

    NASA Technical Reports Server (NTRS)

    Giver, L. P.; Chackerian, C., Jr.; Spencer, N.; Brown, L. R.; Wattson, R. B.; Gore, Warren J. (Technical Monitor)

    1995-01-01

    Carbon dioxide is the major constituent of the atmospheres of both Mars and Venus. Correct interpretations of spectra of these atmospheres require accurate knowledge of a substantial number of absorption bands of this gas. This is especially true for Venus; many weak CO2 bands that are insignificant in the earth's atmosphere are prominent absorbers in Venus' hot, dense lower atmosphere. Yet, recent near-infrared spectra of Venus' nightside have discovered emission windows, which occur between CO2 absorption bands, at 4040-4550 cm(exp-1), 5700-5900 cm(exp-1), and several smaller ones between 7500 and 9400 cm(exp-1). This radiation is due to thermal emission from Venus' lower atmosphere, diminished by scattering and absorption within the sulfuric acid clouds on its way to space. Simulations of these data with radiative transfer models can provide improved information on the abundances of a number of constituents of the lower atmosphere (e.g. H2O, CO, HDO, HCl, HF, and OCS) and the optical properties of the clouds, whose spatial variation modulates the brightness of the emissions. However, the accuracy of these retrievals has been limited by insufficient knowledge of the opacity of some of the gas species, including CO2, at the large pathlengths and high temperatures and pressures that exist on Venus. In particular, modeling the emission spectrum did not produce a good fit for the emission window centered at 7830 cm(exp-1). In an ongoing effort to assist analyses of these Venus spectra, we have been making laboratory intensity measurements of several weak bands of CO2 which are significant absorbers in these Venus emission windows. The CO2 bands that are prominent in the 7830 cm(exp-1) region belong to the vibrational sequence 4v1+v3 and associated hot bands. Only 2 of the 5 bands of this sequence have been previously measured. Modeling Venus' emission spectrum in the 7830 cm(exp-1) region had to rely on calculated intensity values for the weak ground state band at 7921 cm-1 and the associated hot bands. Since the calculated intensities of ground state bands are known to have significant uncertainties, we decided to measure this (40 deg 1)I (left arrow) (00 deg 0) band with the Ames 25 meter multiple reflection absorption cell and Fourier transform spectrometer. We also measured the (40 deg 1) (sub IV) (left arrow) (00 deg 0) band at 7460 cm(exp-1), which also had not been previously measured. These measurements are reported in this article, and we also give our reanalysis of the prior measurements of the (40 deg 1) (sub III) (left arrow) (00 deg 0) bands. These measurements provide the basis for improving calculated intensities for related hot bands as well as simulations of Venus' spectrum.

  18. Free-Space Green’s Functions of the Reduced Wave Equation.

    DTIC Science & Technology

    1982-09-01

    1/2Z) exp(ino)!j J GF( ’n’axRo)Jn( r)exp(iaz)d~da- - - o (4.1) __8 * where the inverse transform is (F2,nr,)o) J (,R)J(;r exp(/in)-iz)rdrddz (4.2) -F...exp(im.) E ?m(cos 8) GF(,nmR (JR)E/2d• M-w n=-= 51 0 s n) -). where the inverse transform is G F(En,m,R) (2n+l)(n-m)!1/2/(4r2(n+m)!). 2w 7r ((RR )exp

  19. Composite Solid Electrolyte Containing Li+- Conducting Fibers

    NASA Technical Reports Server (NTRS)

    Appleby, A. John; Wang, Chunsheng; Zhang, Xiangwu

    2006-01-01

    Improved composite solid polymer electrolytes (CSPEs) are being developed for use in lithium-ion power cells. The matrix components of these composites, like those of some prior CSPEs, are high-molecular-weight dielectric polymers [generally based on polyethylene oxide (PEO)]. The filler components of these composites are continuous, highly-Li(+)-conductive, inorganic fibers. PEO-based polymers alone would be suitable for use as solid electrolytes, were it not for the fact that their room-temperature Li(+)-ion conductivities lie in the range between 10(exp -6) and 10(exp -8) S/cm, too low for practical applications. In a prior approach to formulating a CSPE, one utilizes nonconductive nanoscale inorganic filler particles to increase the interfacial stability of the conductive phase. The filler particles also trap some electrolyte impurities. The achievable increase in conductivity is limited by the nonconductive nature of the filler particles.

  20. Calculating maximum frost depths at Mn/ROAD : winters 1993-94, 1994-95 and 1995-96

    DOT National Transportation Integrated Search

    1997-03-01

    This effort involved calculating maximum frost penetration depths for each of the 40 test cells at Mn/ROAD, the Minnesota Department of Transportation's pavement testing facility, for the 1993-94, 1994-95, and 1995-96 winters. The report compares res...

  1. Meiotic competence of equine oocytes and pronucleus formation after intracytoplasmic sperm injection (ICSI) as related to granulosa cell apoptosis.

    PubMed

    Dell'Aquila, Maria Elena; Albrizio, Maria; Maritato, Filippo; Minoia, Paolo; Hinrichs, Katrin

    2003-06-01

    Follicle atresia and granulosa cell apoptosis may be related to oocyte meiotic and developmental competence. We analyzed the relationships among granulosa cell apoptosis, initial cumulus morphology, oocyte nuclear maturation in vitro, and pronucleus formation after intracytoplasmic sperm injection (ICSI) in the horse. For each follicle, the size was measured and granulosa cells were used for DNA laddering analysis. Oocytes were evaluated for cumulus morphology, cultured for in vitro maturation, and submitted to ICSI. Apoptosis was categorized as absent, intermediate, or advanced according to the relative concentrations of two DNA fragments at 900 and 360 base pairs (bp). In 98 oocyte-follicle pairs, 52 oocytes were classified as expanded (Exp), 39 as compact (Cp), and 7 as having a partial (P) cumulus. Advanced apoptosis was detected in 55% (54/98) of follicles; 37% (36/98) of follicles showed an intermediate level of apoptosis; and 8 follicles (8%) were nonapoptotic. Follicle size was not significantly correlated with granulosa cell apoptosis (P > 0.05). Significantly more Exp than Cp oocytes originated from follicles with advanced apoptosis (P < 0.001). The proportion of oocytes maturing in vitro was significantly higher in oocytes issuing from apoptotic follicles than in oocytes issuing from healthy follicles (P < 0.05). The proportion of normally (two pronuclei) or abnormally fertilized oocytes (one or greater than two pronuclei, or partially decondensed sperm) did not differ in relation to granulosa cell apoptosis. We conclude that, in the mare, granulosa cell apoptosis is related to cumulus expansion and an increase in oocyte meiotic competence but has no effect on the proportion of meiotically competent oocytes that activate after ICSI. These results provide selection criteria for horse oocytes used in assisted reproductive techniques so that embryo production may be maximized.

  2. Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

    PubMed

    Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

    2016-01-01

    Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.

  3. Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

    PubMed Central

    Harisa, Gamaleldin I.; Badran, Mohamed M.; AlQahtani, Saeed A.; Alanazi, Fars K.; Attia, Sabry M.

    2015-01-01

    Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer. PMID:26903771

  4. Magnetometer Based on the Opto-Electronic Oscillator

    NASA Technical Reports Server (NTRS)

    Matsko, Andrey B.; Strekalov, Dmitry; Maleki, Lute

    2005-01-01

    We theoretically propose and discuss properties of two schemes of an all-optical self-oscillating magnetometer based on an opto-electronic oscillator stabilized with an atomic vapor cell. Proof of the principle DC magnetic field measurements characterized with 2 x 10(exp -7) G sensitivity and 1 - 1000 mG dynamic range in one of the schemes are demonstrated.

  5. Next Generation Robust Low Noise Seismometer for Nuclear Monitoring

    DTIC Science & Technology

    2008-09-01

    of four fine platinum mesh electrodes, two anodes, and two cathodes, separated by thin polymer mesh or laser-perforated mica spacers. The stack is...cell (Abramocvich and Daragan, 1992-94): ⎟ ⎠ ⎞ ⎜ ⎝ ⎛ −− )exp(1 00 kT qU l eSDc =I (6) 2008 Monitoring Research Review: Ground-Based

  6. Breast Cancer and Early Onset Childhood Obesity: Cell Specific Gene Expression in Mammary Epithelia and Adipocytes

    DTIC Science & Technology

    2007-07-01

    resistance on neuroendocrine and reproductive functions in transgenic and knock-out mice. Proc Soc Exp Biol Med. 1999 Nov;222(2):113-23. 11. Thordarson ...libitum overfeeding of Sprague- Dawley rats and its modulation by moderate and marked dietary restriction. Toxicol Pathol 2005;33:650–74. 26. Thordarson

  7. Stratospheric OClO and NO2 measured by groundbased UV/Vis-spectroscopy in Greenland in January and February 1990 and 1991

    NASA Technical Reports Server (NTRS)

    Roth, A.; Perner, D.

    1994-01-01

    Groundbased UV/Vis-spectroscopy of zenith scattered sunlight was performed at Sondre Stromfjord (Greenland) during Jan/Feb 1990 and Jan/Feb 1991. Considerable amounts of OClO were observed during both campaigns. Maximum OClO vertical column densities at 92 deg solar zenith angle (SZA) were 7.4 x 10(exp 13) molec/sq cm in 1990 and 5.7 x 10(exp 13) molec/sq cm in 1991 (chemical enhancement is included in the calculation of the air mass factor (AMF)). A threshold seems to exist for OClO detection: OClO was detected on every day when the potential vorticity at the 475 K level of potential temperature was higher than 35 x 10(exp -6)Km(exp 2)kg(exp -1)s(exp -1). NO2 vertical columns lower than 1 x 10(exp 15) molec/sq cm were frequently observed in both winters.

  8. Rosat observations of FK comae berenices

    NASA Technical Reports Server (NTRS)

    Welty, Alan D.; Ramsey, Lawrence W.

    1994-01-01

    We obtained ROSAT PSPC observations of FK Com over a period of 24.4 h, or 0.42 rotation. During the observations the x-ray flux increased by a factor of at least 5 before declining toward its previous level. A single temperature Raymond-Smith model is adequate to model the low signal-to-noise ratio spectrum from each observation interval. Initially the spectrum was that of a 8.5 x 10(exp 6) K plasma, with L9sub x)=0.66 x 10(exp 31) erg s(exp -1). When the x-ray flux was greatest, the model plasma temperature rose to 2.5 x 10(exp 7) K, and L(sub x)=3.46 x 10(exp 31) ergs(exp -1). During the post-maximum decline in luminosity the plasma temperature was approximately 12 x 10(exp 6) K. We conclude that the increase of x-ray flux recorded by ROSAT was due to an x-ray flare with a 1.5 h decline time scale.

  9. Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers.

    PubMed

    Cornell, R P

    1982-02-01

    In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125I-albumin microaggregates, and 125I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans.

  10. Development of transferrin targeted NCL-240 micelles and their evaluation using in-vitro 3D cancer cell culture (spheroid) models

    NASA Astrophysics Data System (ADS)

    Nagelli, Srikar Goud

    The main objective of this project was to develop targeted micellar delivery systems of a novel cytotoxic drug (NCL-240; a second generation DM-PIT-1 analog) and to evaluate their efficacy using optimized 3D cell culture spheroid models. Spheroids were optimized for several cancer cell lines using a range of techniques such as non-adhesive liquid overlay method, hanging drop method, and co-culturing. Transferrin (Tf)-conjugated NCL-240 micelles were prepared with varying Tf amounts and their cytotoxicities were evaluated using the optimized spheroid models. The uptake and penetration of the formulations were also studied using confocal microscopy. The results indicated that the concentration of NCL-240 micelles required to achieve the same cytotoxicity was relatively higher in spheroids compared to the monolayers. Also, In NCI-ADR-RES, Tf-targeted NCL-240 micelles were shown to have a significant increase in cytotoxicity compared to untargeted NCL-240 micelles. Even the penetration and uptake studies indicated that targeting improves the uptake and penetration of formulations. However, in U87-MG spheroids, there was a significant difference in cell viability among micelles compared to free drug but no significant benefit due to targeting was observed. The same formulations penetrated lesser in U87-MG spheroids compared to NCI-ADR-RES spheroids. This study thereby emphasizes the importance of drug screening in spheroid models as the penetration dynamics are varying from cell line to cell line because of the 3D structure.

  11. Design and Performance Assessment of a Stable Astigmatic Herriott Cell for Trace Gas Measurements on Airborne Platforms

    NASA Technical Reports Server (NTRS)

    Dyroff, Christoph; Fried, Alan; Richter, Dirk; Walega, James G.; Zahniser, Mark S.; McManus, J. Barry

    2005-01-01

    The present paper discusses a new, more stable, astigmatic Herriott cell employing carbon fiber stabilizing rods. Laboratory tests using a near-IR absorption feature of CO at 1564.168-nm revealed a factor of two improvement in measurement stability compared with the present commercial design when the sampling pressure was changed by +/-2 Torr around 50 Torr. This new cell should significantly enhance our efforts to measure trace gases employing pathlengths of 100 to 200-meters on airborne platforms with minimum detectable line center absorbances of less than 10(exp -6).

  12. Analysis of Harmonic Distortion in an Integrated Power System for Naval Applications

    DTIC Science & Technology

    2005-06-01

    tdop/xd; tdpp =xdpp*tdopp/xdp; ial =( 1/xd+( 1/Xdp- l/Xd). *exp(-t./tdp)+( l/xdpp- 1/Xdp). *ex p(-t./ tdpp )). *cos(377*t).. -1 ./xdpp*exp(-t./ta); hold...title(’Generator Fault Current’) ylabel(’Phase Current (pu)’) xdpp=. 15; tdp=xdp*tdop/xd; tdpp =xdpp*tdopp/xdp; ial =( 1/xd+( 1/xdp- 1/xd). *exp(-t./tdp...1/Xdpp- 1/xdp). *exp(-t./ tdpp )). *cos(377*t)... -1 ./xdpp*exp(-t./ta); plot(t,-ia 1) h=legend(󈧝% subtransient reactance’,’ 15% subtransient

  13. Novel aqueous dual-channel aluminum-hydrogen peroxide battery

    NASA Astrophysics Data System (ADS)

    Marsh, Catherine; Licht, Stuart

    1994-06-01

    A dual-channel aluminum hydrogen peroxide battery is introduced with an open-circuit voltage of 1.9 volts, polarization losses of 0.9 mV cm(exp 2) mA(exp -1), and power densities of 1 W/cm(exp 2). Catholyte and anolyte cell compartments are separated by an Ir/Pd modified porous nickel cathode. Separation of catholyte and anolyte chambers prevents hydrogen peroxide poisoning of the aluminum anode. The battery is expressed by aluminum oxidation and aqueous solution phase hydrogen peroxide reduction for an overall battery discharge consisting of 2Al + 3H2O2 + 2OH(-) yields 2AlO2(-) + 4H2O E = 2.3 V. The search for electrical propulsion sources which fit the requirements for electrically powered vehicles has blurred the standard characteristics associated with electrochemical storage systems. Presently, electrochemical systems comprised of mechanically rechargeable primary batteries, secondary batteries, and fuel cells are candidates for electrochemical propulsion sources. While important advances in energy and power density continue for nonaqueous and molten electrolytes, aqueous electrolyte batteries often have an advantage in simplicity, conductivity, cost effectiveness, and environmental impact. Systems coupling aluminum anodes and aqueous electrolytes have been investigated. These systems include: aluminum/silver oxide, aluminum/manganese dioxide, aluminum air, aluminum/hydrogen peroxide aqueous batteries, and the recently introduced aluminum/ferricyanide and aluminum sulfur aqueous batteries. Conventional aqueous systems such as the nickel cadmium and lead-acid batteries are characterized by their relatively low energy densities and adverse environmental impact. Other systems have substantially higher theoretical energy capacities. While aluminum-silver oxide has demonstrated the highest steady-state power density, its high cost is an impediment for widespread utilization for electric propulsion.

  14. 40 CFR 80.45 - Complex emissions model.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... this section for the appropriate phase and season Nd = exp d1(t)/exp d1(b) Hd = exp d2(t)/exp d2(b) w1.... d2(t) = Higher emitter 1,3-butadiene equation as defined in paragraph (e)(7)(ii) of this section... the base fuel's properties. d2(b) = Higher emitter 1,3-butadiene equation as defined in paragraph (e...

  15. Occurrence of white striping and wooden breast in broilers fed grower and finisher diets with increasing lysine levels.

    PubMed

    Cruz, R F A; Vieira, S L; Kindlein, L; Kipper, M; Cemin, H S; Rauber, S M

    2017-02-01

    Two experiments were conducted to evaluate the prevalence and severity of white striping (WS) and wooden breast (WB) in breast fillets from broilers fed diets with increasing digestible Lysine (dLys) from 12 to 28 d (Exp. 1) and from 28 to 42 d (Exp. 2). Trials were sequentially conducted using one-d-old male, slow-feathering Cobb 500 × Cobb broilers, both with 6 treatments and 8 replicates. Increasing dLys levels were equally spaced from 0.77 to 1.17% in Exp. 1 and from 0.68 to 1.07% in Exp. 2. The lowest dLys diet was not supplemented with L-Lysine (L-Lys) in either one of the studies and all other essential amino acid (AA) met or exceeded current commercial recommendations such that their dietary concentrations did not limit broiler growth. Four birds per pen were randomly selected from each replication and processed at 35 and 42 d in Exp. 1 and Exp. 2, respectively. Deboned breast fillets (Pectoralis major) were submitted to a 3 subject panel evaluation to detect the presence of WS and WB, as well as to provide scores of WS (0-normal, 1-moderate, 2-severe) and WB (0-normal, 1-moderate light, 2-moderate, 3-severe). Increasing the level of dLys had a positive effect on BW, carcass, and breast weight, as well as breast yield. White striping and WB prevalences were 32.3 and 85.9% in Exp. 1 and 87.1 and 89.2% in Exp. 2. Birds fed diets not supplemented with L-Lys had the lowest average WS and WB scores (0.22 and 0.78 in Exp. 1 and 0.61 and 0.68 in Exp. 2). White striping and WB presented linear responses to performance variables in Exp. 1, whereas quadratic responses were observed for all variables in Exp. 2. In conclusion, increasing the level of dLys improved growth performance and carcass traits as well as induced the occurrence and severity of WS and WB lesions. © 2016 Poultry Science Association Inc.

  16. Effect of feeding an encapsulated source of butyric acid (ButiPEARL) on the performance of male Cobb broilers reared to 42 d of age.

    PubMed

    Levy, April Waguespack; Kessler, James W; Fuller, Lorraine; Williams, Susan; Mathis, Greg F; Lumpkins, Brett; Valdez, Fernando

    2015-08-01

    The objective of this research was to determine the optimal level of an encapsulated butyric acid (ButiPEARL) based on the performance of male Cobb broilers reared to 42 d of age and to investigate its effects on intestinal morphology. Experiment 1 ( EXP 1: ) consisted of 4 treatments with 12 replicate pens that contained 45 broilers, and Experiment 2 ( EXP 2: ) consisted of 6 treatments with 8 replicate pens that contained 50 broilers. Birds were weighed by pen on d 0, 21, 35, and 42. In EXP 1, the treatments were as follows: 1) control ( C: ); 2) C + 100 g ButiPEARL/ton; 3) C + 200 g ButiPEARL/ton; and 4) C + 300 g ButiPEARL/ton. In EXP 2, the treatments were identical to EXP 1, with 2 additional treatments: 5) C + 400 g ButiPEARL/ton and 6) C + 500 g ButiPEARL/ton. In EXP 1, two 42-d-old broilers per pen were randomly selected for duodenal and jejunal tissue collection. Only the samples from the broilers fed the C or 300 g ButiPEARL treatments were analyzed for histology in EXP 1. For EXP 2, on d 21 and 35, two broilers per pen were randomly selected for duodenal, jejunal, and ileal tissue collection. For EXP 1 and 2, BW gain increased linearly with increasing butyric acid levels (P < 0.027 and P < 0.001, respectively). For EXP 1 and 2, feed conversion linearly improved with increasing butyric acid from 0 to 42 d (P < 0.001 and P < 0.001, respectively). In EXP 1, there were no differences in any intestinal morphology at 42 d between broilers fed the C or 300 g ButiPEARL treatments. In EXP 2, there were no differences in villus height at 21 or 35 d of age with any level of butyric acid. Based on the results of this research related to BW gain and feed conversion, the recommended optimum dosage level for ButiPEARL in broilers reared to 42 d of age is up to 500 g/ton. © 2015 Poultry Science Association Inc.

  17. Periodontal Wound Healing Responses to Varying Oxygen Concentrations and Atmospheric Pressures.

    DTIC Science & Technology

    1986-05-01

    Presumably, epithelial and gingival connective tissue exclusion allowed periodontal ligament cells to repopulate the wound and to regenerate a new...However, it seems clear that the periodontal ligament cells provide a major source of connective tissue attachment and regeneration (Nyman et al., 1982a...Connective Tissue Regeneration to Periodontally Diseased Teeth. J. Perio. Res. 15:1. Davis, J. C., Dunn, J. M., Gates, G. A. and Heimbach, R. D. 1979

  18. Inhibition of Granulopoiesis in Diffusion Chambers by a Granulocyte Chalone

    DTIC Science & Technology

    1974-07-01

    culture has o 5_g a been well documented. ’ Breivik et al. , using chamber to chamber transfers in nonpretreated hosts, have illustrated the...1972. 7. Breivik , H. and Benestad, H. B. Regulation of granulocyte and macrophage formation in diffusion chamber cultures of mouse...haematopoietic cells. Exptl. Cell Res. 70:340-348, 1972. 8. Breivik , H., Benestad, H. B. and B^yum, A. Diffusion chamber and spleen colony assay of murine

  19. Differential MDR in Breast Cancer Stem Cells

    DTIC Science & Technology

    2006-05-01

    Source: Sanofi -Aventis Grant Title: CMDRP Era of Hope Scholar Award BC044784 Breast Cancer Stem Cells: A Novel Therapeutic Target Role in Project Co...E.M. and Whiteside, T.L. “Processing of Tumors for Vaccine and/or Tumor Infiltrating Lymphocytes”, p. 817-819 in Rose, N.R., Conway de Macario, E...Counterparts, Ernst Schering Res Foundation Workshop, In Press. [14] E.M. Elder, T.L. Whiteside, Processing of tumors for vaccine and/or tumor

  20. XBP1, Unfolded Protein Response, and Endocrine Responsiveness

    DTIC Science & Technology

    2011-05-01

    initially modeled in yeast cells (21, 22). Components of the unfolded protein response (UPR) are also conserved across species and these include...response in tumors. Mol Cancer Res 2005;3:597–605. 38. Sriburi R, Jackowski S, Mori K, Brewer JW. XBP1: a link between the unfolded protein response

  1. Highly active antiretroviral therapy during gestation: effects on a rat model of pregnancy.

    PubMed

    Carvalho, L P F; Simões, R S; Araujo Júnior, E; Oliveira Filho, R M; Kulay Júnior, L; Nakamura, M U

    2014-04-01

    To assess the adverse effects of the chronic use of zidovudine/lopinavir/ritonavir in a rat pregnancy model.Type of article: Original paper. A prospective experimental study. Department of Obstetrics, São Paulo Federal University (UNIFESP). 40 pregnant EPM-1 albino rats were randomly allocated into four groups of 10 animals each: control (Ctrl) group (untreated) and three experimental groups (Exp1, Exp2 and Exp3), which received zidovudine/lopinavir/ritonavir in the corresponding doses of 10/13.3/3.3; 30/39.9/9.9 and 90/119.7/29.7 mg/Kg/day from the first up to the 20th day of pregnancy, respectively. The rats were treated by gavage daily. Body weights were recorded on days 0, 7, 14 and 20. At term, the rats were sacrificed and the implantation sites, number of live and dead fetuses and placentas, resorptions and fetal and placental weights were recorded. The fetuses were evaluated for external abnormalities under a stereomicroscope. The chi-square test was used to compare death rates between groups. Weight gain during pregnancy no showed significant differences between groups. Average weight gains between the 7th and 20th day were 45.70 ± 5.27 g for Ctrl; 48.49 ± 3.64 g for Exp1; 45.39 ± 6.22 g for Exp2 and 44.19 ± 6.78 g for Exp3. However, the percentage weight gain in the 7th was lower in groups Exp2 and Exp3 and in the 14th in the Group Exp2. All other parameters assessed did not differ significantly between groups. Exp2 and Exp3 in relation of the others. The chronic exposure of pregnant rats to high doses of zidovudine/lopinavir/ritonavir in association resulted in a significant reduction in maternal body weight gain but was not associated with significant adverse fetal parameters.

  2. Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters.

    PubMed

    Freitas, J V; Praça, F S G; Bentley, M V L B; Gaspar, L R

    2015-04-30

    Cutaneous permeation is a critical parameter when topical application of sunscreens containing antioxidants is considered. The aim of this study was to evaluate the cutaneous penetration of most marketed UV-filters combined with trans-resveratrol (RES) and beta-carotene (BTC) since few studies report skin penetration when such compounds are applied. Formulations containing octocrylene, octyl methoxycinnamate, avobenzone and bemotrizinole were prepared and supplemented or not with BTC, or with RES, or with both compounds in combination. Penetration studies were performed using Franz vertical diffusion cells and porcine ear skin as the biological membrane. The quantification of UV-filters and antioxidants in the stratum corneum (SC), viable epidermis plus dermis and receptor fluid was performed by HPLC. Results suggested that UV-filters and antioxidants did not permeate the skin but were retained for 12h post application. About 90% and 80%, respectively, of the total penetrated amount of UV-filters and antioxidants was found in the SC. Interestingly, it was observed that BTC, alone or combined with RES, reduced the skin retention of UV-filters on average by 63%. In conclusion, this study demonstrated that the combination of antioxidants and UV-filters in sunscreens is advantageous for cutaneous penetration, since BTC and BTC+RES improved sunscreen safety by reducing delivery of the four UV-filters in the study into SC and viable epidermis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. In situ detection of tropospheric OH and HO2 by laser-induced fluorescence in a detection chamber at low pressure

    NASA Technical Reports Server (NTRS)

    Brune, William H.; Stevens, Philip S.; Mather, James

    1994-01-01

    Just as in the method of Hard and O'Brien, ambient air is pulled through an approximately 1 mm diameter inlet into a detection chamber that is maintained at a pressure of 2.4 torr. The ambient air stream travels through the detection chamber with a velocity of greater than 100 m sec(exp -1) in a narrow stream, constrained by the addition of an inert gas flow (0.4 torr). The OH molecule is both excited and detected in the A(exp 2)Sigma (v' = 0) yields X(exp 2)II (v'' = 0) transition at 308 nm. Light from a copper vapor-pumped dye laser (rep. rate = 10kHz; pulse length = 20 ns; linewidth = .1 cm(exp -1), and average power = 15 mW), resonant with the Q(sub 1)(3) transition, is multipassed through a White cell and intercepts the air stream as 24 non-overlapping 2mm by 5mm beams. A fast microchannel plate detector is turned off during the laser pulse to prevent saturation of the detector due to Rayleigh and chamber scattering. It is turned on 30-100 nsec after the end of the laser pulse for 300 ns to collect resonance fluorescence from OH. HO2 is detected by chemical conversion to OH by reaction with reagent NO, followed by OH detection. Both the detection sensitivity and the inlet characteristics must be understood for any in situ instrument. For the calibration of the detection sensitivity, OH is produced quantitatively by the fast H + NO2 yields OH + NO reaction in a low pressure, flowing discharge tube connected to the detection chamber. The inlet transmission of OH inlet is calibrated separately.

  4. Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances

    PubMed Central

    Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

    2013-01-01

    The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p < 0.05. The following results were obtained from this study; 1. In the change of fatigue substances : Serotonin in the EXP tended to decreased at the 10 min before exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in the CON was significantly greater than the EXP at the10 min before exercise and recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30 min into exercise, and post exercise, but significantly decreased at the recovery 30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the 10 min before exercise, 30 min into exercise, and post exercise (p < 0.05). Lactate in the EXP was significantly increased at the 30 min into exercise and significantly decreased at the post exercise and recovery 30 min. Lactate in the CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In the change of muscle damage substances : CK in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. CK in the CON was greater than the EXP. LDH in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. LDH in the CON was higher than the EXP. 3. In the change of energy metabolism substances :Glucose in the EXP tended to decrease at the 10 min before exercise, 30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both EXP and CON was increased at the post exercise and recovery 30 min. % increase for FFA in the EXP was greater than the CON at the post exercise and recovery 30 min. 4. The relationship of the fatigue substances, muscle damage substances and energy metabolism substances after endurance exercise indicated strongly a positive relationship between LDH and ammonia and a negative relationship between LDH and FFA in the EXP. Also, there were a strong negative relationship between glucose and FFA and a positive relationship between glucose and serotonin in the EXP. There was a strong positive relationship between CK and LDH and a strong negative relationship between FFA and glucose in the CON. These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise. PMID:25566428

  5. Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances.

    PubMed

    Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

    2013-12-01

    The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p < 0.05. The following results were obtained from this study; 1. In the change of fatigue substances : Serotonin in the EXP tended to decreased at the 10 min before exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in the CON was significantly greater than the EXP at the10 min before exercise and recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30 min into exercise, and post exercise, but significantly decreased at the recovery 30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the 10 min before exercise, 30 min into exercise, and post exercise (p < 0.05). Lactate in the EXP was significantly increased at the 30 min into exercise and significantly decreased at the post exercise and recovery 30 min. Lactate in the CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In the change of muscle damage substances : CK in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. CK in the CON was greater than the EXP. LDH in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. LDH in the CON was higher than the EXP. 3. In the change of energy metabolism substances :Glucose in the EXP tended to decrease at the 10 min before exercise, 30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both EXP and CON was increased at the post exercise and recovery 30 min. % increase for FFA in the EXP was greater than the CON at the post exercise and recovery 30 min. 4. The relationship of the fatigue substances, muscle damage substances and energy metabolism substances after endurance exercise indicated strongly a positive relationship between LDH and ammonia and a negative relationship between LDH and FFA in the EXP. Also, there were a strong negative relationship between glucose and FFA and a positive relationship between glucose and serotonin in the EXP. There was a strong positive relationship between CK and LDH and a strong negative relationship between FFA and glucose in the CON. These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise.

  6. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress.

    PubMed

    Suzuki, Maiko; Bartlett, John D

    2014-02-01

    Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

    PubMed Central

    Suzuki, Maiko; Bartlett, John D.

    2014-01-01

    Sirtuin1 (SIRT1) is an (NAD+)-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum stress and oxidative stress. Previously, we reported that fluoride induces endoplasmic reticulum (ER) stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augmented SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50 and 100 ppm) in drinking water for 6 weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis. PMID:24296261

  8. Quantum Well Infrared Photodetectors (QWIP)

    NASA Technical Reports Server (NTRS)

    Levine, B. F.

    1990-01-01

    There has been a lot of interest in III-V long wavelength detectors in the lambda = 8 to 12 micron spectral range as alternatives to HgCdTe. Recently high performance quantum well infrared photodetectors (QWIP) have been demonstrated. They have a responsivity of R = 1.2 A/W, and a detectivity D(exp asterisk) sub lambda = 2 times 10(exp 10) cm Hz(exp 1/2)/W at 68 K for a QWIP with a cutoff wavelength of lambda sub c = 10.7 micron and a R = 1.0 A/W, and D(exp asterisk) sub lambda = 2 times 10(exp 10) cm Hz(exp 1/2)/W at T = 77 K for lambda sub c = 8.4 micron. These detectors consist of 50 periods of molecular beam epitaxy (MBE) grown layers doped n = 1 times 10(exp 18)cm(exp -3) having GaAs quantum well widths of 40 A and barrier widths of 500 A of Al sub x Ga sub 1-x As. Due to the well-established GaAs growth and processing techniques, these detectors have the potential for large, highly uniform, low cost, high performance arrays as well as monolithic integration with GaAs electronics, high speed and radiation hardness. Latest results on the transport physics, device performance and arrays are discussed.

  9. Quantum Well Infrared Photodetectors (QWIP)

    NASA Astrophysics Data System (ADS)

    Levine, B. F.

    1990-07-01

    There has been a lot of interest in III-V long wavelength detectors in the lambda = 8 to 12 micron spectral range as alternatives to HgCdTe. Recently high performance quantum well infrared photodetectors (QWIP) have been demonstrated. They have a responsivity of R = 1.2 A/W, and a detectivity D(exp asterisk) sub lambda = 2 times 10(exp 10) cm Hz(exp 1/2)/W at 68 K for a QWIP with a cutoff wavelength of lambda sub c = 10.7 micron and a R = 1.0 A/W, and D(exp asterisk) sub lambda = 2 times 10(exp 10) cm Hz(exp 1/2)/W at T = 77 K for lambda sub c = 8.4 micron. These detectors consist of 50 periods of molecular beam epitaxy (MBE) grown layers doped n = 1 times 10(exp 18)cm(exp -3) having GaAs quantum well widths of 40 A and barrier widths of 500 A of Al sub x Ga sub 1-x As. Due to the well-established GaAs growth and processing techniques, these detectors have the potential for large, highly uniform, low cost, high performance arrays as well as monolithic integration with GaAs electronics, high speed and radiation hardness. Latest results on the transport physics, device performance and arrays are discussed.

  10. Fall-Back Disks in Long and Short GRBS

    NASA Technical Reports Server (NTRS)

    Cannizo, John K.; Troja, E.; Gehrels, N.

    2011-01-01

    We present numerical time-dependent calculations for fall-back disks relevant for GRBs in which the disk of material surrounding the black hole (BH) powering the GRB jet modulates the mass flow, and hence the strength of the jet. Given the initial existence of a small mass appr oximately less than 10(exp -4) M(solar) near the progenitor with a circularization radius approximately 10(exp 10) - 10(exp 11) cm, an una voidable consequence will be the formation of an "external disk" whose outer edge continually moves to larger radii due to angular momentum transport and lack of a confining torque. For long GRBs, if the mass distribution in the initial fall-back disk traces the progenitor envelope, then a radius approximates 10(exp 11) cm gives a time scale app roximately 10(exp 4) s for the X-ray plateau. For late times t > 10(exp 7) s a steepening due to a cooling front in the disk may have obser vational support in GRB 060729. For short GRBs, one expects most of t he mass initially to lie at small radii < 10(exp 8) cm; however the presence of even a trace amount approximately 10(exp -9) M(solar) of hi gh angular material can give a brief plateau in the light curve.

  11. Measurements of Heat Transfer and Boundary-Layer Transition on an 8-Inch-Diameter Hemisphere-Cylinder in Free Flight for a Mach Number Range of 2.00 to 3.88

    NASA Technical Reports Server (NTRS)

    Garland, Benjamine J.; Chauvin, Leo T.

    1957-01-01

    Measurements of aerodynamic heat transfer have been made along the hemisphere and cylinder of a hemisphere-cylinder rocket-propelled model in free flight up to a Mach number of 3.88. The test Reynolds number based on free-stream condition and diameter of model covered a range from 2.69 x l0(exp 6) to 11.70 x 10(exp 6). Laminar, transitional, and turbulent heat-transfer coefficients were obtained. The laminar data along the body agreed with laminar theory for blunt bodies whereas the turbulent data along the cylinder were consistently lower than that predicted by the turbulent theory for a flat plate. Measurements of heat transfer at the stagnation point were, in general, lower than the theory for stagnation-point heat transfer. When the Reynolds number to the junction of the hemisphere-cylinder was greater than 6 x l0(exp 6), the transitional Reynolds number varied from 0.8 x l0(exp 6) to 3.0 x 10(exp 6); however, than 6 x l(exp 6) when the Reynolds number to the junction was less, than the transitional Reynolds number varied from 7.0 x l0(exp 6) to 24.7 x 10(exp 6).

  12. Ultra-Sensitive Transition-Edge Sensors for the Background Limited Infrared/Sub-mm Spectrograph (BLISS)

    NASA Technical Reports Server (NTRS)

    Beyer, A. D.; Kenyon, M. E.; Echternach, P. M.; Chui, T.; Eom, B.-H.; Day, P. K.; Bock, J. J.; Holmes, W.A.; Bradford, C. M.

    2011-01-01

    We report progress in fabricating ultra-sensitive superconducting transition-edge sensors (TESs) for BLISS. BLISS is a suite of grating spectrometers covering 35-433 micron with R approx. 700 cooled to 50 mK that is proposed to fly on the Japanese space telescope SPICA. The detector arrays for BLISS are TES bolometers readout with a time domain SQUID multiplexer. The required noise equivalent power (NEP) for BLISS is NEP = 10(exp -19) W/Hz(exp 1/2) with an ultimate goal of NEP= 5 x 10(exp -20) W/Hz(exp 1/2) to achieve background limited noise performance. The required and goal response times are tau = 150 ms and tau = 50ms respectively to achieve the NEP at the required and goal optical chop frequency 1-5 Hz. We measured prototype BLISS arrays and have achieved NEP = 6 x 10(exp -18) W/Hz(exp 1/2) and tau = 1.4 ms with a Ti TES (T(sub C) = 565 mK) and NEP approx. 2.5 x 10(exp -19) W/Hz(exp 1/2) and tau approximates 4.5 ms with an Ir TES (T(sub C) = 130 mK). Dark power for these tests is estimated at 1-5 fW.

  13. Co-encapsulated resveratrol and quercetin in chitosan and peg modified chitosan nanoparticles: For efficient intra ocular pressure reduction.

    PubMed

    Natesan, Subramanian; Pandian, Saravanakumar; Ponnusamy, Chandrasekar; Palanichamy, Rajaguru; Muthusamy, Sivakumar; Kandasamy, Ruckmani

    2017-11-01

    Natural anti-oxidants resveratrol (RES) and quercetin (QUR) posses the ability to reduce intra ocular pressure efficiently. Concurrent administration of RES and QUR was able to enhance the bioavailability of RES. Present research work describes upsurge of QUR in RES loaded chitosan (CS) nanoparticles (NPs) and polyethylene glycol (PEG) modified CS NPs for improved delivery and synergic effects on reducing intra ocular pressure for the treatment of glaucoma. CS NPs and PEG modified CS NPs were prepared by ionic gelation of tripolyphosphate and CS. The synthesised NPs were spherical in shape and RES entrapment and loading efficiency in the formulation decreased with increasing PEG concentration. Particle size of the formulation increased while incorporating PEG and drugs. The crystalline nature of RES and QUR changed in the NPs and that was confirmed by XRD study. Free radical neutralising efficiency improved while incorporating QUR in the formulation. Ex-vivo corneal permeation of RES was higher from RES and QUR loaded formulation than RES alone containing NPs and free RES dispersion. RES and QUR loaded PEG modified CS NPs showed sustained and enhanced reduction of intra ocular pressure (5.5±0.5mmHg) in normotensive rabbits. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Time Correlations and the Frequency Spectrum of Sound Radiated by Turbulent Flows

    NASA Technical Reports Server (NTRS)

    Rubinstein, Robert; Zhou, Ye

    1997-01-01

    Theories of turbulent time correlations are applied to compute frequency spectra of sound radiated by isotropic turbulence and by turbulent shear flows. The hypothesis that Eulerian time correlations are dominated by the sweeping action of the most energetic scales implies that the frequency spectrum of the sound radiated by isotropic turbulence scales as omega(exp 4) for low frequencies and as omega(exp -3/4) for high frequencies. The sweeping hypothesis is applied to an approximate theory of jet noise. The high frequency noise again scales as omega(exp -3/4), but the low frequency spectrum scales as omega(exp 2). In comparison, a classical theory of jet noise based on dimensional analysis gives omega(exp -2) and omega(exp 2) scaling for these frequency ranges. It is shown that the omega(exp -2) scaling is obtained by simplifying the description of turbulent time correlations. An approximate theory of the effect of shear on turbulent time correlations is developed and applied to the frequency spectrum of sound radiated by shear turbulence. The predicted steepening of the shear dominated spectrum appears to be consistent with jet noise measurements.

  15. The effect of nitrate and monensin on in vitro ruminal fermentation.

    PubMed

    Capelari, M; Powers, W

    2017-11-01

    Two experiments evaluated the effect of calcium ammonium nitrate decahydrate (calcium nitrate [NIT]) and monensin sodium (MON) on in vitro fermentation parameters of 2 contrasting diets (100:0 and 10:90 forage-to-concentrate ratios). Diet addition of NIT (0, 1.25, and 2.5 g/100 g DM) and MON (0, 3, and 6 mg/L) were tested alone and combined (9 treatments total; 5 bottles per treatment). Mixed ruminal microorganisms were incubated in anaerobic media containing 0.5 g of substrate diet, 1 of 9 treatments, and 40 mL buffer solution. Incubations were performed in batch cultures for 48 h at 39°C. Headspace gas volume was measured and sampled at 4, 8, 12, 24, and 48 h, and the VFA profile was assessed at the end of the experiment. Total gas production was reduced by NIT (87.9 vs. 94.6 mL; < 0.01) and MON (78.6 vs. 94.6 mL; < 0.01) and, in Exp. 2, further reduced by NIT+MON when the additives were combined (161.1 vs. 196.9 mL; < 0.01). Methane production from control in Exp. 1 and Exp. 2 averaged 9.1 and 15.3 mL, respectively, and was decreased by NIT (3.4 and 8.3 mL in Exp. 1 and Exp. 2, respectively; P < 0.01), MON (4.1 and 7.7 mL; in Exp. 1 and Exp. 2, respectively; < 0.01) and NIT+MON (1.1 and 1.5 mL; in Exp. 1 and Exp. 2, respectively; < 0.01). Both experiments demonstrated a significant increase in nitrous oxide (NO; < 0.01) when NIT was added. Compared to the control treatment, IVDMD was reduced when NIT+MON was added at the higher doses in EXP1 (31.7 vs. 37.4%; < 0.01) and EXP2 (76.6 vs. 79.9 %; < 0.01). Net VFA production was not affected by treatments ( > 0.10), but molar proportions of acetate and butyrate were reduced by MON ( < 0.01). Propionate molar proportion was increased in both experiments by MON ( < 0.01) and further increased in Exp. 2 when the additives were combined at lower doses ( < 0.01). Compared to the control treatment, the acetate:propionate (A:P) ratio was reduced by MON in Exp. 1(1.2 vs. 2.8; < 0.01) and Exp. 2 (1.0 vs. 2.3; < 0.01). Fermentation efficiency (%) was increased by MON (81.7 vs. 73.7%; < 0.01) and further increased in Exp. 2 when the additives were combined at lower doses (87.2 vs. 76.6%; < 0.01). The combination of NIT and MON in 2 contrasting diets proved beneficial by altering fermentation products toward lower CH and more propionate; however, the addition of NIT consistently increased NO production. Negative effects of the additives on IVDMD were found only when the additives were combined at higher doses.

  16. Functional Role for Humoral Antibodies in Leishmaniasis in Laboratory Animal.

    DTIC Science & Technology

    1982-12-01

    vitro; inhibition of growth of intracellular Mycobacterium leprae with lymphokines. Clin. Exp. Immunol. 8:625-637. Herman, R. 1980. Cytophilic and...lymphocytes. Thus, inhibition of intracellular replication of Listeria monocytogenes (Simon and Sheagren, 1972), Mycobacterium tuberculosis (North, 1974...M. leprae (Godal et al., 1971) and Rickettsia tsutsugamushi (Nacy and Meltzer, 1979) have all been demonstrated after infected cells, in vitro, were

  17. Technology, design, simulation, and evaluation for SEP-hardened circuits

    NASA Technical Reports Server (NTRS)

    Adams, J. R.; Allred, D.; Barry, M.; Rudeck, P.; Woodruff, R.; Hoekstra, J.; Gardner, H.

    1991-01-01

    This paper describes the technology, design, simulation, and evaluation for improvement of the Single Event Phenomena (SEP) hardness of gate-array and SRAM cells. Through the use of design and processing techniques, it is possible to achieve an SEP error rate less than 1.0 x 10(exp -10) errors/bit-day for a 9O percent worst-case geosynchronous orbit environment.

  18. DEVELOPMENTAL TOXICITY OF 2-CHLORO-2'-DEOXYADENOSINE IN THE RAT: INDUCTION OF LUMBAR HERNIA

    EPA Science Inventory

    DEVELOPMENTAL TOXICITY OF 2-CHLORO-2'DEOXYADENOSINE IN THE RAT: INDUCTION OF LUMBAR HERNIA. C. Lau1, M.G. Narotsky1, D. Lui1, D. Best1, R.W. Setzer2, T.B. Knudsen3. 1Reprod. Tox. Div., 2Exp. Tox. Div., NHEERL, US EPA, Research Triangle Park, NC, USA, 3Dept. Path. Anat. Cell Bio...

  19. LEO Flight Testing of GaAs on Si Solar Cells Aboard MISSES

    NASA Technical Reports Server (NTRS)

    Wilt, David M.; Clark, Eric B.; Ringel, Steven A.; Andre, Carrie L.; Smith, Mark A.; Scheiman, David A.; Jenkins, Phillip P.; Maurer, William F.; Fitzgerald, Eugene A.; Walters, R. J.

    2004-01-01

    Previous research efforts have demonstrated small area (0.04 cm) GaAs on Si (GaAs/Si) solar cells with AM0 efficiencies in excess of 17%. These results were achieved on Si substrates coated with a step graded buffer of Si(x),Ge(1-x) alloys graded to 100% Ge. Recently, a 100-fold increase in device area was accomplished for these devices in preparation for on-orbit testing of this technology aboard Materials International Space Station Experiment number 5 (MISSE5). The GaAs/Si MISSE5 experiment contains five (5) GaAs/Si test devices with areas of lcm(exp 2) and 4cm(exp 4) as well as two (2) GaAs on GaAs control devices. Electrical performance data, measured on-orbit for three (3) of the test devices and one (1) of the control devices, will be telemetered to ground stations daily. After approximately one year on orbit, the MISSE5 payload will be returned to Earth for post flight evaluation. This paper will discuss the development of the GaAs/Si devices for the MISSE5 flight experiment and will present recent ground and on-orbit performance data.

  20. Effective Thermal Conductivity of High Porosity Open Cell Nickel Foam

    NASA Technical Reports Server (NTRS)

    Sullins, Alan D.; Daryabeigi, Kamran

    2001-01-01

    The effective thermal conductivity of high-porosity open cell nickel foam samples was measured over a wide range of temperatures and pressures using a standard steady-state technique. The samples, measuring 23.8 mm, 18.7 mm, and 13.6 mm in thickness, were constructed with layers of 1.7 mm thick foam with a porosity of 0.968. Tests were conducted with the specimens subjected to temperature differences of 100 to 1000 K across the thickness and at environmental pressures of 10(exp -4) to 750 mm Hg. All test were conducted in a gaseous nitrogen environment. A one-dimensional finite volume numerical model was developed to model combined radiation/conduction heat transfer in the foam. The radiation heat transfer was modeled using the two-flux approximation. Solid and gas conduction were modeled using standard techniques for high porosity media. A parameter estimation technique was used in conjunction with the measured and predicted thermal conductivities at pressures of 10(exp -4) and 750 mm Hg to determine the extinction coefficient, albedo of scattering, and weighting factors for modeling the conduction thermal conductivity. The measured and predicted conductivities over the intermediate pressure values differed by 13%.

  1. MPEG-2 Over Asynchronous Transfer Mode (ATM) Over Satellite Quality of Service (QoS) Experiments: Laboratory Tests

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Frantz, Brian D.; Spells, Marcus J.

    1998-01-01

    Asynchronous transfer mode (ATM) quality of service (QoS) experiments were performed using MPEG-2 (ATM application layer 5, AAL5) over ATM over an emulated satellite link. The purpose of these experiments was to determine the free-space link quality necessary to transmit high-quality multimedia information by using the ATM protocol. The detailed test plan and test configuration are described herein as are the test results. MPEG-2 transport streams were baselined in an errored environment, followed by a series of tests using, MPEG-2 over ATM. Errors were created both digitally as well as in an IF link by using a satellite modem and commercial gaussian noise test set for two different MPEG-2 decoder implementations. The results show that ITU-T Recommendation 1.356 Class 1, stringent ATM applications will require better link quality than currently specified; in particular, cell loss ratios of better than 1.0 x 10(exp -8) and cell error ratios of better than 1.0 x 10(exp -7) are needed. These tests were conducted at the NASA Lewis Research Center in support of satellite-ATM interoperability research.

  2. Optical interferometer in space

    NASA Technical Reports Server (NTRS)

    Bender, Peter L.; Faller, J. E.; Hall, J. L.; Hils, D.; Stebbins, R. T.; Vincent, Mark A.

    1989-01-01

    The present design concepts for a Laser Gravitational Wave Observatory in Space are described. Laser heterodyne distance measurements are made between test masses located in three spacecraft separated by roughly 10(exp 6) km. The major technology issues are: the reduction of spurious acceleration noise for the test masses to below 2 x 10(exp -15) cm/sq sec/Hz(0.5) from 10(exp -5) to 10(exp -3) Hz; and the measurement of changes in the difference of the antenna arm lengths to 5 x 10(exp -11) cm/Hz(0.5) from 10(exp -3) to 1 Hz with high reliability. The science objectives are: to measure discrete sinusoidal gravitational wave signals from individual sources with periods of 1 second to 1 day; to measure the stochastic background due to unresolved binaries; and to search for gravitational wave pulses with periods longer than 1 sec from possible exotic sources such as gravitational collapse of very massive objects.

  3. Thermochemistry and Kinetics of the Cl+O2 Association Reaction

    NASA Technical Reports Server (NTRS)

    Nicovich, J. M.; Kreutter, K. D.; Shackelford, C. J.; Wine, P. H.

    1997-01-01

    Laser flash photolysis of Cl2/O2 mixtures has been employed in conjunction with Cl((sup 2)P(sub 3/2)) detection by time-resolved fluorescence spectroscopy to investigate equilibration kinetics for the reactions Cl + O2 + O is in equilibrium with ClOO + O2 at temperatures of 181-200 K and O2 pressures of 15-40 Torr. The third-order rate coefficient for the association reaction at 186.5 +/- 5.5 K is (8.9 +/- 2.9) x 10(exp -33) cm(exp 6) molecule(exp -2) s(exp -1) and the equilibrium constant (K(p)) at 185.4 K is 18.9 atm(exp -1) (factor of 1.7 uncertainty). A third law analysis of our data leads to a value for the Cl-OO bond dissociation energy of 4.76 +/- 0.49 kcal mol(exp -1).

  4. The microgravity environment of the Space Shuttle Columbia payload bay during STS-32

    NASA Technical Reports Server (NTRS)

    Dunbar, Bonnie J.; Giesecke, Robert L.; Thomas, Donald A.

    1991-01-01

    Over 11 hours of three-axis microgravity accelerometer data were successfully measured in the payload bay of Space Shuttle Columbia as part of the Microgravity Disturbances Experiment on STS-32. These data were measured using the High Resolution Accelerometer Package and the Aerodynamic Coefficient Identification Package which were mounted on the Orbiter keel in the aft payload bay. Data were recorded during specific mission events such as Orbiter quiescent periods, crew exercise on the treadmill, and numerous Orbiter engine burns. Orbiter background levels were measured in the 10(exp -5) G range, treadmill operations in the 10(exp -3) G range, and the Orbiter engine burns in the 10(exp -2) G range. Induced acceleration levels resulting from the SYNCOM satellite deploy were in the 10 (exp -2) G range, and operations during the pre-entry Flight Control System checkout were in the 10(exp -2) to 10(exp -1) G range.

  5. Radio Detections During Two State Transitions of the Intermediate-Mass Black Hole HLX-1

    NASA Technical Reports Server (NTRS)

    Webb, Natalie; Cseh, David; Lenc, Emil; Godet, Olivier; Barret, Didier; Corbel, Stephane; Farrell, Sean; Fender, Robert; Gehrels, Neil; Heywood, Ian

    2012-01-01

    Relativistic jets are streams of plasma moving at appreciable fractions of the speed of light. They have been observed from stellar-mass black holes (approx. 3 to 20 solar masses) as well as supermassive black holes (approx.. 10(exp 6) to 10(exp 9) Solar Mass) found in the centers of most galaxies. Jets should also be produced by intermediate-mass black holes (approx. 10(exp 2) to 10(exp 5) Solar Mass), although evidence for this third class of black hole has, until recently, been weak. We report the detection of transient radio emission at the location of the intermediate-mass black hole candidate ESO 243-49 HLX-1, which is consistent with a discrete jet ejection event. These observations also allow us to refine the mass estimate of the black hole to be between approx. 9 × 10(exp 3) Solar Mass and approx. 9 × 10(exp 4) Solar Mass.

  6. Study of Flow of Superfluid He-II Very Near Tau(sub lambda)

    NASA Technical Reports Server (NTRS)

    Mukharsky, Yury; Sukhatme, Kalyani; Pearson, David; Chui, Talso

    1999-01-01

    We report here, preliminary data from an experiment studying flow of superfluid helium through a slit orifice (of sub-micron width) very close to T(sub lambda). Critical supercurrent (I(sub c)) data is obtained from a step function drive to the diaphragm in a Helmholtz resonator cell. The superfluid density (rho(sub s)) data can be obtained from the resonant frequency of the Helmholtz oscillator, as determined by transfer function of the resonator or from the free ringing after the step function excitation. Preliminary data shows that I(sub c) is proportional to (rho(sub s))(exp 1.27) and rho(sub s)) is proportional to tau(exp 0.73), where tau is the reduced temperature. However, the magnitude of I(sub c) is much larger than expected, indicating a possible parallel flow path. Further investigations are in progress. Keywords: superfluid; hydrodynamics; critical exponent

  7. Solubility of methanol in low-temperature aqueous sulfuric acid and implications for atmospheric particle composition

    NASA Technical Reports Server (NTRS)

    Iraci, Laura T.; Essin, Andrew M.; Golden, David M.; Hipskind, R. Stephen (Technical Monitor)

    2001-01-01

    Using traditional Knudsen cell techniques, we find well-behaved Henry's law uptake of methanol in aqueous 45 - 70 wt% H2SO4 solutions at temperatures between 197 and 231 K. Solubility of methanol increases with decreasing temperature and increasing acidity, with an effective Henry's law coefficient ranging from 10(exp 5) - 10(exp 8) M/atm. Equilibrium uptake of methanol into sulfuric acid aerosol particles in the upper troposphere and lower stratosphere will not appreciably alter gas-phase concentrations of methanol. The observed room temperature reaction between methanol and sulfuric acid is too slow to provide a sink for gaseous methanol at the temperatures of the upper troposphere and lower stratosphere. It is also too slow to produce sufficient quantities of soluble reaction products to explain the large amount of unidentified organic material seen in particles of the upper troposphere.

  8. Use of a commercial probiotic supplement in meat goats.

    PubMed

    Whitley, N C; Cazac, D; Rude, B J; Jackson-O'Brien, D; Parveen, S

    2009-02-01

    Sixty-three Boer crossbred goats were used in 5 separate experiments (Exp. 1 to 5) to evaluate the effects of a commercial probiotic supplement on growth performance (Exp. 1 to 4), diet digestibility (Exp. 5), carcass traits (Exp. 3), and fecal bacterial populations (Exp. 4). Goats were either fed a commercially pelleted concentrate diet and supplemented with a commercial probiotic (PRO) that had shown anecdotal positive effects on goat growth and performance according to local goat producers, or they remained as controls. The dose of PRO used was within the labeled dose for sheep for all studies. For Exp. 1, goat BW and feed intake were measured and G:F was calculated every 7 d for 56 d. For Exp. 2 to 4, BW and feed intake were measured and G:F was calculated every 14 d. The first day of supplementation was considered d 0. Carcass traits were also collected at slaughter on d 57 for Exp. 3, and fecal samples were collected every 14 d for microbial culture for Exp. 4. For Exp. 5, which was a digestibility trial that lasted for 10 d, animals were placed in metabolic pens for collection of feces and orts. Growth performance of goats was not affected by probiotic supplementation, with the exception of performance in Exp. 2, in which ADG and G:F were improved (P < 0.03) in PRO goats compared with control goats on d 56 only (treatment x day interaction; P < 0.05), averaging 0.21 +/- 0.02 kg/d for PRO goats and 0.11 +/- 0.02 kg/d for control goats for ADG and 0.17 +/- 0.02 for PRO goats and 0.10 +/- 0.02 for control goats for G:F. Carcass weights and weights of fabricated cuts (shoulder, loin, leg, rack, shank, and total parts) as well as carcass length, leg circumference, loin eye area, and backfat were not influenced by PRO supplementation. Apparent digestibilities of OM, DM, NDF, ADF, CP, and GE (on a DM basis) were similar for the PRO and control treatments. Fecal culture analysis of Escherichia coli and coliforms, Lactobacillus, and Bifidobacterium populations were not influenced by the PRO treatment. Overall, although the PRO treatment affected goat ADG and G:F in Exp. 2, no PRO treatment effects were noted on growth performance for Exp. 1, 3, and 4. Furthermore, the PRO treatment did not affect diet digestibility, carcass traits, or fecal microbial populations in goats. In conclusion, no consistent benefits were noted from supplementing healthy, growing meat goats with PRO.

  9. Effects of reduced dietary energy and amino acid density on Pectoralis major myopathies in broiler chickens at 36 and 49 days of age1.

    PubMed

    Meloche, K J; Fancher, B I; Emmerson, D A; Bilgili, S F; Dozier, W A

    2018-05-01

    Two experiments (Exp) were conducted to determine if reductions in the incidence and severity of wooden breast (WB) and white striping (WS) may be obtained by reducing dietary nutrient density. In each Exp, Yield Plus × Ross 708 male broiler chicks were placed into 63 pens (22 birds/pen). All birds received an identical prestarter diet until 7 d of age, after which time each pen was randomly assigned to 1 of the following 7 dietary treatments (TRT) for the starter (8 to 14 d), grower (15 to 24 d), finisher 1 (Exp 1: 26 to 35 d; Exp 2: 26 to 42 d), and withdrawal (Exp 2: 43 to 48 d) phases: 1) 100% of primary breeder recommendations for digestible amino acid and metabolizable energy density throughout Exp; 2) 95% of TRT 1 until 14 d of age, then as TRT 1; 3) 95% of TRT 1 until 24 d of age, then as TRT 1; 4) 95% of TRT 1 throughout Exp; 5) 90% of TRT 1 until 14 d of age, then as TRT 1; 6) 90% of TRT 1 until 24 d of age, then as TRT 1; 7) 90% of TRT 1 throughout Exp. At 36 d (Exp 1) and 49 d (Exp 2), 18 birds per pen were processed and evaluated for WS and WB. In Exp 1, reduced dietary density in the starter phase (TRT 2 and TRT 5) resulted in increased (P ≤ 0.05) incidences of severe WB (32.9% and 34.7%) relative to TRT 1 (18.2%). In Exp 2, broilers assigned to TRT 7 had reduced (P < 0.01) incidences of severe WB (20.8%) and WS (42.3%) relative to the control (WB: 36.5%; WS: 64.5%). In both Exp, plasma creatine kinase and lactate dehydrogenase increased (P ≤ 0.05) with increasing scores for WB and WS. Reducing dietary nutrient density from 8 to 14 d may exacerbate fillet myopathies in broilers reared to 35 d of age. Although reducing dietary energy and amino acid density to 90% of recommendations from 1 to 48 d reduced the severity of myopathies, these reductions occurred with compromises in live performance. Altogether, these results indicated that concurrent manipulation of dietary amino acid and energy density is not a viable practical solution for breast myopathies.

  10. Fred Hutchinson Cancer Research Center (FHCRC-1): Functional Exploration of the Druggable Genome in MYCN Amplified and Non-amplified Neuroblastoma | Office of Cancer Genomics

    Cancer.gov

    To identify candidate drugs targets for neuroblastoma with MYCN amplification we performed parallel siRNA screens with a druggable genome collection of ~6,700 genes comparing MYCN amplified and non-MYCN amplified cell lines: SK-N-BE2 (MYCN amplified) and SK-N-AS (non amplified).  The Hits from each cell lines were determined based on their significance with respect to their differential activity in the presence or absence of RA within each cell line.  Hits for each cell line were also ranked according to their P-value, based on the three replicates.  Integration with gene exp

  11. Results of the 1996 JPL Balloon Flight Solar Cell Calibration Program

    NASA Technical Reports Server (NTRS)

    Anspaugh, B. E.; Weiss, R. S.

    1996-01-01

    The 1996 solar cell calibration balloon flight campaign was completed with the first flight on June 30, 1996 and a second flight on August 8, 1996. All objectives of the flight program were met. Sixty-four modules were carried to an altitude of 120,000 ft (36.6 km). Full 1-5 curves were measured on 22 of these modules, and output at a fixed load was measured on 42 modules. This data was corrected to 28 C and to 1 AU (1.496 x 10(exp 8) km). The calibrated cells have been returned to the participants and can now be used as reference standards in simulator testing of cells and arrays.

  12. Low LBNP Tolerance in Men is Associated With Attenuated Activation of The Renin-Angiotensin System

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N.-J.; Warberg, J.; Videbaeck, R.; Simonson, S. R.; Norsk, P.

    1999-01-01

    Vasoactive hormone concentrations [epinephrine (pE), norepinephrine (pNE), angiotensin II (pATII), vasopressin (pVP), endothelin 1 (pET1)] and plasma renin activity (pRA) were measured during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system is related to LBNP tolerance. Healthy men (2,822 cal/day(exp -1), 2 mmol*kg(exp -1)*day(exp -1)) Na(+)) were exposed to 30 minutes of progressive LBNP to -50 mmHg. LBNP was uneventful for seven men (25 +/- 2 years, HiTol group), but eight men (26 +/- 3 years) reached pre-syncope after 11 +/- 1 minutes (P < 0.001, LoTol group). Mean arterial pressure was unchanged. Central venous pressure and left atrial diameter decreased in both groups (5-6 mmHg by approx. 30%, P < 0.05). Control [hormone] were similar but, pRA differed between groups (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng Ang1/(ml(exp -1)*h(exp -1)), P < 0.05). LBNP increased (P < 0.05) pRA and pATII more in HiTol (9.9 +/- 2.2 ng Ang1/(ml(exp -1)*h(exp -1)) and 58 +/- 12 pg/ml(exp -1)) than LoTol (4.3 +/- 0.9 ng Ang1/(ml*h) and 28 +/- 6 pg/ml(exp -1)). In contrast, pVP was higher (P < 0.05) in LoTol than in HiTol. The response of the renin-angiotensin system seems linked to the occurrence of pre-syncope, and measurement of resting pRA may be predictive.

  13. Thermophysical Properties Along Curiosity's Traverse in Gale Crater, Mars, Derived from the REMS Ground Temperature Sensor

    NASA Technical Reports Server (NTRS)

    Vasavada, Ashwin R.; Piqueux, Sylvain; Lewis, Kevin W.; Lemmon, Mark T.; Smith, Michael Doyle

    2016-01-01

    The REMS instrument onboard the Mars Science Laboratory rover, Curiosity, has measured ground temperature nearly continuously at hourly intervals for two Mars years. Coverage of the entire diurnal cycle at 1 Hz is available every few martian days. We compare these measurements with predictions of surface atmosphere thermal models to derive the apparent thermal inertia and thermally derived albedo along the rovers traverse after accounting for the radiative effects of atmospheric water ice during fall and winter, as is necessary to match the measured seasonal trend. The REMS measurements can distinguish between active sand, other loose materials, mudstone, and sandstone based on their thermophysical properties. However, the apparent thermal inertias of bedrock dominated surfaces [approx. 350-550 J m(exp. -2) K(exp. -1 s(exp. -1/2 )] are lower than expected. We use rover imagery and the detailed shape of the diurnal ground temperature curve to explore whether lateral or vertical heterogeneity in the surface materials within the sensor footprint might explain the low inertias. We find that the bedrock component of the surface can have a thermal inertia as high as 650-1700 J m(exp. -2) K(exp. -1) s(exp. -1/2) for mudstone sites and approx. 700 J m(exp. -2) K(exp. -1) s(exp. - 1/2) for sandstone sites in models runs that include lateral and vertical mixing. Although the results of our forward modeling approach may be non-unique, they demonstrate the potential to extract information about lateral and vertical variations in thermophysical properties from temporally resolved measurements of ground temperature.

  14. Near-ambient solid polymer fuel cell

    NASA Technical Reports Server (NTRS)

    Holleck, G. L.

    1993-01-01

    Fuel cells are extremely attractive for extraterrestrial and terrestrial applications because of their high energy conversion efficiency without noise or environmental pollution. Among the various fuel cell systems the advanced polymer electrolyte membrane fuel cells based on sulfonated fluoropolymers (e.g., Nafion) are particularly attractive because they are fairly rugged, solid state, quite conductive, of good chemical and thermal stability and show good oxygen reduction kinetics due to the low specific adsorption of the electrolyte on the platinum catalyst. The objective of this program is to develop a solid polymer fuel cell which can efficiently operate at near ambient temperatures without ancillary components for humidification and/or pressurization of the fuel or oxidant gases. During the Phase 1 effort we fabricated novel integral electrode-membrane structures where the dispersed platinum catalyst is precipitated within the Nafion ionomer. This resulted in electrode-membrane units without interfacial barriers permitting unhindered water diffusion from cathode to anode. The integral electrode-membrane structures were tested as fuel cells operating on H2 and O2 or air at 1 to 2 atm and 10 to 50 C without gas humidification. We demonstrated that cells with completely dry membranes could be self started at room temperature and subsequently operated on dry gas for extended time. Typical room temperature low pressure operation with unoptimized electrodes yielded 100 mA/cm(exp 2) at 0.5V and maximum currents over 300 mA/cm(exp 2) with low platinum loadings. Our results clearly demonstrate that operation of proton exchange membrane fuel cells at ambient conditions is feasible. Optimization of the electrode-membrane structure is necessary to assess the full performance potential but we expect significant gains in weight and volume power density for the system. The reduced complexity will make fuel cells also attractive for smaller and portable power supplies and as replacement for batteries.

  15. Advanced solar panel designs

    NASA Technical Reports Server (NTRS)

    Ralph, E. L.; Linder, E. B.

    1996-01-01

    Solar panel designs that utilize new high-efficiency solar cells and lightweight rigid panel technologies are described. The resulting designs increase the specific power (W/kg) achievable in the near-term and are well suited to meet the demands of higher performance small satellites (smallsats). Advanced solar panel designs have been developed and demonstrated on two NASA SBIR contracts at Applied Solar. The first used 19% efficient, large area (5.5 cm x 6.5 cm) GaAs/Ge solar cells with a lightweight rigid graphite epoxy isogrid substrate configuration. A 1,445 cm(exp 2) coupon was fabricated and tested to demonstrate 60 W/kg with a high potential of achieving 80 W/kg. The second panel design used new 22% efficiency, dual junction GaInP2/GaAs/Ge solar cells combined with a lightweight aluminum core/graphite fiber mesh facesheet substrate. A 1,445 cm(exp 2) coupon was fabricated and tested to demonstrate 105 W/kg with the potential of achieving 115 W/kg. This paper will address the construction details for the GaAs/isogrid and dual-junction GaAs/carbon mesh panel configurations. These are ultimately sized to provide 75 Watts and 119 Watts respectively for smallsats or may be used as modular building blocks for larger systems. GaAs/isogrid and dual-junction GaAs/carbon mesh coupons have been fabricated and tested to successfully demonstrate critical performance parameters and results are also provided here.

  16. The Tumor Suppressor Actions of the Vitamin D Receptor in Skin

    DTIC Science & Technology

    2013-08-01

    S. Yu, et al., Basal cell carcinomas inmiceoverexpressing Gli2 in skin, Nature Genetics 24 (3) (2000) 216–217. 61] M. Nilsson, A.B. Unden, D. Krause ...Meineke V, Gartner BC, Wolfgang T, Holick MF, Reichrath J. Analysis of the vitamin D system in cutaneous malignancies. Recent Results Cancer Res...10700170] 63. Nilsson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, Toftgard R. Induction of basal cell carcinomas and trichoepitheliomas

  17. Evaluation of NF-B Signaling in T Cells

    DTIC Science & Technology

    2009-01-01

    of cancer cells, ranging from myelomas (46) to breast cancer (47) to esophageal cancer (48), to name a few. NF-κB activation is also implicated in...Sonenshein. 1997. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer . J Clin Invest 100:2952-2960. 48. Abdel-Latif, M... Cancer Res 3:345-353. 43. Hinz, M., D. Krappmann, A. Eichten, A. Heder, C. Scheidereit, and M. Strauss. 1999. NF-kappaB function in growth control

  18. Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42

    PubMed Central

    Guallar, D.; Pérez-Palacios, R.; Climent, M.; Martínez-Abadía, I.; Larraga, A.; Fernández-Juan, M.; Vallejo, C.; Muniesa, P.; Schoorlemmer, J.

    2012-01-01

    Rex1/Zfp42 is a Yy1-related zinc-finger protein whose expression is frequently used to identify pluripotent stem cells. We show that depletion of Rex1 levels notably affected self-renewal of mouse embryonic stem (ES) cells in clonal assays, in the absence of evident differences in expression of marker genes for pluripotency or differentiation. By contrast, marked differences in expression of several endogenous retroviral elements (ERVs) were evident upon Rex1 depletion. We demonstrate association of REX1 to specific elements in chromatin-immunoprecipitation assays, most strongly to muERV-L and to a lower extent to IAP and musD elements. Rex1 regulates muERV-L expression in vivo, as we show altered levels upon transient gain-and-loss of Rex1 function in pre-implantation embryos. We also find REX1 can associate with the lysine-demethylase LSD1/KDM1A, suggesting they act in concert. Similar to REX1 binding to retrotransposable elements (REs) in ES cells, we also detected binding of the REX1 related proteins YY1 and YY2 to REs, although the binding preferences of the two proteins were slightly different. Altogether, we show that Rex1 regulates ERV expression in mouse ES cells and during pre-implantation development and suggest that Rex1 and its relatives have evolved as regulators of endogenous retroviral transcription. PMID:22844087

  19. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The Far-Infrared Spectrum of Arp 220

    NASA Technical Reports Server (NTRS)

    Gonzalez-Alfonso, Eduardo; Smith, Howard A.; Fischer, Jacqueline; Cernicharo, Jose

    2005-01-01

    ISO/LWS grating observations of the ultraluminous infrared galaxy Arp 220 shows absorption in molecular lines of OH, H(sub 2)O, CH, NH, and NH(sub 3), as well as in the [O I] 63 micron line and emission in the [C II] 158 micron line. We have modeled the continuum and the emission/absorption of all observed features by means of a non-local radiative transfer code. The continuum from 25 to 1300 microns is modeled as a warm (106 K) nuclear region that is optically thick in the far-infrared, attenuated by an extended region (size 2") that is heated mainly through absorption of nuclear infrared radiation. The molecular absorption in the nuclear region is characterized by high excitation due to the high infrared radiation density. The OH column densities are high toward the nucleus (2 - 6 x 10(exp 17) cm(exp -2)) and the extended region (approximately 2 x 10(exp 17) cm(exp -2)). The H(sub 2)O column density is also high toward the nucleus (2 - 10 x 10(exp 17) cm(exp -2)) and lower in the extended region. The column densities in a halo that accounts for the absorption by the lowest lying levels are similar to what are found in the diffuse clouds toward the star forming regions in the Sgr B2 molecular cloud complex near the Galactic Center. Most notable are the high column densities found for NH and NH(sub 3) toward the nucleus, with values of approximately 1.5 x 10(exp 16) cm(exp -2) and approximately 3 x 10(exp 16) cm(exp -2), respectively, whereas the NH(sub 2) column density is lower than approximately 2 x 10(exp 15) cm(exp -2). A combination of PDRs in the extended region and hot cores with enhanced H(sub 2)O photodissociation and a possible shock contribution in the nuclei may explain the relative column densities of OH and H(sub 2)O, whereas the nitrogen chemistry may be strongly affected by cosmic ray ionization. The [C II] 158 micron line is well reproduced by our models and its deficit relative to the CII/FIR ratio in normal and starburst galaxies is suggested to be mainly a consequence of the dominant non-PDR component of far-infrared radiation, although our models alone cannot rule out extinction effects in the nuclei.

  1. Electrophoretic separation of cells and particles from rat pituitary. [analysis of pituitary cell electrophoresis experiment done on IML-2 (7/94)

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1995-01-01

    In spite of the fact that a vast majority of the electrophoresis effort (approximately 90%) could not be done on this mission (IML-2) due to failure of FFEU hardware, we find some interesting differences in flight samples obtained from other parts of the experiment. These differences are entirely novel and sometimes unexpected. This report is organized into 4 parts. Each part describes the data collected thus far from each of the 4 cell culture kits (CCK) which flew in space. Each CCK was loaded with 40x10(exp 6) fresh pituitary cells; all CCK's were identical at the start of the experiment because we prepared one pool of cells.

  2. Results of the 1999 JPL Balloon Flight Solar Cell Calibration Program

    NASA Technical Reports Server (NTRS)

    Anspaugh, B. E.; Mueller, R. L.; Weiss, R. S.

    2000-01-01

    The 1999 solar cell calibration balloon flight campaign consisted of two flights, which occurred on June 14, 1999, and July 6, 1999. All objectives of the flight program were met. Fifty-seven modules were carried to an altitude of approximately equal to 120,000 ft (36.6 km). Full I-V curves were measured on five of these modules, and output at a fixed load was measured on forty-three modules (forty-five cells), with some modules repeated on the second flight. This data was corrected to 28 C and to 1 AU (1.496 x 10 (exp 8) km). The calibrated cells have been returned to their owners and can now be used as reference standards in simulator testing of cells and arrays.

  3. Too much carbon in NGC253

    NASA Technical Reports Server (NTRS)

    Harrison, Andrew; Brand, Peter; Puxley, Phil; Russell, Adrian

    1995-01-01

    We have observed C(exp 0) across the nucleus of the starburst galaxy NGC253. C(exp 0) is very bright and we find N(C(exp 0))/N(CO) is between 1.5 and 2.3 across the nucleus. Existing PDR models cannot explain the observed C(exp 0) intensity. The size of the observed region seems to rule out 'simultaneous very early time chemistry' across the nucleus. Chemical models in which C(sup 0)/CO is enhanced deep in molecular clouds by large fluxes of cosmic rays also struggle to explain our observations. The most plausible explanation for the observed C(exp 0) is that the C/O elemental ratio is enhanced in NGC253.

  4. FIFI: The MPE Garching/UC Berkeley Far-Infrared Imaging Fabry-Perot Interferometer

    NASA Technical Reports Server (NTRS)

    Geis, Norbert; Genzel, Reinhard; Haggerty, M.; Herrmann, F.; Jackson, J.; Madden, Suzanne C.; Nikola, T.; Poglitsch, Albrecht; Rumitz, M.; Stacey, G. J.

    1995-01-01

    We describe the performance characteristics of the MPE Garching/UC Berkeley Far-Infrared Imaging Fabry-Perot Interferometer (FIFI) for the Kuiper Airborne Observatory (KAO). The spectrometer features two or three cryogenic tunable Fabry-Perot filters in series giving spectral resolution R of up to 10(exp 5) in the range of 40 microns less than lambda less than 200 microns, and an imaging 5x5 array of photoconductive detectors with variable focal plane plate scale. The instrument works at background limited sensitivity of up to 2 x 10(exp -19) W cm(exp -2) Hz(exp -1/2) per pixel per resolution element at R = 10(exp 5) on the KAO.

  5. Supplemental progesterone and timing of resynchronization on pregnancy outcomes in lactating dairy cows.

    PubMed

    Bilby, T R; Bruno, R G S; Lager, K J; Chebel, R C; Moraes, J G N; Fricke, P M; Lopes, G; Giordano, J O; Santos, J E P; Lima, F S; Stevenson, J S; Pulley, S L

    2013-01-01

    The objective was to determine the effect of exogenous progesterone (P4) in a timed artificial insemination (TAI) protocol initiated at 2 different times post-AI on pregnancies per AI (P/AI) in lactating dairy cows. Cows (n=1,982) in 5 dairy herds were assigned randomly at a nonpregnancy diagnosis 32 ± 3 d post-AI to 1 of 4 resynchronization (RES) treatments arranged in a 2 × 2 factorial design using the Ovsynch-56 (GnRH, 7d later PGF2α, 56 h later GnRH, 16 h later TAI) protocol. Treatments were as follows: cows initiating RES 32 ± 3 d after AI with no supplemental P4 (d 32 RES-CON; n=516); same as d 32 RES-CON plus a controlled internal drug release (CIDR) insert containing P4 at the onset of Ovsynch-56 (d 32 RES-CIDR; n=503); cows initiating RES 39 ± 3 d after AI (d 39 RES-CON; n=494); and same as d 39 RES-CON plus a CIDR (d 39 RES-CIDR; n=491). Cows were inseminated if observed in estrus before TAI. The P/AI was determined 32 and 60 d after TAI. In a subgroup of cows (n=1,152), blood samples were collected and ovarian structures examined by ultrasonography on the days of the first GnRH (G1) and PGF2α of Ovsynch-56. Percentage of cows with a corpus luteum (CL) at G1 was unaffected by timing of treatments, but percentage of cows with a CL at PGF2α was greater for d 32 than for d 39 cows (87.9 vs. 79.4%). In addition, percentage of cows with P4 ≥ 1 ng/mL at G1 was unaffected by timing of treatments, but was increased for d 32 compared with d 39 RES cows on the day of the PGF2α of the RES protocols (86.5 vs. 74.3%). Treatment did not affect ovulation to G1 or P/AI 32 d after RES TAI (d 32 RES-CON=30.1%, d 32 RES-CIDR=28.8%, d 39 RES-CON=27.5%, d 39 RES-CIDR=30.5%). A greater percentage of d 39 RES cows underwent premature luteolysis during the RES protocol compared with d 32 RES cows. An interaction was detected between day of RES initiation and CIDR treatment, in which the CIDR increased P/AI 60 d after TAI for d 39 (CON=23.7% vs. CIDR=28.0%), but not for d 32 (CON=26.9% and CIDR=24.2%) cows. Pregnancy loss was unaffected by treatment. In addition, cows had improved P/AI 60 d after TAI when they received a CIDR and did not have a CL (CON-CL=28.2%, CON-No CL=19.2%, CIDR-CL=27.0%, and CIDR-No CL=26.5%) or had P4 <1 ng/mL (CON-High P4=27.8%, CON-Low P4=15.0%, CIDR-High P4=25.0%, and CIDR-Low P4=29.4%) at G1, but not if a CL was present or P4 was ≥ 1 ng/mL at G1. In conclusion, addition of a CIDR insert to supplement P4 during the RES protocol increased P/AI for cows initiating RES 39 ± 3 d after AI but not 32 ± 3 d after AI. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  6. Improvement in Simulation of Eurasian Winter Climate Variability with a Realistic Arctic Sea Ice Condition in an Atmospheric GCM

    NASA Technical Reports Server (NTRS)

    Lim, Young-Kwon; Ham, Yoo-Geun; Jeong, Jee-Hoon; Kug, Jong-Seong

    2012-01-01

    The present study investigates how much a realistic Arctic sea ice condition can contribute to improve simulation of the winter climate variation over the Eurasia region. Model experiments are set up using different sea ice boundary conditions over the past 24 years (i.e., 1988-2011). One is an atmospheric model inter-comparison (AMIP) type of run forced with observed sea-surface temperature (SST), sea ice, and greenhouse gases (referred to as Exp RSI), and the other is the same as Exp RSI except for the sea ice forcing, which is a repeating climatological annual cycle (referred to as Exp CSI). Results show that Exp RSI produces the observed dominant pattern of Eurasian winter temperatures and their interannual variation better than Exp CSI (correlation difference up to approx. 0.3). Exp RSI captures the observed strong relationship between the sea ice concentration near the Barents and Kara seas and the temperature anomaly across Eurasia, including northeastern Asia, which is not well captured in Exp CSI. Lagged atmospheric responses to sea ice retreat are examined using observations to understand atmospheric processes for the Eurasian cooling response including the Arctic temperature increase, sea-level pressure increase, upper-level jet weakening and cold air outbreak toward the mid-latitude. The reproducibility of these lagged responses by Exp RSI is also evaluated.

  7. Properties Data for Adhesion and Surface Chemistry of Aluminum: Sapphire-Aluminum, Single-Crystal Couple

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa; Pohlchuck, Bobby; Whitle, Neville C.; Hector, Louis G., Jr.; Adams, Jim

    1998-01-01

    An investigation was conducted to examine the adhesion and surface chemistry of single-crystal aluminum in contact with single-crystal sapphire (alumina). Pull-off force (adhesion) measurements were conducted under loads of 0. I to I mN in a vacuum of 10(exp -1) to 10(exp -9) Pa (approx. 10(exp -10) to 10(exp -11) torr) at room temperature. An Auger electron spectroscopy analyzer incorporated directly into an adhesion-measuring vacuum system was primarily used to define the chemical nature of the surfaces before and after adhesion measurements. The surfaces were cleaned by argon ion sputtering. With a clean aluminum-clean -sapphire couple the mean value and standard deviation of pull-off forces required to separate the surfaces were 3015 and 298 micro-N, respectively. With a contaminated aluminum-clean sapphire couple these values were 231 and 241 micro-N. The presence of a contaminant film on the aluminum surface reduced adhesion by a factor of 13. Therefore, surfaces cleanliness, particularly aluminum cleanliness, played an important role in the adhesion of the aluminum-sapphire couples. Pressures on the order of 10(exp -8) to 10(exp -9) Pa (approx. 10(exp -10) to 10(exp -11) torr) maintained a clean aluminum surface for only a short time (less then 1 hr) but maintained a clean sapphire surface, once it was achieved, for a much longer time.

  8. Accretion Disks Around Binary Black Holes of Unequal Mass: GRMHD Simulations Near Decoupling

    NASA Technical Reports Server (NTRS)

    Gold, Roman; Paschalidis, Vasileios; Etienne, Zachariah B.; Shapiro, Stuart L.; Pfeiffer, Harald, P.

    2013-01-01

    We report on simulations in general relativity of magnetized disks onto black hole binaries. We vary the binary mass ratio from 1:1 to 1:10 and evolve the systems when they orbit near the binary disk decoupling radius. We compare (surface) density profiles, accretion rates (relative to a single, non-spinning black hole), variability, effective alpha-stress levels and luminosities as functions of the mass ratio. We treat the disks in two limiting regimes: rapid radiative cooling and no radiative cooling. The magnetic field lines clearly reveal jets emerging from both black hole horizons and merging into one common jet at large distances. The magnetic fields give rise to much stronger shock heating than the pure hydrodynamic flows, completely alter the disk structure, and boost accretion rates and luminosities. Accretion streams near the horizons are among the densest structures; in fact, the 1:10 no-cooling evolution results in a refilling of the cavity. The typical effective temperature in the bulk of the disk is approx. 10(exp5) (M / 10(exp 8)M solar mass (exp -1/4(L/L(sub edd) (exp 1/4K) yielding characteristic thermal frequencies approx. 10 (exp 15) (M /10(exp 8)M solar mass) (exp -1/4(L/L (sub edd) (1+z) (exp -1)Hz. These systems are thus promising targets for many extragalactic optical surveys, such as LSST, WFIRST, and PanSTARRS.

  9. Anomalous Variability in Antarctic Sea Ice Extents During the 1960s With the Use of Nimbus Data

    NASA Technical Reports Server (NTRS)

    Gallaher, David W.; Campbell, G. Garrett; Meier, Walter N.

    2013-01-01

    The Nimbus I, II, and III satellites provide a new opportunity for climate studies in the 1960s. The rescue of the visible and infrared imager data resulted in the utilization of the early Nimbus data to determine sea ice extent. A qualitative analysis of the early NASA Nimbus missions has revealed Antarctic sea ice extents that are significant larger and smaller than the historic 1979-2012 passive microwave record. The September 1964 ice mean area is 19.7x10(exp 6) sq. km +/- 0.3x10(exp 6) sq. km. This is more the 250,000 sq. km greater than the 19.44x10(exp 6) sq. km seen in the new 2012 historic maximum. However, in August 1966 the maximum sea ice extent fell to 15.9x10(exp 6) sq. km +/- 0.3x10(exp 6) sq. km. This is more than 1.5x10(exp 6) sq. km below the passive microwave record of 17.5x10(exp 6) sq. km set in September of 1986. This variation between 1964 and 1966 represents a change of maximum sea ice of over 3x10(exp 6) sq. km in just two years. These inter-annual variations while large, are small when compared to the Antarctic seasonal cycle.

  10. Analytic theory of the selection mechanism in the Saffman-Taylor problem. [concerning shape of fingers in Hele-Shaw cell

    NASA Technical Reports Server (NTRS)

    Hong, D. C.; Langer, J. S.

    1986-01-01

    An analytic approach to the problem of predicting the widths of fingers in a Hele-Shaw cell is presented. The analysis is based on the WKB technique developed recently for dealing with the effects of surface tension in the problem of dendritic solidification. It is found that the relation between the dimensionless width lambda and the dimensionless group of parameters containing the surface tension, nu, has the form lambda - 1/2 = nu exp 2/3 in the limit of small nu.

  11. Treatment Induced Autophagy Associated with Tumor Dormancy and Relapse

    DTIC Science & Technology

    2016-07-01

    for the autophagy gene , ATG5 (Figure 2A). Figure 2B confirms that autophagy was inhibited based on interference with the degradation of p62/SQSTM1 and...post IR (6Gy) LC.3.B GAPDH Figure 2. Silencing of autophagy in MMC cells. (A) Sh RNA mediated silencing of the autophagy gene , ATG5, in MMC cells...they sleep ? J Pharmacol Exp Ther 2012; 343(3):763-78. 9. Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec

  12. A new strategy for superior reproductive performance of ewes bred out-of-season utilizing progestagen supplement prior to withdrawal of intravaginal pessaries.

    PubMed

    Husein, M Q; Ababneh, M M

    2008-02-01

    Two experiments were conducted to examine the effect of progestagen supplement 24h prior to intravaginal pessary withdrawal on reproductive performance of seasonal anestrous ewes. Ewes in each experiment were allocated to treatment and control and all were induced to estrus using either intravaginal MAP (Exp. 1; n=24) or CIDR-G (Exp. 2; n=28) pessaries for 12 days. Half of the ewes in each experiment were supplemented 24h before withdrawal of pessaries with either 10mg oral MAP tablets (Exp. 1) or 25mg i.m. progesterone (P(4)) administration (Exp. 2; P(4)-supplement-treated group). Fertile rams were allowed with the ewes at sponge removal (Day 0, 0h) and estrus was monitored at 6-h intervals for 3 days. Blood samples were collected for measurements of P(4) (Exp. 1 and Exp. 2) and LH (Exp. 2). In both experiments, the percent of ewes in estrus was greater (P<0.05) and intervals to estrus were longer (P<0.05) in progestagen-supplement-treated than control ewes. In Exp. 2, the occurrence and magnitude of LH surges were greater (P<0.01) and intervals to onset of LH surge were longer (P<0.01) in P(4)-supplement-treated than control ewes. In Exp. 2, P(4) supplement elevated P(4) levels from 1.8+/-0.1ng/mL on Day -1 to 4.2+/-0.3 on Day 0 (P<0.001). Following pessaries removal, P(4) concentrations fell to basal values on Day 1 in both groups and remained low until Day 5. Then, P(4) concentrations increased and remained elevated through Day 19 in all (100%) progestagen-supplement-treated in Exp. 1 (12/12) and Exp. 2 (14/14) and in only 5/12 (41.7%) and 6/14 (42.9%) control ewes, respectively. These ewes were confirmed pregnant by ultrasonography and lambed on Day 149.2+/-0.2 following Day 0. In conclusion, progestagen supplement 24h prior to removal of pessary can be used successfully to improve reproductive performance of ewes bred out-of-season.

  13. Digestible lysine requirements of male broilers from 1 to 42 days of age reassessed.

    PubMed

    Cemin, Henrique Scher; Vieira, Sergio Luiz; Stefanello, Catarina; Kipper, Marcos; Kindlein, Liris; Helmbrecht, Ariane

    2017-01-01

    Three experiments were conducted separately to estimate the digestible Lys (dig. Lys) requirements of Cobb × Cobb 500 male broilers using different statistical models. For each experiment, 1,200 chicks were housed in 48 floor pens in a completely randomized design with 6 treatments and 8 replicates. Broilers were fed diets with increasing dig. Lys levels from 1 to 12 d (Exp. 1), from 12 to 28 d (Exp. 2), and 28 to 42 d (Exp. 3). Increasing dig. Lys levels were equally spaced from 0.97 to 1.37% in Exp. 1, 0.77 to 1.17% in Exp. 2, and 0.68 to 1.07% in Exp. 3. The lowest dig. Lys diets were not supplemented with L-Lysine and all other essential AA met or exceeded recommendations. In Exp. 3, six birds per pen were randomly selected from each replication to evaluate carcass and breast yields. Digestible Lys requirements were estimated by quadratic polynomial (QP), linear broken-line (LBL), quadratic broken-line (QBL), and exponential asymptotic (EA) models. Overall, dig. Lys requirements varied among response variables and statistical models. Increasing dietary dig. Lys had a positive effect on BW, carcass and breast yields. Levels of dig. Lys that optimized performance using QP, LBL, QBL, and EA models were 1.207, 1.036, 1.113, and 1.204% for BWG and 1.190, 1.027, 1.100, and 1.172% for FCR in Exp. 1; 1.019, 0.853, 0.944; 1.025% for BWG and 1.050, 0.879, 1.032, and 1.167% for FCR in Exp. 2; and 0.960, 0.835, 0.933, and 1.077% for BWG, 0.981, 0.857, 0.963, and 1.146% for FCR in Exp. 3. The QP, LBL, QBL, and EA also estimated dig. Lys requirements as 0.941, 0.846, 0.925, and 1.070% for breast meat yield in Exp. 3. In conclusion, Lys requirements vary greatly according to the statistical analysis utilized; therefore, the origin of requirement estimation must be taken into account in order to allow adequate comparisons between references.

  14. Reconstruction of ionic currents in a molluscan photoreceptor.

    PubMed Central

    Sakakibara, M.; Ikeno, H.; Usui, S.; Collin, C.; Alkon, D. L.

    1993-01-01

    Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+. PMID:8369456

  15. Digestible lysine requirements of male broilers from 1 to 42 days of age reassessed

    PubMed Central

    Cemin, Henrique Scher; Stefanello, Catarina; Kipper, Marcos; Kindlein, Liris; Helmbrecht, Ariane

    2017-01-01

    Three experiments were conducted separately to estimate the digestible Lys (dig. Lys) requirements of Cobb × Cobb 500 male broilers using different statistical models. For each experiment, 1,200 chicks were housed in 48 floor pens in a completely randomized design with 6 treatments and 8 replicates. Broilers were fed diets with increasing dig. Lys levels from 1 to 12 d (Exp. 1), from 12 to 28 d (Exp. 2), and 28 to 42 d (Exp. 3). Increasing dig. Lys levels were equally spaced from 0.97 to 1.37% in Exp. 1, 0.77 to 1.17% in Exp. 2, and 0.68 to 1.07% in Exp. 3. The lowest dig. Lys diets were not supplemented with L-Lysine and all other essential AA met or exceeded recommendations. In Exp. 3, six birds per pen were randomly selected from each replication to evaluate carcass and breast yields. Digestible Lys requirements were estimated by quadratic polynomial (QP), linear broken-line (LBL), quadratic broken-line (QBL), and exponential asymptotic (EA) models. Overall, dig. Lys requirements varied among response variables and statistical models. Increasing dietary dig. Lys had a positive effect on BW, carcass and breast yields. Levels of dig. Lys that optimized performance using QP, LBL, QBL, and EA models were 1.207, 1.036, 1.113, and 1.204% for BWG and 1.190, 1.027, 1.100, and 1.172% for FCR in Exp. 1; 1.019, 0.853, 0.944; 1.025% for BWG and 1.050, 0.879, 1.032, and 1.167% for FCR in Exp. 2; and 0.960, 0.835, 0.933, and 1.077% for BWG, 0.981, 0.857, 0.963, and 1.146% for FCR in Exp. 3. The QP, LBL, QBL, and EA also estimated dig. Lys requirements as 0.941, 0.846, 0.925, and 1.070% for breast meat yield in Exp. 3. In conclusion, Lys requirements vary greatly according to the statistical analysis utilized; therefore, the origin of requirement estimation must be taken into account in order to allow adequate comparisons between references. PMID:28636626

  16. Chromic oxide and acid-insoluble ash as markers in digestibility studies with growing pigs and sows.

    PubMed

    Brestenský, M; Nitrayová, S; Heger, J; Patráš, P

    2017-02-01

    The results of three experiments, focused on the determination of endogenous ileal flow (EIF) of amino acids (AA) and nitrogen (N) (Exp. 1), apparent ileal digestibility (AID) of AA and N (Exp. 2), and apparent total tract digestibility (ATTD) of dry matter (DM), organic matter (OM), N, calcium (Ca) and phosphorus (P) (Exps. 2 and 3), were used to compare chromic oxide (Cr 2 O 3 ) and acid-insoluble ash (AIA) as digestibility markers. In Exps. 1 and 2, a total of six gilts fitted with T-cannula in terminal ileum, and in Exp. 3, a total of 24 pregnant sows were used. In Exps. 1 and 2, the pigs were assigned into four dietary treatments according to 4 × 6 crossover design (Exp. 1; diets with 0%, 4%, 8% and 12% of casein; Exp. 2 basal diet with different levels of phytase). In Exp. 3, the sows were assigned to four dietary treatments (basal diet with different levels of phytase) of six sows. In Exps. 1 and 2 ileal digesta and in Exps. 2 and 3 faeces were collected for the determination of EIF, AID and ATTD. Differences in EIF of AA determined by Cr 2 O 3 and AIA ranged (p ˃ 0.05) from -4.62 to 4.54%. The lowest EIF was for methionine and the greatest one for proline, determined by both markers. Apparent ileal digestibility determined by Cr 2 O 3 was slightly greater (p ˃ 0.05) in comparison with AIA. Differences ranged from 1.88% (Arg) to 7.08% (Gly). The greatest AID was for arginine and the lowest one for glycine, determined by both Cr 2 O 3 and AIA. Similarly for ATTD of DM, OM, N, Ca and P, there were no differences in digestibility determined by Cr 2 O 3 and AIA. Both, Cr 2 O 3 and AIA, are suitable and comparable markers for digestibility studies in pigs. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  17. Determining the Covering Factor of Compton-Thick Active Galactic Nuclei with NuSTAR

    NASA Technical Reports Server (NTRS)

    Brightman, M.; Balokovic, M.; Stern, D.; Arevalo, P.; Ballantyne, D. R.; Bauer, F. E.; Boggs, S. E.; Craig, W. W.; Christensen, F. E.; Zhang, W. W.

    2015-01-01

    The covering factor of Compton-thick (CT) obscuring material associated with the torus in active galactic nuclei (AGNs) is at present best understood through the fraction of sources exhibiting CT absorption along the line of sight (N(sub H) greater than 1.5 x 10(exp 24) cm(exp -2)) in the X-ray band, which reveals the average covering factor. Determining this CT fraction is difficult, however, due to the extreme obscuration. With its spectral coverage at hard X-rays (greater than 10 keV), Nuclear Spectroscopic Telescope Array (NuSTAR) is sensitive to the AGNs covering factor since Compton scattering of X-rays off optically thick material dominates at these energies. We present a spectral analysis of 10 AGNs observed with NuSTAR where the obscuring medium is optically thick to Compton scattering, so-called CT AGNs. We use the torus models of Brightman and Nandra that predict the X-ray spectrum from reprocessing in a torus and include the torus opening angle as a free parameter and aim to determine the covering factor of the CT gas in these sources individually. Across the sample we find mild to heavy CT columns, with N(sub H) measured from 10(exp 24) to 10(exp 26) cm(exp -2), and a wide range of covering factors, where individual measurements range from 0.2 to 0.9. We find that the covering factor, f(sub c), is a strongly decreasing function of the intrinsic 2-10 keV luminosity, L(sub X), where f(sub c) = (-0.41 +/- 0.13)log(sub 10)(L(sub X)/erg s(exp -1))+18.31 +/- 5.33, across more than two orders of magnitude in L(sub X) (10(exp 41.5) - 10(exp 44) erg s(exp -1)). The covering factors measured here agree well with the obscured fraction as a function of LX as determined by studies of local AGNs with L(sub X) greater than 10(exp 42.5) erg s(exp -1).

  18. Protein Phosphatase 2A Signaling in Human Prostate Cancer

    DTIC Science & Technology

    2013-06-01

    family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 2001;353:417-39. (6) Eto M, Bennouna J, Hunter OC...phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res 1999;59:1449-53. (14) Grethe S, Porn -Ares MI. p38 MAPK regulates phosphorylation of Bad

  19. Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model

    EPA Science Inventory

    AbstractDermal exposure to metals may res·ult in irritant contact dermatitis. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from epidermal keratinocytes. These cultured cells form a m...

  20. The Influence of Iron on the Cellular Quota of Prochlorococcus

    DTIC Science & Technology

    2008-01-01

    as chlorosis, is found in many land plants and larger phytoplankton cells but this is the first laboratory documentation of it occurring in...implications for the hybrid-type trace metals. In press Deep Sea Res II. Raven, J.A., 1990. Predictions of Mn and Fe use efficiencies of phototrophic growth as

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